CN116783309A

CN116783309A - Methods for detecting and predicting cancer and/or CIN3

Info

Publication number: CN116783309A
Application number: CN202180050161.XA
Authority: CN
Inventors: M·魏德施温特; J·巴雷特; A·琼斯; I·埃文斯
Original assignee: UCL Business Ltd
Current assignee: UCL Business Ltd
Priority date: 2020-06-17
Filing date: 2021-06-17
Publication date: 2023-09-19
Also published as: GB202107412D0

Abstract

The present application relates to assays for predicting the presence, absence or progression of cancer, in particular endometrial and ovarian cancer, in an individual by determining the methylation status of certain cpgs in a population of DNA molecules in a sample taken from the individual, deriving an index value based on the methylation status of certain cpgs, and predicting the presence, absence or progression of cancer in the individual based on the cancer index value. The application further relates to methods of treating and/or preventing cancer (particularly endometrial and ovarian cancer) in an individual, comprising assessing the presence, absence, or progression of cancer in an individual by performing an assay of the application, and subsequently administering one or more therapeutic treatments or measures to the individual based on the assessment. The application further provides a method of monitoring a cancer status of an individual based on a change in a cancer index value of the individual over a period of time. The application further relates to a chip suitable for carrying out the assay of the application.

Description

Methods for detecting and predicting cancer and/or CIN3

Sequence listing

The present application contains a sequence listing submitted electronically in ASCII format and is incorporated herein by reference in its entirety. The ASCII copy was created on month 9 of 2021, named "sequence listing N417234WO MGW jas. Txt submitted on month 17 of 2021" and is 564,410 bytes in size.

Technical Field

The present invention relates to assays for predicting the presence, absence or progression of cancer and/or grade 3cervical intraepithelial neoplasia (CIN 3) in an individual, in particular endometrial, ovarian and cervical cancers, by determining the methylation status of certain cpgs, deriving an index value based on the methylation status of certain cpgs in a population of DNA molecules in a sample taken from the individual, and predicting the presence, absence or progression of cancer in the individual based on the cancer index value. The invention further relates to methods of treating and/or preventing cancer, particularly endometrial, ovarian, and cervical cancer, and CIN3 in an individual, comprising assessing the presence, absence, or progression of cancer in an individual by performing an assay of the invention, and subsequently administering one or more therapeutic or prophylactic treatments or measures to the individual based on the assessment. The invention further provides a method of monitoring a cancer status of an individual based on a change in a cancer index value of the individual over a period of time. The invention further relates to a chip (array) suitable for carrying out the assay of the invention.

The programs that motivated this application were sponsored by the European Commission Horizon 2020 (Horizon 2020), H2020 FORECEE under the pattern of 634570, european research Congress executive on the European Commission Horizon 2020, H2020 BRCA-ERC under the pattern of 742432, and the charity Eve Apeal.

Background

Endometrial cancer has become the most common gynaecological cancer in developed countries. By 2030, endometrial cancer is expected to be the third most common cancer affecting women in the united states, next to breast and thyroid cancer. About 20% of women with endometrial cancer exhibit high risk and/or more advanced disease characteristics, with an increased incidence of distant metastasis and cancer-related death, and therefore require adjuvant chemotherapy and radiation therapy in addition to surgery, which are associated with high morbidity.

Thus, there is an urgent need for a tool for early diagnosis and specific prediction of high risk endometrial cancer.

Endometrial cancer screening based on imaging is inefficient. In a group-based nested case control study in postmenopausal women, transvaginal ultrasound for one year showed that the sensitivity was only 54.1% and the positive predictive value was 6.1% for endometrial thickness and abnormal performance characteristics of endometrial cancer.

Recent evidence suggests that detection of 18 genetic mutations (termed papeek) and detection of aneuploidy in cervical brush patterns can identify 81% of women with endometrial cancer. However, in this study, the average ages of the case and control groups were 62 and 34 years, respectively. Consistent observation of the high allele frequency of pathogenic driver mutations in DNA from non-malignant normal endometrium with age, plus the age of the cases was almost twice that of the control group, made it impossible to judge the true specificity of the papeek test.

The present inventors and other scientists have shown in the past that DNA methylation in vaginal fluid or cervical smears may be able to identify women with endometrial cancer. All of these studies were relatively small in scale and these findings were not validated in large data sets. Furthermore, none of these studies focused exclusively on high risk endometrial cancer, and most importantly none of them assessed group-based samples from females prior to disease diagnosis.

Here, the inventors have developed and validated DNA methylation signatures (signature) in samples, particularly cervical smear samples, which are able to diagnose and predict the risk of developing cancer.

Disclosure of Invention

The inventors set forth to understand whether DNAme (DNA methylation) features can be used to detect the presence or absence of cancer, particularly endometrial and ovarian cancer. The inventors have also elucidated to understand whether the DNAme features may be associated with the development of cancer, and thus whether these features can serve as surrogate markers for the stratification purposes of individuals associated with cancer.

In this regard, the inventors have successfully developed assays involving "cancer index values" derived from and associated with DNAme characteristics established from tissue samples containing epithelial cells from a given individual. The sample may particularly originate from the cervix, vagina, cheek area, blood and/or urine. The sample is preferably a cytological sample based on cervical fluid, more preferably a cervical smear sample. Subsequent DNAme characteristics from a given individual, and which values are available for stratification of individuals associated with cancer and/or CIN3 status. A preferred sample for any of the assays described and defined herein is a cytological sample based on cervical fluid. A particularly preferred sample for any of the assays described and defined herein is a cervical smear sample.

Thus, in comparison with prior art assays, the inventors have surprisingly determined that it is possible to derive a "cancer index value" derived from and associated with DNAme characteristics established from a free sample, wherein the sample does not contain DNA derived from a tumor. Thus, the tissue from which the DNAme characteristics of the assays of the invention are established can be used to provide a surrogate marker of the presence, absence or progression of cancer, wherein tumor cells (if present) or cells at risk of conversion to tumor cells are located at anatomical sites other than the location at which the sample was obtained.

The cancer index value is determined from data relating to methylation status of one or more cpgs in the group of cpgs, as further defined and described herein. The cpgs of this group are methylation sites in DNA of cells derived from/obtained from a sample containing epithelial cells. The sample may in particular originate from the cervix, vagina, cheek areas, blood and/or urine. The sample is preferably a cytological sample based on cervical fluid, more preferably a cervical smear sample.

For the purposes of the present invention, a cancer index value may be referred to herein as a "WID-EC-index", "WID-index", "cancer index", "index" or "index value" (wid=) FemaleRisk of sexAuthentication) Used interchangeably. Furthermore, in the context of the present invention, any reference to a cancer index value may likewise be used to assess the presence, absence or progression of endometrial and/or ovarian cancer in an individual.

Based on studies on patients known to be free of endometrial cancer, the inventors established cancer index values using specific groups of CPGs, which have been determined to be associated with/have properties of endometrial tissue negative for endometrial cancer (i.e., normal endometrial tissue free of endometrial cancer). Based on studies of patients known to possess endometrial cancer, the inventors have established cancer index values that have been determined to be associated with/have characteristics of endometrial tissue positive for endometrial cancer.

The inventors further demonstrated that the same specific group of CpG associated with endometrial tissue that is negative or positive for endometrial cancer can also be associated with ovarian tissue that is negative or positive for ovarian cancer and/or cervical tissue that is negative or positive for CIN 3. Based on studies of patients known to be free of ovarian cancer and/or CIN3, the present inventors established cancer index values using specific groups of CpG that have been determined to be associated with/have characteristics of ovarian cancer-negative ovarian tissue (i.e., normal ovarian tissue free of ovarian cancer) and/or CIN 3-negative cervical tissue. Based on studies of patients known to possess ovarian cancer and/or CIN3, the present inventors have established cancer index values that have been determined to be associated with/have characteristics of ovarian cancer-positive ovarian tissue and/or CIN 3-positive cervical tissue.

Thus, the inventors have been able to establish cancer index values using specific groups of cpgs, which are able to characterize an individual as having cancer and/or CIN3 or not having cancer and/or CIN3, or having a high risk of developing cancer and/or CIN 3.

By determining cancer index values based on methylation signatures from a sample derived from an individual, it can be seen that the cancer index value possessed by that individual correlates with cancer index values possessed by individuals known to be positive or negative for cancer via the studies described herein by the inventors. Such correlations have been determined with a high degree of statistical accuracy, particularly with respect to parameters related to the bioassay, such as receiver operating characteristics (receiver operating characteristics, ROC) sensitivity and specificity, and area under the curve (AUC). Thus, by determining the cancer index value from a sample from a given individual, it can be determined that the individual possesses cancer-positive endometrial and/or ovarian tissue, i.e., the individual is diagnosed as having endometrial and/or ovarian cancer and/or CIN3, most preferably having endometrial cancer. Conversely, by determining the cancer index value of a sample from a given individual, it can be determined that the individual possesses endometrial and/or ovarian tissue that is negative for cancer, i.e., the individual is diagnosed as not having endometrial and/or ovarian cancer, most preferably not having endometrial cancer.

Assessing the progression of cancer according to the assays of the invention may refer to assessing an increase or decrease in the likelihood of progression of cancer. Assessing the progression of cancer according to the assays of the invention may refer to assessing the progression or worsening of pre-existing cancer lesions in an individual. Assessment of cancer progression according to the assays of the invention may refer to predicting the likelihood of cancer recurrence.

Observations of the cancer index values discussed herein in relation to the stage and severity of female cancers indicate that the cancer index values may serve as surrogate markers indicating the severity of the cancer in an individual. These observations by the inventors further confirm that, as further described and defined herein, the cancer index values are dynamic and can vary depending on at least the stage and severity of the cancer. Thus, the cancer index value can be used to monitor an individual's cancer status and risk of cancer progression. In addition, the cancer index value can be used to monitor the efficacy of cancer treatments, including therapeutic treatments and prophylactic treatments, administered to an individual.

Thus, in the context of the present invention, by determining a cancer index value from a sample from a given individual, it is possible to assess the presence, absence or progression of cancer in the individual, or in other words, stratify the cancer of the individual. In the context of the present invention, stratification of cancer is the process of classifying an individual as a member of the group of individuals possessing a phenotype associated with cancer, including the presence or absence of cancer in the individual, or the progression of cancer, i.e. by having epithelial cells, in particular those derived from the cervix, vagina, cheek areas, blood and/or urine, which have more positive endometrial or ovarian tissue characteristics than cancer negative endometrial or ovarian tissue, or more positive cervical tissue characteristics than CIN3 negative cervical tissue. The sample is preferably a cytological sample based on cervical fluid, more preferably a cervical smear sample.

As explained herein, the assay methods of the invention are based on cancer index values derived from methylation characteristics of DNA derived from a sample comprising epithelial cells. The sample may in particular originate from the cervix, vagina, cheek areas, blood and/or urine. The sample is preferably a cytological sample based on cervical fluid, more preferably a cervical smear sample. Thus, the assay provides a means for correlating samples of DNA methylation signatures derived from cervical, vaginal, buccal, blood and/or urine with high statistical accuracy with states of endometrial or ovarian cancer ranging from cancer negative individuals to cancer positive individuals or with cervical tissue from CIN3 positive individuals to CIN3 negative individuals. Because the assays of the present invention provide correlation between methylation characteristics and disease states, those skilled in the art will appreciate that disease states are specified based on likelihood as part of the stratification process and outcome. Thus, the methods of the invention provide assays for predicting the cancer status of an individual. Thus, the assays of the invention provide a means of predicting the presence or absence of cancer and/or CIN3 in an individual. Thus, the assays of the invention also provide a means of predicting the progression of cancer and/or CIN3 in an individual. The assays of the invention may provide a means for predicting cancer progression in an individual, as the inventors have demonstrated that specific cancer index values may define endometrial and ovarian tissue as negative for cancer, while other cancer index values may define endometrial and ovarian tissue as positive for cancer, and as specific cancer index values may be dynamic and thus increase in association with known risk factors associated with endometrial and ovarian cancer other than CIN3 status, these values may vary with the grade of cancer and/or CIN3 risk.

Although disease states may be specified based on likelihood, the inventors have demonstrated herein that correlation between DNA methylation characteristics using cancer index values and cancer states can be achieved with very high statistical accuracy using parameters related to bioassays, as further described herein. Thus, the assays of the present invention provide means for predicting the presence or absence of cancer and/or CIN3 in an individual, for predicting the progression of cancer in an individual, and for stratifying cancer in an individual, and wherein prediction/stratification can be defined as statistically highly reliable and robust. This in turn means that prediction/layering can be done with high confidence. As further described and defined herein, the assays of the invention may be defined as statistically accurate by means known in the art. The assays of the invention can be defined in terms of parameters related to their statistical specificity and sensitivity. These parameters define the likelihood of false positive and false negative test results. The lower the ratio of false positive to false negative detection results, the more statistically accurate the assay. In this regard, the inventors have established CpG groups, as further described and defined herein, wherein the methylation status of cpgs in the group can be used to establish a cancer index value such that the assay yields a statistically accurate prediction of the cancer status. Thus, the inventors have determined that the assays described herein can be defined in terms of statistical parameters such as percent variability and sensitivity, as well as area under the Receiver Operating Characteristic (ROC) curve (AUC). All such means are known in the art and are known as defined metrics for statistical accuracy of bioassays, such as those described and defined herein.

Thus, the methods of the invention provide assays useful for predicting the presence, absence, or progression of cancer with a high degree of statistical accuracy. The methods of the invention provide assays useful for stratification of an individual's cancer status with a high degree of statistical accuracy. Thus, the method of the present invention provides individuals and their doctors with useful information regarding the cancer status of patients. This information may help to inform of actual therapeutic treatments if the presence of cancer is identified in the individual. By monitoring changes in the value of the cancer index over a period of time, this information can help monitor the progress of therapeutic treatments in an individual. By monitoring changes in the value of the cancer index over a period of time, this information can be useful in monitoring the progression of preventive or prophylactic treatment measures in an individual. Thus, the method of the present invention provides significant advantages in personalized prevention and early detection, and treatment and management of cancer in an individual.

Accordingly, the present invention provides an assay for assessing the presence, absence or progression of cancer and/or grade 3 cervical intraepithelial neoplasia (CIN 3) in an individual, the assay comprising:

1. providing a sample from an individual, the sample comprising a population of DNA molecules;

2. Determining the methylation status of a group of DNA molecules in the sample of:

i. one or more cpgs selected from the CpG set identified in SEQ ID NOs 1 to 500, wherein cpgs are identified at nucleotide positions 61 to 62; and/or

One or more cpgs selected from one or more differentially methylated regions (differentially methylated region, DMR) defined by SEQ ID NOs 501 to 808, wherein cpgs are represented by CG;

3. deriving a cancer index value based on methylation status of one or more cpgs in the group; and

4. assessing the presence, absence, or progression of cancer and/or CIN3 in an individual based on the cancer index value;

wherein the assay is characterized as having an area under the curve (AUC) of 0.60 or greater as determined by the Receiver Operating Characteristics (ROC).

The assay of the invention may be carried out as above and additionally wherein the set of one or more cpgs comprises at least 50 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.90.

The assay of the invention may be carried out as above and additionally wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having an AUC of at least 0.95.

The assay of the invention may be carried out as above and additionally wherein the set of one or more cpgs comprises at least 100 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.93.

The assay of the invention may be carried out as above and additionally wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having an AUC of at least 0.96.

The assay of the invention may be carried out as above and additionally wherein the set of one or more cpgs comprises at least 150 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.93.

The assay of the invention may be carried out as above and additionally wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having an AUC of at least 0.96.

The assay of the invention may be carried out as above and additionally wherein the set of one or more cpgs comprises at least 200 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.93.

The assay of the invention may be carried out as above and additionally wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having an AUC of at least 0.96.

The assay of the invention may be carried out as above and additionally wherein the set of one or more cpgs comprises at least 500 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the assay is characterized by having an AUC of at least 0.97.

The assay of the invention may be carried out as above and additionally wherein the step of determining the methylation status of one or more cpgs in the set in the population of DNA molecules in the sample comprises determining a beta value for each CpG.

The assay of the invention may be practiced as above and additionally wherein the step of deriving the cancer index value based on the methylation status of one or more cpgs in the group comprises:

1. providing a methylation beta value dataset comprising methylation beta values for each CpG in the group;

2. providing a mathematical model capable of generating a cancer index from the methylation beta value dataset; and

3. a mathematical model is applied to the methylation beta value dataset to generate a cancer index.

The assays of the invention may be practiced as above and additionally wherein the cancer index value is a WID-EC-index cancer index value and wherein the mathematical model applied to the methylation beta value dataset to generate the cancer index is an algorithm according to the following formula:

wherein:

1.β ₁ ,…,β _n is methyl groupBeta values (between 0 and 1);

2.w ₁ ,…,w ₅₀₀ is a real value coefficient;

3.μ and σ are real-valued parameters for the scaling factor; and

n refers to the number of cpgs in a group of one or more cpgs;

preferably, wherein the cancer is endometrial cancer.

The assays of the invention may be practiced as above and additionally wherein an individual is assessed as having cancer and/or CIN3 or as having a high risk of developing cancer and/or CIN3 when the individual's cancer index value is about-0.201 or greater or wherein an individual is assessed as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index value is less than about-0.201, preferably wherein:

the set of one or more cpgs comprises at least 50 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 88% and the specificity is at least 76%;

a set of one or more cpgs comprises a CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62 and wherein the sensitivity is at least 90% and the specificity is at least 80%;

A group of one or more cpgs comprises cpgs defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62 and wherein the sensitivity is at least 92% and the specificity is at least 79%; or alternatively

A set of one or more cpgs comprises a CpG defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62 and wherein the sensitivity is at least 93% and the specificity is at least 80%;

preferably, wherein the assay comprises determining the methylation beta value of each CpG in the set of one or more cpgs, more preferably wherein the cancer is endometrial cancer.

The assays of the invention may be practiced as above, and additionally wherein an individual is assessed as having cancer and/or CIN3, or as having a high risk of developing cancer and/or CIN3, when the individual's cancer index value is about 0.269 or greater, or wherein the individual is assessed as not having cancer and/or CIN3, or as having a low risk of developing cancer and/or CIN3, when the individual's cancer index value is less than about 0.269, preferably wherein:

1. the set of one or more cpgs comprises at least 50 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 75% and the specificity is at least 94%;

2. A set of one or more cpgs comprises a CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62 and wherein the sensitivity is at least 73% and the specificity is at least 98%;

3. a group of one or more cpgs comprises a CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62 and wherein the sensitivity is at least 75% and the specificity is at least 98%; or alternatively

4. A group of one or more cpgs comprises cpgs defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62 and wherein the sensitivity is at least 79% and the specificity is at least 97%;

The assay of the invention may be performed as above, and additionally wherein an individual is assessed as having cancer and/or CIN3 or as having a high risk of developing cancer and/or CIN3 when the individual's cancer index value is about 1.072 or greater, or wherein the individual is assessed as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index value is less than about 1.072, preferably wherein:

1. The set of one or more cpgs comprises at least 50 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 58% and the specificity is at least 99%;

2. a group of one or more cpgs comprises cpgs defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62 and wherein the sensitivity is at least 60% and the specificity is 100%;

3. a group of one or more cpgs comprises cpgs defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62 and wherein the sensitivity is at least 63% and the specificity is 100%; or alternatively

4. A group of one or more cpgs comprises cpgs defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62 and wherein the sensitivity is at least 64% and the specificity is 100%;

The assays of the invention may be practiced as above and additionally wherein when the individual has a cancer index value of:

1. less than about-0.660, the individual is assessed as not having cancer and/or CIN3;

2. about-0.660 or greater and less than about-0.430, the individual is assessed as having a low risk of developing cancer and/or CIN3;

3. About-0.430 or greater and less than about-0.230, the individual is assessed as having a moderate risk of developing cancer and/or CIN 3; or alternatively

4. About-0.230 or higher, the individual being assessed as having a high risk of cancer and/or CIN3 development;

The assays of the invention may be practiced as above and additionally wherein the step of determining the methylation status of the set of one or more cpgs comprises determining the methylation status of one or more cpgs, enforcing a CG representation identified in the set of one or more DMRs defined by SEQ ID NOs 501 to 808, optionally wherein the set of one or more cpgs comprises two or more cpgs identified in the set of DMRs as represented by a CG, three or more cpgs identified in the set of DMRs as represented by a CG, four or more cpgs identified in the set of DMRs as represented by a CG, or all cpgs identified in the set of DMRs defined by SEQ ID NOs 501 to 808 as represented by a CG.

The assay of the invention may be practiced as above, and additionally wherein the step of determining the methylation status of the set of one or more cpgs comprises determining five or more, six or more, seven or more, eight or more, or nine or more or all methylation status in the cpgs represented by the CG within any one or more of the DMRs defined by SEQ ID NOs 501 to 808.

The assay of the invention may be practiced as above, and additionally wherein the step of determining the methylation status of the set of one or more cpgs comprises determining the methylation status of two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, or nine or more or all of the cpgs represented by the CG within:

any combination of two, three, four, five, six, seven, eight, or nine or more of dmr 1 to 308;

any combination of ten, twenty, thirty, forty, fifty, sixty, seventy, eighty, or ninety or more of dmrs 1 to 308;

all 308 of dmr 1 to 308;

4. one DMR defined by SEQ ID No. 501, two DMR defined by SEQ ID nos. 501 to 502, three DMR defined by SEQ ID nos. 501 to 503, four DMR defined by SEQ ID nos. 501 to 504, five DMR defined by SEQ ID nos. 501 to 505, six DMR defined by SEQ ID nos. 501 to 506, seven DMR defined by SEQ ID nos. 501 to 507, eight DMR defined by SEQ ID nos. 501 to 508, or nine DMR defined by SEQ ID nos. 501 to 509; or alternatively

5. Ten DMRs defined by SEQ ID nos. 501 to 510, twenty DMRs defined by SEQ ID nos. 501 to 520, thirty DMRs defined by SEQ ID nos. 501 to 530, forty DMRs defined by SEQ ID nos. 501 to 540, fifty DMRs defined by SEQ ID nos. 501 to 550, sixty DMRs defined by SEQ ID nos. 501 to 560, seventy DMRs defined by SEQ ID nos. 501 to 570, eighty DMRs defined by SEQ ID nos. 501 to 580, or ninety DMRs defined by SEQ ID nos. 501 to 590. Or alternatively

6. From SEQ ID NO 501 to 510, SEQ ID NO 511 to 520, SEQ ID NO 521 to 530, SEQ ID NO 531 to 540, SEQ ID NO 541 to 550, SEQ ID NO 551 to 560, SEQ ID NO 561 to 570, SEQ ID NO 571 to 580, SEQ ID NO 581 to 590, SEQ ID NO 591 to 600, SEQ ID NO 601 to 610, SEQ ID NO 611 to 620, SEQ ID NO 621 to 630, SEQ ID NO 631 to 640, SEQ ID NO 641 to 650, SEQ ID NO 651 to 660, SEQ ID NO 661 to 670, SEQ ID NO 671 to 680, SEQ ID NO 681 to 690, SEQ ID NO 691 to 700, SEQ ID NO 701 to 710, SEQ ID NO 711 to 720, SEQ ID NO 721 to 730, SEQ ID NO 731 to 731, SEQ ID NO 741 to 750; 751 to 760; 761 to 770; 771 to 780; SEQ ID NOS 781 to 790; ten DMR defined by SEQ ID NOs 791 to 800 or SEQ ID NOs 801 to 808.

The assay of the invention may be practiced as above, and additionally wherein the step of determining the methylation status of the group of one or more cpgs comprises determining the methylation status of one or more cpgs within any one or more DMRs selected from the group of DMRs 1 to 308 defined by SEQ ID NOs 501 to 808, comprising:

a. one or more cpgs as defined by SEQ ID No. 501 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.911, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

b. one or more cpgs within DMR 2 as defined by SEQ ID No. 502 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.903, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

c. one or more cpgs within DMR 3 as defined by SEQ ID No. 503 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

d. one or more cpgs within DMR 4 as defined by SEQ ID No. 504 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

e. One or more cpgs within DMR 5 as defined by SEQ ID No. 505 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

f. one or more cpgs within DMR 6 as defined by SEQ ID No. 506 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.897, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

g. one or more cpgs within DMR 7 as defined by SEQ ID No. 507 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.894, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

h. one or more cpgs within DMR 8 as defined by SEQ ID No. 508 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.894, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

i. one or more cpgs within DMR 9 as defined by SEQ ID No. 509 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.892, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ]; or alternatively

j. One or more cpgs within DMR 10 as defined by SEQ ID No. 510 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.891, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ].

The assay of the invention may be carried out as above, and additionally wherein:

1. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.025 or greater; or alternatively

2. An individual is classified as not having cancer and/or CIN3 when the individual's cancer index is less than about 0.025;

preferably, wherein the assay has a specificity of 95% or greater, more preferably wherein the assay comprises determining an average β value for each CpG in a group of one or more cpgs.

1. the CpG represented by CG whose cancer index value is determined is at least within DMR 1 defined by SEQ ID NO:501, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.209 or greater, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 1, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 501;

2. The CpG represented by CG whose cancer index value is determined is at least within DMR 1 defined by SEQ ID NO:501, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.209, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 1, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 501;

3. the CpG represented by CG whose cancer index value is determined is at least within DMR 2 defined by SEQ ID No. 502, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.271 or greater, and wherein the sensitivity of the assay is at least 77.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 2, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 502;

4. The CpG represented by CG whose cancer index value is determined is at least within DMR 2 defined by SEQ ID No. 502, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.271, and wherein the sensitivity of the assay is at least 77.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 2, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 502;

5. the CpG represented by CG whose cancer index value is determined is at least within DMR 3 defined by SEQ ID NO:503, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.123 or more, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 3, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 503;

6. The CpG represented by CG whose cancer index value is determined is at least within DMR 3 defined by SEQ ID NO:503, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.123, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 3, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 503;

7. the CpG represented by CG whose cancer index value is determined is at least within DMR 4 defined by SEQ ID No. 504, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.123 or greater, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 4, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 504;

8. The CpG represented by CG whose cancer index value is determined is at least within DMR 4 defined by SEQ ID No. 504, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.123, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 4, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 504;

9. the CpG represented by CG whose cancer index value is determined is at least within DMR 5 defined by SEQ ID NO:505, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.105 or more, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 5, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 505; or alternatively

10. The CpG represented by CG whose cancer index value is determined is at least within DMR 5 defined by SEQ ID NO:505, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.105, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 5, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 505.

The assays of the invention may be performed as above and additionally wherein the step of determining the methylation status of one or more cpgs in the set further comprises or additionally comprises determining the methylation status of each CpG within one or more of the sequences identified by SEQ ID NOs 809 to 919.

The assay of the invention may be practiced as above and additionally wherein the step of determining the methylation status of one or more cpgs in the group comprises determining each CpG within:

SEQ ID NO 809 and/or SEQ ID NO 846 and/or SEQ ID NO 883, and wherein when the cancer index value is about 0.282 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 809 and/or SEQ ID NO 846 and/or SEQ ID NO 883;

SEQ ID NO 809 and/or SEQ ID NO 846 and/or SEQ ID NO 883, and wherein when the cancer index value is less than about 0.282, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 809 and/or SEQ ID NO 846 and/or SEQ ID NO 883;

SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884, and wherein when the cancer index value is about 0.212 or greater, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 55.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884;

d.SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884, and wherein when the cancer index value is less than about 0.212, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 55.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884;

SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885, and wherein when the cancer index value is about 0.002 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 740 and/or SEQ ID NO 777 and/or SEQ ID NO 814;

SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885, and wherein when the cancer index value is less than about 0.002, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885;

SEQ ID NO 812 and/or SEQ ID NO 849 and/or SEQ ID NO 886, and wherein when the cancer index value is about 0.026 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 90.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 812 and/or SEQ ID NO 849 and/or SEQ ID NO 886;

SEQ ID NO 812 and/or SEQ ID NO 849 and/or SEQ ID NO 886, and wherein when the cancer index value is less than about 0.026, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 90.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 812 and/or SEQ ID NO 849 and/or SEQ ID NO 886;

SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887, and wherein when the cancer index value is about 0.003 or greater, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.97, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887; and/or

SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887, and wherein when the cancer index value is less than about 0.003, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.97, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887.

The assays of the invention may be performed as above and additionally wherein the step of determining the methylation status of one or more cpgs in the group further comprises or additionally comprises determining the methylation status of each CpG within one or more of the sequences identified by SEQ ID NOs 809, 846, 883, 811, 848, 885, 813, 850 and 887.

The assay of the invention may be practiced as above and additionally wherein the step of determining the methylation status of each CpG in the group of one or more CpG's in the population of DNA molecules in the sample comprises:

1. performing a sequencing step to determine the sequence of each CpG;

2. hybridizing the DNA to a chip comprising probes capable of distinguishing between methylated and unmethylated forms of CpG, and applying a detection system to the chip to determine the methylation status of each CpG; and/or

3. The PCR step is performed using methylation specific primers, wherein the methylation status of CpG is determined by the presence or absence of PCR products.

The assay of the invention may be practiced as above and additionally wherein the step of determining the methylation status of each CpG in the set of one or more cpgs comprises:

1. bisulfite converts DNA; or alternatively

2. The following steps are carried out: a step of oxidizing the 5-methylcytosine base (5 mC) to a 5-carboxycytosine base (5 cat), preferably by 10-11 translocation (TET), and/or oxidizing the 5-hydroxymethylcytosine base (5 hmC) to a 5-carboxycytosine base (5 cat), preferably by 10-11 translocation (TET); the 5-carboxycytosine base (5 caC) is then optionally reduced to a dihydrouracil base (DHU) with pyridine borane.

The invention also provides a method of treating or preventing cancer in an individual, the method comprising:

1. assessing the presence, absence or progression of cancer in an individual by performing any of the assays of the invention, thereby assessing the cancer status of the individual;

2. one or more therapeutic or prophylactic treatments are administered to the individual based on the evaluation.

The methods of the invention may be practiced as above, and additionally wherein the individual is assessed as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3, and wherein the cancer index value is about-0.660 or greater and less than about-0.430, and preferably wherein the assay comprises determining the methylation β value of each CpG in the group of one or more cpgs, the individual receiving one or more treatments according to its cancer index value, the one or more treatments comprising:

1. evaluating endometrium and ovary via vaginal ultrasound;

2. a repeat assay according to any one of the assays of the invention, preferably wherein the repeat assay is performed about two years after the previous assay.

The methods of the invention may be practiced as above, and additionally wherein the individual is assessed as having a moderate risk of cancer and/or CIN3 or having a moderate risk of cancer and/or CIN3 development, and wherein the cancer index value is about-0.430 or greater and less than about-0.230, and preferably wherein the assay comprises determining a methylation β value for each CpG in the group of one or more cpgs, the individual receiving one or more treatments according to its cancer index value, the one or more treatments comprising any one of:

1. Evaluating endometrium and ovary via vaginal ultrasound;

2. a boost screen, preferably wherein the boost screen comprises one or more of:

i. colposcopy;

HPV test;

cervical cytology test;

testing for ca 125, preferably wherein the test is repeated every six months;

testing for methylation of cell-free tumor DNA in plasma/serum, preferably repeated annually;

testing for methylation of cell-free tumor DNA in vaginal fluid, preferably repeated annually;

pelvic MRI scan, preferably wherein the individual receiving the pelvic MRI scan is postmenopausal, and preferably wherein the scan is repeated annually;

repeated assays according to any of the assays of the invention, preferably wherein the repeated assays are performed about one year after the previous assay;

3. one or more of a progestin, aspirin, metformin, an aromatase inhibitor, and a weight loss regimen are administered, particularly wherein the progestin is delivered locally or systemically.

The method of the invention may be practiced as above and additionally wherein when the colposcopic, HPV and cytological tests are negative, the enhanced screening further comprises hysteroscopy and endocervical and endometrial biopsies.

The method of the invention may be practiced as above, and additionally wherein when both transvaginal ultrasound and enhanced screening are negative:

1. the tests by vaginal ultrasound, CA125 test, cell-free tumor DNA methylation in plasma/serum and cell-free tumor DNA methylation in vaginal fluid were repeated about six months after the previous assay; and

2. colposcopy, HPV testing and cervical cytology testing were repeated approximately one year after the previous assay.

The method of the invention may be practiced as above, and additionally wherein the individual is assessed as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, and wherein the cancer index value is about-0.230 or higher, and preferably wherein the assay comprises determining the methylation β value of each CpG in the group of one or more cpgs, the individual receiving one or more treatments according to its cancer index value, the one or more treatments comprising any one of the following:

1. evaluating endometrium and ovary via vaginal ultrasound;

i. colposcopy;

HPV test;

cervical cytology test;

Testing for ca 125, preferably wherein the test is repeated every six months;

3. administration of one or more of a progestin, aspirin, metformin, an aromatase inhibitor, and a weight loss regimen, particularly wherein the progestin is delivered locally or systemically;

4. total hysterectomy and bilateral tubal ovariectomy.

1. Vaginal ultrasound, CA125 testing, cell-free tumor DNA methylation in plasma/serum testing, cell-free tumor DNA methylation in vaginal fluid testing, colposcopy, HPV testing, and cervical cytology testing were repeated about six months after the previous assay; and

2. pelvic MRI scans were repeated approximately one year after the previous assay.

The method of the invention may be practiced as above and additionally wherein the progestogen is delivered locally via an intrauterine contraceptive device.

The methods of the invention may be practiced as above, and additionally wherein after the first administration, the one or more treatments received by the individual are repeated on a monthly, three month, six month, yearly, or two year basis after the initial administration.

The invention also provides a method of monitoring the cancer status of an individual based on the individual's cancer index value, the method comprising: (a) Assessing the presence, absence or progression of cancer in an individual by performing an assay according to any one of the assays of the invention at a first time point; (b) Assessing the presence, absence or progression of cancer in an individual by performing an assay according to any one of the assays of the invention at one or more additional time points; and (c) monitoring the individual for any change in the cancer index value and/or cancer status and/or CIN3 status between time points.

The method of the invention may be practiced as above and, additionally, after initial assessment, the additional points in time are monthly, every three months, every six months, annually, or every two years.

The methods of the invention may be practiced as above, and additionally wherein one or more treatments according to any one of the methods of the invention are administered to the individual depending on the individual's cancer index value and/or cancer status and/or CIN3 status, or no treatment is administered to the individual when the individual's cancer index value is less than about-0.660.

The methods of the invention may be practiced as described above, and additionally wherein an increase in the value of the cancer index is indicative of a negative response to one or more treatments.

The methods of the invention may be practiced as described above, and additionally wherein one or more treatments are altered if a negative response is identified.

The methods of the invention may be practiced as described above, and additionally wherein a decrease in the value of the cancer index is indicative of a positive response to one or more treatments.

The methods of the invention may be practiced as described above, and additionally wherein one or more treatments are altered if a positive response is identified.

The assay of the invention may be carried out as above and additionally wherein the sample is obtained from tissue comprising epithelial cells, preferably wherein the sample is not obtained from ovarian or endometrial tissue.

The assay of the invention may be carried out as above and additionally wherein the sample is obtained from:

1. cervical tissue;

2. vaginal tissue;

3. cervical vaginal tissue;

4. cheek tissue;

preferably, wherein the sample is obtained from cervical tissue, most preferably wherein the sample is obtained from tissue from a cervical smear.

The assay of the invention may be practiced as above, and additionally wherein the assay is used to assess the presence, absence or development of:

1. endometrial cancer, preferably wherein the endometrial cancer is endometrioid cancer, uterine sarcoma, squamous cell carcinoma, small cell carcinoma, transitional cell carcinoma, serous carcinoma, clear cell carcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma or serous adenocarcinoma;

2. ovarian cancer, particularly where the ovarian cancer is a severe carcinoma, mucinous carcinoma, endometrioid carcinoma, clear cell carcinoma, low malignant potential (lop malignant potential, LMP) tumor, borderline epithelial ovarian carcinoma, teratoma, asexual cell tumor, endoembryo sinoma, choriocarcinoma, granulosa-follicular tumor, ovarian support-stromal tumor (seltoli-Leydig tumor), granulosa cell tumor, ovarian small cell carcinoma, or primary peritoneal carcinoma;

grade 3 cervical intraepithelial neoplasia (CIN 3) and/or cervical cancer, particularly wherein the cervical cancer is squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma.

The invention also provides a chip capable of distinguishing between methylated and unmethylated forms of CpG; the chip comprises oligonucleotide probes specific for the methylated form of each CpG in the set of CpG and oligonucleotide probes specific for the unmethylated form of each CpG in the set; wherein the set consists of at least 50 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62 and identified in SEQ ID NOs 501 to 808 and represented by CG.

The chip of the invention may be implemented as described above, and additionally provided that the chip is not a Infinium MethylationEPIC BeadChip chip or Infinium HumanMethylation chip, and/or provided that the number of CpG-specific oligonucleotide probes of the chip is 482,000 or less, 480,000 or less, 450,000 or less, 440,000 or less, 430,000 or less, 420,000 or less, 410,000 or less, or 400,000 or less.

The chip of the invention may be implemented as above and additionally wherein the set comprises any set of cpgs defined in the assays of any of the assays of the invention.

The chip of the invention may be implemented as above and additionally further comprises one or more oligonucleotides comprising any set of cpgs defined in the assay of any of the assays of the invention, wherein the one or more oligonucleotides hybridize to corresponding oligonucleotide probes of the chip.

The invention also provides a hybridization chip, wherein the chip is obtainable by hybridizing a set of oligonucleotides comprising any set of cpgs as defined in the assay of the invention to the chip of the invention.

The invention also provides a method of preparing a hybridization chip of the invention, comprising contacting the chip of the invention with a set of oligonucleotides comprising any set of cpgs defined in the assay of the invention.

Drawings

FIG. 1 shows an experimental design supporting the discovery and validation of WID-EC-indices.

Fig. 2 shows ROC curves (a plot) for WID-EC-indices in the internal validation set. The box plot (B plot) of WID-EC-indices in the set is validated internally.

Figure 3 shows WID-EC-indices (panel a) for endometrial cancer map cases and health control maps in an external validation dataset. ROC curves in the external validation set (C plot). The WID-EC-index is related to the time of event occurrence (time-to-event) in the validation samples expected to be collected (D plot). ROC curve (E plot) corresponding to expected samples.

FIG. 4 shows WID-EC-indices versus age in samples from both the internal and external validation data sets (A panels). Correlation with Body Mass Index (BMI) in the control chart (Panel B). Menopause (panel C). Parity (D panel). Stage (E panel). Grade (F plot). Graph texture (G panel). The a-D plots are based on a comparison plot from the internal and external validation datasets. The E-G graphs are based on graph cases from internal and external validation datasets.

FIG. 5 shows the relation of WID-EC-index and estimated ratio of tumor DNA (A plot). The estimated proportion of tumor DNA in each cervical smear sample estimated for control (panel B) and endometrial cancer (panel C) using the EpiDISH algorithm.

Figure 6 shows the distribution of p-values obtained by comparing the case and control plots for each CpG site and controlling immune cell proportion and age (a plot). Distribution of different cell types in the discovery dataset inferred using the hepidsh algorithm (< 0.05, <0.01, <0.001, < p) (panel B). The area under the receiver operating characteristic curve (AUROC) in the internal validation set is a function of the number of cpgs used to train the classifier (classifer) (C plot). Distribution of WID-EC-index versus proportion of immune cells in the internal validation set (panel D).

Fig. 7 shows the distribution of different cell types in the externally validated dataset inferred using the hepdis algorithm (< p <0.05, < p <0.01, < p < 0.001) (a graph). Cell type distribution in the data set was expected to be validated (panel B). Average delta-beta for different gene map regions (difference between average beta values from control samples of the expected data set and the discovery data set) (panel C). The odds ratio (p <0.001 compared to 776,725 CpG in the dataset) corresponding to the gene map annotation of 500 CpG containing WID-EC-index (panel D).

Figure 8 shows a control graph of WID-EC-index voluntary participation in the general population and distribution (discovery set) among women in hospital visits due to benign disease in women (a graph). WID-EC-index versus days between sample collection and DNA extraction.

Fig. 9 shows the relationship of inferred tumor DNA ratios to inferred epithelial cell ratios in the discovery set determined using the hepdis algorithm.

Figure 10 shows the WID-EC-index versus immune cell ratio in the ovarian cancer validation dataset (panel a) and the corresponding ROC curve (panel B).

Fig. 11 shows cut-points (cutpoints) applied to patient data, as well as the specificity and sensitivity for cancer status discrimination achieved when these cut-points are applied.

Detailed Description

Identification of CpG

The present inventors aimed at identifying CpG methylation-based assays that are capable of assessing the presence, absence or progression of cancer in an individual. Any of the assays described herein for assessing the presence, absence, or progression of cancer in an individual can be used to assess endometrial cancerAnd/or the presence, absence or progression of ovarian cancer, particularly endometrial cancer. The inventors compared the CpG methylation levels in non-cancerous epithelial tissue, in particular cervical tissue, vaginal tissue or cervical vaginal tissue, of a group of women known to be both endometrial and ovarian cancer negative and/or CIN3 negative, or known to be endometrial and/or ovarian cancer positive and/or CIN3 positive. This results in a surprising build-up of a "cancer index", which in this context can be referred to as "index", "index value", "WID-EC-index" or "WID-index" (wid=) FemaleRisk of sexAuthentication) Used interchangeably.

CpG as defined herein refers to the CG dinucleotide motif identified with respect to each SEQ ID NO, wherein the CG dinucleotide of interest is represented by CG. Thus, by determining the methylation status of any set of one or more cpgs defined or identified by a given SEQ ID NO is meant that the methylation status of cytosines of CG dinucleotide motifs identified in brackets in the set of one or more cpgs within each sequence shown below are determined accepting that variations in the upstream and downstream sequences of any given CpG due to sequencing errors or variations between individuals may be present.

As set forth in more detail in the examples, the methylation status of a sub-selection of 500 cpgs identified in SEQ ID NOs 1 to 500 can be determined such that the presence, absence or progression of cancer in an individual can be assessed with high sensitivity and specificity. The cancer is preferably endometrial or ovarian cancer, most preferably endometrial cancer. In accordance with the invention described herein, a panel of one or more of the cpgs identified in SEQ ID NOs 1 to 500 can be used to derive a cancer index for an individual.

Methylation status of a group of one or more CpG within 500 CpG's defined according to SEQ ID NO. 1 to 500 can be assessed by any suitable technique. As explained in more detail in the examples below, one particular exemplary technique that the inventors have used is a chip-based analysis technique that incorporates beta value analysis. SEQ ID NOS 1 to 500 correspond to the sequences of commercial probes used in the chips.

The inventors further identified 308 Differential Methylation Regions (DMR) associated with cancer, particularly endometrial or ovarian cancer. The nucleotide sequences of 308 DMRs are defined by the nucleotide sequences of SEQ ID NOs 501 to 808, respectively, as shown in table 1 below, and variations in the nucleotide sequence of any given DMR due to sequencing errors and/or variations between individuals are accepted. In each of the sequences shown below, the cytosine of the CG dinucleotide motif identified in brackets or both brackets is a cytosine of a CpG, which CpG may be included in the CpG group when the assay of the present invention is carried out.

The inventors further defined 37 regions of particular relevance to cancers (particularly endometrial and ovarian cancers) and CIN3 in a selected number of 308 DMRs. The nucleotide sequence of the 37 regions is defined by the nucleotide sequences of SEQ ID NOS: 809 to 919, respectively, as shown in Table 10 below, and there may be variations in the nucleotide sequence of any given DMR that are accepted as a result of sequencing errors and/or variations between individuals. When carrying out the assay of the invention, the methylation status of each cytosine within a CG dinucleotide in a 37 region is determined when any one or more of the regions are included in the CpG group. The amplicon sequences generated by the 37 primer and probe reactions shown in table 10 are depicted and defined by SEQ ID NOs 920 to 956 and table 12. In any of the assays described herein, the step of determining the methylation status of the set of one or more cpgs may comprise determining the methylation status of one or more cpgs within any one or more amplicons defined by SEQ ID NOs 920 to 956 and represented by CG. More preferably, in any of the assays described herein, the step of determining the methylation status of the set of one or more cpgs may comprise determining the methylation status of one or more cpgs within any one or more amplicons defined by SEQ ID NOs 920, 922 and 924 and represented by CG, and still more preferably determining the methylation status of all cpgs represented by CG in the amplicons defined by SEQ ID NOs 920, 922 and 924.

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The nucleotide sequences of Table 1.308 DMRs are defined by the nucleotide sequences of SEQ ID NOS: 501 to 808, respectively.

Cancer-related CpG for analysis

In any of the assays described herein, in a sample taken from an individual, the sample comprises a population of DNA molecules.

The assay of the invention further comprises determining the methylation status of the group of:

(i) One or more cpgs selected from the CpG set identified in SEQ ID NOs 1 to 500, wherein cpgs are identified at nucleotide positions 61 to 62; and/or

(ii) One or more CpG selected from the group of one or more Differential Methylation Regions (DMR) defined by SEQ ID NOs 501 to 808,wherein CpG is represented by CG。

Cancer index values are then deduced based on the methylation status of one or more cpgs in the group, which are used to assess the presence, absence, or progression of cancer in the individual based on the cancer index values.

In any of the assays described herein, in DNA derived from cells in the sample, the methylation status of each CpG in the following group is determined:

(ii) One or more cpgs selected from the group of one or more Differential Methylation Regions (DMR) defined by SEQ ID NOs 501 to 808, wherein cpgs are represented by CG;

in any of the assays described herein, the methylation status of each CpG in the set of one or more cpgs from the set of cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 is determined in DNA derived from cells in the sample.

In any of the assays described herein, the set of one or more cpgs may comprise at least 50 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by a Receiver Operating Characteristic (ROC) area under the curve (AUC) of at least 0.92. The set of one or more cpgs may comprise cpgs identified in at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having a ROC AUC of at least 0.95.

In any of the assays described herein, the set of one or more cpgs may comprise at least 100 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by a ROC AUC of at least 0.93. The set of one or more cpgs may comprise cpgs identified in at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having a ROC AUC of at least 0.96.

In any of the assays described herein, the set of one or more cpgs may comprise at least 150 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by a ROC AUC of at least 0.93. The set of one or more cpgs may comprise cpgs identified in at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having a ROC AUC of at least 0.96.

In any of the assays described herein, the set of one or more cpgs may comprise at least 200 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by an AUC of at least 0.93. The set of one or more cpgs may comprise cpgs identified in at least SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having a ROC AUC of at least 0.96.

In any of the assays described herein, the set of one or more cpgs may comprise at least 500 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the assay is characterized by having a ROC AUC of at least 0.97.

In any of the above assays, the assay may be characterized as having an AUC of ROC of 0.60 or greater, 0.61 or greater, 0.62 or greater, 0.63 or greater, 0.64 or greater, 0.65 or greater, 0.66 or greater, 0.67 or greater, 0.68 or greater, 0.69 or greater, 0.70 or greater, 0.71 or greater, 0.72 or greater, 0.73 or greater, 0.74 or greater, 0.75 or greater, 0.76 or greater, 0.77 or greater, 0.78 or greater, 0.79 or greater, 0.80 or greater, 0.81 or greater, 0.82 or greater, 0.83 or greater, 0.84 or greater, 0.85 or greater, 0.86 or greater, 0.87 or greater, 0.88 or greater, 0.89 or greater, or 0.90 or greater.

In any of the described assays, the methylation status of one or more cpgs in the group is preferably determined by beta value analysis, and the cancer is endometrial cancer of ovarian cancer. Preferably, the cancer is endometrial cancer.

In any of the assays described herein, the set of one or more cpgs may comprise at least 50 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, optionally wherein:

1. the assay is characterized by having a ROC AUC (AUC) of at least 0.95, and more preferably wherein a group of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62;

2. The assay is characterized by having an AUC of at least 0.94, and more preferably wherein a group of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 51 to 100 and at nucleotide positions 61 to 62;

3. the assay is characterized by having a ROC AUC (AUC) of at least 0.94, and more preferably wherein a group of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 101 to 150 and at nucleotide positions 61 to 62;

4. the assay is characterized by having a ROC AUC (AUC) of at least 0.93, and more preferably wherein a group of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 151 to 200 and at nucleotide positions 61 to 62;

5. the assay is characterized by having a ROC AUC (AUC) of at least 0.95, and more preferably wherein a group of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 201 to 250 and at nucleotide positions 61 to 62;

6. the assay is characterized by having a ROC AUC (AUC) of at least 0.93, and more preferably wherein a group of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 251 to 300 and identified at nucleotide positions 61 to 62;

7. the assay is characterized by having a ROC AUC (AUC) of at least 0.94, and more preferably wherein a group of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 301 to 350 and at nucleotide positions 61 to 62;

8. The assay is characterized by having a ROC AUC (AUC) of at least 0.93, and more preferably wherein a group of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 351 to 400 and identified at nucleotide positions 61 to 62;

9. the assay is characterized by having a ROC AUC (AUC) of at least 0.93, and more preferably wherein a group of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 401 to 450 and at nucleotide positions 61 to 62; or alternatively

10. The assay is characterized by having a ROC AUC (AUC) of at least 0.92, and more preferably wherein the set of one or more cpgs comprises cpgs identified at least in SEQ ID NOs 451 to 500 and at nucleotide positions 61 to 62.

In any of the assays described herein, the set of one or more cpgs may comprise:

1. at least 50 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.95, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62;

2. at least 100 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.96, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62;

3. at least 150 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.96, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62;

4. at least 200 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.96, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62;

5. At least 250 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.96, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 250 and identified at nucleotide positions 61 to 62;

6. at least 300 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.96, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 300 and identified at nucleotide positions 61 to 62;

7. at least 350 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.96, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 350 and identified at nucleotide positions 61 to 62;

8. at least 400 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.96, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 400 and identified at nucleotide positions 61 to 62;

9. At least 450 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.97, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 1 to 450 and identified at nucleotide positions 61 to 62; or alternatively

10. At least 500 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.97, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500.

1. at least 50 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.92, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62;

2. at least 100 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.93, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 401 to 500 and identified at nucleotide positions 61 to 62;

3. at least 150 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.93, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 351 to 500 and identified at nucleotide positions 61 to 62;

4. at least 200 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.93, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 301 to 500 and identified at nucleotide positions 61 to 62;

5. At least 250 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.93, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 251 to 500 and identified at nucleotide positions 61 to 62;

6. at least 300 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.94, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 201 to 500 and identified at nucleotide positions 61 to 62;

7. at least 350 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.94, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 151 to 500 and identified at nucleotide positions 61 to 62;

8. at least 400 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.94, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 101 to 500 and identified at nucleotide positions 61 to 62;

9. At least 450 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by having an AUC of at least 0.95, and more preferably wherein the set of one or more cpgs comprises a CpG identified at least in SEQ ID NOs 51 to 500 and identified at nucleotide positions 61 to 62; or alternatively

In any of the assays described herein, the step of determining the methylation status of one or more cpgs in the group may comprise determining the methylation status of one or more cpgs selected from the group of one or more Differentially Methylated Regions (DMRs) defined by SEQ ID NOs 501 to 808, wherein the selected CpG in each DMR is represented by a CG. The nucleotide sequences of 308 DMRs are defined by the nucleotide sequences of SEQ ID NOs 501 to 808, respectively, as shown in table 1, accepting variations in the nucleotide sequence of any given DMR due to sequencing errors and/or variations between individuals. In each of the sequences shown below, the cytosine of the CG dinucleotide motif identified in brackets and both brackets is a cytosine of a CpG that may be included in the group of cpgs when the assay of the invention is carried out.

In any of the assays described herein, the step of determining the methylation status of one or more CPGs in the group may comprise determining the methylation status of one or more CPGs represented by CG within any one or more DMRs or within any combination of two or more DMRs defined by SEQ ID NOs 501 to 808, wherein the selected CpG in each DMR is represented by CG. DMR is selected from the group consisting of DMR 1 to 308 (SEQ ID NOs 501 to 808; as listed in table 1).

The step of determining the methylation status of the set of one or more CPGs may include determining a cancer index value for one or more of the CPGs represented by the CG within any one of the DMRs 1 to 308, or within any combination of two or more of the DMRs 1 to 308.

The step of determining the methylation status of the set of one or more cpgs may comprise determining cancer index values of two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, or nine or more of the cpgs represented by the CG within any of the DMRs 1 to 308, optionally within any combination of two or more DMRs 1 to 308.

The set of one or more cpgs may comprise two or more cpgs in the DMR, three or more cpgs in the DMR, four or more cpgs in the DMR, or all cpgs in the DMR.

The step of determining the methylation status of the group of one or more cpgs may include determining a cancer index value of at least two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, or nine or more of the cpgs represented by the CG within any one of the DMRs 1 to 308 or within the following:

all 308 of dmrs 1 to 308;

d. one DMR defined by SEQ ID No. 501, two DMR defined by SEQ ID nos. 501 to 502, three DMR defined by SEQ ID nos. 501 to 503, four DMR defined by SEQ ID nos. 501 to 504, five DMR defined by SEQ ID nos. 501 to 505, six DMR defined by SEQ ID nos. 501 to 506, seven DMR defined by SEQ ID nos. 501 to 507, eight DMR defined by SEQ ID nos. 501 to 508, or nine DMR defined by SEQ ID nos. 501 to 509; or alternatively

e. Ten DMRs defined by SEQ ID nos. 501 to 510, twenty DMRs defined by SEQ ID nos. 501 to 520, thirty DMRs defined by SEQ ID nos. 501 to 530, forty DMRs defined by SEQ ID nos. 501 to 540, fifty DMRs defined by SEQ ID nos. 501 to 550, sixty DMRs defined by SEQ ID nos. 501 to 560, seventy DMRs defined by SEQ ID nos. 501 to 570, eighty DMRs defined by SEQ ID nos. 501 to 580, or ninety DMRs defined by SEQ ID nos. 501 to 590. Or alternatively

f. From SEQ ID NO 501 to 510, SEQ ID NO 511 to 520, SEQ ID NO 521 to 530, SEQ ID NO 531 to 540, SEQ ID NO 541 to 550, SEQ ID NO 551 to 560, SEQ ID NO 561 to 570, SEQ ID NO 571 to 580, SEQ ID NO 581 to 590, SEQ ID NO 591 to 600, SEQ ID NO 601 to 610, SEQ ID NO 611 to 620, SEQ ID NO 621 to 630, SEQ ID NO 631 to 640, SEQ ID NO 641 to 650, SEQ ID NO 651 to 660, SEQ ID NO 661 to 670, SEQ ID NO 671 to 680, SEQ ID NO 681 to 690, SEQ ID NO 691 to 700, SEQ ID NO 701 to 710, SEQ ID NO 711 to 720, SEQ ID NO 721 to 730, SEQ ID NO 731 to 731, SEQ ID NO 741 to 750; 751 to 760; 761 to 770; 771 to 780; SEQ ID NOS 781 to 790; ten DMR defined by SEQ ID NOs 791 to 800 or SEQ ID NOs 801 to 808.

In any of the assays described herein, the step of determining the methylation status of the set of one or more cpgs may comprise determining the methylation status of one or more cpgs within any one or more DMRs selected from the group of DMRs consisting of DMRs 1 to 308 defined by SEQ ID NOs 501 to 808, comprising:

1. one or more cpgs within DMR 1 as defined by SEQ ID No. 501 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.911, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

2. One or more cpgs within DMR 2 as defined by SEQ ID No. 502 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.903, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

3. one or more cpgs within DMR 3 as defined by SEQ ID No. 503 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

4. one or more cpgs within DMR 4 as defined by SEQ ID No. 504 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

5. one or more cpgs within DMR 5 as defined by SEQ ID No. 505 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

6. one or more cpgs within DMR 6 as defined by SEQ ID No. 506 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.897, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

7. One or more cpgs within DMR 7 as defined by SEQ ID No. 507 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.894, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

8. one or more cpgs within DMR 8 as defined by SEQ ID No. 508 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.894, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

9. one or more cpgs within DMR 9 as defined by SEQ ID No. 509 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.892, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

10. one or more cpgs within DMR 10 as defined by SEQ ID No. 510 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.891, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

11. one or more cpgs within DMR 11 as defined by SEQ ID No. 511 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.89, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

12. One or more cpgs within DMR 12 as defined by SEQ ID No. 512 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.888, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

13. one or more cpgs within DMR 13 as defined by SEQ ID No. 513 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.888, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

14. one or more cpgs within DMR 14 as defined by SEQ ID No. 514 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.888, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

15. one or more cpgs within DMR 15 as defined by SEQ ID No. 515 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.888, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

16. one or more cpgs within DMR 16 as defined by SEQ ID No. 516 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.888, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

17. One or more cpgs within DMR 17 as defined by SEQ ID No. 517 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.886, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

18. one or more cpgs within DMR 18 as defined by SEQ ID No. 518 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.886, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

19. one or more cpgs within DMR 19 as defined by SEQ ID No. 519 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.885, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

20. one or more cpgs within DMR 20 as defined by SEQ ID No. 520 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.884, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

21. one or more cpgs within DMR 21 as defined by SEQ ID No. 521 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.882, and more preferably wherein the group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

22. One or more cpgs within DMR 22 as defined by SEQ ID No. 522 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.881, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

23. one or more cpgs within DMR 23 as defined by SEQ ID No. 523 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.88, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

24. one or more cpgs within DMR 24 as defined by SEQ ID No. 524 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.879, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

25. one or more cpgs within DMR 25 as defined by SEQ ID No. 525 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.878, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

26. one or more cpgs within DMR 26 as defined by SEQ ID No. 526 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.878, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

27. One or more cpgs within DMR 27 as defined by SEQ ID No. 527 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.877, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

28. one or more cpgs within DMR 28 as defined by SEQ ID NO 528 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.875, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

preferably, the assay is characterized by having a ROC AUC of at least 0.875, and more preferably, wherein the set of one or more cpgs comprises a CpG represented by at least [ [ CG ] ] within DMR 29 as defined by SEQ ID No. 529 and represented by CG;

30. one or more cpgs within DMR 30 as defined by SEQ ID No. 530 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.874, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

31. one or more cpgs within DMR 31 as defined by SEQ ID NO:531 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.874, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

32. One or more cpgs within DMR 32 as defined by SEQ ID No. 532 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.874, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

33. one or more cpgs within DMR 33 as defined by SEQ ID No. 533 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.874, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

34. one or more cpgs within DMR 34 as defined by SEQ ID No. 534 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.873, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

35. one or more cpgs within DMR 35 as defined by SEQ ID No. 535 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.873, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

36. one or more cpgs within DMR 36 as defined by SEQ ID No. 536 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.873, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

37. One or more cpgs within DMR 37 as defined by SEQ ID No. 537 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.873, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

38. one or more cpgs within DMR 38 as defined by SEQ ID No. 538 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.873, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

39. one or more cpgs within DMR 39 as defined by SEQ ID No. 539 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.872, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

40. one or more cpgs within DMR 40 as defined by SEQ ID No. 540 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.872, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

41. one or more cpgs within DMR 41 as defined by SEQ ID No. 541 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.871, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

42. One or more cpgs within DMR 42 as defined by SEQ ID No. 542 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.871, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

43. one or more cpgs within DMR 43 as defined by SEQ ID No. 543 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.87, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

44. one or more cpgs within DMR 44 as defined by SEQ ID No. 544 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.87, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

45. one or more cpgs within DMR 45 as defined by SEQ ID No. 545 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.869, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

46. one or more cpgs within DMR 46 as defined by SEQ ID No. 546 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.869, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

47. One or more cpgs within DMR 47 as defined by SEQ ID No. 547 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.869, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

48. one or more cpgs within DMR 48 as defined by SEQ ID No. 548 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.867, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

49. one or more cpgs within DMR 49 as defined by SEQ ID No. 549 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.867, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

50. one or more cpgs within DMR 50 as defined by SEQ ID No. 550 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.867, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

51. one or more cpgs within the DMR 551 as defined by SEQ ID NO 551 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.867, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

52. One or more cpgs within DMR 52 as defined by SEQ ID No. 552 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.865, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

53. one or more cpgs within DMR 53 as defined by SEQ ID No. 553 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.864, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

54. one or more cpgs within DMR 54 as defined by SEQ ID No. 554 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.864, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

55. one or more cpgs within DMR 55 as defined by SEQ ID No. 555 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.863, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

56. one or more cpgs within DMR 56 as defined by SEQ ID No. 556 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.863, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

57. One or more cpgs within DMR 57 as defined by SEQ ID No. 557 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.863, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

58. one or more cpgs within DMR 58 as defined by SEQ ID No. 558 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.862, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

59. one or more cpgs within DMR 59 as defined by SEQ ID No. 559 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.862, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

60. one or more cpgs within DMR 60 as defined by SEQ ID No. 560 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.861, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

61. one or more cpgs within DMR 61 as defined by SEQ ID No. 561 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.861, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

62. One or more cpgs within DMR 62 as defined by SEQ ID No. 562 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.861, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

63. one or more cpgs within DMR 63 as defined by SEQ ID No. 563 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.86, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

64. one or more cpgs within DMR 64 as defined by SEQ ID No. 564 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.86, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

65. one or more cpgs within DMR 65 as defined by SEQ ID No. 565 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.86, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

66. one or more cpgs within DMR 66 as defined by SEQ ID No. 566 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.86, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

67. One or more cpgs within DMR 67 as defined by SEQ ID No. 567 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.859, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

68. one or more cpgs within DMR 68 as defined by SEQ ID No. 568 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.859, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

69. one or more cpgs within DMR 69 as defined by SEQ ID No. 569 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.859, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

70. one or more cpgs within DMR 70 as defined by SEQ ID No. 570 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.859, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

71. one or more cpgs within DMR 71 as defined by SEQ ID No. 571 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.859, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

72. One or more cpgs within DMR 72 as defined by SEQ ID No. 572 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.858, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

73. one or more cpgs within DMR 73 as defined by SEQ ID No. 573 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.857, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

74. one or more cpgs within DMR 74 as defined by SEQ ID No. 574 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.857, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

75. one or more cpgs within DMR 75 as defined by SEQ ID No. 575 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.856, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

76. one or more cpgs within DMR 76 as defined by SEQ ID No. 576 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.856, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

77. One or more cpgs within DMR 77 as defined by SEQ ID No. 577 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.856, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

78. one or more cpgs within DMR 78 as defined by SEQ ID No. 578 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.855, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

79. one or more cpgs within DMR 79 as defined by SEQ ID No. 579 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.855, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

80. one or more cpgs within DMR 80 as defined by SEQ ID No. 580 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.855, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

81. one or more cpgs within DMR 81 as defined by SEQ ID No. 581 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.854, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

82. One or more cpgs within DMR 82 as defined by SEQ ID No. 582 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.854, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

83. one or more cpgs within DMR 83 as defined by SEQ ID No. 583 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.854, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

84. one or more cpgs within DMR 84 as defined by SEQ ID No. 584 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.854, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

85. one or more cpgs within DMR 85 as defined by SEQ ID No. 585 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.853, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

86. one or more cpgs within DMR 86 as defined by SEQ ID No. 586 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.853, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

87. One or more cpgs within DMR 87 as defined by SEQ ID No. 587 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.853, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

88. one or more cpgs within DMR 88 as defined by SEQ ID No. 588 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.853, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

89. one or more cpgs within DMR 89 as defined by SEQ ID No. 589 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.852, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

90. one or more cpgs within DMR 90 as defined by SEQ ID No. 590 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.852, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

91. one or more cpgs within DMR 91 as defined by SEQ ID No. 591 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.852, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

92. One or more cpgs within DMR 92 as defined by SEQ ID No. 592 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.851, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

93. one or more cpgs within DMR 93 as defined by SEQ ID No. 593 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.851, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

94. one or more cpgs within DMR 94 as defined by SEQ ID No. 594 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.851, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

95. one or more cpgs within DMR 95 as defined by SEQ ID No. 595 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.851, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

96. one or more cpgs within DMR 96 as defined by SEQ ID No. 596 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.85, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

97. One or more cpgs within DMR 97 as defined by SEQ ID No. 597 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.849, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

98. one or more cpgs within DMR 98 as defined by SEQ ID No. 598 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.849, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

99. one or more cpgs within DMR 99 as defined by SEQ ID No. 599 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.849, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

100. one or more cpgs within DMR 100 as defined by SEQ ID No. 600 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.849, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

101. one or more cpgs within DMR 101 as defined by SEQ ID No. 601 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.849, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

102. One or more cpgs within DMR 102 as defined by SEQ ID No. 602 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.848, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

103. one or more cpgs within DMR 103 as defined by SEQ ID No. 603 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.847, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

104. one or more cpgs within DMR 104 as defined by SEQ ID No. 604 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.847, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

105. one or more cpgs within DMR 105 as defined by SEQ ID No. 605 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.847, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

106. one or more cpgs within DMR 106 as defined by SEQ ID No. 606 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.847, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

107. One or more cpgs within DMR 107 as defined by SEQ ID No. 607 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.846, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

108. one or more cpgs within DMR 108 as defined by SEQ ID No. 608 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.845, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

109. one or more cpgs within DMR 109 as defined by SEQ ID No. 609 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.845, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

110. one or more cpgs within DMR 110 as defined by SEQ ID No. 610 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.845, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

111. one or more cpgs within DMR 111 as defined by SEQ ID NO 611 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.845, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

112. One or more cpgs within DMR 112 as defined by SEQ ID NO:612 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.844, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

113. one or more cpgs within DMR 113 as defined by SEQ ID No. 613 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.843, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

114. one or more cpgs within DMR 114 as defined by SEQ ID No. 614 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.843, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

115. one or more cpgs within DMR 115 as defined by SEQ ID No. 615 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.842, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

116. one or more cpgs within DMR 116 as defined by SEQ ID No. 616 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.842, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

117. One or more cpgs within DMR 117 as defined by SEQ ID No. 617 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.841, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

118. one or more cpgs within DMR 118 as defined by SEQ ID No. 618 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.841, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

119. one or more cpgs within DMR 119 as defined by SEQ ID No. 619 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.841, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

120. one or more cpgs within DMR 120 as defined by SEQ ID No. 620 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.84, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

121. one or more cpgs within DMR 121 as defined by SEQ ID No. 621 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.839, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

122. One or more cpgs within DMR 122 as defined by SEQ ID No. 622 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.839, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

123. one or more cpgs within DMR 123 as defined by SEQ ID No. 623 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.838, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

124. one or more cpgs within DMR 124 as defined by SEQ ID No. 624 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.838, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

125. one or more cpgs within DMR 125 as defined by SEQ ID No. 625 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.838, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

126. one or more cpgs within DMR 126 as defined by SEQ ID No. 626 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.835, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

127. One or more cpgs within DMR 127 as defined by SEQ ID No. 627 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.835, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

128. one or more cpgs within DMR 128 as defined by SEQ ID No. 628 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.833, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

129. one or more cpgs within DMR 129 as defined by SEQ ID No. 629 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.832, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

130. one or more cpgs within DMR 130 as defined by SEQ ID No. 630 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.832, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

131. one or more cpgs within DMR 131 as defined by SEQ ID NO 631 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.832, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

132. One or more cpgs within DMR 132 as defined by SEQ ID No. 632 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.831, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

133. one or more cpgs within DMR 133 as defined by SEQ ID No. 633 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.831, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

134. one or more cpgs within DMR 134 as defined by SEQ ID No. 634 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.83, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

135. one or more cpgs within DMR 135 as defined by SEQ ID No. 635 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.83, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

136. one or more cpgs within DMR 136 as defined by SEQ ID No. 636 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.83, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

137. One or more cpgs within DMR 137 as defined by SEQ ID No. 637 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.829, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

138. one or more cpgs within DMR 138 as defined by SEQ ID No. 638 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.829, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

139. one or more cpgs within DMR 139 as defined by SEQ ID No. 639 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.829, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

140. one or more cpgs within DMR 140 as defined by SEQ ID No. 640 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.829, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

141. one or more cpgs within DMR 141 as defined by SEQ ID NO:641 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.828, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

142. One or more cpgs within DMR 142 as defined by SEQ ID No. 642 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.828, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

143. one or more cpgs within DMR 143 as defined by SEQ ID No. 643 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.828, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

144. one or more cpgs within DMR 144 as defined by SEQ ID No. 644 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.828, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

145. one or more cpgs within DMR 145 as defined by SEQ ID No. 645 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.828, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

146. one or more cpgs within DMR 146 as defined by SEQ ID No. 646 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.825, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

147. One or more cpgs within DMR 147 as defined by SEQ ID No. 647 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.825, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

148. one or more cpgs within DMR 148 as defined by SEQ ID No. 648 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.824, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

149. one or more cpgs within DMR 149 as defined by SEQ ID No. 649 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.824, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

150. one or more cpgs within DMR 150 as defined by SEQ ID No. 650 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.824, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

151. one or more cpgs within DMR 151 as defined by SEQ ID No. 651 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.824, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

152. One or more cpgs within DMR 152 as defined by SEQ ID No. 652 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.823, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

153. one or more cpgs within DMR 153 as defined by SEQ ID No. 653 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.82, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

154. one or more cpgs within DMR 154 as defined by SEQ ID No. 654 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.82, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

155. one or more cpgs within DMR 155 as defined by SEQ ID No. 655 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.819, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

156. one or more cpgs within DMR 156 as defined by SEQ ID No. 656 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.816, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

157. One or more cpgs within DMR 157 as defined by SEQ ID No. 657 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.816, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

158. one or more cpgs within DMR 158 as defined by SEQ ID No. 658 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.814, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

159. one or more cpgs within DMR 159 as defined by SEQ ID No. 659 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.814, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

160. one or more cpgs within DMR 160 as defined by SEQ ID No. 660 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.814, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

161. one or more cpgs within DMR 161 as defined by SEQ ID NO:661 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.813, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

162. One or more cpgs within DMR 162 as defined by SEQ ID No. 662 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.812, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

163. one or more cpgs within DMR 163 as defined by SEQ ID No. 663 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.811, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

164. one or more cpgs within DMR 164 as defined by SEQ ID NO 664 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.811, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

165. one or more cpgs within DMR 165 as defined by SEQ ID No. 665 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.81, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

166. one or more cpgs within DMR 166 as defined by SEQ ID No. 666 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.809, and more preferably wherein the set of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

167. One or more cpgs within DMR 167 as defined by SEQ ID No. 667 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.808, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

168. one or more cpgs within DMR 168 as defined by SEQ ID NO 668 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.807, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

169. one or more cpgs within DMR 169 as defined by SEQ ID No. 669 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.807, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

170. one or more cpgs within DMR 170 as defined by SEQ ID No. 670 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.806, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

171. one or more cpgs within DMR 171 as defined by SEQ ID No. 671 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.806, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

172. One or more cpgs within DMR 172 as defined by SEQ ID No. 672 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.805, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

173. one or more cpgs within DMR 173 as defined by SEQ ID No. 673 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.805, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

174. one or more cpgs within DMR 174 as defined by SEQ ID No. 674 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.803, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

175. one or more cpgs within DMR 175 as defined by SEQ ID NO:675 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.803, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

176. one or more cpgs within DMR 176 as defined by SEQ ID No. 676 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.801, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

177. One or more cpgs within DMR 177 as defined by SEQ ID No. 677 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.799, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

178. one or more cpgs within DMR 178 as defined by SEQ ID No. 678 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.799, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

179. one or more cpgs within DMR 179 as defined by SEQ ID No. 679 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.799, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

180. one or more cpgs within DMR 180 as defined by SEQ ID No. 680 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.799, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

181. one or more cpgs within DMR 181 as defined by SEQ ID No. 681 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.798, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

182. One or more cpgs within DMR 182 as defined by SEQ ID No. 682 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.797, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

183. one or more cpgs within DMR 183 as defined by SEQ ID No. 683 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.796, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

184. one or more cpgs within DMR 184 as defined by SEQ ID No. 684 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.793, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

185. one or more cpgs within DMR 185 as defined by SEQ ID No. 685 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.792, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

186. one or more cpgs within DMR 186 as defined by SEQ ID No. 686 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.792, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

187. One or more cpgs within DMR 187 as defined by SEQ ID No. 687 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.791, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

188. one or more cpgs within DMR 188 as defined by SEQ ID No. 688 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.79, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

189. one or more cpgs within DMR 189 as defined by SEQ ID No. 689 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.79, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

190. one or more cpgs within DMR 190 as defined by SEQ ID No. 690 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.789, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

191. one or more cpgs within DMR 191 as defined by SEQ ID No. 691 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.788, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

192. One or more cpgs within DMR 192 as defined by SEQ ID No. 692 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.788, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

193. one or more cpgs within the DMR 193 as defined by SEQ ID No. 693 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.787, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

194. one or more cpgs within DMR 194 as defined by SEQ ID No. 694 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.787, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

195. one or more cpgs within DMR 195 as defined by SEQ ID No. 695 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.787, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

196. one or more cpgs within DMR 196 as defined by SEQ ID No. 696 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.784, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

197. One or more cpgs within DMR 197 as defined by SEQ ID No. 697 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.784, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

198. one or more cpgs within DMR 198 as defined by SEQ ID No. 698 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.783, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

199. one or more cpgs within DMR 199 as defined by SEQ ID No. 699 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.781, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

200. one or more cpgs within DMR 200 as defined by SEQ ID No. 700 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.78, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

201. one or more cpgs within DMR 201 as defined by SEQ ID No. 701 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.777, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

202. One or more cpgs within DMR 202 as defined by SEQ ID No. 702 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.777, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

203. one or more cpgs within DMR 203 as defined by SEQ ID No. 703 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.777, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

204. one or more cpgs within DMR 204 as defined by SEQ ID No. 704 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.777, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

205. one or more cpgs within DMR 205 as defined by SEQ ID No. 705 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.777, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

206. one or more cpgs within DMR 206 as defined by SEQ ID No. 706 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.777, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

207. One or more cpgs within DMR 207 as defined by SEQ ID No. 707 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.777, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

208. one or more cpgs within DMR 208 as defined by SEQ ID No. 708 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.776, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

209. one or more cpgs within DMR 209 as defined by SEQ ID No. 209 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.776, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

210. one or more cpgs within DMR 210 as defined by SEQ ID No. 710 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.776, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

211. one or more cpgs within DMR 211 as defined by SEQ ID No. 711 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.775, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

212. One or more cpgs within DMR 212 as defined by SEQ ID No. 712 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.775, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

213. one or more cpgs within DMR 213 as defined by SEQ ID No. 713 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.775, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

214. one or more cpgs within DMR 214 as defined by SEQ ID No. 714 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.771, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

215. one or more cpgs within DMR 215 as defined by SEQ ID No. 715 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.769, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

216. one or more cpgs within DMR 216 as defined by SEQ ID No. 716 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.767, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

217. One or more cpgs within DMR 217 as defined by SEQ ID No. 717 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.762, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

218. one or more cpgs within DMR 218 as defined by SEQ ID No. 718 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.76, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

219. one or more cpgs within DMR 219 as defined by SEQ ID No. 719 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.758, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

220. one or more cpgs within DMR 220 as defined by SEQ ID No. 720 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.757, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

221. one or more cpgs within DMR 221 as defined by SEQ ID No. 721 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.751, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

222. One or more cpgs within DMR 222 as defined by SEQ ID No. 722 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.742, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

223. one or more cpgs within DMR 223 as defined by SEQ ID NO:723 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.738, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

224. one or more cpgs within DMR 224 as defined by SEQ ID NO 724 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.73, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

225. one or more cpgs within DMR 225 as defined by SEQ ID No. 725 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.726, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

226. one or more cpgs within DMR 226 as defined by SEQ ID No. 726 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.726, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

227. One or more cpgs within DMR 227 as defined by SEQ ID NO 727 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.72, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

228. one or more cpgs within DMR 228 as defined by SEQ ID NO 728 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.715, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

229. one or more cpgs within DMR 229 as defined by SEQ ID NO 729 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.713, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

230. one or more cpgs within DMR 230 as defined by SEQ ID No. 730 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.713, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

231. one or more cpgs within DMR 231 as defined by SEQ ID No. 731 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.708, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

232. One or more cpgs within DMR 232 as defined by SEQ ID No. 732 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.707, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

233. one or more cpgs within DMR 233 as defined by SEQ ID No. 733 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.704, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

234. one or more cpgs within DMR 234 as defined by SEQ ID No. 734 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.697, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

235. one or more cpgs within DMR 235 as defined by SEQ ID No. 735 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.697, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

236. one or more cpgs within DMR 236 as defined by SEQ ID No. 736 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.693, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

237. One or more cpgs within DMR 237 as defined by SEQ ID No. 737 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.638, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

238. one or more cpgs within DMR 238 as defined by SEQ ID NO:738 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.903, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

239. one or more cpgs within DMR 239 as defined by SEQ ID No. 739 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.903, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

240. one or more cpgs within DMR 240 as defined by SEQ ID No. 740 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

241. one or more cpgs within DMR 241 as defined by SEQ ID No. 741 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

242. One or more cpgs within DMR 242 as defined by SEQ ID No. 742 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

243. one or more cpgs within DMR 243 as defined by SEQ ID No. 743 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

244. one or more cpgs within DMR 244 as defined by SEQ ID No. 744 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

245. one or more cpgs within DMR 245 as defined by SEQ ID No. 745 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

246. one or more cpgs within DMR 246 as defined by SEQ ID No. 746 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.895, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

247. One or more cpgs within DMR 247 as defined by SEQ ID No. 747 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.895, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

248. one or more cpgs within DMR 248 as defined by SEQ ID No. 748 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.893, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

249. one or more cpgs within DMR 249 as defined by SEQ ID No. 749 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.893, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

250. one or more cpgs within DMR 250 as defined by SEQ ID No. 750 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.891, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

251. one or more cpgs within DMR 251 as defined by SEQ ID No. 751 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.891, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

252. One or more cpgs within DMR 252 as defined by SEQ ID No. 752 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.886, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

253. one or more cpgs within DMR 253 as defined by SEQ ID No. 753 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.886, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

254. one or more cpgs within DMR 254 as defined by SEQ ID No. 754 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.886, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

255. one or more cpgs within DMR 255 as defined by SEQ ID No. 755 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.886, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

256. one or more cpgs within DMR 256 as defined by SEQ ID No. 756 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.878, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

257. One or more cpgs within DMR 257 as defined by SEQ ID No. 757 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.878, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

258. one or more cpgs within DMR 258 as defined by SEQ ID NO 758 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.875, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

259. one or more cpgs within DMR 259 as defined by SEQ ID No. 759 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.875, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

260. one or more cpgs within DMR 260 as defined by SEQ ID NO 760 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.874, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

261. one or more cpgs within DMR 261 as defined by SEQ ID No. 761 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.874, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

262. One or more cpgs within DMR 262 as defined by SEQ ID No. 762 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.865, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

263. one or more cpgs within DMR 263 as defined by SEQ ID No. 763 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.865, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

264. one or more cpgs within DMR 264 as defined by SEQ ID No. 764 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.863, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

265. one or more cpgs within DMR 265 as defined by SEQ ID No. 765 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.863, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

266. one or more cpgs within DMR 267 as defined by SEQ ID No. 767 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.863, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

267. One or more cpgs within DMR 268 as defined by SEQ ID No. 768 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.862, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

268. one or more cpgs within DMR 269 as defined by SEQ ID No. 769 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.862, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

269. one or more cpgs within DMR 270 as defined by SEQ ID NO 770 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.862, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

270. one or more cpgs within DMR 271 as defined by SEQ ID No. 771 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.862, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

271. one or more cpgs within DMR 272 as defined by SEQ ID NO 772 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.862, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

272. One or more cpgs within DMR 273 as defined by SEQ ID No. 773 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.862, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

273. one or more cpgs within DMR 274 as defined by SEQ ID No. 774 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.862, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

274. one or more cpgs within DMR 275 as defined by SEQ ID No. 775 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.862, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

275. one or more cpgs within DMR 276 as defined by SEQ ID No. 776 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.861, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

276. one or more cpgs within DMR 277 as defined by SEQ ID No. 777 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.861, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

277. One or more cpgs within DMR 278 as defined by SEQ ID No. 778 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.860, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

278. one or more cpgs within DMR 279 as defined by SEQ ID No. 779 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.860, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

279. one or more cpgs within DMR 280 as defined by SEQ ID NO 780 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.859, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

280. one or more cpgs within DMR 281 as defined by SEQ ID No. 781 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.859, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

281. one or more cpgs within DMR 282 as defined by SEQ ID No. 782 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.853, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

282. One or more cpgs within DMR 283 as defined by SEQ ID No. 783 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.853, and more preferably wherein the set of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

283. one or more cpgs within DMR 284 as defined by SEQ ID No. 784 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.851, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

284. one or more cpgs within DMR 285 as defined by SEQ ID No. 785 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.851, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

285. one or more cpgs within DMR 286 as defined by SEQ ID No. 786 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.849, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

286. one or more cpgs within DMR 287 as defined by SEQ ID No. 787 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.849, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

287. One or more cpgs within DMR 288 as defined by SEQ ID No. 788 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.846, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

288. one or more cpgs within DMR 289 as defined by SEQ ID No. 789 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.846, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

289. one or more cpgs within the DMR 290 as defined by SEQ ID No. 790 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.842, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

290. one or more cpgs within DMR 291 as defined by SEQ ID No. 791 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.842, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

291. one or more cpgs within DMR 292 as defined by SEQ ID No. 792 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.841, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

292. One or more cpgs within DMR 293 as defined by SEQ ID NO 793 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.841, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

293. one or more cpgs within DMR 294 as defined by SEQ ID No. 794 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.838, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

294. one or more cpgs within DMR 295 as defined by SEQ ID No. 795 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.838, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

295. one or more cpgs within DMR 296 as defined by SEQ ID No. 796 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.833, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

296. one or more cpgs within DMR 297 as defined by SEQ ID NO 797 and represented by CG, preferably wherein the assay is characterized as having a ROC AUC of at least 0.833, and more preferably wherein the set of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

297. One or more cpgs within DMR 298 as defined by SEQ ID No. 798 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.832, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

298. one or more cpgs within DMR 299 as defined by SEQ ID No. 799 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.832, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

299. one or more cpgs within DMR 300 as defined by SEQ ID No. 800 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.831, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

300. one or more cpgs within DMR 301 as defined by SEQ ID No. 801 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.831, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

301. one or more cpgs within DMR 302 as defined by SEQ ID No. 802 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.826, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

302. One or more cpgs within DMR 303 as defined by SEQ ID NO 803 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.826, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

303. one or more cpgs within DMR 304 as defined by SEQ ID No. 804 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.806, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

304. one or more cpgs within DMR 305 as defined by SEQ ID No. 805 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.806, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

305. one or more cpgs within DMR 306 as defined by SEQ ID No. 806 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.911, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

306. one or more cpgs within DMR 307 as defined by SEQ ID No. 807 and represented by CG, preferably wherein the assay is characterized by a ROC AUC of at least 0.905, and more preferably wherein a group of one or more cpgs comprises a CpG represented by at least [ [ CG ] ];

307. One or more CpG's within the DMR 308 as defined by SEQ ID NO 808 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.905, and more preferably wherein a group of one or more CpG's comprises a CpG represented by at least [ [ CG ] ],

preferably, wherein the methylation status of one or more cpgs in the group is preferably determined by beta value analysis and the cancer is endometrial cancer of ovarian cancer.

In any of the assays described herein, the step of determining the methylation status of the set of one or more cpgs comprises determining the methylation status of two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more or all of the cpgs represented by the CG within any combination of:

i. one or more DMR defined by SEQ ID NOs 525, 756, and 757, preferably within all of SEQ ID NOs 525, 756, and 757;

one or more DMR defined by SEQ ID NOs 503, 504, 526, 740, 741, 743 and 744, preferably within all of SEQ ID NOs 503, 504, 526, 740, 741, 743 and 744; and

One or more DMR defined by SEQ ID NOs 525, 756, 757, 503, 504, 526, 740, 741, 743 and 744, preferably within all of SEQ ID NOs 525, 756, 757, 503, 504, 526, 740, 741, 743 and 744.

In any of the assays described herein, the step of determining the methylation status of one or more cpgs in the group may include or may additionally include determining the methylation status of each CpG within one or more of the sequences identified by SEQ ID NOs 809 to 919.

In any of the assays described herein, the step of determining the methylation status of one or more cpgs in the group may preferably or preferably additionally comprise determining the methylation status of each CpG within one or more of the sequences identified by SEQ ID NOs 809, 746, 883, 811, 848, 885, 813, 850 and 887. More preferably, in any of the assays described herein, the step of determining the methylation status of one or more cpgs in the set may include or may additionally include determining the methylation status of each CpG within all of the sequences identified by SEQ ID NOs 809, 746, 883, 811, 848, 885, 813, 850 and 887.

The invention also provides a plurality of assays, each comprising any 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more (or any range derivable therein) of the plurality of steps and without a specific order, comprising the following methods: measuring in a sample; analyzing the sample; evaluating the sample; evaluating the sample; measuring nucleic acid in the sample; assessing nucleic acid in a sample; detecting nucleic acid in the sample; measuring methylation in nucleic acids in the sample; analyzing nucleic acids in the sample; assessing nucleic acid in a sample; measuring methylation at one or more CpG dinucleotides in the sample; detecting methylation at one or more CpG dinucleotides in the sample; determining methylation at one or more CpG dinucleotides in the sample; assessing methylation at one or more CpG dinucleotides in the sample; measuring methylation status in the sample; determining the methylation status in the sample; detecting methylation status in the sample; determining the methylation status in the sample; identifying methylation status in the sample; measuring one or more DNA methylation markers in the sample; assessing one or more DNA methylation markers in the sample; detecting one or more DNA methylation markers in the sample; measuring the presence of methylation at one or more markers in the sample; detecting the presence of methylation at one or more markers in the sample; assessing the presence of methylation at one or more markers in the sample; determining the presence of one or more markers in the sample; measuring one or more DNA methylation markers in the sample, but excluding one or more other DNA methylation markers in the measurement sample; assessing one or more DNA methylation markers in the sample, but excluding one or more other DNA methylation markers in the assessment sample; analyzing the sample for one or more DNA methylation markers, but excluding the analysis sample for one or more other DNA methylation markers; detecting one or more DNA methylation markers in the sample, but excluding one or more other DNA methylation markers in the sample; measuring the methylation state in nucleic acid in a sample from a tissue of an individual, the tissue being different from tissue from an individual suspected of having or at risk of having cancer; detecting a methylation state in nucleic acid in a sample of tissue from an individual, the tissue being different from tissue from an individual suspected of having or at risk of having cancer; analyzing methylation status in nucleic acid in a sample from a tissue of an individual, the tissue being different from tissue from an individual suspected of having or at risk of having cancer; assessing methylation status in nucleic acid in a sample from tissue of an individual, the tissue being different from tissue from an individual suspected of having or at risk of having cancer; measuring methylation at one or more CpG dinucleotides in the sample, but excluding methylation at one or more CpG dinucleotides in the sample; assessing methylation at one or more CpG dinucleotides in the sample, but excluding methylation at one or more CpG dinucleotides in the sample; analyzing methylation at one or more CpG dinucleotides in the sample, but excluding methylation at one or more CpG dinucleotides in the sample; detecting methylation at one or more CpG dinucleotides in the sample, but excluding methylation at one or more CpG dinucleotides in the sample; measuring methylation at one or more CpG dinucleotides in a nucleic acid in a sample from a tissue of the individual, the tissue being different from a tissue from the individual suspected of having or at risk of having cancer; detecting methylation at one or more CpG dinucleotides in a nucleic acid in a sample from a tissue of the individual, the tissue being different from a tissue from the individual suspected of having or at risk of having cancer; analyzing methylation at one or more CpG dinucleotides in a nucleic acid in a sample from a tissue of the individual, the tissue being different from a tissue from the individual suspected of having or at risk of having cancer; assessing methylation at one or more CpG dinucleotides in a nucleic acid in a sample from a tissue of the individual, the tissue being different from tissue from the individual suspected of having or at risk of having cancer; treating cancer in an individual when the individual has been determined to have a methylation state at one or more methylation markers; treating cancer in an individual when the individual has been determined to have methylation at one or more CpG dinucleotides;

Any of the foregoing methods, or any other methods encompassed by the present disclosure, may comprise any one or more of the following method steps:

measuring methylation status, wherein the measurement identifies methylation status of one or more markers in nucleic acid from the sample;

measuring methylation status, wherein the measurement identifies the presence of one or more markers from nucleic acids in the sample;

measuring the presence of one or more methylation markers from the sample;

providing DNA from a sample

Providing nucleic acid from a sample;

determining whether one or more methylation markers in a nucleic acid from the sample are methylated;

measuring whether one or more methylation markers in a nucleic acid from the sample are methylated;

performing a sequencing step on nucleic acid from the sample;

determining the sequence of nucleic acid from the sample;

performing bisulfite conversion on the one or more markers;

performing bisulfite conversion on one or more CpG dinucleotides;

hybridizing DNA to a chip comprising probes capable of determining methylated and unmethylated markers;

hybridizing the DNA to a chip comprising probes capable of determining methylated and unmethylated CpG dinucleotides;

Hybridizing DNA to a chip comprising probes capable of distinguishing between methylated and unmethylated markers;

hybridizing the DNA to a chip comprising probes capable of distinguishing between methylated and unmethylated CpG dinucleotides;

performing an amplification step on a nucleic acid sequence from a sample;

performing an amplification step on a sequence from the nucleic acid using methylation specific primer pairs;

amplifying a sequence comprising one or more regions suspected of being methylated or in need of determining methylation status;

performing PCR on a sequence comprising one or more regions suspected of being methylated or requiring methylation status determination;

implementing a capturing step;

implementing a combining step;

performing a purification step;

performing a capturing step comprising binding a polynucleotide comprising one or more methylation markers to a binding molecule specific for the one or more methylation markers, and collecting complexes thereof;

stratification of the grade of cancer;

determining the risk of cancer;

determining the risk of cancer recurrence;

obtaining a sample from an individual;

obtaining DNA from a sample in an individual;

administering a treatment to an individual;

providing DNA from a sample;

determining whether one or more methylation markers from the group of methylation markers comprise a specific sequence; and/or

Data is obtained identifying whether each of a set of methylation markers from the set comprises a particular sequence.

Furthermore, in some aspects of the invention, the individual to whom the therapy or treatment is administered has received any of the methods and steps described herein.

Described herein are assays utilizing a statistically robust panel of one or more CPGs, the methylation status of CpG can be determined to provide a reliable prediction of the presence or progression of cancer in an individual. By determining the methylation status of each CpG within a group of one or more CpG's, a cancer index value can be deduced, enabling stratification of an individual with statistically robust sensitivity and specificity according to the individual's risk of developing or suffering from cancer, particularly endometrial and/or ovarian cancer. Those of skill in the art will appreciate that the methylation status of each CpG within a group of one or more CpG's can be determined by any suitable means to derive a cancer index value. Any method or combination of methods may be used to determine the methylation status of each CpG within a group of one or more CpG's.

Various exemplary methods for determining the methylation status of each CpG within a group of one or more CpG's are described herein. For example, in one approach, the methylation reference (PMR) percent value of CpG can be determined. In another method, the methylation beta value of CpG can be determined. Different mechanisms may be employed to determine the particular value depending on the situation, such as a PCR-based mechanism or a chip-based mechanism.

Cancer index values as diagnostic and risk assessment tools

In any of the assays described herein, the assessment of the presence, absence, or progression of cancer in the individual is based on the individual's cancer index value at the time of detection.

As explained herein, using the set of specific cpgs disclosed herein, cancer index values corresponding to cancer negative samples can be established, as they are based on values derived from individuals known to be cancer negative, and are obtained from tissue samples from anatomical sites other than the endometrium or ovary, such as from the cervix, vagina, cheek areas, blood and/or urine, in particular from liquid-based cytological samples, more preferably cervical smear samples. Similarly, using the specific CpG sets disclosed herein, cancer index values corresponding to cancer positive samples can be established because they are based on values derived from anatomical sites other than ovaries or endometrium, as described above, from tissue samples from individuals known to be cancer positive. The user may then apply these cancer index values to assess the presence, absence, or progression of cancer in any test individual whose cancer status is to be tested. As also explained herein, the assays of the present invention can be implemented with high statistical accuracy.

As explained herein, the described assays relate in particular to the assessment of the presence, absence or progression of endometrial and/or ovarian cancer, in particular endometrial cancer.

One of skill in the art will readily appreciate that a cancer index value provides a value indicative of the "likelihood" or "risk" or "prognosis" of any of the assays of the invention that correctly evaluates the presence, absence, or progression of cancer in an individual. This is because the assessment is based on the correlation between DNA methylation characteristics of tissue samples and individual disease states. However, as shown in the examples and data elsewhere herein, the assays of the present invention provide such correlations with high statistical accuracy, thereby providing the skilled artisan with a high degree of confidence that any test individual whose cancer status needs to be tested will provide an accurate correlation with the actual disease status of that individual.

In the context of the present invention, "likelihood", "risk" and "prediction" may be used synonymously with each other.

Any reference herein to sequences, genomic sequences and/or genomic coordinates is based on the homo sapiens (human) genome assembly GRCh37 (hg 19). The skilled artisan will appreciate that there may be variations in any given sequence, particularly the nucleotide sequences of DMR 1 to 308, due to sequencing errors and/or variations between individuals.

The assay representation of the present invention represents a 'prediction' in that any cancer index value (WID-EC-index) derived according to the present invention is unlikely to diagnose whether each individual has cancer with 100% specificity and 100% sensitivity. In contrast, depending on the cancer index cutoff threshold that the user applies to positively predict the presence of cancer in an individual, the false positive and false negative rates will change. In other words, the inventors have found that depending on the cancer index cut-off threshold selected and applied by the user, the assay of the invention can achieve a variable level of sensitivity and specificity for predicting the presence, absence or progression of cancer, as defined by the recipient operating characteristics. As can be seen from the data disclosed herein, such sensitivity and specificity are achievable at high ratios, demonstrating accurate and statistically significant discrimination capability.

Similarly, cancer index values that have been predetermined to be associated with a particular cancer phenotype, such as the presence or absence of cancer, have been defined to have a high level of statistical accuracy, as further explained herein.

In the context of the present invention, assessing the 'progression' of cancer may refer to assessing whether an individual is likely or unlikely to progress to cancer. The inventors have shown that CpG, measured in order to derive the cancer index value of the assay of the invention, represents cells from anatomical sites other than endometrium or ovary, such as from cervical, vaginal, buccal area, blood and/or urine, in particular from liquid-based cytological samples, more preferably from normal tissue of cervical smear samples. Assessing the progression of cancer according to the assays of the invention may refer to assessing the progression of cancer (in particular endometrial and ovarian cancer) and/or CIN3, preferably an increased or decreased likelihood of endometrial cancer. Assessing the progression of cancer according to the assays of the invention may refer to assessing the progression or worsening of pre-existing cancer lesions in an individual. Assessment of cancer progression according to the assays of the invention may refer to predicting the likelihood of cancer recurrence.

In any of the assays described herein, the step of assessing the presence or progression of cancer in the individual based on the cancer index value may involve applying a threshold value. The threshold may provide a risk-based indication of the individual's cancer status, whether positive or negative for cancer. The threshold may also provide a means for identifying whether the cancer index value is between a positive cancer value and a negative cancer value. As explained herein, cancer index values may be dynamic and vary depending on genetic and/or environmental factors. Thus, the cancer index value may provide a means for assessing and monitoring cancer progression. Thus, a cancer index value may indicate that an individual has a positive status of cancer or has at least a low or high risk of indicating a status of cancer progression. If an individual's cancer index value is determined by the assay of the invention at two or more time points, an increase or decrease in the individual's cancer index value may indicate that the individual has or is developing cancer, particularly endometrial and/or ovarian cancer, most preferably an increased or decreased risk of endometrial cancer.

Throughout the disclosure herein, the terms "threshold," "intercept," and "intercept threshold" are considered synonymous and interchangeable.

As further explained herein, any of the assays of the invention are assays for assessing the presence, absence or progression of cancer in an individual. The types of cancers are further described herein. As further explained herein, the assays of the present invention provide a means to assess whether an individual is at risk of having or developing cancer based on a particular cut-off threshold. Such risk assessment may be provided with a high degree of confidence based on statistical parameters characterizing the assay. Thus, in any of the assays described herein that involve a cancer index cut-off threshold, the cut-off threshold may be used for risk assessment purposes. Likewise, in any of the assays described herein that involve a cancer index cut-off threshold, the cut-off threshold can be used to specify whether an individual has cancer as a pure diagnostic test. Also, such diagnostic tests may have a high degree of confidence based on statistical parameters characterizing the assay. Thus, in any assay described herein that specifies an individual with a cancer index value of a particular value or greater, or "about" a particular value or greater, the individual can be assessed as having cancer. In any of the assays described herein that specify an individual with a cancer index value less than a particular value or less than "about" a particular value, the individual may be assessed as not having cancer. The term "about" is understood to provide a range of +/-5% of this value.

Thus, any of the assays of the invention are assays for assessing the presence, absence or progression of cancer in an individual comprising:

a. providing a sample from an individual, the sample comprising a population of DNA molecules;

b. determining the methylation status of a group of DNA molecules in the sample of:

(ii) One or more cpgs selected from one or more Differential Methylation Regions (DMR) defined by SEQ ID NOs 501 to 808, wherein cpgs are represented by CG;

c. deriving a cancer index value based on methylation status of one or more cpgs in the group; and

d. assessing the presence, absence, or progression of cancer in the individual based on the cancer index value;

Any of the assays of the invention are particularly useful for assessing the presence or absence of cancer and/or CIN3 in an individual.

Such assays may be performed according to any of the methods disclosed and defined herein.

As further explained herein, any of the assays of the invention for assessing the presence, absence or progression of cancer in an individual may alternatively be referred to as an assay for stratifying an individual according to their cancer status.

Thus, any of the assays of the invention are assays for stratifying an individual to determine the presence, absence or progression of cancer in the individual, comprising:

d. stratification for the presence, absence, or progression of cancer in an individual based on the cancer index value;

Thus, any of the assays of the invention are assays for stratifying cancer in an individual comprising:

d. cancer stratification of the individual based on the cancer index value;

The cancer index value may be derived by any suitable means. Preferably, the cancer index value can be deduced by assessing the methylation status of the group of:

(ii) One or more CpG selected from one or more Differential Methylation Regions (DMR) defined by SEQ ID NOs 501 to 808, wherein CpG is represented by CG,

In a sample provided by an individual. The methylation status of CpG can be determined by any suitable means. For example, in any of the assays described herein, the step of determining the methylation status of each CpG in the set of one or more cpgs may comprise:

a. performing a sequencing step to determine the sequence of each CpG;

b. hybridizing the DNA to a chip comprising probes capable of distinguishing between methylated and unmethylated forms of CpG, and applying a detection system to the chip to determine the methylation status of each CpG; and/or

c. The PCR step is performed using methylation specific primers, wherein the methylation status of CpG is determined by the presence or absence of PCR products.

The step of determining the methylation state of the group of one or more cpgs in the population of DNA molecules in the sample may comprise determining a β value for each CpG. Deriving the cancer index value may involve providing a methylation beta value dataset comprising methylation beta values for each CpG in the set of one or more CpG. Additionally or alternatively, the step of determining the methylation state of the set of one or more CPGs in the population of DNA molecules in the sample may comprise determining a methylation reference value percentage for each of the set of one or more CPGs. Optionally, deriving the cancer index value may also involve estimating the fraction of contaminating DNA in the DNA provided by the sample.

The DNA may be DNA derived from a particular source organism, tissue or cell type. Preferably, the contaminating DNA is derived from one or more different cell types to one or more cell types of interest. The cell type of interest may be particularly an epithelial cell. In some aspects of the invention, it may be preferable to estimate the fraction of contaminating DNA after the step of providing a sample taken from the individual. The assays described herein may optionally involve estimating the fraction of contaminating DNA within DNA in the sample by any suitable means. Preferably, the contaminating DNA fraction of the sample is estimated via any suitable bioinformatic analysis tool. The bioinformatic analysis tool that can be used to estimate the fraction of contaminating DNA can be EpIDISH. As described herein, it may be desirable to estimate the fraction of contaminating DNA from one or more cell types other than the one or more cell types of interest, because in some cases the cancer index value used to predict the presence or progression of cancer in an individual may only reliably originate from determining the methylation status of a set of cpgs from DNA of a particular cell type of interest. In particular, methylation status beta values for one or more cell types of interest within a sample may be different relative to methylation status beta values for contaminating DNA from different cell types in the same sample. Thus, the derived cancer index value may have a reduced predictive power in some cases without estimating and controlling the contaminating DNA fraction in the DNA provided by the sample. In the assay of the invention involving estimating the fraction of contaminating DNA and controlling the contaminating DNA accordingly, the immune cell DNA fraction in the DNA provided by the sample is preferably estimated. In particular assays of the invention, wherein an individual has more than 50% immune cell contamination (i.e., wherein more than 50% of the DNA in the sample is considered to be from immune cells), the assay may preferably involve controlling immune cell contamination by deriving a cancer index from only epithelial-derived DNA molecules in accordance with the invention.

Any of the assays described herein that include the step of deriving a cancer index value based on the methylation status of one or more cpgs in the group may further include applying an algorithm to the methylation beta value dataset to obtain the cancer index value. Preferably, in any of the assays described herein, the step of deriving the cancer index value based on the methylation status of the CpG groups comprises providing a methylation beta value dataset comprising a methylation beta value for each CpG in the group, and applying an algorithm to the methylation beta value dataset to obtain the cancer index value.

In any of the assays described herein, the step of deriving the cancer index value based on the methylation status of one or more cpgs in the group comprises:

a. providing a methylation beta value dataset comprising methylation beta values for each CpG in the group;

b. providing a mathematical model capable of generating a cancer index from the methylation beta value dataset; and

c. a mathematical model is applied to the methylation beta value dataset to generate a cancer index.

In any of the assays described herein, the cancer index value may be calculated by any suitable mathematical model, such as an algorithm or formula. Preferably, the cancer index value is referred to as a female endometrial cancer risk identification index (WID-EC-index), and wherein the mathematical model applied to the methylation beta value dataset to generate the cancer index is calculated by an algorithm according to the following formula:

Wherein:

1.β ₁ ,…,β _n is the methylation beta value (between 0 and 1);

2.w ₁ ,…,w ₅₀₀ is a real value coefficient;

3.μ and σ are real-valued parameters for the scaling factor; and

n refers to the number of cpgs in the group tested for cpgs;

preferably, wherein the cancer is endometrial cancer.

In any of the assays described herein, the WID-EC-index algorithm applies the real-valued coefficients inferred by initial training of the dataset (which in the exemplary embodiment of the invention described in the examples consists of 144 endometrial cancer cases and 572 control groups) to fit a ridge classifier using R-bag glmcet with mixed parameter values of α=0 (ridge penalty) and a binomial response type. The glmnet function internally uses a ten-fold cross-validation to determine the optimal value of the regularization parameter λ. From the upsilon of the individual,The beta value of n cpgs of (c) is used as input to the ridge classifier. Coefficient w ₁ ,…,w _n Obtained from the fitted model. The following amounts are calculated for each individual v in the training set:

any suitable real-valued coefficient may be applied to the WID-EC-index in any of the assays described herein.

The values of the parameters mu and sigma are respectively determined by the training dataset x _υ Is given by the mean and standard deviation of (c).

Thus, any suitable μ and σ real value parameter may be applied to the WID-EC-index in any of the assays described herein. Any suitable training data set may be applied to the assays described herein to infer real-valued parameters and coefficients that may then be applied to the WID-EC-index formulation according to the invention. Exemplary ways of utilizing training data sets in accordance with the present invention are further described in the "statistical analysis of classifier development" section of the materials and methods section of the examples.

Exemplary μ and σ real value parameters for the CpG subsets identified in SEQ ID NOs 1 to 500 are provided in table 2. These real-valued parameters can be applied to any of the assays described herein, wherein the real-valued parameters correspond to any of the sets of cpgs identified in SEQ ID NOs 1 to 500 and listed in the left column of table 2.

SEQ ID NO:	μ	σ
			1-50	2.880073	4.148988
1-100	3.43488	4.076555
			1-150	3.897919	4.129713
1-200	3.861902	3.842672
			1-250	3.774098	4.12993
1-300	3.807151	4.17154
			1-350	3.662246	4.109188
1-400	3.316238	3.984151
			1-450	3.351052	3.982014
1-500	3.667061	4.171657

Table 2. Exemplary μ and σ real value parameters for the CpG subsets identified in SEQ ID NOs 1 through 500 are provided in Table 2

Exemplary w of the CpG identified at positions 61 to 62 in SEQ ID NO 1 to 500 are provided below ₁ ,…,w _n Real value coefficients. These real-valued coefficients can be applied to any of the assays described herein, wherein the real-valued parameters correspond to any CpG set identified in SEQ ID NOs 1 to 500, wherein the next 500 real-valued coefficients in turn correspond to cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500. Thus, the coefficients listed below correspond in numerical order to the identifiers in SEQ ID NO 1 to 5000, respectivelyIs a CpG of (C). Thus, the first number below corresponds to SEQ ID NO 1, the second number corresponds to SEQ ID NO 2, and so on. Exemplary real-valued coefficients are as follows:

the method comprises the steps of (a) forming a first pattern on a first substrate, (a) forming a second pattern on a second substrate, (b) forming a second pattern on a second substrate, (a) forming a third pattern on the second substrate, (b) forming a fourth pattern on the second substrate, (c) forming a fourth pattern on the second substrate, (a) forming a fourth pattern on the third pattern, and (b) forming a fourth pattern on the fourth pattern, and (c) forming a fourth pattern on the fourth pattern, wherein the fourth pattern is a first pattern on the fourth pattern, and the fourth pattern is a second pattern on the fourth pattern The method comprises the steps of (a) forming a metal pattern on a metal substrate, (a) forming a metal pattern on the metal substrate, (b) forming a metal pattern on the metal substrate, (c) forming a metal pattern on the metal pattern, and (d) forming a metal pattern on the metal pattern, wherein the metal pattern is a metal pattern on the metal pattern, and (c) forming a metal pattern on the metal pattern. The method comprises the steps of (a) forming a metal pattern on a metal substrate, (a) forming a metal pattern on the metal substrate, (b) forming a metal pattern on the metal substrate, (c) forming a metal pattern on the metal pattern, and (d) forming a metal pattern on the metal pattern, wherein the metal pattern is a metal pattern on the metal pattern, and (c) forming a metal pattern on the metal pattern -a metal oxide semiconductor device comprising a metal oxide semiconductor layer and a metal oxide semiconductor device comprising a metal oxide semiconductor device. -, and/or about 0.1745-, -0.1745-, -, 0.1186, -, -a metal-metal alloy-metal alloy the method comprises the steps of (a) forming a metal pattern on a metal substrate, (b) forming a metal pattern on a metal substrate, wherein the metal pattern comprises (a) and (b) forming a metal pattern on the metal substrate, and (c) forming a metal pattern on the metal substrate, wherein the metal pattern comprises (a) and (b) forming a metal pattern on the metal substrate, and (b) forming a metal pattern on the metal pattern 0.05772, 0.05563, -0.05531, -0.05395, -0.05349, -0.05207, -0.05088, -0.04909, 0.04894, 0.04817, -0.0475, 0.04684, -0.0437, -0.04325, 0.04069, 0.04061, 0.03859, -0.0379, -0.03773, 0.03649, 0.03592, -0.03564, 0.03468, 0.03356, -0.03242, 0.03235, 0.02751, -0.0273, -0.02729, 0.02726, -0.02588, -0.02556, -0.02538, -0.02536, -0.02408, 0.02189, 0.01846, -0.01608, 0.01572, 0.01462, -0.01254, -0.0117, 0.01122, -0.01112, -0.01092, -0.00938, -0.00906, -0.00851, -0.00846, -0.00818, -0.00662, -0.00621, -0.00543, 0.00291, 0.00232, 0.00112, -0.00063, -0.00034 and-0.00021.

Predicting the presence, absence or progression of cancer in an individual may particularly involve applying a cancer index threshold to assess or stratify whether the individual has cancer or has a high or low risk of cancer progression.

The assays of the invention may involve the use of a threshold index to assess the presence or absence of cancer and/or CIN3 in an individual. The assessment may be characterized by recipient operating characteristics, particularly area under the curve (AUC), sensitivity, and specificity, which are indicative of the reliability of thresholds applied to assess the presence or absence of cancer and/or CIN3 in an individual.

In any of the assays described herein, wherein an individual is assessed as having cancer and/or CIN3 or as having a high risk of developing cancer and/or CIN3 when the individual's cancer index value is about-0.201 or greater, or wherein an individual is assessed as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index value is less than about-0.201, preferably wherein the assay comprises determining the methylation β value for each CpG in the set of one or more cpgs, more preferably wherein assessing the presence, absence, or development of cancer in the individual is based on the WID-EC-index. The set of one or more cpgs used to derive the cancer index value may comprise:

1. At least 50 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 88% and the specificity is at least 76%;

2. at least 100 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and the specificity is at least 78%;

3. at least 150 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and the specificity is at least 76%;

4. at least 200 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and the specificity is at least 78%;

5. at least 250 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 88% and the specificity is at least 78%;

6. at least 300 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 89% and the specificity is at least 79%;

7. at least 350 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and the specificity is at least 78%;

8. at least 400 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 90% and the specificity is at least 79%;

9. At least 450 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 89% and the specificity is at least 79%; or alternatively

At least 500 cpgs identified at nucleotide positions 61 to 62 in seq ID NOs 1 to 500 and wherein the sensitivity is at least 95% and the specificity is at least 76%.

a. at least 50 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 88% and the specificity is at least 76%;

b. CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 90% and the specificity is at least 80%;

c. CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 92% and the specificity is at least 79%; or alternatively

d. CpG, defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 93% and the specificity is at least 80%.

1. CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 90% and the specificity is at least 80%;

2. CpG defined by at least SEQ ID NOs 51 to 100 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 89% and the specificity is at least 79%;

3. CpG defined by at least SEQ ID NOs 101 to 150 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 92% and the specificity is at least 80%;

4. CpG defined by at least SEQ ID NOs 151 to 200 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 89% and the specificity is at least 71%;

5. CpG defined by at least SEQ ID NOs 201 to 250 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 90% and the specificity is at least 76%;

6. CpG defined by at least SEQ ID NOs 251 to 300 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 89% and the specificity is at least 79%;

7. CpG defined by at least SEQ ID NOs 301 to 350 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 89% and the specificity is at least 80%;

8. CpG defined by at least SEQ ID NOs 351 to 400 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 90% and the specificity is at least 77%;

9. CpG defined by at least SEQ ID NOs 401 to 450 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 88% and the specificity is at least 76%;

10. CpG defined by at least SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 88% and the specificity is at least 76%;

11. CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 90% and the specificity is at least 80%;

12. CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 92% and the specificity is at least 79%;

13. CpG defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 93% and the specificity is at least 80%;

14. CpG defined by at least SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 93% and the specificity is at least 78%;

15. CpG defined by at least SEQ ID NOs 1 to 250 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 95% and the specificity is at least 78%;

16. CpG defined by at least SEQ ID NOs 1 to 300 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 95% and the specificity is at least 77%;

17. CpG defined by at least SEQ ID NOs 1 to 350 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 95% and the specificity is at least 77%;

18. CpG defined by at least SEQ ID NOs 1 to 400 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 95% and the specificity is at least 78%;

19. CpG defined by at least SEQ ID NOs 1 to 450 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 95% and the specificity is at least 78%;

20. CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 95% and the specificity is at least 76%;

21. CpG defined by at least SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and the specificity is at least 76%;

22. CpG defined by at least SEQ ID NOs 401 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and the specificity is at least 78%;

23. CpG defined by at least SEQ ID NOs 351 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and the specificity is at least 76%;

24. CpG defined by at least SEQ ID NOs 301 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and the specificity is at least 78%;

25. CpG defined by at least SEQ ID NOs 251 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and the specificity is at least 78%;

26. CpG defined by at least SEQ ID NOs 201 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 89% and the specificity is at least 79%;

27. CpG defined by at least SEQ ID NOs 151 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and the specificity is at least 78%;

28. CpG defined by at least SEQ ID NOs 101 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 90% and the specificity is at least 79%;

29. CpG defined by at least SEQ ID NOs 51 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 89% and the specificity is at least 79%; or alternatively

30. CpG, defined by at least SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 95% and the specificity is at least 76%.

In any of the assays described herein, wherein an individual is assessed as having cancer and/or CIN3 or as having a high risk of developing cancer and/or CIN3 when the individual's cancer index value is about 0.269 or greater, or wherein an individual is assessed as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index value is less than about 0.269, preferably, wherein the assay comprises determining the methylation beta value of each CpG in the set of one or more cpgs, more preferably, wherein assessing the presence, absence, or development of cancer in the individual is based on the WID-EC-index. The set of one or more cpgs used to derive the cancer index value may comprise:

1. at least 50 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 75% and the specificity is at least 94%;

2. at least 100 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 73% and the specificity is at least 96%;

3. at least 150 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 74% and the specificity is at least 95%;

4. At least 200 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 73% and the specificity is at least 96%;

5. at least 250 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 73% and the specificity is at least 96%;

6. at least 300 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 73% and the specificity is at least 97%;

7. at least 350 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 73% and the specificity is at least 96%;

8. at least 400 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 77% and the specificity is at least 96%;

9. at least 450 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 77% and the specificity is at least 97%; or alternatively

10. At least 500 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 79% and the specificity is at least 96%.

a. At least 50 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 75% and the specificity is at least 94%;

b. CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 73% and the specificity is at least 98%;

c. CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 75% and the specificity is at least 98%;

d. CpG, defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 79% and the specificity is at least 97%.

1. CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 73% and the specificity is at least 98%;

2. CpG defined by at least SEQ ID NOs 51 to 100 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 73% and the specificity is at least 98%;

3. CpG defined by at least SEQ ID NOs 101 to 150 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 74% and the specificity is at least 96%;

4. CpG defined by at least SEQ ID NOs 151 to 200 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 77% and the specificity is at least 95%;

5. CpG defined by at least SEQ ID NOs 201 to 250 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 75% and the specificity is at least 97%;

6. CpG defined by at least SEQ ID NOs 251 to 300 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 71% and the specificity is at least 96%;

7. CpG defined by at least SEQ ID NOs 301 to 350 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 70% and the specificity is at least 97%;

8. CpG defined by at least SEQ ID NOs 351 to 400 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 73% and the specificity is at least 96%;

9. CpG defined by at least SEQ ID NOs 401 to 450 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 71% and the specificity is at least 95%;

10. CpG defined by at least SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 75% and the specificity is at least 94%;

11. CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 73% and the specificity is at least 98%;

12. CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 75% and the specificity is at least 98%;

13. CpG defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 79% and the specificity is at least 97%;

14. CpG defined by at least SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 79% and the specificity is at least 97%;

15. CpG defined by at least SEQ ID NOs 1 to 250 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and the specificity is at least 96%;

16. CpG defined by at least SEQ ID NOs 1 to 300 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 79% and the specificity is at least 96%;

17. CpG defined by at least SEQ ID NOs 1 to 350 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and the specificity is at least 97%;

18. CpG defined by at least SEQ ID NOs 1 to 400 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 79% and the specificity is at least 96%;

19. CpG defined by at least SEQ ID NOs 1 to 450 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and the specificity is at least 97%;

20. CpG defined by at least SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and the specificity is at least 96%;

21. CpG defined by at least SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 75% and the specificity is at least 94%;

22. CpG defined by at least SEQ ID NOs 401 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and the specificity is at least 96%;

23. CpG defined by at least SEQ ID NOs 351 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 74% and the specificity is at least 95%;

24. CpG defined by at least SEQ ID NOs 301 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and the specificity is at least 96%;

25. CpG defined by at least SEQ ID NOs 251 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and the specificity is at least 96%;

26. CpG defined by at least SEQ ID NOs 201 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and the specificity is at least 97%;

27. CpG defined by at least SEQ ID NOs 151 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and the specificity is at least 96%;

28. CpG defined by at least SEQ ID NOs 101 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 77% and the specificity is at least 96%;

29. CpG defined by at least SEQ ID NOs 51 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 77% and the specificity is at least 97%; or alternatively

30. CpG, defined by at least SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and the specificity is at least 96%.

In any of the assays described herein, wherein an individual is assessed as having cancer and/or CIN3 or as having a high risk of developing cancer and/or CIN3 when the individual's cancer index value is about 1.072 or greater, or wherein an individual is assessed as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index value is less than about 1.072, preferably wherein the assay comprises determining the methylation beta value for each CpG in the set of one or more cpgs, more preferably wherein assessing the presence, absence, or development of cancer in the individual is based on the WID-EC-index. The set of one or more cpgs used to derive the cancer index value may comprise:

1. at least 50 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 58% and the specificity is at least 99%;

2. at least 100 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 53% and the specificity is at least 99%;

3. at least 150 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 53% and the specificity is at least 99%;

4. At least 200 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 53% and the specificity is at least 99%;

5. at least 250 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 53% and the specificity is at least 99%;

6. at least 300 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 55% and the specificity is at least 99%;

7. at least 350 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 58% and the specificity is at least 99%;

8. at least 400 of the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 58% and the specificity is at least 99%;

9. at least 450 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 59% and the specificity is 100%; or alternatively

10. At least 500 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 64% and the specificity is 100%.

a. At least 50 cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 58% and the specificity is at least 99%;

b. CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 60% and the specificity is 100%;

c. CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 63% and the specificity is 100%;

d. CpG, defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 64% and the specificity is 100%.

1. CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 60% and the specificity is 100%;

2. CpG defined by at least SEQ ID NOs 51 to 100 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 60% and the specificity is at least 99%;

3. CpG defined by at least SEQ ID NOs 101 to 150 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 58% and the specificity is 100%;

4. CpG defined by at least SEQ ID NOs 151 to 200 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 60% and the specificity is at least 99%;

5. CpG defined by at least SEQ ID NOs 201 to 250 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 58% and the specificity is at least 99%;

6. CpG defined by at least SEQ ID NOs 251 to 300 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 53% and the specificity is at least 99%;

7. CpG defined by at least SEQ ID NOs 301 to 350 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 52% and the specificity is 100%;

8. CpG defined by at least SEQ ID NOs 351 to 400 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 56% and the specificity is at least 99%;

9. CpG defined by at least SEQ ID NOs 401 to 450 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 52% and the specificity is at least 99%;

10. CpG defined by at least SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 58% and the specificity is at least 99%;

11. CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 60% and the specificity is 100%;

12. CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 63% and the specificity is 100%;

13. CpG defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and the specificity is 100%;

14. CpG defined by at least SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and the specificity is 100%;

15. CpG defined by at least SEQ ID NOs 1 to 250 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and the specificity is 100%;

16. CpG defined by at least SEQ ID NOs 1 to 300 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 64% and the specificity is 100%;

17. CpG defined by at least SEQ ID NOs 1 to 350 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and the specificity is 100%;

18. CpG defined by at least SEQ ID NOs 1 to 400 and identified at nucleotide positions 61 to 62, wherein the sensitivity is at least 63% and the specificity is 100%;

19. CpG defined by at least SEQ ID NOs 1 to 450 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and the specificity is 100%;

20. CpG defined by at least SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and the specificity is 100%;

21. CpG defined by at least SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 58% and the specificity is at least 99%;

22. CpG defined by at least SEQ ID NOs 401 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 53% and the specificity is at least 99%;

23. CpG defined by at least SEQ ID NOs 351 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 53% and the specificity is at least 99%;

24. CpG defined by at least SEQ ID NOs 301 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 53% and the specificity is at least 99%;

25. CpG defined by at least SEQ ID NOs 251 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 53% and the specificity is at least 99%;

26. CpG defined by at least SEQ ID NOs 201 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 55% and the specificity is at least 99%;

27. CpG defined by at least SEQ ID NOs 151 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 58% and the specificity is at least 99%;

28. CpG defined by at least SEQ ID NOs 101 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 58% and the specificity is at least 99%;

29. CpG defined by at least SEQ ID NOs 51 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 59% and the specificity is 100%; or alternatively

30. CpG, defined by at least SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and the specificity is 100%.

The ROC data set forth in tables 3, 4 and 5 for each particular group of SEQ ID NOs 1 to 500 was obtained by determining the cancer index value for that group.

TABLE 3 Table 3

TABLE 4 Table 4

TABLE 5

Predicting the presence, absence or progression of cancer in an individual may particularly involve determining the average β value of any group of one or more cpgs as defined herein. The threshold mean β value may be applied to stratify an individual as having or not having cancer, or having a high or low risk of cancer development, preferably wherein the cancer is endometrial or ovarian cancer, more preferably wherein the cancer is endometrial cancer.

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.025 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.025;

In any of the assays described herein, wherein:

a. An individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.050 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.050;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.075 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.075;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.100 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.100;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.125 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.125;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.150 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.150;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.175 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.175;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.200 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.200;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.225 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.225;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.250 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.250;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.275 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.275;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.300 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.300;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.325 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.325;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.350 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.350;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.375 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.375;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.400 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.400;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.425 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.425;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.450 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.450;

In any of the assays described herein, wherein:

a. when an individual has a cancer index of about 0.475 or greater, the individual is classified as having cancer and/or CIN3 or has a high risk of developing cancer and/or CIN 3; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.475;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.500 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.500;

In any of the assays described herein, wherein:

a. when an individual has a cancer index of about 0.525 or greater, the individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN 3; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.525;

In any of the assays described herein, wherein:

a. an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.550 or greater; or alternatively

b. An individual is classified as not having cancer when the individual's cancer index is less than about 0.550;

In any of the assays described herein:

9. the CpG represented by CG whose cancer index value is determined is at least within DMR 5 defined by SEQ ID NO:505, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.105 or more, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 5, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 505;

10. The CpG represented by CG whose cancer index value is determined is at least within DMR 5 defined by SEQ ID NO:505, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.105, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 5, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 505;

11. the CpG represented by CG whose cancer index value is determined is at least within DMR 6 defined by SEQ ID NO:506, and wherein an individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.056 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 6, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 506;

12. The CpG represented by CG whose cancer index value is determined is at least within DMR 6 defined by SEQ ID NO:506, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.056, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 6, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 506;

13. the CpG represented by CG whose cancer index value is determined is at least within DMR 7 defined by SEQ ID NO:507, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.155 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 7, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 507;

14. The CpG represented by CG whose cancer index value is determined is at least within DMR 7 defined by SEQ ID NO:507, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.155, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 7, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 507;

15. the CpG represented by CG whose cancer index value is determined is at least within DMR 8 defined by SEQ ID NO:508, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.083 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 8, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 508;

16. The CpG represented by CG whose cancer index value is determined is at least within DMR 8 defined by SEQ ID No. 508, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.083, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 8, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 508;

17. the CpG represented by CG whose cancer index value is determined is at least within DMR 9 defined by SEQ ID No. 509, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.168 or more, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 9, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 509;

18. The CpG represented by CG whose cancer index value is determined is at least within DMR 9 defined by SEQ ID No. 509, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.168, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 9, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 509;

19. the CpG represented by CG whose cancer index value is determined is at least within DMR 10 defined by SEQ ID NO:510, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.265 or greater, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 10, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 510;

20. The CpG represented by CG whose cancer index value is determined is at least within DMR 10 defined by SEQ ID NO:510, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.265, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 10, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 510;

21. the CpG represented by CG whose cancer index value is determined is at least within DMR 11 defined by SEQ ID No. 511, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.128 or more, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 11, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 511;

22. The CpG represented by CG whose cancer index value is determined is at least within DMR 11 defined by SEQ ID No. 511, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.128, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 11, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 511;

23. the CpG represented by CG whose cancer index value is determined is at least within DMR 12 defined by SEQ ID No. 512, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.127 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 12, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 512;

24. The CpG represented by CG whose cancer index value is determined is located at least within DMR 12 defined by SEQ ID No. 512, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.127, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 12, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID No. 512;

25. the CpG represented by CG whose cancer index value is determined is at least within DMR 13 defined by SEQ ID No. 513 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.127 or more and wherein the sensitivity of the assay is at least 64.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 13 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 513;

26. The CpG represented by CG whose cancer index value is determined is at least within DMR 13 defined by SEQ ID No. 513, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.127, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 13, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 513;

27. the CpG represented by CG whose cancer index value is determined is at least within DMR 14 defined by SEQ ID No. 514, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.133 or greater, and wherein the sensitivity of the assay is at least 74.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 14, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 514;

28. The CpG represented by CG whose cancer index value is determined is located at least within DMR 14 defined by SEQ ID No. 514, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.133, and wherein the sensitivity of the assay is at least 74.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 14, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 514;

29. the CpG represented by CG whose cancer index value is determined is at least within DMR 15 defined by SEQ ID No. 515, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.125 or more, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 15, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID No. 515;

30. The CpG represented by CG whose cancer index value is determined is at least within DMR 15 defined by SEQ ID No. 515, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.125, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 15, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 515;

31. the CpG represented by CG whose cancer index value is determined is at least within DMR 16 defined by SEQ ID NO:516, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.127 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 16, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 516;

32. The CpG represented by CG whose cancer index value is determined is located at least within DMR 16 defined by SEQ ID NO:516, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.127, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 16, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 516;

33. the CpG represented by CG whose cancer index value is determined is at least within DMR 17 defined by SEQ ID NO:517 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.113 or greater and wherein the sensitivity of the assay is at least 71.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 17 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 517;

34. The CpG represented by CG whose cancer index value is determined is at least within DMR 17 defined by SEQ ID NO:517 and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.113 and wherein the sensitivity of the assay is at least 71.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 17 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 517;

35. the CpG represented by CG whose cancer index value is determined is at least within DMR 18 defined by SEQ ID No. 518, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.113 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 18, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 518;

36. The CpG represented by CG whose cancer index value is determined is located at least within DMR 18 defined by SEQ ID No. 518, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.113, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 18, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 518;

37. the CpG represented by CG whose cancer index value is determined is at least within DMR 19 defined by SEQ ID NO:519, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.143 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 19, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 519;

38. The CpG represented by CG whose cancer index value is determined is at least within DMR 19 defined by SEQ ID NO:519, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.143, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 19, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 519;

39. the CpG represented by CG whose cancer index value is determined is at least within DMR 20 defined by SEQ ID No. 520, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.095 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 20, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID No. 520;

40. The CpG represented by CG whose cancer index value is determined is at least within DMR 20 defined by SEQ ID No. 520, and wherein an individual is classified as not suffering from cancer or having a low risk of developing cancer when the individual's cancer index is less than about 0.095, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least four cpgs from DMR 20, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 520;

41. the CpG represented by CG whose cancer index value is determined is at least within DMR 21 defined by SEQ ID NO:521, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.146 or greater, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 21, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 521;

42. The CpG represented by CG whose cancer index value is determined is at least within DMR 21 defined by SEQ ID NO:521, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.146, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 21, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 521;

43. the CpG represented by CG whose cancer index value is determined is at least within DMR 22 defined by SEQ ID No. 522, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.098 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twenty cpgs from DMR 22, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID No. 522;

44. The CpG represented by CG whose cancer index value is determined is located at least within DMR 22 defined by SEQ ID No. 522, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.098, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twenty cpgs from DMR 22, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID No. 522;

45. the CpG represented by CG whose cancer index value is determined is at least within DMR 23 defined by SEQ ID NO:523, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.177 or more, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 23, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 523;

46. The CpG represented by CG whose cancer index value is determined is located at least within DMR 23 defined by SEQ ID NO:523, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.177, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 23, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 523;

47. the CpG represented by CG whose cancer index value is determined is at least within DMR 24 defined by SEQ ID NO:524, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.098 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least twenty-one cpgs from DMR 24, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 524;

48. The CpG represented by CG whose cancer index value is determined is at least within DMR 24 defined by SEQ ID No. 524, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.098, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least twenty-one cpgs from DMR 24, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 524;

49. the CpG represented by CG whose cancer index value is determined is at least within DMR 25 defined by SEQ ID NO:525, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.039 or greater, and wherein the sensitivity of the assay is at least 74.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 25, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 525;

50. The CpG represented by CG whose cancer index value is determined is at least within DMR 25 defined by SEQ ID NO:525, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.039, and wherein the sensitivity of the assay is at least 74.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 25, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 525;

51. the CpG represented by CG whose cancer index value is determined is at least within DMR 26 defined by SEQ ID NO:526, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.154 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 26, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 526;

52. The CpG represented by CG whose cancer index value is determined is located at least within DMR 26 defined by SEQ ID NO:526, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.154, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 26, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 526;

53. the CpG represented by CG whose cancer index value is determined is at least within DMR 27 defined by SEQ ID NO:527, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.1 or greater, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least twenty-one cpgs from DMR 27, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 527;

54. The CpG represented by CG whose cancer index value is determined is at least within DMR 27 defined by SEQ ID NO:527, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.1, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least twenty-one cpgs from DMR 27, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 527;

55. the CpG represented by CG whose cancer index value is determined is at least within DMR 28 defined by SEQ ID NO 528, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.124 or more, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least twenty-three cpgs from DMR 28, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO 528;

56. The CpG represented by CG whose cancer index value is determined is at least within DMR 28 defined by SEQ ID NO:528, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.124, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twenty-three cpgs from DMR 28, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 528;

57. the CpG represented by CG whose cancer index value is determined is at least within DMR 29 defined by SEQ ID No. 529, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.171 or more, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least ten cpgs from DMR 29, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 529 s;

58. The CpG represented by CG whose cancer index value is determined is at least within DMR 29 defined by SEQ ID No. 529, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.171, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least ten cpgs from DMR 29, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 529 s;

59. the CpG represented by CG whose cancer index value is determined is at least within DMR 30 defined by SEQ ID NO:530, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.108 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least twenty cpgs from DMR 30, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 530;

60. The CpG represented by CG whose cancer index value is determined is at least within DMR 30 defined by SEQ ID NO:530, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.108, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twenty cpgs from DMR 30, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 530;

61. the CpG represented by CG whose cancer index value is determined is located at least within DMR 31 defined by SEQ ID NO:531 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.108 or more and wherein the sensitivity of the assay is at least 68.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least twenty cpgs from DMR 31 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 531;

62. The CpG represented by CG whose cancer index value is determined is located at least within DMR 31 defined by SEQ ID NO:531, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.108, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twenty cpgs from DMR 31, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 531;

63. the CpG represented by CG whose cancer index value is determined is at least within DMR 32 defined by SEQ ID NO:532, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.091 or greater, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 32, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 532;

64. The CpG represented by CG whose cancer index value is determined is located at least within DMR 32 defined by SEQ ID No. 532, and wherein an individual is classified as not suffering from cancer or having a low risk of developing cancer when the individual's cancer index is less than about 0.091, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least four cpgs from DMR 32, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 532;

65. the CpG represented by CG whose cancer index value is determined is at least within DMR 33 defined by SEQ ID No. 533, and wherein an individual is classified as suffering from cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.174 or greater, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 33, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 533;

66. The CpG represented by CG whose cancer index value is determined is at least within DMR 33 defined by SEQ ID No. 533, and wherein an individual is classified as not suffering from cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.174, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 33, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 533;

67. the CpG represented by CG whose cancer index value is determined is at least within DMR 34 defined by SEQ ID No. 534, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.123 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twenty cpgs from DMR 34, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 534;

68. The CpG represented by CG whose cancer index value is determined is located at least within DMR 34 defined by SEQ ID No. 534, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.123, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twenty cpgs from DMR 34, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 534;

69. the CpG represented by CG whose cancer index value is determined is at least within DMR 35 defined by SEQ ID No. 535, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.123 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twenty cpgs from DMR 35, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 535;

70. The CpG represented by CG whose cancer index value is determined is at least within DMR 35 defined by SEQ ID No. 535, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.123, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twenty cpgs from DMR 35, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 535;

71. the CpG represented by CG whose cancer index value is determined is at least within DMR 36 defined by SEQ ID No. 536, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.176 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 36, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 536;

72. The CpG represented by CG whose cancer index value is determined is at least within DMR 36 defined by SEQ ID No. 536, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.176, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 36, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 536;

73. the CpG represented by CG whose cancer index value is determined is at least within DMR 37 defined by SEQ ID NO:537, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.257 or greater, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least one CpG from DMR 37, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 537;

74. The CpG represented by CG whose cancer index value is determined is at least within DMR 37 defined by SEQ ID NO:537, and wherein when the individual's cancer index is less than about 0.257, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least one CpG from DMR 37, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 537;

75. the CpG represented by CG whose cancer index value is determined is at least within DMR 38 defined by SEQ ID NO:538, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.123 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises cpgs from at least DMR 38, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 538;

76. The CpG represented by CG whose cancer index value is determined is at least within DMR 38 defined by SEQ ID NO:538, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.123, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least twenty cpgs from DMR 38, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 538;

77. the CpG represented by CG whose cancer index value is determined is at least within DMR 39 defined by SEQ ID NO:539, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.195 or greater, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 39, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 539;

78. The CpG represented by CG whose cancer index value is determined is at least within DMR 39 defined by SEQ ID NO:539, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.195, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 39, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 539;

79. the CpG represented by CG whose cancer index value is determined is at least within DMR 40 defined by SEQ ID No. 540, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.195 or greater, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 40, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 540;

80. The CpG represented by CG whose cancer index value is determined is at least within DMR 40 defined by SEQ ID No. 540, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.195, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 40, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 540;

81. the CpG represented by CG whose cancer index value is determined is located at least within DMR 41 defined by SEQ ID NO:541, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.051 or more, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least five cpgs from DMR 41, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 541;

82. The CpG represented by CG whose cancer index value is determined is at least within DMR 41 defined by SEQ ID No. 41, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.051, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least five cpgs from DMR 341, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 541;

83. the CpG represented by CG whose cancer index value is determined is at least within DMR 42 defined by SEQ ID No. 542, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.055 or more, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twelve cpgs from DMR 42, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID No. 542;

84. The CpG represented by CG whose cancer index value is determined is at least within DMR 42 defined by SEQ ID No. 542, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.055, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twelve cpgs from DMR 42, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID No. 542;

85. the CpG represented by CG whose cancer index value is determined is at least within DMR 43 defined by SEQ ID No. 543, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.098 or greater, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 43, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 543;

86. The CpG represented by CG whose cancer index value is determined is located at least within DMR 43 defined by SEQ ID No. 543, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.098, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 43, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 543;

87. the CpG represented by CG whose cancer index value is determined is at least within DMR 44 defined by SEQ ID NO:544, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.071 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 44, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 544;

88. The CpG represented by CG whose cancer index value is determined is at least within DMR 44 defined by SEQ ID NO:544, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.071, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 44, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 544;

89. the CpG represented by CG whose cancer index value is determined is at least within DMR 45 defined by SEQ ID NO:545, and wherein an individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.094 or more, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twelve cpgs from DMR 45, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 545;

90. The CpG represented by CG whose cancer index value is determined is at least within DMR 45 defined by SEQ ID NO:545, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.094, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least twelve cpgs from DMR 45, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 545;

91. the CpG represented by CG whose cancer index value is determined is at least within DMR 46 defined by SEQ ID NO:546, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.374 or greater, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 46, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 546;

92. The CpG represented by CG whose cancer index value is determined is at least within DMR 46 defined by SEQ ID NO:546, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.374, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 46, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 546;

93. the CpG represented by CG whose cancer index value is determined is at least within DMR 47 defined by SEQ ID No. 547, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.104 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 47, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 547;

94. The CpG represented by CG whose cancer index value is determined is at least within DMR 47 defined by SEQ ID No. 547, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.104, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 47, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID No. 547;

95. the CpG represented by CG whose cancer index value is determined is located at least within DMR 48 defined by SEQ ID NO:548, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.119 or greater, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 48, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 548;

96. The CpG represented by CG whose cancer index value is determined is located at least within DMR 48 defined by SEQ ID NO:548, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.119, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 48, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 548;

97. the CpG represented by CG whose cancer index value is determined is at least within DMR 49 defined by SEQ ID No. 549, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.119 or greater, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 49, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 549;

98. The CpG represented by CG whose cancer index value is determined is at least within DMR 49 defined by SEQ ID No. 549, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.119, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 49, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 549;

99. the CpG represented by CG whose cancer index value is determined is at least within the DMR 50 defined by SEQ ID NO:550, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.168 or more, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 50, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 550;

100. The CpG represented by CG whose cancer index value is determined is at least within the DMR 50 defined by SEQ ID No. 550, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.168, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 50, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 550;

101. the CpG represented by CG whose cancer index value is determined is at least within DMR 51 defined by SEQ ID NO:551, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.231 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 51, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 551;

102. The CpG represented by CG whose cancer index value is determined is at least within DMR 51 defined by SEQ ID NO:551, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.231, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 51, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 551;

103. the CpG represented by CG whose cancer index value is determined is located at least within DMR 52 defined by SEQ ID No. 552 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.101 or more and wherein the sensitivity of the assay is at least 60.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least two cpgs from DMR 52 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 552;

104. The CpG represented by CG whose cancer index value is determined is located at least within DMR 52 defined by SEQ ID No. 552, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.101, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 52, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 552;

105. the CpG represented by CG whose cancer index value is determined is at least within DMR 53 defined by SEQ ID NO:553, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.259 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 53, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 553;

106. The CpG represented by CG whose cancer index value is determined is at least within DMR 53 defined by SEQ ID NO:553, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.259, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 53, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 553;

107. the CpG represented by CG whose cancer index value is determined is at least within DMR 54 defined by SEQ ID NO:554, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.259 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 54, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 554;

108. The CpG represented by CG whose cancer index value is determined is at least within DMR 54 defined by SEQ ID NO:554, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.259, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 54, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 554;

109. the CpG represented by CG whose cancer index value is determined is at least within DMR 55 defined by SEQ ID NO:555, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.279 or greater, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 55, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 555;

110. The CpG represented by CG whose cancer index value is determined is at least within DMR 55 defined by SEQ ID NO:555, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.279, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 55, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 555;

111. the CpG represented by CG whose cancer index value is determined is at least within DMR 56 defined by SEQ ID NO:556, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.14 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 56, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 556;

112. The CpG represented by CG whose cancer index value is determined is at least within DMR 56 defined by SEQ ID NO:556, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.14, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 56, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 556;

113. the CpG represented by CG whose cancer index value is determined is at least within DMR 57 defined by SEQ ID NO:557, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.093 or greater, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 57, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 557;

114. The CpG represented by CG whose cancer index value is determined is at least within DMR 57 defined by SEQ ID NO:557, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.093, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 57, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 557;

115. the CpG represented by CG whose cancer index value is determined is at least within DMR 58 defined by SEQ ID NO:558, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.119 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least four cpgs from DMR 58, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 558;

116. The CpG represented by CG whose cancer index value is determined is at least within DMR 58 defined by SEQ ID No. 558, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.119, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 58, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 558;

117. the CpG represented by CG whose cancer index value is determined is at least within DMR 59 defined by SEQ ID NO:559, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.119 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 59, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 559;

118. The CpG represented by CG whose cancer index value is determined is at least within DMR 59 defined by SEQ ID NO:559, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.119, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 59, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 559;

119. the CpG represented by CG whose cancer index value is determined is at least within DMR 60 defined by SEQ ID NO:560, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.311 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 60, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 560;

120. The CpG represented by CG whose cancer index value is determined is at least within DMR 60 defined by SEQ ID NO:560, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.311, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 60, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 560;

121. the CpG represented by CG whose cancer index value is determined is at least within DMR 61 defined by SEQ ID NO:561 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.073 or more and wherein the sensitivity of the assay is at least 66.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 61 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 561;

122. The CpG represented by CG whose cancer index value is determined is at least within DMR 61 defined by SEQ ID NO:561, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.073, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 61, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 561;

123. the CpG represented by CG whose cancer index value is determined is at least within DMR 62 defined by SEQ ID NO:562, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.073 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 62, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 562;

124. The CpG represented by CG whose cancer index value is determined is located at least within DMR 62 defined by SEQ ID NO:562, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.073, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 62, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 562;

125. the CpG represented by CG whose cancer index value is determined is at least within DMR 63 defined by SEQ ID NO:563, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.171 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 63, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 563;

126. The CpG represented by CG whose cancer index value is determined is at least within DMR 63 defined by SEQ ID NO:563, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.171, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 63, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 563;

127. the CpG represented by CG whose cancer index value is determined is at least within DMR 64 defined by SEQ ID No. 564 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.206 or more and wherein the sensitivity of the assay is at least 59.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 64 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 564;

128. The CpG represented by CG whose cancer index value is determined is at least within DMR 64 defined by SEQ ID No. 564, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.206, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 64, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 564;

129. the CpG represented by CG whose cancer index value is determined is at least within DMR 65 defined by SEQ ID No. 565 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.206 or more and wherein the sensitivity of the assay is at least 59.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 65 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 565;

130. The CpG represented by CG whose cancer index value is determined is at least within DMR 65 defined by SEQ ID No. 565 and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.206 and wherein the sensitivity of the assay is at least 59.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 65 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 565;

131. the CpG represented by CG whose cancer index value is determined is at least within DMR 66 defined by SEQ ID NO:566 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.171 or greater and wherein the sensitivity of the assay is at least 66.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 66 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 566;

132. The CpG represented by CG whose cancer index value is determined is at least within DMR 66 defined by SEQ ID NO:566, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.171, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 66, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 566;

133. the CpG represented by CG whose cancer index value is determined is at least within DMR 67 defined by SEQ ID NO:567, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.133 or greater, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 67, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 567;

134. The CpG represented by CG whose cancer index value is determined is at least within DMR 67 defined by SEQ ID NO:567, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.133, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 67, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 567;

135. the CpG represented by CG whose cancer index value is determined is at least within DMR 68 defined by SEQ ID No. 568 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.233 or greater and wherein the sensitivity of the assay is at least 49.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least five cpgs from DMR 68 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 568;

136. The CpG represented by CG whose cancer index value is determined is at least within DMR 68 defined by SEQ ID No. 568, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.233, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 68, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 568;

137. the CpG represented by CG whose cancer index value is determined is at least within DMR 69 defined by SEQ ID NO:569, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.09 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 69, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 569;

138. The CpG represented by CG whose cancer index value is determined is at least within DMR 69 defined by SEQ ID NO:569, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.09, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least two cpgs from DMR 69, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 569;

139. the CpG represented by CG whose cancer index value is determined is at least within DMR 70 defined by SEQ ID NO:570, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.072 or greater, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 70, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 570;

140. The CpG represented by CG whose cancer index value is determined is at least within DMR 70 defined by SEQ ID NO:570, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.072, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 70, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 570;

141. the CpG represented by CG whose cancer index value is determined is at least within DMR 71 defined by SEQ ID No. 571, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.129 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 71, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 571;

142. The CpG represented by CG whose cancer index value is determined is at least within DMR 71 defined by SEQ ID No. 571, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.129, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 71, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 571;

143. the CpG represented by CG whose cancer index value is determined is at least within DMR 72 defined by SEQ ID NO:572, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.257 or more, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 72, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 572;

144. The CpG represented by CG whose cancer index value is determined is at least within DMR 72 defined by SEQ ID NO:572, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.257, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 72, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 572;

145. the CpG represented by CG whose cancer index value is determined is at least within DMR 73 defined by SEQ ID NO:573, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.189 or greater, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 73, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 573;

146. The CpG represented by CG whose cancer index value is determined is at least within DMR 73 defined by SEQ ID NO:573, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.189, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 73, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 573;

147. the CpG represented by CG whose cancer index value is determined is at least within DMR 74 defined by SEQ ID NO:574, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.175 or greater, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 74, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 574;

148. The CpG represented by CG whose cancer index value is determined is at least within DMR 74 defined by SEQ ID NO:574, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.175, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 74, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 574;

149. the CpG represented by CG whose cancer index value is determined is at least within DMR 75 defined by SEQ ID No. 575 and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.157 or greater and wherein the sensitivity of the assay is at least 64.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 75 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 575;

150. The CpG represented by CG whose cancer index value is determined is at least within DMR 75 defined by SEQ ID No. 575 and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.157 and wherein the sensitivity of the assay is at least 64.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 75 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 575;

151. the CpG represented by CG whose cancer index value is determined is at least within DMR 76 defined by SEQ ID NO:576, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.172 or greater, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 76, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 576;

152. The CpG represented by CG whose cancer index value is determined is located at least within DMR 76 defined by SEQ ID NO:576, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.172, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 76, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 576;

153. the CpG represented by CG whose cancer index value is determined is at least within DMR 77 defined by SEQ ID NO:577, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.059 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 77, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 577;

154. The CpG represented by CG whose cancer index value is determined is at least within DMR 77 defined by SEQ ID NO:577, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.059, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 77, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 577;

155. the CpG represented by CG whose cancer index value is determined is at least within DMR 78 defined by SEQ ID No. 578, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.064 or greater, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least ten cpgs from DMR 78, more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 578;

156. The CpG represented by CG whose cancer index value is determined is at least within DMR 78 defined by SEQ ID No. 578, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.064, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least ten cpgs from DMR 78, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 578;

157. the CpG represented by CG whose cancer index value is determined is at least within DMR 79 defined by SEQ ID NO:579, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.043 or greater, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 79, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 579;

158. The CpG represented by CG whose cancer index value is determined is at least within DMR 79 defined by SEQ ID NO:579, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.043, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 79, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 579;

159. the CpG represented by CG whose cancer index value is determined is at least within DMR 80 defined by SEQ ID No. 580, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.178 or greater, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 80, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 580;

160. The CpG represented by CG whose cancer index value is determined is located at least within DMR 80 defined by SEQ ID No. 580, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.178, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 80, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 580;

161. the CpG represented by CG whose cancer index value is determined is at least within DMR 81 defined by SEQ ID NO:581, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.169 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eighteen cpgs from DMR 81, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 581;

162. The CpG represented by CG whose cancer index value is determined is at least within DMR 81 defined by SEQ ID NO:581, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.169, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eighteen cpgs from DMR 81, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 581;

163. the CpG represented by CG whose cancer index value is determined is at least within DMR 82 defined by SEQ ID NO:582 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.169 or greater and wherein the sensitivity of the assay is at least 67.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eighteen cpgs from DMR 82, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 582;

164. The CpG represented by CG whose cancer index value is determined is at least within DMR 82 defined by SEQ ID No. 582, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.169, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eighteen cpgs from DMR 82, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 582;

165. the CpG represented by CG whose cancer index value is determined is at least within DMR 83 defined by SEQ ID NO:583, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.162 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nineteen cpgs from DMR 83, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 583;

166. The CpG represented by CG whose cancer index value is determined is at least within DMR 83 defined by SEQ ID NO:583, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.162, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nineteen cpgs from DMR 83, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 583;

167. the CpG represented by CG whose cancer index value is determined is at least within DMR 84 defined by SEQ ID NO:584, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.075 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 84, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 584;

168. The CpG represented by CG whose cancer index value is determined is at least within DMR 84 defined by SEQ ID NO:584, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.075, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 84, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 584;

169. the CpG represented by CG whose cancer index value is determined is at least within DMR 85 defined by SEQ ID NO:585, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.219 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 85, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 585;

170. The CpG represented by CG whose cancer index value is determined is at least within DMR 85 defined by SEQ ID NO:585, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.219, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 85, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 585;

171. the CpG represented by CG whose cancer index value is determined is at least within DMR 86 defined by SEQ ID No. 586, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.219 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 86, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 586;

172. The CpG represented by CG whose cancer index value is determined is at least within DMR 86 defined by SEQ ID No. 586, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.219, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 86, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 586;

173. the CpG represented by CG whose cancer index value is determined is at least within DMR 87 defined by SEQ ID NO:587, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.126 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 87, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 587;

174. The CpG represented by CG whose cancer index value is determined is at least within DMR 87 defined by SEQ ID NO:587, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.126, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 87, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 587;

175. the CpG represented by CG whose cancer index value is determined is at least within DMR 88 defined by SEQ ID NO:588, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.058 or greater, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least seven cpgs from DMR 88, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 588;

176. The CpG represented by CG whose cancer index value is determined is at least within DMR 88 defined by SEQ ID NO:588, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.058, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 88, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 588;

177. the CpG represented by CG whose cancer index value is determined is at least within DMR 89 defined by SEQ ID NO:589, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.147 or greater, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 89, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 589;

178. The CpG represented by CG whose cancer index value is determined is at least within DMR 89 defined by SEQ ID NO:589, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.147, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 89, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 589;

179. the CpG represented by CG whose cancer index value is determined is at least within DMR 90 defined by SEQ ID NO:590, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.179 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eleven cpgs from DMR 90, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 590;

180. The CpG represented by CG whose cancer index value is determined is at least within DMR 90 defined by SEQ ID NO:590, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.179, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eleven cpgs from DMR 90, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 590;

181. the CpG represented by CG whose cancer index value is determined is at least within DMR 91 defined by SEQ ID NO:591, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.179 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eleven cpgs from DMR 91, more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 591;

182. The CpG represented by CG whose cancer index value is determined is at least within DMR 91 defined by SEQ ID NO:591, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.179, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eleven cpgs from DMR 91, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 591;

183. the CpG represented by CG whose cancer index value is determined is at least within DMR 92 defined by SEQ ID NO:592, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.198 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 92, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 592;

184. The CpG represented by CG whose cancer index value is determined is at least within DMR 92 defined by SEQ ID No. 592, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.198, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 92, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 592;

185. the CpG represented by CG whose cancer index value is determined is at least within DMR 93 defined by SEQ ID NO:593, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.198 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 93, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 593;

186. The CpG represented by CG whose cancer index value is determined is at least within DMR 93 defined by SEQ ID NO:593, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.198, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 93, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 593;

187. the CpG represented by CG whose cancer index value is determined is located at least within DMR 94 defined by SEQ ID NO:594, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.387 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 94, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 594;

188. The CpG represented by CG whose cancer index value is determined is located at least within DMR 94 defined by SEQ ID NO:594, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.387, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 94, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 594;

189. the CpG represented by CG whose cancer index value is determined is at least within DMR 95 defined by SEQ ID NO:595, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.165 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 95, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 595;

190. The CpG represented by CG whose cancer index value is determined is at least within DMR 95 defined by SEQ ID NO:595, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.165, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 95, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 595;

191. the CpG represented by CG whose cancer index value is determined is at least within DMR 96 defined by SEQ ID NO:596, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.109 or greater, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 96, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 596;

192. The CpG represented by CG whose cancer index value is determined is at least within DMR 96 defined by SEQ ID NO:596, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.109, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 96, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 596;

193. the CpG represented by CG whose cancer index value is determined is at least within DMR 97 defined by SEQ ID NO:597, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.063 or greater, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least 11 cpgs from DMR 97, more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 597;

194. The CpG represented by CG whose cancer index value is determined is at least within DMR 97 defined by SEQ ID NO:597, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.063, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eleven cpgs from DMR 97, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 597;

195. the CpG represented by CG whose cancer index value is determined is at least within DMR 98 defined by SEQ ID NO:598, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.253 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 98, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 598;

196. The CpG represented by CG whose cancer index value is determined is at least within DMR 98 defined by SEQ ID NO:598, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.253, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 98, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 598;

197. the CpG represented by CG whose cancer index value is determined is at least within DMR 99 defined by SEQ ID NO:599, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.253 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 99, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 599;

198. The CpG represented by CG whose cancer index value is determined is at least within DMR 99 defined by SEQ ID NO:599, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.253, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 99, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 599;

199. the CpG represented by CG whose cancer index value is determined is at least within DMR 100 defined by SEQ ID NO:600, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.178 or more, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 100, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 600;

200. The CpG represented by CG whose cancer index value is determined is at least within DMR 100 defined by SEQ ID NO:600, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.178, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 100, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 600;

201. the CpG represented by CG whose cancer index value is determined is at least within DMR 101 defined by SEQ ID NO:601, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.208 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 101, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 601;

202. The CpG represented by CG whose cancer index value is determined is located at least within DMR 101 defined by SEQ ID NO:601, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.208, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 101, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 601;

203. the CpG represented by CG whose cancer index value is determined is located at least within DMR 102 defined by SEQ ID No. 602, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.186 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least fourteen cpgs from DMR 102, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 602;

204. The CpG represented by CG whose cancer index value is determined is located at least within DMR 102 defined by SEQ ID No. 602, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.186, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least fourteen cpgs from DMR 102, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 602;

205. the CpG represented by CG whose cancer index value is determined is at least within DMR 103 defined by SEQ ID NO:603, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.106 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 103, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 603;

206. The CpG represented by CG whose cancer index value is determined is located at least within DMR 103 defined by SEQ ID NO:603, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.106, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 103, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 603;

207. the CpG represented by CG whose cancer index value is determined is at least within DMR 104 defined by SEQ ID No. 604, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.315 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 104, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 604;

208. The CpG represented by CG whose cancer index value is determined is located at least within DMR 104 defined by SEQ ID No. 604, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.315, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 104, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 604;

209. the CpG represented by CG whose cancer index value is determined is at least within DMR 105 defined by SEQ ID No. 605 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.16 or more and wherein the sensitivity of the assay is at least 58.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 105 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 605;

210. The CpG represented by CG whose cancer index value is determined is located at least within DMR 105 defined by SEQ ID No. 605, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.16, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 105, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 605;

211. the CpG represented by CG whose cancer index value is determined is located at least within DMR 106 defined by SEQ ID No. 606, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.192 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 106, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 606;

212. The CpG represented by CG whose cancer index value is determined is located at least within DMR 106 defined by SEQ ID No. 606, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.192, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 106, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 606;

213. the CpG represented by CG whose cancer index value is determined is at least within DMR 107 defined by SEQ ID NO:607, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.17 or greater, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least five cpgs from DMR 107, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 607;

214. The CpG represented by CG whose cancer index value is determined is at least within DMR 107 defined by SEQ ID NO:607, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.17, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 107, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 607;

215. the CpG represented by CG whose cancer index value is determined is at least within DMR 108 defined by SEQ ID NO:608, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.245 or more, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least nine cpgs from DMR 108, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 608;

216. The CpG represented by CG whose cancer index value is determined is at least within DMR 108 defined by SEQ ID NO:608, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.245, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 108, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 608;

217. the CpG represented by CG whose cancer index value is determined is located at least within DMR 109 defined by SEQ ID No. 609, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.245 or more, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 109, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 609;

218. The CpG represented by CG whose cancer index value is determined is located at least within DMR 109 defined by SEQ ID No. 609, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.245, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 109, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 609;

219. the CpG represented by CG whose cancer index value is determined is located at least within DMR 110 defined by SEQ ID NO:610, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.245 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 110, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 610;

220. The CpG represented by CG whose cancer index value is determined is located at least within DMR 110 defined by SEQ ID NO:610, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.245, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 110, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 610;

221. the CpG represented by CG whose cancer index value is determined is at least within DMR 111 defined by SEQ ID NO:611, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.245 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 111, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 611;

222. The CpG represented by CG whose cancer index value is determined is located at least within DMR 111 defined by SEQ ID No. 611, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.245, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 111, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 611;

223. the CpG represented by CG whose cancer index value is determined is at least within DMR 112 defined by SEQ ID NO:612, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.079 or greater, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 112, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 612;

224. The CpG represented by CG whose cancer index value is determined is at least within DMR 112 defined by SEQ ID NO:612, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.079, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 112, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 612;

225. the CpG represented by CG whose cancer index value is determined is located at least within DMR 113 defined by SEQ ID No. 613 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.178 or more and wherein the sensitivity of the assay is at least 55.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least five cpgs from DMR 113 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 613;

226. The CpG represented by CG whose cancer index value is determined is located at least within DMR 113 defined by SEQ ID No. 613, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.178, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 113, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 613;

227. the CpG represented by CG whose cancer index value is determined is at least within DMR 114 defined by SEQ ID No. 614, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.178 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 114, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 614;

228. The CpG represented by CG whose cancer index value is determined is at least within DMR 114 defined by SEQ ID No. 614, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.178, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 114, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 614;

229. the CpG represented by CG whose cancer index value is determined is at least within DMR 115 defined by SEQ ID No. 615, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.079 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 115, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 615;

230. The CpG represented by CG whose cancer index value is determined is at least within DMR 115 defined by SEQ ID No. 615, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.079, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 115, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 615;

231. the CpG represented by CG whose cancer index value is determined is located at least within DMR 116 defined by SEQ ID No. 616, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.185 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 116, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 616;

232. The CpG represented by CG whose cancer index value is determined is located at least within DMR 116 defined by SEQ ID No. 616, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.185, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 116, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 616;

233. the CpG represented by CG whose cancer index value is determined is at least within DMR 117 defined by SEQ ID NO:617 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.323 or more and wherein the sensitivity of the assay is at least 53.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least one CpG from DMR 117 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 617;

234. The CpG represented by CG whose cancer index value is determined is located at least within DMR 117 defined by SEQ ID NO:617, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.323, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 117, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 617;

235. the CpG represented by CG whose cancer index value is determined is at least within DMR 118 defined by SEQ ID NO:618, and wherein an individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.044 or greater, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 118, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 618;

236. The CpG represented by CG whose cancer index value is determined is located at least within DMR 118 defined by SEQ ID NO:618, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.044, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 118, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 618;

237. the CpG represented by CG whose cancer index value is determined is at least within DMR 119 defined by SEQ ID No. 619 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.059 or greater and wherein the sensitivity of the assay is at least 62.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 119 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 619;

238. The CpG represented by CG whose cancer index value is determined is at least within DMR 119 defined by SEQ ID No. 619, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.059, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 119, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 619;

239. the CpG represented by CG whose cancer index value is determined is at least within DMR 120 defined by SEQ ID No. 620, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.089 or greater, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 120, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 620;

240. The CpG represented by CG whose cancer index value is determined is located at least within DMR 120 defined by SEQ ID No. 620, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.089, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 120, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 620;

241. the CpG represented by CG whose cancer index value is determined is at least within DMR 121 defined by SEQ ID NO:621, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.261 or more, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 121, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 621;

242. The CpG represented by CG whose cancer index value is determined is at least within DMR 121 defined by SEQ ID NO:621, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.261, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 121, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 621;

243. the CpG represented by CG whose cancer index value is determined is located at least within DMR 122 defined by SEQ ID No. 622, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.108 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 122, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 622;

244. The CpG represented by CG whose cancer index value is determined is located at least within DMR 122 defined by SEQ ID No. 622, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.108, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 122, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 622;

245. the CpG represented by CG whose cancer index value is determined is located at least within DMR 123 defined by SEQ ID NO:623 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.062 or more and wherein the sensitivity of the assay is at least 68.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 123 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 623;

246. The CpG represented by CG whose cancer index value is determined is located at least within DMR 123 defined by SEQ ID NO:623 and wherein when the individual's cancer index is less than about 0.062, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 and wherein the sensitivity of the assay is at least 68.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 123 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 623;

247. the CpG represented by CG whose cancer index value is determined is located at least within DMR 124 defined by SEQ ID No. 624, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.086 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 124, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 624;

248. The CpG represented by CG whose cancer index value is determined is located at least within DMR 124 defined by SEQ ID NO:624, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.086, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 124, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 624;

249. the CpG represented by CG whose cancer index value is determined is at least within DMR 125 defined by SEQ ID No. 625, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.146 or greater, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 125, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID No. 625;

250. The CpG represented by CG whose cancer index value is determined is at least within DMR 125 defined by SEQ ID No. 625, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.146, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 125, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 625;

251. the CpG represented by CG whose cancer index value is determined is located at least within DMR 126 defined by SEQ ID No. 626 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.209 or greater and wherein the sensitivity of the assay is at least 47.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 126 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 626;

252. The CpG represented by CG whose cancer index value is determined is located at least within DMR 126 defined by SEQ ID No. 626, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.209, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 126, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 626;

253. the CpG represented by CG whose cancer index value is determined is at least within DMR 127 defined by SEQ ID NO:627, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.077 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 127, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 627;

254. The CpG represented by CG whose cancer index value is determined is at least within DMR 127 defined by SEQ ID NO:627, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.077, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 127, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 627;

255. the CpG represented by CG whose cancer index value is determined is at least within DMR 128 defined by SEQ ID No. 628, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.051 or more, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least two cpgs from DMR 128, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 628;

256. The CpG represented by CG whose cancer index value is determined is at least within DMR 128 defined by SEQ ID No. 628, and wherein when the cancer index of the individual is less than about 0.051, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least two cpgs from DMR 128, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 628;

257. the CpG represented by CG whose cancer index value is determined is at least within DMR 129 defined by SEQ ID No. 629, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.174 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 129, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 629;

258. The CpG represented by CG whose cancer index value is determined is at least within DMR 129 defined by SEQ ID No. 629, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.174, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 129, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 629;

259. the CpG represented by CG whose cancer index value is determined is at least within DMR 130 defined by SEQ ID No. 630, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.148 or greater, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 130, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 630;

260. The CpG represented by CG whose cancer index value is determined is located at least within DMR 130 defined by SEQ ID No. 630, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.148, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 130, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 630;

261. the CpG represented by CG whose cancer index value is determined is located at least within DMR 131 defined by SEQ ID No. 631, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.069 or greater, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 131, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 631;

262. The CpG represented by CG whose cancer index value is determined is located at least within DMR 131 defined by SEQ ID No. 631, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.069, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 131, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 631;

263. the CpG represented by CG whose cancer index value is determined is at least within DMR 132 defined by SEQ ID NO:632, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.136 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 132, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 632;

264. The CpG represented by CG whose cancer index value is determined is at least within DMR 132 defined by SEQ ID NO:632, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.136, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 132, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 632;

265. the CpG represented by CG whose cancer index value is determined is at least within DMR 133 defined by SEQ ID NO:633 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.103 or more and wherein the sensitivity of the assay is at least 56.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 133 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 633;

266. The CpG represented by CG whose cancer index value is determined is at least within DMR 133 defined by SEQ ID NO:633 and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.103 and wherein the sensitivity of the assay is at least 56.00% and the specificity of the assay is at least 95.00%, preferably wherein a group of one or more cpgs comprises at least eight cpgs from DMR 133 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 633;

267. the CpG represented by CG whose cancer index value is determined is at least within DMR 134 defined by SEQ ID NO:634, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.157 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 134, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 634;

268. The CpG represented by CG whose cancer index value is determined is at least within DMR 134 defined by SEQ ID NO:634, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.157, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 134, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 634;

269. the CpG represented by CG whose cancer index value is determined is at least within DMR 135 defined by SEQ ID No. 635, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.18 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least ten cpgs from DMR 135, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 635;

270. The CpG represented by CG whose cancer index value is determined is located at least within DMR 135 defined by SEQ ID No. 635, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.18, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least ten cpgs from DMR 135, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 635;

271. the CpG represented by CG whose cancer index value is determined is at least within DMR 136 defined by SEQ ID No. 636, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.298 or greater, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 136, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 636;

272. The CpG represented by CG whose cancer index value is determined is at least within DMR 136 defined by SEQ ID No. 636, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.298, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 136, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 636;

273. the CpG represented by CG whose cancer index value is determined is located at least within DMR 137 defined by SEQ ID No. 637, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.048 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 137, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 637;

274. The CpG represented by CG whose cancer index value is determined is located at least within DMR 137 defined by SEQ ID No. 637, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.048, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 137, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 637;

275. the CpG represented by CG whose cancer index value is determined is at least within DMR 138 defined by SEQ ID NO:638 and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.048 or greater and wherein the sensitivity of the assay is at least 55.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 138 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 638;

276. The CpG represented by CG whose cancer index value is determined is at least within DMR 138 defined by SEQ ID NO:638 and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.048 and wherein the sensitivity of the assay is at least 55.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 138 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 638;

277. the CpG represented by CG whose cancer index value is determined is at least within DMR 139 defined by SEQ ID No. 639 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.154 or more and wherein the sensitivity of the assay is at least 59.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 139 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 639;

278. The CpG represented by CG whose cancer index value is determined is located at least within DMR 139 defined by SEQ ID No. 639, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.154, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 139, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 639;

279. the CpG represented by CG whose cancer index value is determined is at least within DMR 140 defined by SEQ ID No. 640, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.048 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 140, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 640;

280. The CpG represented by CG whose cancer index value is determined is at least within DMR 140 defined by SEQ ID No. 640, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.048, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 140, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 640;

281. the CpG represented by CG whose cancer index value is determined is at least within DMR 141 defined by SEQ ID NO:641 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.083 or greater and wherein the sensitivity of the assay is at least 66.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 141 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 641;

282. The CpG represented by CG whose cancer index value is determined is at least within DMR 141 defined by SEQ ID NO:641 and wherein when the individual's cancer index is less than about 0.083, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 and wherein the sensitivity of the assay is at least 66.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 141 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 641;

283. the CpG represented by CG whose cancer index value is determined is located at least within DMR 142 defined by SEQ ID NO:642, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.188 or greater, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 142, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 642;

284. The CpG represented by CG whose cancer index value is determined is located at least within DMR 142 defined by SEQ ID NO:642, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.188, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 142, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 642;

285. the CpG represented by CG whose cancer index value is determined is at least within DMR 143 defined by SEQ ID No. 643 and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.183 or greater and wherein the sensitivity of the assay is at least 64.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 143 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 643;

286. The CpG represented by CG whose cancer index value is determined is at least within DMR 143 defined by SEQ ID No. 643 and wherein an individual is classified as not having cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.183 and wherein the sensitivity of the assay is at least 64.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 143 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 643;

287. the CpG represented by CG whose cancer index value is determined is at least within DMR 144 defined by SEQ ID No. 644, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.101 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 144, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 644;

288. The CpG represented by CG whose cancer index value is determined is located at least within DMR 144 defined by SEQ ID No. 644, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.101, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 144, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 644;

289. the CpG represented by CG whose cancer index value is determined is at least within DMR 145 defined by SEQ ID No. 645, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.034 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 145, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 645;

290. The CpG represented by CG whose cancer index value is determined is at least within DMR 145 defined by SEQ ID No. 645, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.034, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least two cpgs from DMR 145, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 645;

291. the CpG represented by CG whose cancer index value is determined is at least within DMR 146 defined by SEQ ID NO:646 and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.037 or greater and wherein the sensitivity of the assay is at least 58.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 146 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 646;

292. The CpG represented by CG whose cancer index value is determined is at least within DMR 146 defined by SEQ ID NO:646 and wherein when the individual's cancer index is less than about 0.037, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 and wherein the sensitivity of the assay is at least 58.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 146 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 646;

293. the CpG represented by CG whose cancer index value is determined is at least within DMR 147 defined by SEQ ID No. 647 and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.072 or greater and wherein the sensitivity of the assay is at least 55.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 147 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 647;

294. The CpG represented by CG whose cancer index value is determined is located at least within DMR 147 defined by SEQ ID No. 647 and wherein when the cancer index of an individual is less than about 0.072, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of cancer and/or CIN3 development and wherein the sensitivity of the assay is at least 55.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 147 and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] 647 in SEQ ID No.;

295. the CpG represented by CG whose cancer index value is determined is at least within DMR 148 defined by SEQ ID NO:648, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.552 or greater, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 148, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 648;

296. The CpG represented by CG whose cancer index value is determined is located at least within DMR 148 defined by SEQ ID No. 648, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.552, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 148, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 648;

297. the CpG represented by CG whose cancer index value is determined is at least within DMR 149 defined by SEQ ID No. 649 and wherein an individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.214 or greater and wherein the sensitivity of the assay is at least 53.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least thirteen cpgs from DMR 149, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 649;

298. The CpG represented by CG whose cancer index value is determined is at least within DMR 149 defined by SEQ ID No. 649 and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.214 and wherein the sensitivity of the assay is at least 53.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least thirteen cpgs from DMR 149, more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 649;

299. the CpG represented by CG whose cancer index value is determined is at least within DMR 150 defined by SEQ ID NO:650, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.065 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 150, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 650;

300. The CpG represented by CG whose cancer index value is determined is at least within DMR 150 defined by SEQ ID NO:650, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.065, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 150, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 650;

301. the CpG represented by CG whose cancer index value is determined is at least within DMR 151 defined by SEQ ID NO:651, and wherein an individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.185 or greater, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 151, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 651;

302. The CpG represented by CG whose cancer index value is determined is located at least within DMR 151 defined by SEQ ID NO:651, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.185, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 151, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 651;

303. the CpG represented by CG whose cancer index value is determined is at least within DMR 152 defined by SEQ ID No. 652, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.294 or greater, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 152, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 652;

304. The CpG represented by CG whose cancer index value is determined is at least within DMR 152 defined by SEQ ID No. 652, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.294, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 152, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 652;

305. the CpG represented by CG whose cancer index value is determined is at least within DMR 153 defined by SEQ ID No. 653, and wherein when the individual's cancer index is about 0.129 or greater, the individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 153, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 653;

306. The CpG represented by CG whose cancer index value is determined is at least within DMR 153 defined by SEQ ID NO:653, and wherein when the cancer index of an individual is less than about 0.129, the individual is classified as not suffering from cancer and/or CIN3 or having a lower risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 153, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 653;

307. the CpG represented by CG whose cancer index value is determined is at least within DMR 154 defined by SEQ ID No. 654 and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.138 or greater and wherein the sensitivity of the assay is at least 52.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 154 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 654;

308. The CpG represented by CG whose cancer index value is determined is at least within DMR 154 defined by SEQ ID No. 654 and wherein when the individual's cancer index is less than about 0.138, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 and wherein the sensitivity of the assay is at least 52.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 154 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 654;

309. the CpG represented by CG whose cancer index value is determined is located at least within DMR 155 defined by SEQ ID NO:655, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.118 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 155, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 655;

310. The CpG represented by CG whose cancer index value is determined is located at least within DMR 155 defined by SEQ ID NO:655, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.118, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 155, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 655;

311. the CpG represented by CG whose cancer index value is determined is at least within DMR 156 defined by SEQ ID NO:656, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.254 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 156, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 656;

312. The CpG represented by CG whose cancer index value is determined is at least within DMR 156 defined by SEQ ID NO:656, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.254, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 156, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 656;

313. the CpG represented by CG whose cancer index value is determined is at least within DMR 157 defined by SEQ ID NO:657, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.18 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 157, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 657;

314. The CpG represented by CG whose cancer index value is determined is at least within DMR 157 defined by SEQ ID NO:657, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.18, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 157, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 657;

315. the CpG represented by CG whose cancer index value is determined is at least within DMR 158 defined by SEQ ID No. 658 and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.301 or greater and wherein the sensitivity of the assay is at least 53.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 158 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 658;

316. The CpG represented by CG whose cancer index value is determined is at least within DMR 158 defined by SEQ ID No. 658 and wherein an individual is classified as not suffering from cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.301 and wherein the sensitivity of the assay is at least 53.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 158 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 658;

317. the CpG represented by CG whose cancer index value is determined is at least within DMR 159 defined by SEQ ID NO:659, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.176 or greater, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 159, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 659;

318. The CpG represented by CG whose cancer index value is determined is at least within DMR 159 defined by SEQ ID NO:659, and wherein an individual is classified as not suffering from cancer or having a high risk of cancer development when the individual's cancer index is less than about 0.176, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least two cpgs from DMR 159, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 659;

319. the CpG represented by CG whose cancer index value is determined is at least within DMR 160 defined by SEQ ID NO:660, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.411 or greater, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 160, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 660;

320. The CpG represented by CG whose cancer index value is determined is at least within DMR 160 defined by SEQ ID NO:660, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.411, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 160, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 660;

321. the CpG represented by CG whose cancer index value is determined is located at least within DMR 161 defined by SEQ ID NO:661, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.072 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 161, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 661;

322. The CpG represented by CG whose cancer index value is determined is located at least within DMR 161 defined by SEQ ID NO:661, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.072, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 161, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 661;

323. the CpG represented by CG whose cancer index value is determined is at least within DMR 162 defined by SEQ ID NO:662 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.358 or greater and wherein the sensitivity of the assay is at least 41.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 162 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 662;

324. The CpG represented by CG whose cancer index value is determined is located at least within DMR 162 defined by SEQ ID NO:662 and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.358 and wherein the sensitivity of the assay is at least 41.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 162 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 662;

325. the CpG represented by CG whose cancer index value is determined is at least within DMR 163 defined by SEQ ID NO:663, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.313 or greater, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 163, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 663;

326. The CpG represented by CG whose cancer index value is determined is at least within DMR 163 defined by SEQ ID NO:663, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.313, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least one CpG from DMR 163, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 663;

327. the CpG represented by CG whose cancer index value is determined is at least within DMR 164 defined by SEQ ID NO:664, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.221 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 164, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 664;

328. The CpG represented by CG whose cancer index value is determined is at least within DMR 164 defined by SEQ ID NO:664, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.221, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 164, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 664;

329. the CpG represented by CG whose cancer index value is determined is at least within DMR 165 defined by SEQ ID No. 665 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.256 or more and wherein the sensitivity of the assay is at least 44.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least six cpgs from DMR 165 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 665;

330. The CpG represented by CG whose cancer index value is determined is at least within DMR 165 defined by SEQ ID No. 665 and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.256 and wherein the sensitivity of the assay is at least 44.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 165 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 665;

331. the CpG represented by CG whose cancer index value is determined is at least within DMR 166 defined by SEQ ID NO:666 and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.202 or greater and wherein the sensitivity of the assay is at least 55.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least five cpgs from DMR 166 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 666;

332. The CpG represented by CG whose cancer index value is determined is at least within DMR 166 defined by SEQ ID NO:666 and wherein when the cancer index of an individual is less than about 0.202, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 and wherein the sensitivity of the assay is at least 55.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 166 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 666;

333. the CpG represented by CG whose cancer index value is determined is at least within DMR 167 defined by SEQ ID NO:667, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.345 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 167, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 667;

334. The CpG represented by CG whose cancer index value is determined is at least within DMR 167 defined by SEQ ID NO:667, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.345, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 167, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 667;

335. the CpG represented by CG whose cancer index value is determined is at least within DMR 168 defined by SEQ ID NO:668, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.165 or greater, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 168, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 668;

336. The CpG represented by CG whose cancer index value is determined is at least within DMR 168 defined by SEQ ID NO:668, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.165, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 168, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 668;

337. the CpG represented by CG whose cancer index value is determined is at least within DMR 169 defined by SEQ ID NO:669, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.134 or greater, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 169, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 669;

338. The CpG represented by CG whose cancer index value is determined is at least within DMR 169 defined by SEQ ID NO:669, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.134, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 169, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 669;

339. the CpG represented by CG whose cancer index value is determined is at least within DMR 170 defined by SEQ ID No. 670, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.3 or more, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 170, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 670;

340. The CpG represented by CG whose cancer index value is determined is located at least within DMR 170 defined by SEQ ID NO:670, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.3, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 170, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 670;

341. the CpG represented by CG whose cancer index value is determined is located at least within DMR 171 defined by SEQ ID NO:671, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.153 or greater, and wherein the sensitivity of the assay is at least 45.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 171, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 671;

342. The CpG represented by CG whose cancer index value is determined is located at least within DMR 171 defined by SEQ ID NO:671, and wherein when the cancer index of an individual is less than about 0.153, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 45.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 171, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 671;

343. the CpG represented by CG whose cancer index value is determined is at least within DMR 172 defined by SEQ ID No. 672, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.416 or greater, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 172, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 672;

344. The CpG represented by CG whose cancer index value is determined is at least within DMR 172 defined by SEQ ID No. 672 and wherein when the cancer index of the individual is less than about 0.416, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 and wherein the sensitivity of the assay is at least 47.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 172 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 672;

345. the CpG represented by CG whose cancer index value is determined is at least within DMR 173 defined by SEQ ID NO:673, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.416 or greater, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 173, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 673;

346. The CpG represented by CG whose cancer index value is determined is at least within DMR 173 defined by SEQ ID NO:673, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.416, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 173, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 673;

347. the CpG represented by CG whose cancer index value is determined is at least within DMR 174 defined by SEQ ID No. 674, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.223 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 174, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 674;

348. The CpG represented by CG whose cancer index value is determined is located at least within DMR 174 defined by SEQ ID No. 674, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.223, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 174, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 674;

349. the CpG represented by CG whose cancer index value is determined is at least within DMR 175 defined by SEQ ID NO:675, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.232 or greater, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 175, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 675;

350. The CpG represented by CG whose cancer index value is determined is at least within DMR 175 defined by SEQ ID NO:675, and wherein when the individual's cancer index is less than about 0.232, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 175, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 675;

351. the CpG represented by CG whose cancer index value is determined is located at least within DMR 176 defined by SEQ ID NO:676, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.047 or greater, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 176, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 676;

352. The CpG represented by CG whose cancer index value is determined is located at least within DMR 176 defined by SEQ ID NO:676, and wherein when the individual's cancer index is less than about 0.047, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 176, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 676;

353. the CpG represented by CG whose cancer index value is determined is at least within DMR 177 defined by SEQ ID NO:677, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.162 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 177, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 677;

354. The CpG represented by CG whose cancer index value is determined is at least within DMR 177 defined by SEQ ID NO:677, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.162, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least two cpgs from DMR 177, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 677;

355. the CpG represented by CG whose cancer index value is determined is at least within DMR 178 defined by SEQ ID No. 678, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.311 or greater, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 178, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 678;

356. The CpG represented by CG whose cancer index value is determined is at least within DMR 178 defined by SEQ ID NO:678, and wherein when the cancer index of the individual is less than about 0.311, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 178, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 678;

357. the CpG represented by CG whose cancer index value is determined is at least within DMR 179 defined by SEQ ID NO:679, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.17 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least fourteen cpgs from DMR 179, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 679;

358. The CpG represented by CG whose cancer index value is determined is at least within DMR 179 defined by SEQ ID NO:679, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.17, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least fourteen cpgs from DMR 179, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 679;

359. the CpG represented by CG whose cancer index value is determined is at least within DMR 180 defined by SEQ ID NO:680, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.314 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 180, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 680;

360. The CpG represented by CG whose cancer index value is determined is at least within DMR 180 defined by SEQ ID NO:680, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.314 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 180, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 680;

361. the CpG represented by CG whose cancer index value is determined is located at least within DMR 181 defined by SEQ ID NO:681, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.2 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 181, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 681;

362. The CpG represented by CG whose cancer index value is determined is located at least within DMR 181 defined by SEQ ID NO:681, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.2, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 181, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 681;

363. the CpG represented by CG whose cancer index value is determined is at least within DMR 182 defined by SEQ ID No. 682 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.08 or greater and wherein the sensitivity of the assay is at least 59.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 182 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 682;

364. The CpG represented by CG whose cancer index value is determined is at least within DMR 182 defined by SEQ ID No. 682, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.08, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 182, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 682;

365. the CpG represented by CG whose cancer index value is determined is at least within DMR 183 defined by SEQ ID NO:683, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.089 or greater, and wherein the sensitivity of the assay is at least 45.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least five cpgs from DMR 183, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 683;

366. The CpG represented by CG whose cancer index value is determined is at least within DMR 183 defined by SEQ ID NO:683, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.089, and wherein the sensitivity of the assay is at least 45.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 183, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 683;

367. the CpG represented by CG whose cancer index value is determined is at least within DMR 184 defined by SEQ ID NO:684, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.253 or greater, and wherein the sensitivity of the assay is at least 40.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 184, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 684;

368. The CpG represented by CG whose cancer index value is determined is at least within DMR 184 defined by SEQ ID NO:684, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.253, and wherein the sensitivity of the assay is at least 40.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 184, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 684;

369. the CpG represented by CG whose cancer index value is determined is at least within DMR 185 defined by SEQ ID NO:685, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.274 or greater, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 185, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 685;

370. The CpG represented by CG whose cancer index value is determined is at least within DMR 185 defined by SEQ ID NO:685, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.274, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 185, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 685;

371. the CpG represented by CG whose cancer index value is determined is at least within DMR 186 defined by SEQ ID NO:686, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.451 or greater, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 186, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 686;

372. The CpG represented by CG whose cancer index value is determined is at least within DMR 186 defined by SEQ ID NO:686, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.451, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 186, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 686;

373. the CpG represented by CG whose cancer index value is determined is at least within DMR 187 defined by SEQ ID NO:687, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.346 or greater, and wherein the sensitivity of the assay is at least 37.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 187, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 687;

374. The CpG represented by CG whose cancer index value is determined is at least within DMR 187 defined by SEQ ID NO:687, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.346, and wherein the sensitivity of the assay is at least 37.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 187, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 687;

375. the CpG represented by CG whose cancer index value is determined is at least within DMR 188 defined by SEQ ID NO:688, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.181 or greater, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 188, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 688;

376. The CpG represented by CG whose cancer index value is determined is at least within DMR 188 defined by SEQ ID NO:688, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.181, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 188, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 688;

377. the CpG represented by CG whose cancer index value is determined is at least within DMR 189 defined by SEQ ID NO:689, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.181 or greater, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 189, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 689;

378. The CpG represented by CG whose cancer index value is determined is at least within DMR 189 defined by SEQ ID NO:689, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.181, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 189, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 689;

379. the CpG represented by CG whose cancer index value is determined is at least within DMR 190 defined by SEQ ID No. 690, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.287 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 190, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 690;

380. The CpG represented by CG whose cancer index value is determined is at least within DMR 190 defined by SEQ ID No. 690, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.287, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 190, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 690;

381. the CpG represented by CG whose cancer index value is determined is at least within DMR 191 defined by SEQ ID NO:691, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.057 or greater, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 191, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 691;

382. The CpG represented by CG whose cancer index value is determined is located at least within DMR 191 defined by SEQ ID NO:691, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.057, and wherein the sensitivity of the assay is at least 59.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 191, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 691;

383. the CpG represented by CG whose cancer index value is determined is at least within DMR 192 defined by SEQ ID NO:692, and wherein an individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.292 or greater, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 192, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 692;

384. The CpG represented by CG whose cancer index value is determined is at least within DMR 192 defined by SEQ ID NO:692, and wherein when the cancer index of an individual is less than about 0.292, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 192, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 692;

385. the CpG represented by CG whose cancer index value is determined is at least within the DMR 193 defined by SEQ ID NO:693, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.11 or greater, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from the DMR 193, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 693;

386. The CpG represented by CG whose cancer index value is determined is at least within the DMR 193 defined by SEQ ID NO:693, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.11, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from the DMR 193, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 693;

387. the CpG represented by CG whose cancer index value is determined is located at least within DMR 194 defined by SEQ ID NO:694, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.081 or greater, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 194, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 694;

388. The CpG represented by CG whose cancer index value is determined is located at least within DMR 194 defined by SEQ ID NO:694, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.081, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 194, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 694;

389. the CpG represented by CG whose cancer index value is determined is at least within DMR 195 defined by SEQ ID NO:695, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.11 or greater, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 195, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 695;

390. The CpG represented by CG whose cancer index value is determined is at least within DMR 195 defined by SEQ ID NO:695, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.11, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 195, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 695;

391. the CpG represented by CG whose cancer index value is determined is at least within DMR 196 defined by SEQ ID NO:696, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.057 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least seven cpgs from DMR 196, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 696;

392. The CpG represented by CG whose cancer index value is determined is at least within DMR 196 defined by SEQ ID NO:696, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.057, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least seven cpgs from DMR 196, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 696;

393. the CpG represented by CG whose cancer index value is determined is at least within DMR 197 defined by SEQ ID NO:697, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.076 or greater, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 197, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 697;

394. The CpG represented by CG whose cancer index value is determined is at least within DMR 197 defined by SEQ ID NO:697, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.076, and wherein the sensitivity of the assay is at least 52.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 197, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 697;

395. the CpG represented by CG whose cancer index value is determined is at least within DMR 198 defined by SEQ ID NO:698, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.076 or greater, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 198, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 698;

396. The CpG represented by CG whose cancer index value is determined is at least within DMR 198 defined by SEQ ID NO:698, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.076, and wherein the sensitivity of the assay is at least 47.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 198, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 698;

397. the CpG represented by CG whose cancer index value is determined is at least within DMR 199 defined by SEQ ID NO:699, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.198 or greater, and wherein the sensitivity of the assay is at least 41.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 199, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 699;

398. The CpG represented by CG whose cancer index value is determined is at least within DMR 199 defined by SEQ ID NO:699, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.198, and wherein the sensitivity of the assay is at least 41.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 199, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 699;

399. the CpG represented by CG whose cancer index value is determined is at least within DMR 200 defined by SEQ ID NO:700, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.183 or more, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 200, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 700;

400. The CpG represented by CG whose cancer index value is determined is located at least within DMR 200 defined by SEQ ID NO:700, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.183, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 200, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 700;

401. the CpG represented by CG whose cancer index value is determined is at least within DMR 201 defined by SEQ ID No. 701, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.063 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least ten cpgs from DMR 201, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] 701 in SEQ ID No. 701;

402. The CpG represented by CG whose cancer index value is determined is at least within DMR 201 defined by SEQ ID No. 701, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.063, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least ten cpgs from DMR 201, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 701;

403. the CpG represented by CG whose cancer index value is determined is located at least within DMR 202 defined by SEQ ID NO:702, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.095 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 202, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 702;

404. The CpG represented by CG whose cancer index value is determined is located at least within DMR 202 defined by SEQ ID NO:702, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.095, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 202, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 702;

405. the CpG represented by CG whose cancer index value is determined is at least within DMR 203 defined by SEQ ID No. 703 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.426 or more and wherein the sensitivity of the assay is at least 42.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least nine cpgs from DMR 203 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 703;

406. The CpG represented by CG whose cancer index value is determined is at least within DMR 203 defined by SEQ ID No. 703 and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.426 and wherein the sensitivity of the assay is at least 42.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 203 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 703;

407. the CpG represented by CG whose cancer index value is determined is at least within DMR 204 defined by SEQ ID NO:704, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.095 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 204, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 704;

408. The CpG represented by CG whose cancer index value is determined is at least within DMR 204 defined by SEQ ID NO:704, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.095, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 204, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 704;

409. the CpG represented by CG whose cancer index value is determined is located at least within DMR 205 defined by SEQ ID NO:705, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.074 or greater, and wherein the sensitivity of the assay is at least 45.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 205, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 705;

410. The CpG represented by CG whose cancer index value is determined is located at least within DMR 205 defined by SEQ ID NO:705, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.074, and wherein the sensitivity of the assay is at least 45.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 205, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 705;

411. the CpG represented by CG whose cancer index value is determined is at least within DMR 206 defined by SEQ ID NO:706, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.426 or greater, and wherein the sensitivity of the assay is at least 42.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 206, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 706;

412. The CpG represented by CG whose cancer index value is determined is at least within DMR206 defined by SEQ ID NO:706, and wherein an individual is classified as not suffering from cancer or having a low risk of cancer progression when the individual's cancer index is less than about 0.426 or more, and wherein the sensitivity of the assay is at least 42.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least nine cpgs from DMR206, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 706;

413. the CpG represented by CG whose cancer index value is determined is at least within DMR 207 defined by SEQ ID NO:707, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.109 or more, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 207, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 707;

414. The CpG represented by CG whose cancer index value is determined is located at least within DMR 207 defined by SEQ ID NO:707, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.109, and wherein the sensitivity of the assay is at least 51.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 207, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 707;

415. the CpG represented by CG whose cancer index value is determined is at least within DMR 208 defined by SEQ ID NO:708, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.099 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 208, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 708;

416. The CpG represented by CG whose cancer index value is determined is at least within DMR 208 defined by SEQ ID NO:708, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.099, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 208, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 708;

417. the CpG represented by CG whose cancer index value is determined is located at least within DMR 209 defined by SEQ ID NO:709, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.099 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 209, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 709;

418. The CpG represented by CG whose cancer index value is determined is located at least within DMR 209 defined by SEQ ID NO:709, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.099, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 209, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 709;

419. the CpG represented by CG whose cancer index value is determined is at least within DMR 210 defined by SEQ ID NO:710, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.099 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 210, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 710;

420. The CpG represented by CG whose cancer index value is determined is at least within DMR 210 defined by SEQ ID NO:710, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.099, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 210, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 710;

421. the CpG represented by CG whose cancer index value is determined is at least within DMR 211 defined by SEQ ID No. 711, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.392 or greater, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least one CpG from DMR 211, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 711;

422. The CpG represented by CG whose cancer index value is determined is at least within DMR 211 defined by SEQ ID No. 711, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.392, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 211, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 711;

423. the CpG represented by CG whose cancer index value is determined is at least within DMR 212 defined by SEQ ID NO:712, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.245 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 212, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 712;

424. The CpG represented by CG whose cancer index value is determined is at least within DMR 212 defined by SEQ ID No. 712, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.245, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 212, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 712;

425. the CpG represented by CG whose cancer index value is determined is at least within DMR 213 defined by SEQ ID NO:713 and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.362 or greater and wherein the sensitivity of the assay is at least 34.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 213 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 713;

426. The CpG represented by CG whose cancer index value is determined is at least within DMR 213 defined by SEQ ID NO:713, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.362, and wherein the sensitivity of the assay is at least 34.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least six cpgs from DMR 213, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 713;

427. the CpG represented by CG whose cancer index value is determined is at least within DMR 214 defined by SEQ ID NO:714, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.049 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 214, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 714;

428. The CpG represented by CG whose cancer index value is determined is located at least within DMR 214 defined by SEQ ID NO:714, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.049, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 214, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 714;

429. the CpG represented by CG whose cancer index value is determined is at least within DMR 215 defined by SEQ ID No. 715, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.263 or greater, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 215, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 715;

430. The CpG represented by CG whose cancer index value is determined is located at least within DMR 215 defined by SEQ ID No. 715, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.263, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 215, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 715;

431. the CpG represented by CG whose cancer index value is determined is at least within DMR 216 defined by SEQ ID No. 716 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.533 or greater and wherein the sensitivity of the assay is at least 40.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 216 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 716;

432. The CpG represented by CG whose cancer index value is determined is located at least within DMR 216 defined by SEQ ID No. 716, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.533, and wherein the sensitivity of the assay is at least 40.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 216, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 716;

433. the CpG represented by CG whose cancer index value is determined is located at least within DMR 217 defined by SEQ ID No. 717, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.171 or greater, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 217, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 717;

434. The CpG represented by CG whose cancer index value is determined is located at least within DMR 217 defined by SEQ ID No. 717, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.171, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 217, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 717;

435. the CpG represented by CG whose cancer index value is determined is at least within DMR 218 defined by SEQ ID No. 718, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.257 or greater, and wherein the sensitivity of the assay is at least 36.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 218, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 718;

436. The CpG represented by CG whose cancer index value is determined is located at least within DMR 218 defined by SEQ ID No. 718, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.257, and wherein the sensitivity of the assay is at least 36.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 218, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 718;

437. the CpG represented by CG whose cancer index value is determined is at least within DMR 219 defined by SEQ ID NO:719, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.162 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least four cpgs from DMR 219, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 719;

438. The CpG represented by CG whose cancer index value is determined is at least within DMR 219 defined by SEQ ID NO:719, and wherein an individual is classified as not having cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.162, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least four cpgs from DMR 219, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 719;

439. the CpG represented by CG whose cancer index value is determined is at least within DMR 220 defined by SEQ ID NO:720, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.211 or greater, and wherein the sensitivity of the assay is at least 40.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 220, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 720;

440. The CpG represented by CG whose cancer index value is determined is at least within DMR 220 defined by SEQ ID NO:720, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.211, and wherein the sensitivity of the assay is at least 40.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 220, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 720;

441. the CpG represented by CG whose cancer index value is determined is located at least within DMR 221 defined by SEQ ID NO:721, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.296 or greater, and wherein the sensitivity of the assay is at least 33.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 221, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 721;

442. The CpG represented by CG whose cancer index value is determined is located at least within DMR 221 defined by SEQ ID NO:721, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.296, and wherein the sensitivity of the assay is at least 33.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 221, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 721;

443. the CpG represented by CG whose cancer index value is determined is at least within DMR 222 defined by SEQ ID No. 722, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.361 or greater, and wherein the sensitivity of the assay is at least 32.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 222, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 722;

444. The CpG represented by CG whose cancer index value is determined is located at least within DMR 222 defined by SEQ ID No. 722, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.361, and wherein the sensitivity of the assay is at least 32.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 222, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 722;

445. the CpG represented by CG whose cancer index value is determined is at least within DMR 223 defined by SEQ ID NO:723, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.056 or greater, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least ten cpgs from DMR 223, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 723;

446. The CpG represented by CG whose cancer index value is determined is located at least within DMR 223 defined by SEQ ID NO:723, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.056, and wherein the sensitivity of the assay is at least 49.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least ten cpgs from DMR 223, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 723;

447. the CpG represented by CG whose cancer index value is determined is at least within DMR 224 defined by SEQ ID NO:724 and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.257 or greater and wherein the sensitivity of the assay is at least 34.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 224 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 724;

448. The CpG represented by CG whose cancer index value is determined is at least within DMR 224 defined by SEQ ID NO:724, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.257, and wherein the sensitivity of the assay is at least 34.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 224, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 724;

449. the CpG represented by CG whose cancer index value is determined is at least within DMR 225 defined by SEQ ID No. 725, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.409 or greater, and wherein the sensitivity of the assay is at least 36.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least four cpgs from DMR 225, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 725;

450. The CpG represented by CG whose cancer index value is determined is located at least within DMR 225 defined by SEQ ID No. 725, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.409, and wherein the sensitivity of the assay is at least 36.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 225, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 725;

451. the CpG represented by CG whose cancer index value is determined is at least within DMR 226 defined by SEQ ID No. 726, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.46 or greater, and wherein the sensitivity of the assay is at least 26.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 226, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 726;

452. The CpG represented by CG whose cancer index value is determined is at least within DMR 226 defined by SEQ ID No. 726, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.46, and wherein the sensitivity of the assay is at least 26.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 226, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 726;

453. the CpG represented by CG whose cancer index value is determined is at least within DMR 227 defined by SEQ ID NO 727, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.086 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least ten cpgs from DMR 227, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO 727;

454. The CpG represented by CG whose cancer index value is determined is at least within DMR 227 defined by SEQ ID NO 727, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.086, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least ten cpgs from DMR 227, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO 727;

455. the CpG represented by CG whose cancer index value is determined is at least within DMR 228 defined by SEQ ID NO 728 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.081 or more and wherein the sensitivity of the assay is at least 48.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 228 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO 728;

456. The CpG represented by CG whose cancer index value is determined is at least within DMR 228 defined by SEQ ID No. 728, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.081, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least nine cpgs from DMR 228, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 728;

457. the CpG represented by CG whose cancer index value is determined is at least within DMR 229 defined by SEQ ID NO 729, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.257 or more, and wherein the sensitivity of the assay is at least 33.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eighteen cpgs from DMR 229, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO 729;

458. The CpG represented by CG whose cancer index value is determined is located at least within DMR 229 defined by SEQ ID NO:729, and wherein an individual is classified as not having cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.257, and wherein the sensitivity of the assay is at least 33.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eighteen cpgs from DMR 229, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 729;

459. the CpG represented by CG whose cancer index value is determined is at least within DMR 230 defined by SEQ ID No. 730, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.088 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 230, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 730;

460. The CpG represented by CG whose cancer index value is determined is at least within DMR 230 defined by SEQ ID No. 730, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.088, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least eight cpgs from DMR 230, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 730;

461. the CpG represented by CG whose cancer index value is determined is at least within DMR 231 defined by SEQ ID No. 731 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.025 or greater and wherein the sensitivity of the assay is at least 44.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 231 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 731;

462. The CpG represented by CG whose cancer index value is determined is located at least within DMR 231 defined by SEQ ID No. 731, and wherein an individual is classified as not suffering from cancer or having a low degree of cancer progression when the individual's cancer index is less than about 0.025, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR 231, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 731;

463. the CpG represented by CG whose cancer index value is determined is at least within DMR 232 defined by SEQ ID No. 732, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.459 or more, and wherein the sensitivity of the assay is at least 25.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 232, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 732;

464. The CpG represented by CG whose cancer index value is determined is at least within DMR 232 defined by SEQ ID No. 732, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.459, and wherein the sensitivity of the assay is at least 25.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 232, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 732;

465. the CpG represented by CG whose cancer index value is determined is located at least within DMR 233 defined by SEQ ID No. 733, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.089 or greater, and wherein the sensitivity of the assay is at least 45.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least two cpgs from DMR 233, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 733;

466. The CpG represented by CG whose cancer index value is determined is at least within DMR 233 defined by SEQ ID No. 733, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.089, and wherein the sensitivity of the assay is at least 45.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least two cpgs from DMR 233, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 733;

467. the CpG represented by CG whose cancer index value is determined is at least within DMR 234 defined by SEQ ID NO:734, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.199 or more, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 234, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 734;

468. The CpG represented by CG whose cancer index value is determined is located at least within DMR 234 defined by SEQ ID NO:734, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.199, and wherein the sensitivity of the assay is at least 44.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 234, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 734;

469. the CpG represented by CG whose cancer index value is determined is at least within DMR 235 defined by SEQ ID NO:735, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.329 or greater, and wherein the sensitivity of the assay is at least 15.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 235, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 735;

470. The CpG represented by CG whose cancer index value is determined is at least within DMR235 defined by SEQ ID NO:735, and wherein an individual is classified as not having cancer or having a low risk of cancer progression when the individual's cancer index is less than about 0.329 or greater, and wherein the sensitivity of the assay is at least 15.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR235, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 735;

471. the CpG represented by CG whose cancer index value is determined is located at least within DMR 236 defined by SEQ ID NO:736, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.271 or greater, and wherein the sensitivity of the assay is at least 27.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 236, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 736;

472. The CpG represented by CG whose cancer index value is determined is located at least within DMR 236 defined by SEQ ID NO:736, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.271, and wherein the sensitivity of the assay is at least 27.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least four cpgs from DMR 236, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 736;

473. the CpG represented by CG whose cancer index value is determined is at least within DMR 237 defined by SEQ ID NO:737, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.297 or greater, and wherein the sensitivity of the assay is at least 36.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 237, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 737;

474. The CpG represented by CG whose cancer index value is determined is at least within DMR 237 defined by SEQ ID NO:737, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.297, and wherein the sensitivity of the assay is at least 36.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 237, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 737;

475. the CpG represented by CG whose cancer index value is determined is at least within DMR 238 defined by SEQ ID NO:738 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.271 or more and wherein the sensitivity of the assay is at least 77.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 238 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 738;

476. The CpG represented by CG whose cancer index value is determined is located at least within DMR 238 defined by SEQ ID NO:738, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.271, and wherein the sensitivity of the assay is at least 77.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 238, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 738;

477. the CpG represented by CG whose cancer index value is determined is located at least within DMR 239 defined by SEQ ID NO:739, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.271 or greater, and wherein the sensitivity of the assay is at least 77.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 239, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 739;

478. The CpG represented by CG whose cancer index value is determined is located at least within DMR 239 defined by SEQ ID NO:739, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.271, and wherein the sensitivity of the assay is at least 77.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 239, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 739;

479. the CpG represented by CG whose cancer index value is determined is at least within DMR 240 defined by SEQ ID No. 740, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.123 or greater, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 240, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 740;

480. The CpG represented by CG whose cancer index value is determined is at least within DMR 240 defined by SEQ ID No. 740, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.123, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 240, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 740;

481. the CpG represented by CG whose cancer index value is determined is located at least within DMR 241 defined by SEQ ID NO:741, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.123 or greater, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 239, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 741;

482. The CpG represented by CG whose cancer index value is determined is located at least within DMR 241 defined by SEQ ID NO:741, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.123, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 241, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 741;

483. the CpG represented by CG whose cancer index value is determined is located at least within DMR 242 defined by SEQ ID NO:742, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.105 or more, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 242, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 742;

484. The CpG represented by CG whose cancer index value is determined is located at least within DMR 242 defined by SEQ ID NO:742, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.105, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 242, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 742;

485. the CpG represented by CG whose cancer index value is determined is at least within DMR 243 defined by SEQ ID NO:743, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.123 or greater, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 243, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 743;

486. The CpG represented by CG whose cancer index value is determined is at least within DMR 243 defined by SEQ ID NO:743, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.123, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 243, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 743;

487. the CpG represented by CG whose cancer index value is determined is at least within DMR 244 defined by SEQ ID NO:744, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.123 or greater, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 244, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 744;

488. The CpG represented by CG whose cancer index value is determined is located at least within DMR 244 defined by SEQ ID No. 744, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.123, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 244, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 744;

489. the CpG represented by CG whose cancer index value is determined is at least within DMR 245 defined by SEQ ID No. 745, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.105 or more, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 245, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 745;

490. The CpG represented by CG whose cancer index value is determined is at least within DMR 245 defined by SEQ ID No. 745, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.105, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 245, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 745;

491. the CpG represented by CG whose cancer index value is determined is at least within DMR 246 defined by SEQ ID NO:746, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.119 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 246, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 746;

492. The CpG represented by CG whose cancer index value is determined is located at least within DMR 246 defined by SEQ ID NO:746, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.119, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 246, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 746;

493. the CpG represented by CG whose cancer index value is determined is at least within DMR 247 defined by SEQ ID NO:747, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.119 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 247, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 747;

494. The CpG represented by CG whose cancer index value is determined is at least within DMR 247 defined by SEQ ID NO:747, and wherein when the cancer index of an individual is less than about 0.119, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 247, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 747;

495. the CpG represented by CG whose cancer index value is determined is at least within DMR 248 defined by SEQ ID NO:748, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.083 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 248, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 748;

496. The CpG represented by CG whose cancer index value is determined is at least within DMR 248 defined by SEQ ID NO:748, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.083, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 248, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 748;

497. the CpG represented by CG whose cancer index value is determined is located at least within DMR 249 defined by SEQ ID NO:749, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.083 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 249, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 749;

498. The CpG represented by CG whose cancer index value is determined is located at least within DMR 249 defined by SEQ ID NO:749, and wherein when the cancer index of an individual is less than about 0.083, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 249, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 749;

499. the CpG represented by CG whose cancer index value is determined is at least within DMR 250 defined by SEQ ID No. 750, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.265 or greater, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 250, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 750;

500. The CpG represented by CG whose cancer index value is determined is at least within DMR 250 defined by SEQ ID NO:750, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.265, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 250, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 750;

501. the CpG represented by CG whose cancer index value is determined is at least within DMR 251 defined by SEQ ID NO:751, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.265 or more, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 251, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 751;

502. The CpG represented by CG whose cancer index value is determined is at least within DMR 251 defined by SEQ ID NO:751, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.265, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 251, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 751;

503. the CpG represented by CG whose cancer index value is determined is at least within DMR 252 defined by SEQ ID NO:752 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.113 or more and wherein the sensitivity of the assay is at least 71.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 252 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 752;

504. The CpG represented by CG whose cancer index value is determined is located at least within DMR 252 defined by SEQ ID NO:752 and wherein when the cancer index of an individual is less than about 0.113, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 and wherein the sensitivity of the assay is at least 71.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 252 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 752;

505. the CpG represented by CG whose cancer index value is determined is at least within DMR 252 defined by SEQ ID NO:752 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.113 or more and wherein the sensitivity of the assay is at least 71.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 252 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 752;

506. The CpG represented by CG whose cancer index value is determined is located at least within DMR 252 defined by SEQ ID NO:752 and wherein when the cancer index of an individual is less than about 0.113, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 and wherein the sensitivity of the assay is at least 71.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 252 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 752;

507. the CpG represented by CG whose cancer index value is determined is at least within DMR 253 defined by SEQ ID NO:753, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.113 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 253, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 753;

508. The CpG represented by CG whose cancer index value is determined is at least within DMR 253 defined by SEQ ID NO:753, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.113, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 253, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 753;

509. the CpG represented by CG whose cancer index value is determined is at least within DMR 254 defined by SEQ ID NO:754, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.113 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 254, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 754;

510. The CpG represented by CG whose cancer index value is determined is at least within DMR 254 defined by SEQ ID NO:754, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.113, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 254, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 754;

511. the CpG represented by CG whose cancer index value is determined is at least within DMR 255 defined by SEQ ID NO:755, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.113 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 255, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 755;

512. The CpG represented by CG whose cancer index value is determined is at least within DMR 255 defined by SEQ ID NO:755, and wherein when the individual's cancer index is less than about 0.113, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 255, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 755;

513. the CpG represented by CG whose cancer index value is determined is at least within DMR 256 defined by SEQ ID NO:756, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.039 or more, and wherein the sensitivity of the assay is at least 74.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 256, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 756;

514. The CpG represented by CG whose cancer index value is determined is at least within DMR 256 defined by SEQ ID NO:756, and wherein when the cancer index of an individual is less than about 0.039, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 74.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 256, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 756;

515. the CpG represented by CG whose cancer index value is determined is at least within DMR 257 defined by SEQ ID NO:757, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.039 or greater, and wherein the sensitivity of the assay is at least 74.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 257, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 757;

516. The CpG represented by CG whose cancer index value is determined is at least within DMR 257 defined by SEQ ID No. 757, and wherein when the individual's cancer index is less than about 0.039, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 74.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 257, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 757;

517. the CpG represented by CG whose cancer index value is determined is at least within DMR 258 defined by SEQ ID NO 758, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.171 or greater, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 258, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO 758;

518. The CpG represented by CG whose cancer index value is determined is at least within DMR 258 defined by SEQ ID NO:758, and wherein when the cancer index of an individual is less than about 0.171, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 258, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 758;

519. the CpG represented by CG whose cancer index value is determined is at least within DMR 259 defined by SEQ ID NO:759, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.171 or greater, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 259, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 759;

520. The CpG represented by CG whose cancer index value is determined is at least within DMR 259 defined by SEQ ID NO:759, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.171, and wherein the sensitivity of the assay is at least 62.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 259, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 759;

521. the CpG represented by CG whose cancer index value is determined is at least within DMR 260 defined by SEQ ID No. 760, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.091 or greater, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 260, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 760;

522. The CpG represented by CG whose cancer index value is determined is located at least within DMR 260 defined by SEQ ID No. 760, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.091, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 260, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 760;

523. the CpG represented by CG whose cancer index value is determined is at least within DMR 261 defined by SEQ ID No. 761, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.091 or greater, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 261, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 761;

524. The CpG represented by CG whose cancer index value is determined is at least within DMR 261 defined by SEQ ID No. 761, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.091, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 261, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 761;

525. the CpG represented by CG whose cancer index value is determined is at least within DMR 262 defined by SEQ ID No. 762, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.101 or more, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 262, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 762;

526. The CpG represented by CG whose cancer index value is determined is at least within DMR 262 defined by SEQ ID No. 762, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.101, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 262, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 762;

527. the CpG represented by CG whose cancer index value is determined is at least within DMR 263 defined by SEQ ID No. 763, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.101 or greater, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 263, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 763;

528. The CpG represented by CG whose cancer index value is determined is at least within DMR 263 defined by SEQ ID No. 763, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.101, and wherein the sensitivity of the assay is at least 60.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 263, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 763;

529. the CpG represented by CG whose cancer index value is determined is located at least within DMR 264 defined by SEQ ID No. 764, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.140 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 264, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 764;

530. The CpG represented by CG whose cancer index value is determined is located at least within DMR 264 defined by SEQ ID No. 764, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.140, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 264, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 764;

531. the CpG represented by CG whose cancer index value is determined is at least within DMR 265 defined by SEQ ID No. 765, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.082 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 265, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 765;

532. The CpG represented by CG whose cancer index value is determined is at least within DMR 265 defined by SEQ ID No. 765, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.082, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 265, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 765;

533. the CpG represented by CG whose cancer index value is determined is at least within DMR 266 defined by SEQ ID No. 766, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.140 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 266, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 766;

534. The CpG represented by CG whose cancer index value is determined is at least within DMR 266 defined by SEQ ID No. 766, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.140, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 266, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 766;

535. the CpG represented by CG whose cancer index value is determined is at least within DMR 267 defined by SEQ ID No. 767, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.082 or greater, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 267, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 767;

536. The CpG represented by CG whose cancer index value is determined is at least within DMR 267 defined by SEQ ID No. 767, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.082, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 267, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 767;

537. the CpG represented by CG whose cancer index value is determined is at least within DMR 268 defined by SEQ ID No. 768, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.146 or more, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 268, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 768;

538. The CpG represented by CG whose cancer index value is determined is located at least within DMR 268 defined by SEQ ID No. 768, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.146, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 268, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 768;

539. the CpG represented by CG whose cancer index value is determined is at least within DMR 269 defined by SEQ ID No. 769, and wherein an individual is classified as suffering from cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.146 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 269, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID No. 769;

540. The CpG represented by CG whose cancer index value is determined is at least within DMR 269 defined by SEQ ID No. 769, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.146, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 269, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID No. 769;

541. the CpG represented by CG whose cancer index value is determined is at least within DMR 270 defined by SEQ ID No. 770, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.146 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 270, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 770;

542. The CpG represented by CG whose cancer index value is determined is at least within DMR 270 defined by SEQ ID No. 770, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.146, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 270, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 770;

543. the CpG represented by CG whose cancer index value is determined is located at least within DMR 271 defined by SEQ ID NO:771, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.146 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 271, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 771;

544. The CpG represented by CG whose cancer index value is determined is located at least within DMR 271 defined by SEQ ID NO:771, and wherein an individual is classified as not having cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.146, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 271, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 771;

545. the CpG represented by CG whose cancer index value is determined is at least within DMR 272 defined by SEQ ID NO 772, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.146 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 272, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO 772;

546. The CpG represented by CG whose cancer index value is determined is located at least within DMR 272 defined by SEQ ID NO 772, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.146, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 272, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO 772;

547. the CpG represented by CG whose cancer index value is determined is at least within DMR 273 defined by SEQ ID NO:773, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.146 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 273, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 773;

548. The CpG represented by CG whose cancer index value is determined is at least within DMR 273 defined by SEQ ID NO:773, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.146, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 273, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 773;

549. the CpG represented by CG whose cancer index value is determined is at least within DMR 274 defined by SEQ ID NO:774, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.146 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 274, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 774;

550. The CpG represented by CG whose cancer index value is determined is at least within DMR 274 defined by SEQ ID NO:774, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.146, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 274, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 774;

551. the CpG represented by CG whose cancer index value is determined is at least within DMR 275 defined by SEQ ID NO:775, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.146 or greater, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 275, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 775;

552. The CpG represented by CG whose cancer index value is determined is at least within DMR 275 defined by SEQ ID No. 775, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.146, and wherein the sensitivity of the assay is at least 68.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 275, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 775;

553. the CpG represented by CG whose cancer index value is determined is located at least within DMR 276 defined by SEQ ID NO:776, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.311 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 276, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 776;

554. The CpG represented by CG whose cancer index value is determined is located at least within DMR 276 defined by SEQ ID NO:776, and wherein when the cancer index of an individual is less than about 0.311, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 276, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 776;

555. the CpG represented by CG whose cancer index value is determined is at least within DMR 277 defined by SEQ ID NO:777, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.311 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 277, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 777;

556. The CpG represented by CG whose cancer index value is determined is at least within DMR 277 defined by SEQ ID NO:777, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.311, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 277, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 777;

557. the CpG represented by CG whose cancer index value is determined is at least within DMR 278 defined by SEQ ID NO:778, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.171 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 278, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 778;

558. The CpG represented by CG whose cancer index value is determined is at least within DMR 278 defined by SEQ ID NO:778, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.171, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 278, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 778;

559. the CpG represented by CG whose cancer index value is determined is at least within DMR 279 defined by SEQ ID NO:779, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.171 or greater, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 279, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 779;

560. The CpG represented by CG whose cancer index value is determined is at least within DMR 279 defined by SEQ ID NO:779, and wherein when the cancer index of an individual is less than about 0.171, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 66.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 279, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 779;

561. the CpG represented by CG whose cancer index value is determined is at least within DMR 280 defined by SEQ ID NO:780, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.129 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 280, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 780;

562. The CpG represented by CG whose cancer index value is determined is at least within DMR 280 defined by SEQ ID NO:780, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.171, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 280, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 780;

563. the CpG represented by CG whose cancer index value is determined is at least within DMR 281 defined by SEQ ID NO:781, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.129 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 281, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 781;

564. The CpG represented by CG whose cancer index value is determined is at least within DMR 281 defined by SEQ ID NO:781, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.171, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 281, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 781;

565. the CpG represented by CG whose cancer index value is determined is at least within DMR 282 defined by SEQ ID NO:782, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.219 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 282, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 782;

566. The CpG represented by CG whose cancer index value is determined is at least within DMR 282 defined by SEQ ID NO:782, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.219, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 282, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 782;

567. the CpG represented by CG whose cancer index value is determined is at least within DMR 283 defined by SEQ ID NO:783, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.219 or greater, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 283, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 783;

568. The CpG represented by CG whose cancer index value is determined is at least within DMR 283 defined by SEQ ID NO:783, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.219, and wherein the sensitivity of the assay is at least 64.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 283, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] 783 in SEQ ID NO: 3;

569. the CpG represented by CG whose cancer index value is determined is at least within DMR 284 defined by SEQ ID NO:784, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.198 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 284, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] 784 in SEQ ID NO: 784;

570. The CpG represented by CG whose cancer index value is determined is at least within DMR 284 defined by SEQ ID NO:784, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.198, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 284, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG 78 ] ] in SEQ ID NO: 4;

571. the CpG represented by CG whose cancer index value is determined is at least within DMR 285 defined by SEQ ID NO:785, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.198 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 285, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG 78 ] ] in SEQ ID NO: 5;

572. The CpG represented by CG whose cancer index value is determined is at least within DMR 285 defined by SEQ ID NO:785, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.198, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 285, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 785;

573. the CpG represented by CG whose cancer index value is determined is at least within DMR 286 defined by SEQ ID NO:786, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.063 or greater, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 286, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 786;

574. The CpG represented by CG whose cancer index value is determined is at least within DMR 286 defined by SEQ ID NO:786, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.063, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 286, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 786;

575. the CpG represented by CG whose cancer index value is determined is at least within DMR 287 defined by SEQ ID NO:787, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.063 or greater, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 287, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 787;

576. The CpG represented by CG whose cancer index value is determined is at least within DMR 287 defined by SEQ ID NO:787, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.063, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 287, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] 787 in SEQ ID NO: 787;

577. the CpG represented by CG whose cancer index value is determined is at least within DMR 288 defined by SEQ ID NO:788, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.080 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 288, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 788;

578. The CpG represented by CG whose cancer index value is determined is at least within DMR 288 defined by SEQ ID NO:788, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.080, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 288, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 788;

579. the CpG represented by CG whose cancer index value is determined is at least within DMR 289 defined by SEQ ID NO:789, and wherein an individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.080 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 289, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 789;

580. The CpG represented by CG whose cancer index value is determined is at least within DMR 289 defined by SEQ ID NO:789, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.080, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 289, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 789;

581. the CpG represented by CG whose cancer index value is determined is at least within DMR 290 defined by SEQ ID No. 790 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.185 or greater and wherein the sensitivity of the assay is at least 53.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 290 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 790;

582. The CpG represented by CG whose cancer index value is determined is at least within DMR 290 defined by SEQ ID No. 790, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.185, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 290, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 790;

583. the CpG represented by CG whose cancer index value is determined is at least within DMR 291 defined by SEQ ID NO:791, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.185 or greater, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 291, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 791;

584. The CpG represented by CG whose cancer index value is determined is at least within DMR 291 defined by SEQ ID NO:791, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.185, and wherein the sensitivity of the assay is at least 53.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 291, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 791;

585. the CpG represented by CG whose cancer index value is determined is at least within DMR 292 defined by SEQ ID NO:792, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.044 or greater, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 292, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 792;

586. The CpG represented by CG whose cancer index value is determined is at least within DMR 292 defined by SEQ ID NO:792, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.044, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 292, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 792;

587. the CpG represented by CG whose cancer index value is determined is located at least within DMR 293 defined by SEQ ID NO:793, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.044 or more, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 293, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 793;

588. The CpG represented by CG whose cancer index value is determined is located at least within DMR 293 defined by SEQ ID NO:793, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.044, and wherein the sensitivity of the assay is at least 63.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 293, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 793;

589. the CpG represented by CG whose cancer index value is determined is at least within DMR 294 defined by SEQ ID NO:794, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.086 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 294, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 794;

590. The CpG represented by CG whose cancer index value is determined is at least within DMR 294 defined by SEQ ID NO:794, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.086, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 294, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 794;

591. the CpG represented by CG whose cancer index value is determined is at least within DMR 295 defined by SEQ ID NO:795, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.086 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 295, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 795;

592. The CpG represented by CG whose cancer index value is determined is at least within DMR 295 defined by SEQ ID NO:795, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.086, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 295, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 795;

593. the CpG represented by CG whose cancer index value is determined is at least within DMR 296 defined by SEQ ID NO:796, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.051 or more, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 296, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 796;

594. The CpG represented by CG whose cancer index value is determined is at least within DMR 296 defined by SEQ ID NO:796, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.051, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 296, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 796;

595. the CpG represented by CG whose cancer index value is determined is at least within DMR 297 defined by SEQ ID NO:797, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.051 or more, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 297, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 797;

596. The CpG represented by CG whose cancer index value is determined is at least within DMR 297 defined by SEQ ID NO:797, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.051, and wherein the sensitivity of the assay is at least 67.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 297, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 797;

597. the CpG represented by CG whose cancer index value is determined is at least within DMR 298 defined by SEQ ID NO:798, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.174 or greater, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 298, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 798;

598. The CpG represented by CG whose cancer index value is determined is located at least within DMR 298 defined by SEQ ID NO:798, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.174, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 298, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 798;

599. the CpG represented by CG whose cancer index value is determined is at least within DMR 299 defined by SEQ ID NO:799, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.174 or more, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 299, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] in SEQ ID NO: 799;

600. The CpG represented by CG whose cancer index value is determined is at least within DMR 299 defined by SEQ ID NO:799, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.174, and wherein the sensitivity of the assay is at least 58.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 299, and more preferably wherein the cancer index value is the average β value of cpgs represented by [ [ CG ] ] in SEQ ID NO: 799;

601. the CpG represented by CG whose cancer index value is determined is at least within DMR 300 defined by SEQ ID No. 800, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.136 or greater, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 300, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 800;

602. The CpG represented by CG whose cancer index value is determined is at least within DMR 300 defined by SEQ ID No. 800, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.136, and wherein the sensitivity of the assay is at least 48.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 300, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 800;

603. the CpG represented by CG whose cancer index value is determined is at least within DMR 301 defined by SEQ ID No. 801 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.136 or greater and wherein the sensitivity of the assay is at least 48.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 301 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 801;

604. The CpG represented by CG whose cancer index value is determined is at least within DMR 301 defined by SEQ ID No. 801 and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.136 and wherein the sensitivity of the assay is at least 48.00% and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 301 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID No. 801;

605. the CpG represented by CG whose cancer index value is determined is at least within DMR 302 defined by SEQ ID No. 802, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.293 or greater, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 302, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 802;

606. The CpG represented by CG whose cancer index value is determined is located at least within DMR 302 defined by SEQ ID No. 802, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.293, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 302, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 802;

607. the CpG represented by CG whose cancer index value is determined is at least within DMR 303 defined by SEQ ID No. 803 and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.293 or more and wherein the sensitivity of the assay is at least 55.00% and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 303 and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 803;

608. The CpG represented by CG whose cancer index value is determined is located at least within DMR 303 defined by SEQ ID No. 803, and wherein an individual is classified as not suffering from cancer and/or CIN3 or having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.293, and wherein the sensitivity of the assay is at least 55.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 303, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 803;

609. the CpG represented by CG whose cancer index value is determined is at least within DMR 304 defined by SEQ ID No. 804, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.300 or more, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 304, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 804;

610. The CpG represented by CG whose cancer index value is determined is located at least within DMR 304 defined by SEQ ID No. 804, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.300, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 304, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 804;

611. the CpG represented by CG whose cancer index value is determined is at least within DMR 305 defined by SEQ ID No. 805, and wherein an individual is classified as suffering from cancer and/or CIN3 or has a high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.300 or greater, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 305, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 805;

612. The CpG represented by CG whose cancer index value is determined is located at least within DMR 305 defined by SEQ ID No. 805, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.300, and wherein the sensitivity of the assay is at least 56.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 305, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 805;

613. the CpG represented by CG whose cancer index value is determined is at least within DMR 306 defined by SEQ ID No. 806, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.209 or greater, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 306, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 806;

614. The CpG represented by CG whose cancer index value is determined is at least within DMR 306 defined by SEQ ID No. 806, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.209, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 306, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 806;

615. the CpG represented by CG whose cancer index value is determined is at least within DMR 307 defined by SEQ ID NO:807, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.104 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the group of one or more cpgs comprises at least three cpgs from DMR 307, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] in SEQ ID NO: 807;

616. The CpG represented by CG whose cancer index value is determined is at least within DMR 307 defined by SEQ ID NO:807, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.104, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 307, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 807;

617. the CpG represented by CG whose cancer index value is determined is at least within DMR 308 defined by SEQ ID No. 808, and wherein an individual is classified as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3 when the individual's cancer index is about 0.104 or greater, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 308, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 808;

618. The CpG represented by CG whose cancer index value is determined is located at least within DMR 308 defined by SEQ ID No. 808, and wherein an individual is classified as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the individual's cancer index is less than about 0.104, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 308, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 808.

The ROC data listed in Table 6 corresponding to each of SEQ ID NOs 501 to 808 were obtained by determining the cancer index value from a group of CpG's in each case, wherein the group contains CpG's represented by [ [ CG ] ].

In any of the assays of the invention described herein, an individual may be stratified according to their cancer index value and thus defined according to their cancer and/or CIN3 status and/or cancer and/or CIN3 risk. In any of the assays described herein, wherein when the cancer index value of the individual is:

a. Less than about-0.660, the individual is assessed as not having cancer and/or CIN3;

b. about-0.660 or greater and less than about-0.430, the individual is assessed as having a low risk of developing cancer and/or CIN3;

c. about-0.430 or greater and less than about-0.230, the individual is assessed as having a moderate risk of cancer and/or CIN3;

d. about-0.230 or greater, the individual is assessed as having a high risk of developing cancer and/or CIN3;

TABLE 6

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Predicting the presence, absence or progression of cancer in an individual may particularly involve determining a methylation reference percentage of a group of one or more cpgs. The threshold for the methylation reference percentage may be applied to stratify the individual as having or not having cancer and/or CIN3, or having a high or low risk of developing cancer and/or CIN3, preferably wherein the cancer is endometrial or ovarian cancer, more preferably wherein the cancer is endometrial cancer.

In any of the assays described herein, the step of determining the methylation status of one or more cpgs in the group may comprise determining each CpG within:

SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884, and wherein when the cancer index value is less than about 0.212, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 55.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884;

SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885, and wherein when the cancer index value is about 0.002 or greater, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885;

SEQ ID NO 812 and/or SEQ ID NO 849 and/or SEQ ID NO 886 815, and wherein when the cancer index value is less than about 0.026, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 90.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 812 and/or SEQ ID NO 849 and/or SEQ ID NO 886 815;

SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887, and wherein when the cancer index value is about 0.003 or greater, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.97, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887;

SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887, and wherein when the cancer index value is less than about 0.003, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.97, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887;

SEQ ID NO 814 and/or SEQ ID NO 851 and/or SEQ ID NO 888, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.000 or more, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.96, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 814 and/or SEQ ID NO 851 and/or SEQ ID NO 888;

SEQ ID NO 814 and/or SEQ ID NO 851 and/or SEQ ID NO 888, and wherein when the cancer index value is less than about 0.000, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.96, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 814 and/or SEQ ID NO 851 and/or SEQ ID NO 888;

SEQ ID NO 815 and/or SEQ ID NO 852 and/or SEQ ID NO 889, and wherein when the cancer index value is about 0.001 or more, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.96, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 815 and/or SEQ ID NO 852 and/or SEQ ID NO 889;

SEQ ID NO 815 and/or SEQ ID NO 852 and/or SEQ ID NO 889, and wherein when the cancer index value is less than about 0.001, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.96, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 815 and/or SEQ ID NO 852 and/or SEQ ID NO 889;

SEQ ID NO 816 and/or SEQ ID NO 853 and/or SEQ ID NO 890, and wherein the individual is classified as having endometrial cancer or is at high risk of endometrial cancer progression when the cancer index value is about 0.025 or greater, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.96, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 816 and/or SEQ ID NO 853 and/or SEQ ID NO 890;

SEQ ID NO 816 and/or SEQ ID NO 853 and/or SEQ ID NO 890, and wherein when the cancer index value is less than about 0.025, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.96, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 816 and/or SEQ ID NO 853 and/or SEQ ID NO 890;

SEQ ID NO 817 and/or SEQ ID NO 854 and/or SEQ ID NO 891, and wherein when the cancer index value is about 0.052 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 70.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.95, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 817 and/or SEQ ID NO 854 and/or SEQ ID NO 891;

SEQ ID NO 817 and/or SEQ ID NO 854 and/or SEQ ID NO 891, and wherein when the cancer index value is less than about 0.052, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 70.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.95, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 817 and/or SEQ ID NO 854 and/or SEQ ID NO 891;

SEQ ID NO 818 and/or SEQ ID NO 855 and/or SEQ ID NO 892, and wherein when the cancer index value is about 0.001 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.94, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 818 and/or SEQ ID NO 855 and/or SEQ ID NO 892;

SEQ ID NO 818 and/or SEQ ID NO 855 and/or SEQ ID NO 892, and wherein when the cancer index value is less than about 0.001, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.94, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 818 and/or SEQ ID NO 855 and/or SEQ ID NO 892;

SEQ ID NO 819 and/or SEQ ID NO 856 and/or SEQ ID NO 893, and wherein when the cancer index value is about 0.470 or more, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.93, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 819 and/or SEQ ID NO 856 and/or SEQ ID NO 893;

SEQ ID NO 819 and/or SEQ ID NO 856 and/or SEQ ID NO 893, and wherein when the cancer index value is less than about 0.470, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.93, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 819 and/or SEQ ID NO 856 and/or SEQ ID NO 893;

SEQ ID NO 820 and/or SEQ ID NO 857 and/or SEQ ID NO 894, and wherein when the cancer index value is about 0.010 or more, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 70.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.92, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 820 and/or SEQ ID NO 857 and/or SEQ ID NO 894;

SEQ ID NO 820 and/or SEQ ID NO 857 and/or SEQ ID NO 894, and wherein when the cancer index value is less than about 0.010, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 70.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.92, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 820 and/or SEQ ID NO 857 and/or SEQ ID NO 894;

SEQ ID NO 821 and/or SEQ ID NO 858 and/or SEQ ID NO 895, and wherein when the cancer index value is about 0.321 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.92, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 821 and/or SEQ ID NO 858 and/or SEQ ID NO 895;

SEQ ID NO 821 and/or SEQ ID NO 858 and/or SEQ ID NO 895, and wherein when the cancer index value is less than about 0.321, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.92, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 821 and/or SEQ ID NO 858 and/or SEQ ID NO 895;

SEQ ID NO 822 and/or SEQ ID NO 859 and/or SEQ ID NO 896, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.067 or greater, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.92, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 822 and/or SEQ ID NO 859 and/or SEQ ID NO 896;

SEQ ID NO 822 and/or SEQ ID NO 859 and/or SEQ ID NO 896, and wherein when the cancer index value is less than about 0.067, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.92, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 822 and/or SEQ ID NO 859 and/or SEQ ID NO 896;

SEQ ID NO 823 and/or SEQ ID NO 860 and/or SEQ ID NO 897, and wherein when the cancer index value is about 0.062 or more, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.91, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 823 and/or SEQ ID NO 860 and/or SEQ ID NO 897;

SEQ ID NO 823 and/or SEQ ID NO 860 and/or SEQ ID NO 897, and wherein when the cancer index value is less than about 0.062, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.91, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 823 and/or SEQ ID NO 860 and/or SEQ ID NO 897;

SEQ ID NO 824 and/or SEQ ID NO 861 and/or SEQ ID NO 898, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.106 or more, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.90, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 824 and/or SEQ ID NO 861 and/or SEQ ID NO 898;

SEQ ID NO 824 and/or SEQ ID NO 861 and/or SEQ ID NO 898, and wherein when the cancer index value is less than about 0.106, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.90, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 824 and/or SEQ ID NO 861 and/or SEQ ID NO 898;

SEQ ID NO 825 and/or SEQ ID NO 862 and/or SEQ ID NO 899, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.354 or more, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.89, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 825 and/or SEQ ID NO 862 and/or SEQ ID NO 899;

SEQ ID NO 825 and/or SEQ ID NO 862 and/or SEQ ID NO 899, and wherein when the cancer index value is less than about 0.354, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.89, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 825 and/or SEQ ID NO 862 and/or SEQ ID NO 899;

SEQ ID NO 826 and/or SEQ ID NO 863 and/or SEQ ID NO 900, and wherein when the cancer index value is about 0.075 or greater, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 70.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.89, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 826 and/or SEQ ID NO 863 and/or SEQ ID NO 900;

SEQ ID NO 826 and/or SEQ ID NO 863 and/or SEQ ID NO 900, and wherein when the cancer index value is less than about 0.075, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 70.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.89, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 826 and/or SEQ ID NO 863 and/or SEQ ID NO 900;

SEQ ID NO 827 and/or SEQ ID NO 864 and/or SEQ ID NO 901, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.305 or more, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.89, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 827 and/or SEQ ID NO 864 and/or SEQ ID NO 901;

SEQ ID NO 827 and/or SEQ ID NO 864 and/or SEQ ID NO 901, and wherein when the cancer index value is less than about 0.305, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.89, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 827 and/or SEQ ID NO 864 and/or SEQ ID NO 901;

SEQ ID NO 828 and/or SEQ ID NO 865 and/or SEQ ID NO 902, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.110 or greater, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.88, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 828 and/or SEQ ID NO 865 and/or SEQ ID NO 902;

SEQ ID NO 828 and/or SEQ ID NO 865 and/or SEQ ID NO 902, and wherein when the cancer index value is less than about 0.110, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.88, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 828 and/or SEQ ID NO 865 and/or SEQ ID NO 902;

SEQ ID NO 829 and/or SEQ ID NO 866 and/or SEQ ID NO 903, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.139 or more, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.88, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 829 and/or SEQ ID NO 866 and/or SEQ ID NO 903;

SEQ ID NO 829 and/or SEQ ID NO 866 and/or SEQ ID NO 903, and wherein when the cancer index value is less than about 0.139, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.88, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 829 and/or SEQ ID NO 866 and/or SEQ ID NO 903;

SEQ ID NO 830 and/or SEQ ID NO 867 and/or SEQ ID NO 904, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.453 or more, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.87, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 830 and/or SEQ ID NO 867 and/or SEQ ID NO 904;

SEQ ID NO 830 and/or SEQ ID NO 867 and/or SEQ ID NO 904, and wherein when the cancer index value is less than about 0.453, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.87, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 830 and/or SEQ ID NO 867 and/or SEQ ID NO 904;

SEQ ID NO 831 and/or SEQ ID NO 868 and/or SEQ ID NO 905, and wherein when the cancer index value is about 0.511 or greater, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 831 and/or SEQ ID NO 868 and/or SEQ ID NO 905;

SEQ ID NO 831 and/or SEQ ID NO 868 and/or SEQ ID NO 905, and wherein when the cancer index value is less than about 0.511, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 831 and/or SEQ ID NO 868 and/or SEQ ID NO 905;

SEQ ID NO 832 and/or SEQ ID NO 869 and/or SEQ ID NO 906, and wherein when the cancer index value is about 0.425 or greater, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 832 and/or SEQ ID NO 869 and/or SEQ ID NO 906;

SEQ ID NO 832 and/or SEQ ID NO 869 and/or SEQ ID NO 906, and wherein when the cancer index value is less than about 0.425, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 832 and/or SEQ ID NO 869 and/or SEQ ID NO 906;

SEQ ID NO 833 and/or SEQ ID NO 870 and/or SEQ ID NO 907, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.636 or more, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 833 and/or SEQ ID NO 870 and/or SEQ ID NO 907;

SEQ ID NO 833 and/or SEQ ID NO 870 and/or SEQ ID NO 907, and wherein when the cancer index value is less than about 0.636, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 833 and/or SEQ ID NO 870 and/or SEQ ID NO 907;

SEQ ID NO 834 and/or SEQ ID NO 871 and/or SEQ ID NO 908, and wherein when the cancer index value is about 0.349 or more, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 833 and/or SEQ ID NO 870 and/or SEQ ID NO 907;

SEQ ID NO 833 and/or SEQ ID NO 870 and/or SEQ ID NO 907, and wherein when the cancer index value is less than about 0.349, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 833 and/or SEQ ID NO 870 and/or SEQ ID NO 907;

SEQ ID NO 834 and/or SEQ ID NO 871 and/or SEQ ID NO 908, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.109 or more, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 834 and/or SEQ ID NO 871 and/or SEQ ID NO 908;

SEQ ID NO 835 and/or SEQ ID NO 872 and/or SEQ ID NO 909 and wherein when the cancer index value is less than about 0.109, the individual is classified as not suffering from endometrial cancer or having a low risk of endometrial cancer development and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 75.00% and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 835 and/or SEQ ID NO 872 and/or SEQ ID NO 909;

SEQ ID NO 836 and/or SEQ ID NO 873 and/or SEQ ID NO 910, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer development when the cancer index value is about 0.106 or more, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 836 and/or SEQ ID NO 873 and/or SEQ ID NO 910;

SEQ ID NO 836 and/or SEQ ID NO 873 and/or SEQ ID NO 910, and wherein when the cancer index value is less than about 0.106, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 75.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.86, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 836 and/or SEQ ID NO 873 and/or SEQ ID NO 910;

SEQ ID NO 837 and/or SEQ ID NO 874 and/or SEQ ID NO 911, and wherein when the cancer index value is about 0.220 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.85, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 837 and/or SEQ ID NO 874 and/or SEQ ID NO 911;

SEQ ID NO 837 and/or SEQ ID NO 874 and/or SEQ ID NO 911, and wherein when the cancer index value is less than about 0.220, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.85, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 837 and/or SEQ ID NO 874 and/or SEQ ID NO 911;

SEQ ID NO 838 and/or SEQ ID NO 875 and/or SEQ ID NO 912, and wherein when the cancer index value is about 0.123 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 70.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.85, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 838 and/or SEQ ID NO 875 and/or SEQ ID NO 912;

SEQ ID NO 838 and/or SEQ ID NO 875 and/or SEQ ID NO 912, and wherein when the cancer index value is less than about 0.123, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 70.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.85, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 838 and/or SEQ ID NO 875 and/or SEQ ID NO 912;

SEQ ID NO 839 and/or SEQ ID NO 876 and/or SEQ ID NO 913, and wherein when the cancer index value is about 0.146 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.85, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 839 and/or SEQ ID NO 876 and/or SEQ ID NO 913;

SEQ ID NO 839 and/or SEQ ID NO 876 and/or SEQ ID NO 913, and wherein when the cancer index value is less than about 0.146, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 80.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.85, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 839 and/or SEQ ID NO 876 and/or SEQ ID NO 913;

SEQ ID NO 840 and/or SEQ ID NO 877 and/or SEQ ID NO 914, and wherein when the cancer index value is about 0.488 or greater, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 65.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.83, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 840 and/or SEQ ID NO 877 and/or SEQ ID NO 914;

SEQ ID NO 840 and/or SEQ ID NO 877 and/or SEQ ID NO 914, and wherein when the cancer index value is less than about 0.488, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 65.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.83, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 840 and/or SEQ ID NO 877 and/or SEQ ID NO 914;

SEQ ID NO 841 and/or SEQ ID NO 878 and/or SEQ ID NO 915, and wherein when the cancer index value is about 2.096 or greater, the individual is classified as having endometrial cancer or has a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 60.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.82, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 841 and/or SEQ ID NO 878 and/or SEQ ID NO 915;

SEQ ID NO 841 and/or SEQ ID NO 878 and/or SEQ ID NO 915, and wherein when the cancer index value is less than about 2.096, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 60.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.82, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 841 and/or SEQ ID NO 878 and/or SEQ ID NO 915;

SEQ ID NO 842 and/or SEQ ID NO 879 and/or SEQ ID NO 916, and wherein when the cancer index value is about 0.803 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 70.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.82, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 842 and/or SEQ ID NO 879 and/or SEQ ID NO 916;

SEQ ID NO 842 and/or SEQ ID NO 879 and/or SEQ ID NO 916, and wherein when the cancer index value is less than about 0.803, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 70.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.82, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 842 and/or SEQ ID NO 879 and/or SEQ ID NO 916;

SEQ ID NO 843 and/or SEQ ID NO 880 and/or SEQ ID NO 917, and wherein when the cancer index value is about 1.138 or more, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 65.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.80, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 843 and/or SEQ ID NO 880 and/or SEQ ID NO 917;

SEQ ID NO 843 and/or SEQ ID NO 880 and/or SEQ ID NO 917, and wherein when the cancer index value is less than about 1.138, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 65.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.80, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 843 and/or SEQ ID NO 880 and/or SEQ ID NO 917;

SEQ ID NO 844 and/or SEQ ID NO 881 and/or SEQ ID NO 918, and wherein when the cancer index value is about 0.500 or greater, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 65.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.80, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 844 and/or SEQ ID NO 881 and/or SEQ ID NO 918;

SEQ ID NO 844 and/or SEQ ID NO 881 and/or SEQ ID NO 918, and wherein when the cancer index value is less than about 0.500, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 65.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.80, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 844 and/or SEQ ID NO 881 and/or SEQ ID NO 918;

SEQ ID NO 845 and/or SEQ ID NO 882 and/or SEQ ID NO 919, and wherein when the cancer index value is about 0.162 or greater, the individual is classified as having endometrial cancer or is at high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 65.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.78, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 845 and/or SEQ ID NO 882 and/or SEQ ID NO 919; and/or

SEQ ID NO 845 and/or SEQ ID NO 882 and/or SEQ ID NO 919, and wherein when the cancer index value is less than about 0.162, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 65.00%, the specificity of the assay is about 75.00%, and the AUC is about 0.78, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 845 and/or SEQ ID NO 882 and/or SEQ ID NO 919.

In any of the described assays, the methylation status of one or more cpgs in the group is preferably determined by methylation reference percentage analysis and the assay is used to assess the presence, absence or progression of cancer and/or CIN3, preferably the cancer is endometrial or ovarian cancer. Most preferably, the cancer is endometrial cancer.

The ROC data set forth in Table 11, corresponding to each of SEQ ID NOS 809 to 919, was obtained by determining the cancer index value from a group of CpG's, wherein the group in each case contains all of the CPGs in the sequence(s) defined by the SEQ ID NOS.

The ROC data in table 13 corresponds to an assay of the invention wherein the sample taken from the individual is a self-collected cervical-vaginal sample and wherein the set of cpgs comprises cpgs represented by CG in the amplicon defined by any of SEQ ID NOs 920, 922 and 924. In such an assay of the invention, the step of determining the methylation status of one or more cpgs in the group comprises determining each CpG within:

SEQ ID NO 920, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer progression when the cancer index value is about 0.280 or greater, and wherein the sensitivity of the assay is about 100%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 920;

SEQ ID NO 920, and wherein when the cancer index value is less than about 0.280, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is about 100%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 920;

SEQ ID NO 922, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer progression when the cancer index value is about 0.000 or greater, and wherein the sensitivity of the assay is about 100%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 922;

d.seq ID NO 922, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer progression when the cancer index value is about 0.000 or greater, and wherein the sensitivity of the assay is about 100%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 922;

e.seq ID NO 924, and wherein when the cancer index value is about 0.000 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is about 100%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 924; or alternatively

SEQ ID NO 924, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer progression when the cancer index value is about 0.000 or greater, and wherein the sensitivity of the assay is about 100%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 924.

The ROC data in table 14 corresponds to the assay of the invention wherein the sample taken from the individual is a vaginal swab taken from a female with post-menopausal bleeding, and wherein the set of cpgs comprises cpgs represented by CG in amplicons defined by SEQ ID NO SEQ ID NO 920, 922 and 924. In such an assay of the invention, the step of determining the methylation status of one or more cpgs in the group comprises determining each CpG within:

SEQ ID NO 920, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer progression when the cancer index value is about 0.280 or greater, and wherein the sensitivity of the assay is at least 88.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 920;

SEQ ID NO 920, and wherein when the cancer index value is less than about 0.280, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 88.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 920;

SEQ ID NO 922, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer progression when the cancer index value is about 0.000 or greater, and wherein the sensitivity of the assay is about 100%, the specificity of the assay is at least 87.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 922;

d.seq ID NO 922, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer progression when the cancer index value is about 0.000 or greater, and wherein the sensitivity of the assay is about 100%, the specificity of the assay is about 87.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 922;

e.seq ID NO 924, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer progression when the cancer index value is about 0.000 or greater, and wherein the sensitivity of the assay is about 100%, the specificity of the assay is at least 84.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 924; or alternatively

SEQ ID NO 924, and wherein the individual is classified as having endometrial cancer or having a high risk of endometrial cancer progression when the cancer index value is about 0.000 or greater, and wherein the sensitivity of the assay is about 100%, the specificity of the assay is at least 84.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 924.

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TABLE 13

rxn_name	Gene_name	auc	average_EC_case	Average_control	Cut-off value	Specificity (specificity)	Sensitivity of	Amplicon SEQ ID NO
									ML_cg25060829_ii	ZSCAN12	1	3.82	0	0.28	1	1	920
ML_cg15768103_ii	GYPC	1	4.26	0	0	1	1	922
									ML_cg15975865_i	GYPC	1	4.92	0	0	1	1	924

TABLE 14

Relation of cancer index value to determining methylation status of CpG

In view of the observations described herein (see examples), the inventors derive a cancer index based on analysis of methylation status (DNAme, described above) for use in an assay to assess the presence or progression of cancer in an individual.

As explained herein, the described assays are particularly relevant to assessing endometrial and/or ovarian cancer, in particular the presence, absence or progression of endometrial cancer.

As described and defined herein, any of the assays described herein involve deriving a cancer index value based on the methylation status of a group of one or more CPGs assayed in a sample provided by an individual.

The cancer index value may be derived by any suitable means.

The inventors have identified specific cpgs as described and defined herein that can be used to form a set of cpgs whose methylation status is determined to establish a cancer index value according to the assays described and defined herein. Using these groups, the inventors have demonstrated that it is possible to derive a cancer index value that correlates with and is indicative of normal tissue, i.e. cancer-negative tissue, in particular cancer-negative endometrial and/or ovarian tissue. Thus, the individual may be assessed as not having cancer. Using these groups, the inventors have demonstrated that a cancer index value associated with and indicative of cancer tissue, i.e. cancer positive tissue, in particular cancer negative endometrial and/or ovarian tissue, can be deduced. Thus, the presence of cancer in an individual can be assessed. As explained herein, the inventors have shown that a group using cpgs that have been identified as cancer can be assessed as present in an individual. As explained herein, the inventors have shown that using the identified set of cpgs, DNA methylation signatures of epithelial cells from normal tissue (such as from the cervical, vaginal, buccal regions, or from blood and/or urine, particularly from liquid-based cytological samples, more preferably from cervical smear samples) can be shown to be dynamic as indicated by cancer index values and subject to change in continuum from indicative of cancer negative to cancer positive tissue. In particular, the cancer index values described herein are used as substitutes of high statistical accuracy to indicate whether an individual's endometrial and/or ovarian tissue is cancer negative or cancer positive. Thus, using the identified set of cpgs, it is possible to build a table of cancer index values that can be used to assess the presence, absence or progression of cancer in an individual.

As described herein, the inventors have used certain methods to determine the methylation status of a particular CpG in a population of DNA molecules in a sample. For example, in one approach, the methylation reference (PMR) percent value of CpG can be determined. In another method, the methylation beta value of CpG can be determined. Different mechanisms may be employed to determine the particular value depending on the situation, such as a PCR-based mechanism or a chip-based mechanism.

It will be apparent to those skilled in the art that the step of determining the methylation status of a particular CpG in a population of DNA molecules in a sample in an assay of the invention is not limited to any one particular methodology. As will be appreciated by those of skill in the art, since the cancer index value is based on the methylation status of cpgs, and since the methylation status of cpgs may be represented by values that are specific to a particular methodology, such as a methylation reference (PMR) percent value or a methylation beta value, the range of cancer index values that define cancer negative and cancer positive samples may depend on the methodology used to determine the methylation status of cpgs. However, the user may use any suitable methodology to determine the methylation status of CpGs, so that the assay of the invention is easily reproducible and implementable, provided that the same methodology is consistently used. Furthermore, the user can easily re-establish the cancer index values defining the cancer negative and cancer positive samples by determining the methylation status of cpgs in the group of specific cpgs disclosed herein from known cancer negative and cancer positive patient samples. Once such cancer index values are established using the cpgs identified herein, the user can use these values as a basis to assess the presence, absence, or progression of cancer in any test individual whose cancer status is to be determined. Thus, the cancer index values according to the present invention are not limited to a particular method of determining CpG methylation status. In contrast, one of skill in the art will appreciate that cancer index values reflecting the CpG intrinsic ability identified herein can be established to correlate methylation status with cancer disease status.

Thus, the cancer index value may be deduced by assessing the methylation status of one or more cpgs in a group in a sample provided by the individual by any suitable means.

The step of determining the methylation status of each CpG in the group of one or more CpG's may be accomplished by determining a methylation reference (PMR) percent value for each of the one or more CpG's. The step of determining the methylation status of each CpG in the group of one or more CpG's may be accomplished by determining a methylation beta value for each of the one or more CpG's.

In any of the assays described herein, the methylation status of CpG can be determined by any suitable means. For example, in any of the assays described herein, the step of determining the methylation status of each CpG in the set of one or more cpgs may comprise:

a. performing a sequencing step to determine the sequence of each CpG;

The step of determining the methylation status of each CpG in the group of one or more CpG's may comprise a conversion step to distinguish between methylated CpG dinucleotides and unmethylated CpG dinucleotides. The conversion step may comprise, for example, bisulphite conversion or TAPS (TET assisted pyridine borane sequencing) conversion of the DNA in the sample, which will be applied to any one or more of a.through c.above. TAPS may particularly involve oxidation of a 5-methylcytosine base (5 mC) to a 5-carboxycytosine base (5 caC), preferably by 10-11 translocation (TET), and/or oxidation of a 5-hydroxymethylcytosine base (5 hmC) to a 5-carboxycytosine base (5 caC), preferably by 10-11 translocation (TET); the 5-carboxycytosine base (5 caC) is then optionally reduced to a dihydrouracil base (DHU) with pyridine borane.

The step of determining the methylation status of each CpG in the set of one or more cpgs may additionally or alternatively comprise sequencing using a TempO-seq (template oligonucleotide). Oligonucleotides in the context of TempO-seq may or may not be designed to hybridize to methylated CpG dinucleotides after pre-transformation as described herein.

The step of determining the methylation status of each CpG in the set of one or more cpgs may comprise contacting the DNA in the sample with one or more methylation sensitive restriction enzymes that cleave the methylated and/or unmethylated form of their restriction sites, and preferably contacting the DNA prior to performing any of a.through c.described above. In the assays of the invention using methylation sensitive restriction enzymes, one or more control reactions are performed. Preferably, one or more control reactions involve interrogation of a known locus containing (i) an unlimited endonuclease site; (ii) a methylated restriction site; (iii) an unmethylated restriction site.

Using any of the methods for determining the methylation status of each CpG in a group of one or more CpG's, the ratio of methylated and unmethylated CpG's at any given locus can be determined, thereby enabling the generation of a cancer index value.

Preferably, the step of determining the methylation state of the group of one or more cpgs in the population of DNA molecules in the sample further comprises determining a β value for each CpG. Deriving the cancer index value may involve providing a methylation beta value dataset comprising methylation beta values for each CpG in the set of one or more CpG.

Assessment of methylation status of CpG

Methylation of DNA is a well-established form of epigenetic modification that has the ability to alter expression of genes and other elements such as micrornas. Methylation may have the effect of, for example, silencing tumor suppressor genes and/or increasing oncogene expression in cancer progression and progression. Methylation may lead to other forms of deregulation. Methylation of DNA occurs at discrete loci that are predominantly dinucleotides composed of CpG motifs, but may also occur at CHH motifs (where H is A, C or T). During methylation, a methyl group is added to the fifth carbon of the cytosine base to produce a methylcytosine.

Methylation may occur throughout the genome and is not limited to regions associated with expressed sequences (e.g., genes). Methylation typically, but not always, occurs in promoters or other regulatory regions of expressed sequences, such as enhancer elements. Most often, the methylation status of cpgs is aggregated in CpG islands, e.g. CpG islands are present in regulatory regions of genes, in particular their promoter regions.

Typically, the assessment of the methylation status of DNA involves analysis of DNA for the presence or absence of a methyl group, e.g., a methyl group at the 5-position of one or more cytosine nucleotides. Preferably, the methylation status of one or more cytosine nucleotides present as CpG dinucleotides (wherein C represents cytosine, G represents guanine, p represents a phosphate group linking the two) is assessed.

Various techniques can be used to identify and assess CpG methylation status, as will be briefly outlined below. The assays described herein encompass any suitable technique for determining CpG methylation status.

In conventional in vitro processing steps such as PCR, methyl groups are lost from the starting DNA molecule. To avoid this, the technique of detecting methyl groups typically involves pre-treating the DNA prior to subsequent processing in a manner that preserves methylation state information of the original DNA molecule. Such preliminary techniques involve three main processing categories, namely bisulfite modification, restriction enzyme digestion, and affinity-based analysis. The products of these techniques can then be combined with sequencing or chip-based platforms for subsequent identification or qualitative assessment of CpG methylation status.

Techniques involving DNA bisulfite modification have become the most common assay for detecting and assessing the methylation status of CpG dinucleotides. Treatment of DNA with bisulfite (e.g., sodium bisulfite) converts cytosine bases to uracil bases, but has no effect on 5-methylcytosine. Thus, the presence of cytosine in the bisulfite treated DNA indicates the presence of cytosine bases that were previously methylated in the starting DNA molecule. Such cytosine bases can be detected by a variety of techniques. For example, primers specific for unmethylated and methylated DNA can be generated and used for PCR-based identification of methylated CpG dinucleotides. The DNA may be amplified before or after bisulfite conversion. The separation/capture step may be performed, for example, using a binding molecule, such as a complementary oligonucleotide sequence. Standard and next generation DNA sequencing protocols can also be used.

In other methods, methylation sensitive enzymes can be employed that digest or cleave only in the presence of methylated DNA. Analysis of the resulting fragments is typically performed using a microchip.

Affinity-based techniques utilize binding interactions to capture fragments of methylated DNA for enrichment purposes. Binding molecules, such as anti-5-methylcytosine antibodies, are typically employed prior to subsequent processing steps (e.g., PCR and sequencing).

Olkhov-Mitsel and Bapat (2012) provide an overall overview of techniques that can be used to identify and evaluate biomarkers involving methylcytosine.

To assess the methylation status of the CpG-based biomarkers characterized and described herein, any suitable assay may be employed.

The assays described herein may include determining the methylation status of CpG by bisulfite conversion of DNA. Preferred assays involve bisulfite treatment of DNA, including amplification of identified CpG loci for methylation-specific PCR and/or sequencing and/or evaluation of methylation status of target loci using methylation discrimination microchips.

Amplification of CpG loci can be accomplished by a variety of methods. Preferably, the CpG loci are amplified using PCR. Various PCR-based methods may be used. For example, methylation specific primers can hybridize to DNA containing CpG sequences of interest. Such primers can be designed to anneal sequences from methylated or unmethylated CpG loci. After annealing, a PCR reaction is performed, and the presence of the PCR product then indicates the presence of annealed CpG of the identifiable sequence. In such assays, the DNA is bisulfite converted prior to amplification. Such techniques are commonly referred to as Methylation Specific PCR (MSP).

In other techniques, PCR primers can anneal CpG sequences of interest independent of methylation status, and further processing steps can be used to determine the status of CpG. The detection method is designed so that CpG sites are located between primer annealing sites. The assay protocol is used in techniques such as bisulfite genomic sequencing, COBRA, ms-SNuPE, and the like. In such assays, the DNA may be bisulfite converted before or after amplification.

A small scale PCR method can be used. Such methods typically involve mass separation of the sample (e.g., digital PCR). These techniques provide strong accuracy and sensitivity in highly miniaturized systems (picoliter-sized droplets), well suited for the subsequent processing of small amounts of DNA obtained from small amounts of cellular material potentially present in biological samples, particularly urine samples. Various such small scale PCR techniques are widely available. For example, droplet-based PCR instruments are available from a variety of suppliers including RainDance Technologies (Bi Laika; http:// rain-tech. Com /) and Bio-Rad (http:// www.bio-Rad. Com /). Microchip platforms can also be used to perform small scale PCR. Such platforms may include microfluidic network based chips, such as those available from Fluidigm corporation (www.fluidigm.com).

After amplification of the CpG locus, the amplified PCR product can be coupled to a subsequent analysis platform to determine the methylation status of the CpG of interest. For example, PCR products can be sequenced directly to determine the presence or absence of methylcytosine at the target CpG, or analyzed by chip-based techniques.

Any suitable sequencing technique may be used to determine the sequence of the target DNA. In the assays of the invention, high throughput so-called "second generation", "third generation" and "next generation" techniques can be used to sequence bisulfite-treated DNA.

In the second generation technique, a large number of DNA molecules are sequenced in parallel. Typically, thousands of molecules are anchored at a given location at high density, and sequences are determined in a process that is dependent on DNA synthesis. The reaction generally consists of sequential reagent delivery and washing steps, such as a scanning step that allows for incorporation of terminator bases of reversible markers, and determining the order of base incorporation. Chip-based systems of this type are commercially available, for example from Illumina corporation (san Diego, calif.; http:// www.illumina.com /).

Third generation techniques are generally defined as those that do not require stopping the sequencing process between detection steps and thus can be considered real-time systems. For example, the base-specific release of hydrogen ions that occurs during the doping process can be detected in microwell systems (see, e.g., ion Torrent systems of Life Technologies; http:// www.lifetechnologies.com /). Similarly, in pyrosequencing, the base-specific release of pyrophosphate (PPi) is detected and analyzed. In nanopore technology, a DNA molecule passes through or is located near a nanopore, and as the DNA molecule moves relative to the nanopore, the identity of a single base is determined. Systems of this type are commercially available, for example from Oxford Nanopore (https:// www.nanoporetech.com /). In another assay, the DNA polymerase is confined in a "zero-mode waveguide" and the identity of the incorporated base is determined by fluorescent detection of the phosphonucleotide of the gamma-marker (see, e.g., pacific Biosciences; http:// www.pacificbiosciences.com /).

In other assays, the sequencing step may be omitted. For example, amplified PCR products can be directly applied to hybridization chips based on the principle that two complementary nucleic acid strands anneal to form a double-stranded molecule. Hybridization chips can be designed to include probes that hybridize to amplified products of CpG and allow discrimination between methylated and unmethylated loci. For example, probes can be designed that selectively hybridize to CpG loci that contain thymine, indicating uracil formation following bisulfite conversion of unmethylated cytosines in the starting template DNA. In contrast, probes can be designed that selectively hybridize to CpG loci containing cytosine, indicating that uracil is not converted after bisulfite treatment. This corresponds to the methylated CpG locus in the starting template DNA.

After application of a suitable detection system to the chip, computer-based analysis techniques can be used to determine the methylation status of CpG. The detection system may include, for example, the addition of fluorescent molecules after methylation state specific probe extension reactions. Such techniques allow for the determination of CpG status without the special need to sequence CpG amplification products. Such chip-based discrimination probes may be referred to as methylation-specific probes.

Any suitable methylation discriminating microchip can be used to assess the methylation status of the cpgs described herein. Illumina (san Diego, calif.; http:// www.illumina.com /) provides a specific methylation-discriminating microchip system. In particular, infinium MethylationEPIC BeadChip and Infinium HumanMethylation BeadChip chip systems can be used to evaluate the methylation status of CpG to predict cancer progression, as described herein. Such systems utilize chemical modification of DNA after bisulfite treatment of the starting DNA molecule. Briefly, the chip comprises beads coupled with oligonucleotide probes specific for the unmethylated form of DNA sequences corresponding to CpG, and separate beads coupled with oligonucleotide probes specific for the methylated form of DNA sequences corresponding to CpG. Candidate DNA molecules are applied to the chip and selectively hybridized under appropriate conditions to oligonucleotide probes corresponding to the relevant epigenetic form. Thus, DNA molecules derived from CpG that are methylated in the corresponding genomic DNA will be selectively attached to beads containing methylation-specific oligonucleotide probes, but will not be attached to beads containing non-methylation-specific oligonucleotide probes. Only a single base of the hybridization probe extends the ddNTP incorporating the marker, followed by staining with a fluorescent reagent and imaging. The methylation status of CpG is determined by calculating the ratio of fluorescent signals from methylated and unmethylated sites.

Infinium HumanMethylation450 BeadChip chip System can be used to interrogate CpG in the assays described herein. However, alternative or custom chips can be used to interrogate the cancer specific CpG biomarkers defined herein, provided that they contain means for interrogating all cpgs of a given assay, as defined herein.

Techniques involving combinations of the above assays may also be used. For example, DNA containing CpG sequences of interest can be hybridized to a microchip, followed by DNA sequencing to determine the status of CpG, as described above.

In the above assays, sequences corresponding to CpG loci can also be subjected to enrichment procedures, if desired. DNA containing the CpG sequence of interest may be captured by a binding molecule, such as an oligonucleotide probe complementary to the CpG target sequence of interest. The sequence corresponding to the CpG locus may be captured before or after bisulfite conversion or before or after amplification. The probe may be designed to be complementary to bisulfite converted DNA. The captured DNA may then be subjected to further processing steps to determine the status of the CpG, such as DNA sequencing steps.

The capture/separation step may be custom designed. Alternatively, various such techniques are available commercially, for example, from Agilent technologies (http:// www.agilent.com/home) as SureSelect target enrichment systems. In this system, biotinylated "bait" or "probe" sequences (e.g., RNA) complementary to DNA containing the CpG sequence of interest hybridize to the sample nucleic acid. The sequence of interest hybridized to the bait sequence was then captured with streptavidin-coated beads. Unbound fraction is discarded. The decoy sequences are then removed (e.g., by RNA digestion) to provide an enriched pool of CpG target sequences separated from non-CpG sequences. Template DNA can be subjected to bisulfite conversion and target loci amplified by small-scale PCR (such as microdroplet PCR) using primers that are independent of CpG methylation status. After amplification, a capture step may be performed on the sample to enrich the PCR product containing the target CpG, e.g., using beads for capture and purification, as described above. After capture, standard PCR reactions were performed to integrate the DNA sequencing barcodes into CpG-containing amplicons. The PCR product is again purified and then subjected to DNA sequencing and analysis to determine the presence or absence of methylcytosine at the target genomic CpG.

The CpG biomarker loci defined herein by SEQ ID NOs 1 to 500 correspond to those known in the artAn identifier (IlmnID). These CpG locus identifiers are indicated at the commercially available +.>Infinium Methylation EPIC BeadChip kit and->Infinium Human Methylation450 single CpG sites used in the BeadChip kit. The identity of each CpG site represented by each CpG locus identifier is publicly available from Illumina corporation website, referenced to the CpG sites used in the Infinium Methylation EPIC BeadChip kit and Infinium Human Methylation450 loadchip kit.

To supplement the evolving public databases to provide accurate CpG locus identifiers and strand orientations,a method was developed to consistently assign CpG loci based on the actual or contextual sequence of each individual CpG locus. To explicitly indicate the CpG loci in any species, < +.>A consistent and defined CpG locus database was developed to ensure consistency of methylation data reporting. />The method utilizes sequences flanking the CpG loci to generate unique CpG locus cluster IDs. This number is based on sequence information only and is not affected by the genome version. The standardized nomenclature of Illumina is also parallel to the TOP/BOT strand nomenclature (indicating strand orientation) commonly used for Single Nucleotide Polymorphism (SNP) naming.

Infinium MethylationEPIC BeadChip and Infinium Human Methylation BeadChip systemsThe identifiers may also be obtained from a common repository, such as the gene expression integrated database (Gene Expression Omnibus, GEO) (http:// www.ncbi.nlm.nih.gov/GEO /).

By assessing the methylation status of cpgs is meant determining whether a given CpG is methylated or unmethylated. Furthermore, this means determining the degree of methylation of a given CpG site in a population of CpG loci in a sample.

The CpG methylation status can be measured indirectly using a detection system such as fluorescence. Methylation can be used to distinguish microchips. When calculating the methylation degree of a given CpG, the beta value can be usedAnd (5) defining. Calculating the +.about.certain CpG sites based on the intensity of the methylated (M) and unmethylated (U) alleles>Methylation beta value, i.e. fluorescence signal beta = Max (M, 0)/[ Max (M, 0) +max (U, 0) +100]. Within this range, 0<β<A beta value of 1 or close to 1 indicates 100% methylation, while a value of 0 or close to 0 indicates 0% methylation.

Methylation status of any one or more of the CpG's defined in SEQ ID NOS.1 to 500 or identified in SEQ ID NOS.501 to 808 can be assessed by any suitable technique. As explained in more detail in the examples below, one particular exemplary technique used by the inventors is methylation discrimination chips, such as Illumina InfiniumMethylation EPIC BeadChip. These assays utilize probes for methylated and unmethylated CpG at a given locus.

Another exemplary technique used by the inventors to determine the methylation status of any one or more cpgs is a fluorescence-based PCR technique, known as methyl light. These assays utilize forward and reverse PCR primers specific for sequences covering any one or more of the 500 CpG's defined according to SEQ ID NOS.1 to 500 or identified in SEQ ID NOS.501 to 808. Thus, the methylation status of one or more CpG's defined by SEQ ID NOS.1 to 500 or identified in SEQ ID NOS.501 to 808 can be determined by a MethyLight assay. In view of the bisulfite conversion step in a typical methyl light protocol, the detectable probes are typically designed to hybridize only to the methylated form of the CpG(s) to be analyzed.

Bioinformatics tools and statistical metrics for CpG-based assays

Software programs that facilitate computer analysis of bisulfite converted DNA sequences (in silico analysis) and primer design for methylation specific analysis purposes are generally available and have been described previously.

In a risk model for predicting cancer, recipient Operating Characteristic (ROC) curve analysis is often used, wherein the area under the curve (AUC) is assessed. Each point on the ROC curve shows the effect of rules that translate risk/likelihood estimates into predictions of the presence, absence, or progression of cancer in an individual. AUC measurement model ability to distinguish case subjects from control subjects. The ROC curve corresponding to the randomized class of case subjects and control subjects is a line with an AUC of 50%. AUC of ROC curve corresponding to perfect classification was 100%.

In any of the methods described herein, the 95% confidence interval for ROC AUC may be between 0.60 and 1.

In any of the methods described herein, an interval may be defined as a range having an upper limit of any number between 0.60 and 1. The upper limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82,0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, 0.99, or 1.00.

In any of the methods described herein, an interval may be defined as a range having a lower limit of any number between 0.60 and 1. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82,0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, 0.99, or 1.00.

In any of the methods described herein, the interval range may include any suitable combination of any of the above lower limit numbers and any of the above upper limit numbers.

Preferably, the upper limit value is 1. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 1 and a lower limit of 0.60 and 1. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79,0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, 0.99, or 1.00.

The upper limit value may be 0.99. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.99 and a lower limit of between 0.60 and 0.99. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79,0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, or 0.99.

The upper limit value may be 0.98. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.98 and a lower limit of 0.60 and 0.98. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79,0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, or 0.98.

The upper limit value may be 0.97. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.97 and a lower limit of between 0.60 and 0.97. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, or 0.97.

The upper limit value may be 0.96. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.96 and a lower limit of between 0.60 and 0.96. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, 0.92, 0.93, 0.94, 0.95, or 0.96.

The upper limit value may be 0.95. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.95 and a lower limit of between 0.60 and 0.95. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, 0.92, 0.93, 0.94, or 0.95.

The upper limit value may be 0.94. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.94 and a lower limit of 0.60 and 0.94. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, 0.92, 0.93, or 0.94.

The upper limit value may be 0.93. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.93 and a lower limit of between 0.60 and 0.93. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, 0.92, or 0.93.

The upper limit value may be 0.92. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.92 and a lower limit of 0.60 and 0.92. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, 0.91, or 0.92.

The upper limit value may be 0.91. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.91 and a lower limit of 0.60 and 0.91. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.90, or 0.91.

The upper limit value may be 0.90. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.90 and a lower limit of between 0.60 and 0.90. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, or 0.90.

The upper limit value may be 0.89. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.89 and a lower limit of 0.60 and 0.89. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, or 0.89.

The upper limit value may be 0.88. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.88 and a lower limit of 0.60 and 0.88. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, or 0.88.

The upper limit value may be 0.87. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.87 and a lower limit of between 0.60 and 0.87. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, or 0.87.

The upper limit value may be 0.86. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.86 and a lower limit of between 0.60 and 0.86. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, 0.85, or 0.86.

The upper limit value may be 0.85. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.85 and a lower limit of between 0.60 and 0.85. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, 0.84, or 0.85.

The upper limit value may be 0.84. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.84 and a lower limit of between 0.60 and 0.84. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, 0.83, or 0.84.

The upper limit value may be 0.83. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.83 and a lower limit of between 0.60 and 0.83. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, 0.82, or 0.83.

The upper limit value may be 0.82. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.82 and a lower limit of between 0.60 and 0.82. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, 0.81, or 0.82.

The upper limit value may be 0.81. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.81 and a lower limit of 0.60 and 0.81. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.80, or 0.81.

The upper limit value may be 0.80. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.80 and a lower limit of between 0.60 and 0.80. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, or 0.80.

The upper limit value may be 0.79. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.79 and a lower limit of 0.60 and 0.79. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, or 0.79.

The upper limit value may be 0.78. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.78 and a lower limit of 0.60 and 0.78. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, or 0.78.

The upper limit value may be 0.77. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.77 and a lower limit of between 0.60 and 0.77. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, or 0.77.

The upper limit value may be 0.76. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.76 and a lower limit of 0.60 and 0.76. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, or 0.76.

The upper limit value may be 0.75. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.75 and a lower limit of between 0.60 and 0.75. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, 0.74, or 0.75.

The upper limit value may be 0.74. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.74 and a lower limit of between 0.60 and 0.74. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, 0.73, or 0.74.

The upper limit value may be 0.73. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.73 and a lower limit of between 0.60 and 0.73. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, 0.72, or 0.73.

The upper limit value may be 0.72. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.72 and a lower limit of between 0.60 and 0.72. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, 0.71, or 0.72.

The upper limit value may be 0.71. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value between an upper limit of 0.71 and a lower limit of 0.60 and 0.71. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.70, or 0.71.

The upper limit value may be 0.70. Thus, the 95% confidence ROC AUC interval can be defined as a range of any value with an upper limit of 0.70 and a lower limit of between 0.60 and 0.70. The lower limit value may be 0.60, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, or 0.70.

Methods of treatment and diagnosis

The term "treatment" as used herein refers to any intervention or procedure performed on an individual, including surgical or pharmacological intervention, such as administration of a compound or drug. Any such treatment may be carried out for therapeutic (therapeutic) purposes or for prophylactic (prophylactic) or prophylactic (prophlactic) purposes.

The invention also encompasses the implementation of one or more treatment steps following positive classification of cancer, particularly endometrial and/or ovarian cancer, based on any of the methods described herein. The treatment may be considered "therapeutic" treatment.

The invention also encompasses the administration of one or more therapeutic steps after a cancer-negative classification or prediction of an individual at risk of developing cancer, in particular endometrial and/or ovarian cancer, based on any of the methods described herein. The treatment may be considered as "risk prevention", "prophylactic" or "prophylactic" treatment.

The invention also encompasses administering one or more treatment steps in an individual having one or more mutations that predispose the individual to an increased risk of developing cancer after a cancer negative classification or prediction of the individual being at risk of developing cancer based on any of the methods described herein.

Accordingly, the present invention encompasses a method of treating a patient with cancer, the method comprising administering chemotherapy, radiation therapy, immunotherapy, or any cancer therapy described herein to a patient determined to have a cancer index value that indicates that the patient is positive for cancer based on any of the assays described herein, preferably wherein the cancer is endometrial cancer.

Accordingly, the present invention encompasses a method of treating and/or preventing cancer in a subject, the method comprising:

a. assessing the presence, absence, or progression of cancer in an individual by performing any of the assays described herein, thereby assessing the cancer status of the individual;

b. based on the evaluation of the administration of one or more therapeutic or prophylactic treatments to the individual,

preferably, wherein the cancer is endometrial and/or ovarian cancer, most preferably endometrial cancer.

Accordingly, the present invention encompasses a method of treating and/or preventing cancer in an individual, the method comprising:

a. assessing the cancer status of an individual by assessing the presence, absence, or progression of cancer in the individual, comprising:

i. providing a sample from an individual, the sample comprising a population of DNA molecules;

determining the methylation status of the group of:

1. One or more cpgs selected from the CpG set identified in SEQ ID NOs 1 to 500, wherein cpgs are identified at nucleotide positions 61 to 62; and/or

2. One or more cpgs selected from one or more Differential Methylation Regions (DMR) defined by SEQ ID NOs 501 to 808, wherein cpgs are represented by CG;

deriving a cancer index value based on methylation status of one or more cpgs in the group; and

assessing the presence, absence or progression of cancer in the individual based on the cancer index value, wherein the assay is characterized by having an area under the curve (AUC) of 0.90 or greater as determined by the Recipient Operating Characteristic (ROC);

b. based on the evaluation of the administration of one or more therapeutic treatments to the individual,

In any of the methods of treatment contemplated by the present invention, the step of predicting the presence or progression of cancer in the individual, preferably wherein the cancer is endometrial and/or ovarian cancer, may involve deriving a cancer index value.

In any of the methods of treatment contemplated by the present invention, the step of predicting the presence or progression of cancer in the individual may involve the use of any of the chips described herein.

In any of the methods of treatment contemplated by the present invention, the step of stratifying the individual may involve applying any of the thresholds according to any of the assays of the present invention described herein.

The step of administering one or more treatments may comprise different treatment steps depending on stratification of the individual based on the cancer status of the individual or the risk of developing cancer or based on the risk of developing cancer, in particular endometrial and/or ovarian cancer, most preferably endometrial cancer. In particular, the amount of invasive (invasives) therapy administered may vary depending on the stratification of the individual based on the individual's cancer status or risk of developing cancer or based on the risk of developing cancer. The treatment administered to the individual may comprise any treatment deemed appropriate by the person skilled in the art.

For example, when an individual is assessed as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3, and wherein the cancer index value is about-0.660 or greater and less than about-0.430, and preferably wherein the assay comprises determining the methylation β value of each CpG in the group of one or more cpgs, the individual receives one or more treatments according to its cancer index value, the one or more treatments may comprise any one of:

a. Evaluating endometrium and ovary via vaginal ultrasound;

b. a repeat assay according to any one of the assays of the invention, preferably wherein the repeat assay is performed about two years after the previous assay,

preferably, wherein the cancer is endometrial and/or ovarian cancer, most preferably wherein the cancer is endometrial cancer.

When an individual is assessed as having cancer and/or CIN3 or as having a moderate risk of developing CIN3 and/or cancer, and wherein the cancer index value is about-0.430 or greater and less than about-0.230, and preferably wherein the assay comprises determining the methylation β value of each CpG in the group of one or more cpgs, the individual receiving one or more treatments according to its cancer index value, the one or more treatments comprising any one of:

a. evaluating endometrium and ovary via vaginal ultrasound;

b. a boost screen, preferably wherein the boost screen comprises one or more of:

colposcopy;

hpv testing;

cervical cytology test;

testing for CA 125, preferably wherein the test is repeated every six months;

testing of cell-free tumor DNA methylation in plasma/serum, preferably wherein the test is repeated annually;

Testing for methylation of cell-free tumor DNA in vaginal fluid, preferably wherein the test is repeated annually;

xv. pelvic MRI scan, preferably wherein the individual receiving the pelvic MRI scan is postmenopausal, and preferably wherein the scan is repeated annually;

a repeat assay according to any of the assays described herein, preferably wherein the repeat assay is performed about one year after the previous assay;

c. one or more of a progestin, aspirin, metformin, an aromatase inhibitor, and a weight loss regimen are administered, particularly wherein the progestin is delivered locally or systemically.

In any of the methods of treatment described herein, when the colposcopy, HPV, and cytologic tests are negative, the enhanced screening may further comprise hysteroscopy as well as endocervical and endometrial biopsies. More preferably, when both transvaginal ultrasound and intensive screening are negative:

a. the vaginal ultrasound, CA125 test, test for methylation of cell-free tumor DNA in plasma/serum and test for methylation of cell-free tumor DNA in vaginal fluid can be repeated about six months after the previous assay; and

b. Colposcopy, HPV testing, and cervical cytology testing may be repeated approximately one year after the previous assay.

When an individual is assessed as having cancer and/or CIN3 or is at high risk of developing cancer and/or CIN3, and wherein the cancer index value is about-0.230 or higher, and preferably, wherein the assay comprises determining a methylation β value for each CpG in the set of one or more cpgs, and the individual receives one or more treatments according to its cancer index value, the one or more treatments comprising any one of the following:

a. evaluating endometrium and ovary via vaginal ultrasound;

i. colposcopy;

HPV test;

cervical cytology test;

testing for ca 125, preferably wherein the test is repeated every six months;

Repeated assays according to any of the assays described herein, preferably wherein the repeated assays are performed about one year after the previous assay;

c. administration of one or more of a progestin, aspirin, metformin, an aromatase inhibitor, and a weight loss regimen, particularly wherein the progestin is delivered locally or systemically;

d. total hysterectomy and bilateral tubal ovariectomy,

a. transvaginal ultrasound, CA125 testing, testing for methylation of cell-free tumor DNA in plasma/serum, testing for methylation of cell-free tumor DNA in vaginal fluid, colposcopy, HPV testing, and cervical cytology testing can be repeated about six months after the previous assay; and

b. pelvic MRI scans were repeated approximately one year after the previous assay.

In any of the assays described herein, wherein the testing is performed as part of a boost screen, the testing may be repeated for any suitable time interval. The detection of CA125 may be performed every three months, every six months, annually or about every two years, every three years or every four years. The test for methylation of cell-free tumor DNA in plasma/serum can be performed every three months, every six months, every year or about every two years, every three years or every four years. Testing for cell-free tumor DNS methylation in vaginal fluid can be performed every three months, every six months, every year, or about every two years, every three years, or every four years. Pelvic MRI scans may be performed every three months, every six months, each year or about every two years, every three years or every four years.

Wherein the individual is assessed as having a moderate to high risk of having cancer and/or CIN3, or having a moderate to high risk of having cancer and/or CIN3 development, the one or more treatments may include administration of one or more of a progestin, aspirin, metformin, an aromatase inhibitor, and a weight loss regimen, particularly wherein the progestin is delivered locally or systemically.

Other exemplary treatments include one or more surgical procedures, one or more chemotherapeutic agents, one or more cytotoxic chemotherapeutic agents, one or more radiotherapeutic agents, one or more immunotherapeutic agents, one or more biological treatments, one or more anti-hormonal treatments, or any combination thereof following a positive diagnosis of cancer.

In any of the methods of treatment described herein, the treatment described in table 9 can be administered to the individual in particular. Four subgroups defined by the range of cancer index values are designated in table 9 as corresponding to preferred clinical behaviors, including intensive screening, administration of therapeutic agents, and surgery.

The cancer treatment may be administered to an individual having or at risk of developing cancer in an amount sufficient to prevent, treat, cure, alleviate or partially inhibit the cancer or one or more symptoms thereof. Such treatment may reduce the severity of symptoms of cancer and/or reduce the value of the cancer index, or increase the frequency or duration of the asymptomatic phase. A therapeutic amount sufficient to achieve this is defined as a "therapeutically effective amount". The effective amount for a given purpose will depend on the severity of the cancer and/or the cancer index value of the individual as well as the weight and general state of the individual. As used herein, the term "individual" includes any human, preferably wherein the human is a female. As used herein, "treatment" is considered synonymous with "therapeutic agent".

Based on the risk of cancer in the individual, the following therapeutic agents may be administered to the individual alone or in combination with any of the other treatments described herein. The therapeutic agent may be directly attached to the antibody, for example by chemical conjugation. Methods of conjugating reagents or markers to antibodies are known in the art. For example, carbodiimide conjugation (Bauminger & Wilchek (1980) Methods enzymes mol.70, 151-159) can be used to conjugate a variety of drugs including doxorubicin with antibodies or peptides. Water-soluble carbodiimides, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC), are particularly useful for conjugating a functional moiety to a binding moiety. Other methods of conjugating a portion to an antibody may also be used. For example, sodium periodate oxidation may be used followed by reductive alkylation of the appropriate reactants, and glutaraldehyde crosslinking may also be used. However, it is acknowledged that whichever method is chosen to produce the conjugates of the invention, it must be determined that the antibody maintains its targeting ability and the functional moiety maintains its associated function.

The cytotoxic moiety may be directly and/or indirectly cytotoxic. By "direct cytotoxicity" is meant that the moiety itself is cytotoxic. By "indirect cytotoxicity" is meant that the moiety, although not itself cytotoxic, may induce cytotoxicity, e.g., by its effect on another molecule or by further effects thereon. The cytotoxic moiety may be cytotoxic only when intracellular, preferably not extracellular.

Cytotoxic chemotherapeutic agents are well known in the art. Cytotoxic chemotherapeutic agents, such as anticancer agents, include: alkylating agents, including nitrogen mustards, such as dichloromethyl diethylamine (HN 2), cyclophosphamide, ifosfamide, melphalan (melphalan) (L-phenylalanine nitrogen mustard) and chlorambucil; ethyleneimine and methyl melamine, such as hexamethylmelamine (thiotepa); alkyl sulfonates such as busulfan (busulfan); nitrosoureas such as carmustine (BCNU), lomustine (lomustine, CCNU), semustine (semustine, methyl-CCNU) and streptozotocin (streptozotocin); and triazenes such as dacarbazine (DTIC; dimethyl triazaimidazole-carboxamide); antimetabolites (Antimetabolites) comprising: folic acid analogs such as methotrexate (methotrexate); pyrimidine analogs such as fluorouracil (5-fluorouracil; 5-FU), fluorouridine (fluorodeoxyuridine; FUdR) and cytarabine (cytosine cytarabine); and purine analogs and related inhibitors such as mercaptopurine (6-mercaptopurine; 6-MP), thioguanine (6-thioguanine; TG) and pentastatin (2' -deoxyhelomycin). Natural products include: vinca alkaloids, such as Vinblastine (VLB) and vincristine; epipodophyllotoxins, such as etoposide (etoposide) and teniposide (teniposide); antibiotics such as actinomycin (actinomycin D), daunorubicin (daunorubicin), rububicin (rubidomycin), doxorubicin (doxorubicin), bleomycin (bleomycin), plicamycin (plicamycin) (mithramycin), and mitomycin (mitomycin C); enzymes such as L-asparaginase; and biological response modifiers, such as interferon phenotypes (alphenones). Other reagents include: platinum coordination complexes such as cisplatin (cis-DDP) and carboplatin; anthraquinones, such as mitoxantrone (mitoxantrone) and anthracycline (anthracycline); substituted ureas, such as hydroxyurea; methylhydrazine derivatives such as methylbenzyl hydrazine (N-methylhydrazine, MIH); and adrenocortical inhibitors such as mitotane (o, p' -DDD) and aminoglutethimide (aminoglutethimide); paclitaxel and its analogues/derivatives; and hormonal agonists/antagonists such as flutamide and tamoxifen (tamoxifen).

The cytotoxic chemotherapeutic agent may be a cytotoxic peptide or polypeptide moiety that causes cell death. Cytotoxic peptide and polypeptide moieties are well known in the art and include, for example, ricin, abrin (abrin), pseudomonas exotoxin, tissue factor, and the like. Methods of linking them to targeting moieties (e.g., antibodies) are also known in the art. Other ribosome inactivating proteins are described in WO 96/06641 as cytotoxic agents. Pseudomonas exotoxins may also be used as cytotoxic polypeptides. Certain cytokines, such as tnfα and IL-2, may also be used as cytotoxic agents.

Some radioactive atoms may also be cytotoxic if delivered in sufficient doses. The radiotherapeutic agent may comprise a radioactive atom which in use delivers a sufficient amount of radioactivity to the target site, thereby being cytotoxic. Suitable radioactive atoms include phosphorus-32, iodine-125, iodine-131, indium-111, rhenium-186, rhenium-188, or yttrium-90, or any other isotope that emits sufficient energy to destroy adjacent cells, organelles, or nucleic acids. Preferably, the isotope and density of radioactive atoms in the agent of the invention is such that a dose of more than 4000cGy (preferably at least 6000, 8000 or 10000 cGy) is delivered to the target site, and preferably to cells and organelles thereof, in particular the nucleus of the target site.

The radioactive atom may be attached to the antibody, antigen-binding fragment, variant, fusion or derivative thereof in a known manner. For example, EDTA or another chelator may be attached to the binding moiety and used to attach 111In or 90Y. Tyrosine residues can be directly tagged with 125I or 131I.

The cytotoxic chemotherapeutic agent may be a suitable indirect cytotoxic polypeptide. In a particularly preferred embodiment, the indirect cytotoxic polypeptide is a polypeptide having enzymatic activity and capable of converting a non-toxic and/or relatively non-toxic prodrug into a cytotoxic drug. For antibodies, this type of system is commonly referred to as ADEPT (Antibody directed enzyme prodrug therapy (anti-Directed Enzyme Prodrug Therapy)). The system requires that the antibody localize the enzyme moiety to a desired site in the patient and, after allowing the enzyme to localize to that site for a period of time, a prodrug is administered as a substrate for the enzyme, the end product of catalysis being a cytotoxic compound. The purpose of this approach is to maximize the drug concentration at the desired site and minimize the drug concentration in normal tissue. In a preferred embodiment, the cytotoxic moiety is capable of converting a non-cytotoxic prodrug into a cytotoxic drug.

In any of the methods of treatment described herein, one or more treatments received by the individual may be repeated at one or more occasions. The one or more treatments may be repeated periodically. The nature of the repetition of therapeutic administration may depend on the particular treatment being administered. Some treatments may require repeated administration more frequently than others. The skilled artisan knows the frequency of administration required for treatment as known in the art. The one or more treatments may be repeated weekly, biweekly, tricyclically, four weeks, monthly, tricyclically, six months, annually, bi-annually, tri-annually, tetra-annually, or penta-annually.

In any of the methods described herein, when an individual is assessed as having a cancer index value of less than about-0.660, and preferably, wherein the assay comprises determining a methylation beta value for each CpG in a group of one or more cpgs, no treatment is administered to the individual.

Monitoring method

The invention also provides methods of monitoring an individual for the presence or risk of the presence or progression of cancer.

"monitoring" in the context of the present invention may refer to a longitudinal assessment of an individual's cancer status, risk of having cancer, or risk of developing cancer. Such longitudinal assessment may be performed according to any of the assays of the invention described herein. Such longitudinal assessment may involve the practice of any of the assays of the invention described herein to predict the presence or progression of cancer in an individual at more than one point in time within an indeterminate time window. The time window may be any period of time that the individual is still alive. The time window may last throughout the lifetime of the individual. The time window may be continued until the cancer status of the individual, the risk of having cancer or the risk of developing cancer falls below a certain level. The level may be a specific cancer index value.

Thus, the present invention encompasses a method of monitoring the presence, absence or progression of cancer, in particular endometrial and/or ovarian cancer, most preferably endometrial cancer, in an individual, the method comprising:

a. assessing the presence or absence of cancer and/or CIN3 in an individual, or assessing the progression of cancer in an individual, by performing any of the assays of the invention described herein at a first time point, to establish the cancer status of the individual;

b. assessing the presence or absence of cancer in an individual or assessing the progression of cancer in an individual by performing any of the assays of the invention described herein at one or more additional time points to establish a cancer status of the individual, preferably wherein the cancer status of the individual in steps a and b is assessed using the same assay; and

c. any changes in the individual's cancer status between time points are monitored.

The invention also encompasses a method of monitoring the presence, absence or progression of cancer (particularly endometrial and/or ovarian cancer) in an individual, the method comprising:

a. assessing the presence or absence of cancer and/or CIN3 in an individual, or assessing the progression of cancer in an individual, by performing an assay at a first time point to establish a cancer status of the individual, comprising:

a. one or more cpgs selected from the CpG set identified in SEQ ID NOs 1 to 500, wherein cpgs are identified at nucleotide positions 61 to 62; and/or

b. One or more cpgs selected from one or more Differential Methylation Regions (DMR) defined by SEQ ID NOs 501 to 808, wherein cpgs are represented by CG;

4. assessing the presence, absence, or progression of cancer in the individual based on the cancer index value, wherein the assay is characterized as having an area under the curve (AUC) of 0.90 or greater as determined by the Recipient Operating Characteristic (ROC);

b. assessing the presence or absence of cancer in an individual or assessing the progression of cancer in an individual by performing the assays of steps a (1) to a (4) or by performing any of the assays of the invention described herein at one or more additional time points to establish the cancer status of the individual; and

In any of the monitoring methods described herein, the step of assessing the presence, absence, or progression of cancer in the individual based on the cancer index value may involve application of a threshold. The threshold value may provide an indication of the status of the cancer, the risk of developing the cancer, or the risk of developing the cancer in the individual. For example, a cancer index value may indicate the presence or absence of cancer, or a high or low risk of having or developing cancer. In any of the monitoring methods contemplated by the present invention, the step of predicting the presence, absence or progression of cancer in the individual involves deriving a cancer index value.

The invention further encompasses a method of measuring methylation in a patient at a plurality of time points, comprising (a) assessing the presence, absence, or progression of cancer in an individual by performing any of the assays of the invention described herein at a first time point; (b) Assessing the presence, absence or progression of cancer in an individual by performing any of the assays of the invention described herein at one or more additional time points, and (c) detecting a differential methylation state between (a) and (b).

In any of the monitoring methods described herein, the individual may already have cancer, in particular endometrial and/or ovarian cancer, most preferably endometrial cancer. The individual may not have cancer. The individual may not have cancer. The individual may not have cancer, but may have one or more genetic mutations that predispose the individual to an increased risk of developing cancer, e.g., the individual may have Lynch syndrome (Lynch syndrome), and thus have one or more mutations in the MLH1, MSH2, MSH6, PMS2, or EPCAM genes. Other mutations may include any mutation known in the art to predispose an individual to cancer. In any of the monitoring methods described herein, the individual may not have cancer, but may have one or more genetic mutations that predispose the individual to cancer, and the individual may receive any of the monitoring methods described herein to become a determination of his or her risk of developing cancer. For example, in any of the methods described herein, the individual does not have cancer and has one or more mutations that predispose the individual to cancer, particularly endometrial and/or ovarian cancer, and wherein the individual is administered one or more treatments according to any of the treatment methods described herein as a prophylactic method. In any of the methods described herein, the individual does not have cancer and has one or more mutations that predispose the individual to an increased risk of cancer, and wherein one or more treatments are administered to the individual according to any of the methods of treatment described herein as a prophylactic method, and wherein the one or more treatments administered to the individual comprise one or more doses of a progestin (particularly wherein the progestin is delivered locally or systemically), aspirin, metformin, an aromatase inhibitor, and/or a weight loss regimen.

In any of the monitoring methods described herein, depending on the risk of the presence or progression of cancer in an individual, one or more treatments are administered to the individual according to any of the treatment methods contemplated by the present invention and described herein, or wherein the individual has a cancer index value of less than about-0.660 and no treatment is administered to the individual. Depending on the stratification of the individual, different treatments may be administered based on the individual's cancer status, risk of having cancer, or risk of developing cancer. The method may further comprise administering one or more treatments according to any of the methods of treatment described herein.

The cancer index value may vary between any two or more time points. For this reason, longitudinal monitoring of individual cancer index values may be particularly beneficial for assessing, for example, cancer progression, prevention of cancer recurrence, efficacy of cancer treatment, or efficacy of cancer treatment.

In any of the monitoring methods described herein, the one or more additional points in time may be any suitable point in time. Preferably, the one or more additional time points are spaced apart by an appropriate distance for screening frequently enough to predict the presence or progression of cancer in the individual in any particularly early onset case. Preferably, one or more additional time points may be spaced apart by an appropriate distance to assess the efficacy of one or more treatments. Preferably, the one or more additional time points may be spaced apart by an appropriate distance for predicting whether an individual remains cancer-free after a successful course of treatment. The one or more additional points in time may be about monthly, about every two months, about every three months, about every four months, about every five months, about every six months, about every seven months, about every eight months, about every nine months, about every ten months, about every eleven months, about every year, about every two years or more.

In any of the monitoring methods described herein, a change can be made to one or more treatments, wherein a positive or negative response to the one or more treatments is observed. Treatment may be varied according to the methods of treatment described herein. Treatment may particularly be altered if the individual's cancer status or risk stratification changes based on the individual's cancer index value.

In any of the monitoring methods contemplated by the present invention, the step of predicting the presence or progression of cancer in the individual may involve the use of any of the chips described herein.

Biological sample

The assays described herein are preferably performed on samples comprising epithelial cells, in particular tissue from anatomical sites other than endometrium or ovary. The sample may in particular originate from the cervix, vagina, cheek areas, blood and/or urine. The sample is preferably a cytological sample based on cervical fluid, more preferably a cervical smear sample.

Preferably, any of the assays described herein for assessing the presence, absence or progression of cancer in an individual comprise providing a sample taken from the individual. Preferably, the individual is a female.

In any of the assays described herein, the assay may or may not encompass the step of obtaining a sample from an individual. In assays that do not involve the step of obtaining a sample from an individual, a sample previously obtained from the individual is provided.

The sample may be provided directly by the individual for analysis, or may be derived from stored material, such as frozen, preserved, fixed, or cryopreserved material.

In any of the assays described herein, the sample may be self-collected or collected by any suitable medical professional.

In any of the assays described herein, the sample may comprise cells. The sample may comprise genetic material, such as DNA and/or RNA.

Any of the assays described herein may involve providing a biological sample from a patient as a source of patient DNA for methylation analysis.

Any of the assays described herein may involve obtaining patient DNA from a biological sample previously obtained from a patient.

Any of the assays described herein may involve obtaining a biological sample from a patient as a source of patient DNA for methylation analysis. The sample may be self-collected or collected by any suitable medical professional. Methods of obtaining biological samples include biopsies.

In any of the assays described herein, the sample may be obtained from a woman with abnormal vaginal bleeding (e.g., post-menopausal bleeding). Women with post-menopausal bleeding in particular should be assessed by any of the assays described herein.

Methods for sample isolation and subsequent extraction and isolation of DNA from such cell or tissue samples in preparation for assessment of DNA methylation are well known to those skilled in the art. In the context of the assays or methods described herein, the entire sample may be used, or alternatively, the cells or fractionated cell types may be concentrated to apply only a subset of one or more cell types to the assays or methods of the invention. Any suitable concentration or fractionation method may be used.

In any of the assays described and defined herein, if a tumor is present in an individual, the sample from the individual or the sample taken from the individual may be derived from a tissue other than the tissue with the tumor. Thus, in any of the assays described and defined herein, the sample from or taken from the individual may not comprise tumor-derived nucleic acids, including DNA, i.e., tumor-specific nucleic acids, including tumor-specific DNA. Thus, consistent with the data set forth in the examples and disclosure herein, methylation signatures derived from DNA molecules in a sample are used as surrogate markers for tumor-specific nucleic acids (including tumor-specific DNA) that are present in an individual at anatomical sites remote from anatomical sites derived from the sample. The absence of tumor-specific DNA in any given population of sample-specific DNA molecules can be identified by one of ordinary skill in the art by routine means, such as by sequence-based screening, to determine the absence of known genetic mutations that have the characteristics of a particular cancer. However, the practice of any of the assays described and defined herein does not require any evaluation to confirm the absence of tumor-specific DNA in any given population of DNA molecules.

Type of cancer

The methods described herein may be applied to any cancer and/or CIN3. Preferably, the methods described herein are applicable to endometrial and/or ovarian cancer and/or CIN3, in particular endometrial cancer. The methods described herein are most preferably applied to endometrial cancer.

The cancer may be a primary cancer lesion. The cancer may be a secondary cancer lesion. The cancer may be a metastatic lesion.

In the assays described herein, wherein the assays are used to assess the presence, absence or progression of endometrial cancer, the endometrial cancer may preferably be endometrioid cancer, uterine sarcoma, squamous cell carcinoma, small cell carcinoma, transitional cell carcinoma, serous carcinoma, clear cell carcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma or serous adenocarcinoma. Any of the assays described herein may additionally or alternatively be used to assess the presence, absence, or progression of ovarian cancer.

In the assays described herein, wherein the assay is used to assess the presence, absence or progression of ovarian cancer, the ovarian cancer may preferably be serous cancer, mucinous cancer, endometrioid cancer, clear cell cancer, low Malignant Potential (LMP) tumor, borderline epithelial ovarian cancer, teratoma, asexual cell tumor, endoembryo sinus tumor, choriocarcinoma, granulosa-follicular tumor, ovarian support-stromal cell tumor, granulosa cell tumor, ovarian small cell cancer or primary peritoneal cancer.

Chip and kit

The invention also encompasses chips capable of distinguishing between methylated and unmethylated forms of CpG as defined herein; the chip may comprise oligonucleotide probes specific for a methylated form of CpG as defined herein and oligonucleotide probes specific for an unmethylated form of CpG as defined herein.

In any of the chips described herein, the chip may comprise an oligonucleotide probe specific for a methylated form of each CpG in the CpG group and an oligonucleotide probe specific for an unmethylated form of each CpG in the group; wherein the panel consists of at least 50 CpG selected from the CpG identified in SEQ ID NO 1 through 808.

The panel may consist of at least 50 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 808, preferably wherein the cpgs comprise the cpgs identified in SEQ ID NOs 1 to 50.

The panel may consist of at least 100 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 808, preferably wherein the cpgs comprise the cpgs identified in SEQ ID NOs 1 to 100.

The panel may consist of at least 150 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 808, preferably wherein the cpgs comprise the cpgs identified in SEQ ID NOs 1 to 150.

The panel may consist of at least 200 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 808, preferably wherein the cpgs comprise the cpgs identified in SEQ ID NOs 1 to 200.

The panel may consist of at least 250 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 808, preferably wherein the cpgs comprise the cpgs identified in SEQ ID NOs 1 to 250.

The panel may consist of at least 300 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 808, preferably wherein the cpgs comprise the cpgs identified in SEQ ID NOs 1 to 300.

The panel may consist of at least 350 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 808, preferably wherein the cpgs comprise the cpgs identified in SEQ ID NOs 1 to 350.

The panel may consist of at least 400 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 808, preferably wherein the cpgs comprise the cpgs identified in SEQ ID NOs 1 to 400.

The panel may consist of at least 450 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 808, preferably wherein the cpgs comprise the cpgs identified in SEQ ID NOs 1 to 450.

The panel may consist of at least 500 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 808, preferably wherein cpgs are the cpgs identified in SEQ ID NOs 1 to 500.

This group may consist of all the CpG identified in SEQ ID NOs 1 to 808.

In some embodiments, the chip is not a Infinium MethylationEPIC BeadChip chip or a Illumina Infinium HumanMethylation450 loadchip chip.

Separately or additionally, in some embodiments, the number of CpG-specific oligonucleotide probes of the chip is 482,000 or less, 480,000 or less, 450,000 or less, 440,000 or less, 430,000 or less, 420,000 or less, 410,000 or less, 400,000 or less, 375,000 or less, 350,000 or less, 325,000 or less, 300,000 or less, 275,000 or less, 250,000 or less, 225,000 or less, 200,000 or less, 175,000 or less, 150,000 or less, 125,000 or less, 100,000 or less, 75,000 or less, 50,000 or less, 45,000 or less, 40,000 or less, 35,000 or less, 30,000 or less, 25,000 or less, 20,000 or less, 15,000 or less, 10,000 or less, 5,000 or less, 4,000 or less, 3,000 or less, or 2,000 or less.

The CpG groups may comprise any of the groups of cpgs defined in the assays of the invention described herein.

The chip of the invention may comprise one or more oligonucleotides comprising any set of cpgs as defined in the assay of the invention, wherein the one or more oligonucleotides hybridize to corresponding oligonucleotide probes in the chip.

The invention also encompasses a method of preparing a hybridization chip as described herein, comprising contacting a chip according to the invention with a set of oligonucleotides comprising any set of cpgs as defined in the assay of the invention.

Any of the chips defined herein may be included in a kit. The kit may comprise any chip as defined herein and instructions for use.

The invention further contemplates the use of any of the chips defined herein in any of the assays to determine the methylation status of CpGs to predict the presence or progression of cancer in an individual.

The following examples are intended to illustrate, but not limit, the invention.

Examples

In the embodiments described herein, WID-EC-index is a cancer index value, wherein the index value is determined by determining the methylation status of groups of CpG selected from the group of CpG defined by SEQ ID NOs 1 to 500 in a population of DNA molecules from a given sample of an individual.

In some cases of the embodiments, all CpG's defined by SEQ ID NOs 1 to 500 are included in the group, which have been determined to obtain a cancer index value. Furthermore, a specific subset of CpG's selected from the 500 CpG's defined in SEQ ID NO 1 to 500 has been included in this group, which has been determined to obtain a cancer index value. In these cases, the ability of a cancer index value to distinguish between cancer positive and cancer negative females is described, wherein the ability to distinguish the index is characterized by AUC and received operating characteristics.

The present inventors and other scientists have shown in the past that DNA methylation in vaginal fluid or cervical smears may be able to identify women with endometrial cancer. All of these studies were relatively small in scale and these findings were not validated in large data sets. Furthermore, none of these studies focused exclusively on high risk endometrial cancer, and most importantly none of them evaluated group-based female samples prior to disease diagnosis.

Alterations in DNA methylation can be used as both tools, (i) surrogate reads of factors driving the formation of cancer, thereby predicting cancer risk, and (ii) diagnostic tools that indicate the presence of cancer. Most of the DNA extracted from cervical smear samples contains: (i) DNA from normal cells (e.g., hormone sensitive cervical epithelial cells, whose DNA methylation may capture a long term effect triggered by unopposed estrogens-a core risk factor for endometrial cancer), which provides a characteristic cancer risk component, and (ii) DNA from cell-detritus excreted from the endometrial cavity, whose number may be increased relative to endometrial cancer, which provides a characteristic diagnostic component.

Here, the inventors have developed and validated DNA methylation signatures in cervical smear samples that are able to diagnose and predict the risk of developing endometrial cancer.

Materials and methods

Study design and epidemiological data acquisition

The study was conducted as part of a multicenter study involving several recruitment sites in 5 european countries (i.e. uk, czech republic, italy, norway and germany). The participants were all older than 18 years. Prior to participation, each prospective study volunteer received a participant information table and an agreement and explained the basic principles of the study. Additional resources are also provided, including interpreted video and more online resources. Women diagnosed with breast or ovarian cancer (cases) or non-malignant benign gynaecological disease (control group) are contacted in a hospital clinic while women recruited as BRCA mutation carriers or healthy volunteers from the general population (control group) are contacted by ex-situ activity, public participation and as part of a cervical screening regimen. After signing the informed consent, the participants completed an epidemiological questionnaire and a post-participation feedback form. This study itself is a sub-study of the forecte (4C) program which has obtained ethical approval from the uk health institute (REC 14/LO/1633) and other donation centers.

Epidemiological investigation was performed by qualitrics application on a proprietary iPad. The survey contains questions about hygiene habits, related risk factors, also inquires about historical hygiene habits, and obtains complete medical and obstetrical medical history. Cervical samples are collected by trained staff at the appropriate clinical sites and cervical smears are performed by a group of research midwives or doctors to establish standard practices. Cheek samples were collected using a Copan 4N6FLOQ swab of Thermofisher Scientific.

The biological sample is assigned an anonymous participant ID number assigned to the name of the person in a securely stored link file. After sampling, an email survey was sent to each participant to allow them to provide feedback on the recruitment procedure. Women currently diagnosed with grade 3 and/or stage IB or more malignant endometrial cancer and recruited prior to receiving any systemic treatment (chemotherapy or anti-hormone or Herceptin (Herceptin), etc.) or surgery or radiation therapy are eligible as endometrial cancer cases. For the forecoe discovery dataset, the control group was initially matched one-to-one with cases based on menopausal status, age (5 years of age range, where possible) and recruitment center/country. However, many cases only match in age and menopausal status due to imbalance in recruiting cases and control in some centers. After recruitment, cancer histological data is collected by a clinician directly involved in cancer case diagnosis/treatment or designated data manager having access to an internal hospital system.

Cervical smear sample collection

Cervical smear examinations were performed at cooperating hospitals and recruitment centers using the ThinPrep system (Hologic corporation, cat# 70098-002). Cervical cell samples were collected from the cervix using a cervical brush (Rovers Medical Devices, cat# 70671-001) that was rotated 5 times at 360 degrees while in contact with the cervix to maximize cell sampling. The brush was removed from the vagina and immersed in a ThinPrep vial containing stored cell fluid, and then the bottom of the vial was pushed 10 times to facilitate release of cells from the brush into the solution. The sample vials were sealed and stored in place at room temperature. Cheek cells were collected using two Copan4N6FLOQ cheek swabs (Copan Medical Diagnostics, cat#4504C) by forcefully brushing the swab head 5-6 times over the cheek mucosa of each cheek. The swab was recapped and dried at room temperature in a sampling tube containing a desiccating desiccant. 2.5ml venous whole blood was collected in PAX gene blood DNA tubes (BD Biosciences # 761165) and stored locally at 4 ℃. All samples were transported to the UCL at ambient temperature.

Vaginal swab endometrial cancer groups (55 control groups and 8 endometrial cancers) consisted of swabs from women who had been treated at UCLH due to post-menopausal bleeding.

Self-collected sample

Two endometrial cancer patients and three age-matched control groups provided cervical-vaginal samples using the self-collection device Evalyn brush at the clinic after simple explanation by medical personnel. Once introduced into the vagina as indicated by the fabric protocol, the Evalyn brush was rotated 5 times at 360 degrees to maximize cell sampling. Samples were stored using ThinPrep.

Sample processing and DNA extraction

When the sample is ready to be stored in the laboratory, the cervical smear sample is poured into a 50ml Falcon tube and allowed to settle for 2 hours at room temperature. The enriched cell pellet was then transferred to a 2mL vial using a 1mL width Kong Jianduan. Cervical deposits were washed twice with PBS, lysed, and stored temporarily at-20 ℃ prior to extraction.

DNA methylation chip analysis

Cervical DNA was normalized to 25ng/ul using EZ-96DNA methylation-lighting kit (Zymo Research Corp, cat#d 5047) on a Hamilton Star liquid treatment platform and bisulphite modification was performed on 500ng total DNA. 8ul of modified DNA was subjected to methylation analysis on UCL Genomics company Illumina InfiniumMethylation EPIC BeadChip (Illumina, calif., USA) according to the manufacturer's standard protocol.

Methylation analysis

All methylated microchip data were processed through the same standardized tubing. Raw data was loaded using R-packet minfi. Any samples with a median methylation and unmethylation intensity of <9.5 were removed. Any probe that detects a p-value >0.01 is considered to be failed. Any samples with failure probe rate >10% and any probes with failure rate >10% were removed from the dataset. Beta values from the failed probe (about 0.001% of the dataset) were interpolated using an inputte. Knn function as part of the interpolation R-package. .

non-CpG probes were removed from the dataset (2,932), SNP-related probes identified by peri et al (82,108), and chrysy probes. Another 6,102 previously identified probes were removed that followed the trimodal (trimodal) methylation pattern of the properties possessed by the potential SNPs.

Background intensity correction and dye bias correction were performed using a minfi single sample pre-treatment Noob function. Probe bias correction was performed using a beta mixed quantile normalization (BMIQ) algorithm.

The fraction of immune cell contamination and the relative proportion of different immune cell subtypes in each sample were estimated using the EpiDISH algorithm using epithelial, fibroblast and immune cell reference datasets. The first 1,000 most variable probes (ordered by standard deviation) were used in the principal component analysis. Statistical tests were performed to identify any abnormal associations between plates, sentrix location, chip processing date, DNA production date, study center, immune contamination score, age, type (comparison of case to control group) and the first ten principal components. Finally, two-thirds of the discovery data set is randomly selected for use as the training data set, and the remaining one-third is assigned to the internal validation data set. This splitting is done only once, using the same training set and validation set in all subsequent analyses.

Methyl photoreaction design

Two CpG ordered lists were generated. The first one was ranked according to the epithelial delta-beta estimate (estimated difference in methylation between cases and controls in cervical epithelial cells). The second is ranking based on p-value (derived from a linear model comparing cases and control groups after adjustment of immune cell ratio and age). For each CpG we identified any consecutive CpG within +/-500 bp. The inventors calculated and plotted the average methylation for all cases and control CpG groups within this 1000bp region. From a visual inspection of the first 50 cpgs (in both ordered lists), we determined a number of candidate regions according to the following criteria:

1. the healthy control group had a region with a methylation level near zero.

2. Areas of relatively low variability within the control.

3. Areas of elevated methylation levels in the case.

4. A region comprising two or more CpG sites

Cervical smear samples from 20 healthy control groups (age range 34 to 75 years, 11 postmenopausal and 9 pre-menopausal) and 20 women with endometrial cancer (age range 34 to 75 years, 11 postmenopausal and 9 pre-menopausal) were analyzed.

Statistical analysis for classifier development

Contamination of immune cells presents challenges for identification of the location of Differential Methylation (DMP), as differential methylation that occurs only in epithelial cells is reduced in samples with high IC, and vice versa. To overcome this, the inventors linearly regressed the β value on the IC for each CpG site, and a linear model was applied to the case and control group, respectively. Cut-off values at ic=0 were used as estimates of the mean β values for the case and control groups in the pure epithelial cell population. The difference between these cut-off values provides an estimate of delta-beta in the epithelial cells. The difference between cut-off values at ic=1 provides an immune cell delta-beta estimate. Based on the delta-beta estimates in the epithelial cells, a ordered list of CpG's was generated.

R-packet glrnet is used to train a classifier with mixed parameter values α=0 (ridge (penalty)) and α=1 (lasso) penalty) for the binomial response type. Data from the training dataset is used to fit the classifier. By taking the CpG with the largest epithelium delta-beta, followed by the CpG with the largest immunity delta-beta, followed by the CpG of the next largest epithelium delta-beta, and so on, an ordered list of CpG's is generated (any duplicate term removed). The first n cpgs from the ordered CpG list are used as input to the classifier. The glmnet function uses a ten-fold cross-validation in the training set to determine the optimal value of the regularization parameter λ. AUC is used as a measure of classifier performance, which is evaluated on an internal validation dataset as a function of n, the number of cpgs used as input during training. The maximum value of n is 30,000.

The best classifier is selected based on the highest AUC obtained in the internal validation dataset. Once the optimal number of inputs is determined, the training and internal validation datasets are combined and the classifier is reassembled using the entire discovery dataset, with α and λ fixed at their optimal values. The finalized classifier is then applied to the external validation dataset and the corresponding AUC is calculated.

The first n CpG are denoted as x ₁ ,…,x _n And the regression coefficients from the trained classifier are expressed as w ₁ ,…,w _n ThenWherein μ and σ are defined as the amount +.>The index is scaled to have zero mean and unit standard deviation in the training dataset).

Data availability

DNAme data has been deposited in the European Genome-phenotype group Archive (EGA), which is hosted by EBI and CRG under accession number EGASXXXXXXXXXXX.

Examples:

the inventors performed an epigenomic-wide DNAme analysis in cervical smear samples from women subsequently diagnosed with endometrial cancer and matched control groups, and established a WID-EC-index (female endometrial cancer risk identification index), which was further validated in a set of independent cervical samples.

For the discovery set (fig. 1), the inventors collected samples from 217 women (before endometrial biopsies were used for diagnostic purposes or before starting hysterectomy) with at least one poor prognostic feature (i.e. grade 3 or clear cell or serous histology or >50% myometrial infiltration) at diagnosis of endometrial cancer from 15 european centers, and samples from 869 women not suffering from cancer (593 from the general population, 276 from women hospitalized for benign female specific conditions) (table 8; samples from a larger proportion of young women were deliberately used in the discovery set to develop risk predictors for young women as well; the external validation set consisted of age-matched cases and control groups). The epigenomic-wide DNAme was analyzed using a Illumina Infinium EPIC bead chip covering over 850,000 CpG sites.

Sample heterogeneity and differential methylation

The inventors assessed the number of cpgs that significantly differentially methylated between cancer cases and control groups (fig. 6A); 116,658 CpG showed significant differential methylation after Bonfronni multiplex assay adjustment. Previously, the inventors found that methylation differences compared to the control group may vary depending on the immune cell type composition in the case. Thus, the inventors evaluated the level of cell type heterogeneity in each cervical smear sample using HEPIDISH, an algorithm that extrapolates the relative proportions of epithelial cells, fibroblasts, and seven immune cell subtypes in each sample. The cell type distribution was approximately similar between the cancer case and the control group (although there were minor but significant differences in some immune cell subtypes; fig. 6B).

Development of differentiation index

To derive a diagnostic methylation signature, known as the WID-EC-index, the inventors used ridge and lasso regression to classify individuals as cases or control groups. Classifier was trained on two-thirds of the discovery dataset (572 non-cancerous controls, 144 endometrial cancer cases), the remaining third being used as an internal validation set (297 controls, 73 cases) in order to evaluate their performance as a function of CpG number used to construct the index. The area under the receiver operating characteristic curve (AUC) was used as a measure of the predicted performance. CpG are ordered according to their epithelium delta-beta.

The predicted performance was evaluated using the internal validation dataset as a function of the number of CPGs used to train the classifier, and 500 CPG-binding ridge regression was used to achieve the best performance of 0.97 (FIG. 2;95% Confidence Interval (CI): 0.94-0.99) (FIG. 6C). The differential performance was largely independent of immune cell proportion (fig. 6D). In the case of the immunocyte ratio.ltoreq.0.5, the AUC is 0.98 (95% CI: 0.97-1.00), and in the case of the ratio >0.5, the AUC is 0.95 (95% CI: 0.91-0.99). In the control group, WID-EC-index correlated with IC score nuances (linear regression coefficient of 0.29, p < 0.001), and a negative trend in cancer cases (linear regression coefficient of-0.28, p=0.6).

External authentication

An isolated independent external validation dataset consisting of 63 endometrial cancer cases and 225 controls was used to validate the exponential expression (fig. 1). The WID-EC-indices (FIG. 3A) were calculated for each female, resulting in AUCs with IC.ltoreq.0.5 and >0.5 of 0.92 (95% CI: 0.87-0.97) and 0.93 (95% CI: 0.88-0.99) and 0.89 (95% CI: 0.80-0.98), respectively. Table 7 shows the dominance ratios of the external validation sets corresponding to the quartiles defined by the internal validation sets.

To assess whether WID-EC-index could predict endometrial cancer risk, in stockholm, the inventors analyzed samples taken from healthy females (cases; n=55; average time between sample collection and cancer diagnosis 304 days) and females not collecting samples (control, n=99) who developed endometrial cancer later as part of a routine cervical screening program. The inventors have observed that for IC.ltoreq.0.5 and >0.5, the overall AUC is 0.83 (95% CI: 0.76-0.90), 0.82 (95% CI: 0.72-0.93) and 0.85 (95% CI: 0.75-0.95), respectively.

Sample degradation in the expected concentration

The cell type composition of these three data sets was substantially similar to the discovery data set used to develop the index, and did not show any significant differences between the case and control groups (fig. 7A, 7B). However, compared to the discovery set, the inventors observed a systematic deletion of methylation in the cancer-free control of the prospective set, which occurs mainly in the CpG sparse "open sea" and "land" regions of the genome (fig. 7C). The inventors hypothesize that these changes may be due to storage-related degradation caused by long-term bio-pool storage (median storage time of 95 days, ranging from 15 days to 1001 days).

The WID-EC-index was highly enriched in CpG-dense CpG islands and depleted in open sea CpG areas relative to the entire illumina EPIC chip (FIG. 7D). The inventors split the index into two sub-parts consisting of only cpgs from islands (237 CpG) and cpgs from open sea areas (228 CpG). CpG island sub-components performed well in the expected samples (AUC: 0.87, 95% CI:0.81-0.94; FIG. 7E), whereas open sea sub-components suffered severe disruption of the distinguishing signal (FIG. 7F), indicating that the overall performance of WID-EC-index was reduced by degradation of open sea CpG regions. In the external validation set, the AUC values derived for the island and open sea components were 0.92 and 0.53, respectively, indicating that the discrimination signal was driven mainly by CpG island components (fig. 7G, fig. 7H).

Correlation with epidemiological, clinical and technical factors

The inventors focused on internal and external validation on the relationship between WID-EC-index and various epidemiological and clinical variables. In the control group, a significant statistical correlation was found between WID-EC-index and age (correlation coefficient=0.37, p<10 ^-16 The method comprises the steps of carrying out a first treatment on the surface of the Fig. 4A). A similar trend was observed in cancer cases (correlation coefficient=0.16, p=0.06). A significant correlation between index and Body Mass Index (BMI) of 0.14 (p <0.01). The WID-EC-index of the postmenopausal control group was significantly increased (fig. 4C), reflecting the relationship with age. In the postmenopausal control group, no significant association with the warp status was observed (fig. 4D). The index of grade III/IV cancers (fig. 4E) and grade II cancers were significantly elevated compared to grade I cancers (fig. 4F). No association with histological subtypes was observed (fig. 4G).

The inventors investigated whether there was any correlation between the WID-EC-index and various technical parameters including sample processing date, plate number (samples were processed on 96 well sample plates) and sentrix position, but no significant correlation was found. The inventors compared 593 control samples from healthy volunteers to 276 control samples from females with benign female-specific disease, but did not find any significant differences (fig. 8A). The inventors also observed that there was no significant dependence of time from sample collection to DNA extraction (fig. 8B).

Putative tumor DNA ratio

Due to anatomical proximity between the cancer (i.e., endometrium) and the area where the inventors collected the sample (i.e., cervix), the inventors studied whether the signal was driven by tumor DNA flowing from uterus to cervix, or whether the signal was a general risk signal retained in cervical epithelial cells . The inventors used 11 epithelial cell samples, 7 fibroblast samples, 42 immune cell samples and 9 endometrial cancer tissue samples to develop a new reference set for the EpiDISH algorithm (see methods). For each sample, the inventors obtained an estimate of the proportion of DNA from each of the four cell types. The inventors observed that the proportion of tumor DNA in the case was significantly higher than that in the control group (fig. 5A), whereas the proportion of tumor DNA in the control group was close to zero. The inventors found that 43% of cancer cases provided a composition comprising>Cervical smear samples of 10% tumor DNA. Although the WID-EC-index increased significantly with increasing tumor DNA ratio (correlation coefficient of 0.70, p<10 ^-16 ) But also increased significantly in the absence of tumor DNA (fig. 5B), indicating that the discrimination signal is independent of the presence of tumor DNA.

Cancer index value and clinical behavior

Four subgroups defined by the range of cancer index values are designated in table 9 as corresponding to preferred clinical behaviors, including intensive screening, administration of therapeutic agents, and surgery. The subgroup is based on the quartiles of the quality control samples from the internal validation group. That is, these index values divide the control samples into four equal-sized groups. The odds ratio is calculated by comparing the number of cases and the number of controls in a given quartile with the first quartile (as a reference). The odds ratio of endometrial cancer risk, ovarian cancer risk, and CIN3 risk are determined. For example, the fourth quartile woman is about 25 times more likely to have endometrial cancer than the first quartile woman.

Discussion of

Endometrial cancer is the most common gynaecological cancer and is also one of the most rapidly growing cancers.

Here, the inventors have for the first time established a test-WID-EC-index-based on DNA methylation characteristics in cervical smear samples, capable of identifying women with endometrial cancer and at risk of endometrial cancer with very high sensitivity and specificity.

The WID-EC-index is capable of identifying 70% of women with endometrial cancer with 99% specificity and 90% of women with endometrial cancer with 78% specificity. More importantly, the inventors demonstrated that based on the cervical screening group of the general population, the inventors identified 50% of women who developed endometrial cancer after cancer diagnosis with 100% specificity. The inventors expect that in this cohort setting the sensitivity (under similar specificity) can be even higher, as long-term storage of smear samples in liquids for liquid-based cytology (e.g. Preservcyt) at-25 ℃ (i.e. years) has a strong effect on DNA methylation (unpublished), minimal effect on CpG islands (which contribute to a large extent to diagnostic components of WID-EC-index), and maximal effect on open sea CpG (i.e. CpG contributing to risk prediction components of the index).

The inventors propose that-once validated in the intended setting-the first 10% of women should receive an endometrial biopsy, which can be easily done in the outpatient setting for the vast majority of cases, and-using, for example, a negative pressure pipette (catheter) biopsy-is easily accepted by the patient.

Prior to validating the WID-EC-index in the general population, it was expected to be validated, especially in women at high risk of endometrial cancer, including women with high body mass index (38% of all endometrial cancers currently being attributable to high body mass index and having an increasing trend) or lindera syndrome. Lindgy syndrome is an autosomal dominant inherited cancer susceptibility, caused by DNA mismatch repair mutations, associated with 33-60% of endometrial cancer incidence risks. These women appear to be characterized by advanced stages of endometrial cancer, higher than the general population, more aggressive in histological types (clear cell carcinoma, papillary serous carcinoma, and carcinoma sarcoma), and less advanced endometrial carcinogenesis in these women. It should be demonstrated whether the WID-EC-index test allows these women, ideally based on self-collected samples, to customize the risk-reducing measures.

TABLE 7A

Number of digits	Control	Cancer of the human body	OR (unregulated)	OR (adjusted)
					(-1.36,-0.66)	35	1	1.00 (reference)	1.00 (reference)
(-0.66,-0.43)	45	1	0.78(0.02,31.16)	0.61(0.01,20.2)
					(-0.43,-0.23)	77	4	1.65(0.22,46.2)	0.66(0.05,16.74)
(-0.23,1.03)	68	57	25.5(5.27,612.01)	13.66(2.54,254.56)

TABLE 7B

Number of digits	Control	Cancer of the human body	OR (unregulated)	OR (adjusted)
					(-1.36,-0.66)	20	3	1.00 (reference)	1.00 (reference)
(-0.66,-0.43)	32	3	0.63(0.1,3.99)	0.63(0.11,3.74)
					(-0.43,-0.23)	22	8	2.33(0.57,12.47)	3.64(0.83,20.4)
(-0.23,1.03)	25	41	10.26(3.09,49.01)	13.47(3.4,71.78)

TABLE 7C expected sample dominance ratio Table

TABLE 7D ovarian cancer dominance ratio Table

Number of digits	Control	Cancer of the human body	OR (unregulated)	OR (adjusted)
					(-1.36,-0.66)	75	17	1.00 (reference)	1.00 (reference)
(-0.66,-0.43)	74	35	2.07(1.08,4.11)	1.61(0.8,3.3)
					(-0.43,-0.23)	74	61	3.6(1.95,6.91)	1.97(0.97,4.07)
(-0.23,1.03)	74	129	7.59(4.25,14.23)	3.42(1.71,7.04)

TABLE 8A internal verification

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TABLE 8A external verification

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TABLE 8B internal verification

Factors of	Group of	Collection set
			Age (age)	<52	16(8％)
	52-64	66(32％)
				>64	125(60％)
Menopausal status	Front part	19(9％)
				Rear part (S)	188(91％)
Stage by stage	T1	125(60％)
				T2	14(7％)
	T3	44(21％)
				T4	15(7％)
Grade	I	45(22％)
				II	49(24％)
	III	94(45％)
			Histological examination	Endometrium sample	132(64％)
	Slurry liquid	37(18％)
				Others	38(18％)

TABLE 8B external verification

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TABLE 8B expected validation

Factors of	Group of
			Age (age)	<52	17(31％)
	52-64	18(33％)
				>64	20(36％)
Stage by stage	I	34(62％)
				II	5(9％)
	III	6(11％)
				IV	5(9％)

Table 9.

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Claims

1. An assay for assessing the presence, absence or progression of cancer and/or grade 3 cervical intraepithelial neoplasia (CIN 3) in an individual, the assay comprising:

a. providing a sample from the individual, the sample comprising a population of DNA molecules;

b. determining the methylation status of a group of:

i. one or more cpgs selected from the group of cpgs identified in SEQ ID NOs 1 to 500, wherein the cpgs are identified at nucleotide positions 61 to 62; and/or

One or more cpgs selected from one or more Differential Methylation Regions (DMR) defined by SEQ ID NOs 501 to 808, wherein the cpgs are represented by CG;

c. deriving a cancer index value based on the methylation status of the one or more cpgs in the group; and

d. assessing the presence, absence or progression of cancer and/or CIN3 in the individual based on the cancer index value;

wherein the assay is characterized by having an area under the curve (AUC) of 0.60 or greater as determined by the Receiver Operating Characteristics (ROC).

2. The assay of claim 1, wherein the set of one or more cpgs comprises at least 50 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by an AUC of at least 0.90.

3. The assay of claim 2, wherein the set of one or more cpgs comprises the cpgs identified in at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having an AUC of at least 0.95.

4. The assay of claim 1, wherein the set of one or more cpgs comprises at least 100 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by an AUC of at least 0.93.

5. The assay of claim 4, wherein the set of one or more cpgs comprises the cpgs identified at least in SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having an AUC of at least 0.96.

6. The assay of claim 1, wherein the set of one or more cpgs comprises at least 150 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by an AUC of at least 0.93.

7. The assay of claim 6, wherein the set of one or more cpgs comprises the cpgs identified at least in SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having an AUC of at least 0.96.

8. The assay of claim 1, wherein the set of one or more cpgs comprises at least 200 cpgs selected from the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterized by an AUC of at least 0.93.

9. The assay of claim 9, wherein the set of one or more cpgs comprises the cpgs identified in at least SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterized by having an AUC of at least 0.96.

10. The assay of claim 1, wherein the set of one or more cpgs comprises at least the 500 cpgs identified at nucleotide positions 61-62 in SEQ ID NOs 1-500, and further wherein the assay is characterized by having an AUC of at least 0.97.

11. The assay of any one of claims 1 to 10, wherein the step of determining the methylation status of the one or more cpgs in the set in the population of DNA molecules in the sample comprises determining a β value for each CpG.

12. The assay of claim 11, wherein the step of deriving the cancer index value based on the methylation status of the one or more cpgs in the group comprises:

a. providing a methylation beta value dataset comprising the methylation beta value for each CpG in the group;

b. providing a mathematical model capable of generating the cancer index from the methylation beta value dataset; and

c. the mathematical model is applied to the methylation beta value dataset to generate the cancer index.

13. The assay of claim 12, wherein the cancer index value is a WID-EC-index cancer index value, and wherein the mathematical model applied to the methylation beta value dataset to generate the cancer index is an algorithm according to the formula:

Wherein:

a.β ₁ ,…,β _n is the methylation beta value (between 0 and 1);

b.w ₁ ,…,w ₅₀₀ is a real value coefficient;

c. μ and σ are real-valued parameters used to scale the exponent; and

d.n refers to said number of cpgs in said group of one or more cpgs;

preferably, wherein the cancer is endometrial cancer.

14. The assay of any one of claims 1 to 13, wherein the individual is assessed as having cancer and/or CIN3 or as having a high risk of developing cancer and/or CIN3 when the cancer index value of the individual is about-0.201 or greater, or wherein the individual is assessed as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the cancer index value of the individual is less than about-0.201, preferably wherein:

a. the set of one or more cpgs comprises at least 50 of the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 88% and the specificity is at least 76%;

b. the set of one or more cpgs comprises the CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 90% and the specificity is at least 80%;

c. The set of one or more cpgs comprises the CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 92% and the specificity is at least 79%; or alternatively

d. The set of one or more cpgs comprises the CpG defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 93% and the specificity is at least 80%;

preferably, wherein the assay comprises determining the methylation β value for each CpG in the set of one or more cpgs, more preferably wherein the cancer is endometrial cancer.

15. The assay of any one of claims 1 to 13, wherein the individual is assessed as having cancer and/or CIN3 or as having a high risk of developing cancer and/or CIN3 when the cancer index value of the individual is about 0.269 or greater, or wherein the individual is assessed as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the cancer index value of the individual is less than about 0.269, preferably wherein:

a. the set of one or more cpgs comprises at least 50 of the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 75% and the specificity is at least 94%;

b. The set of one or more cpgs comprises the CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and the specificity is at least 98%;

c. the set of one or more cpgs comprises the CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 75% and the specificity is at least 98%; or alternatively

d. The set of one or more cpgs comprises the CpG defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and the specificity is at least 97%;

16. The assay of any one of claims 1 to 13, wherein the individual is assessed as having cancer and/or CIN3 or as having a high risk of developing cancer and/or CIN3 when the cancer index value of the individual is about 1.072 or greater, or wherein the individual is assessed as not having cancer and/or CIN3 or as having a low risk of developing cancer and/or CIN3 when the cancer index value of the individual is less than about 1.072, preferably wherein:

a. The set of one or more cpgs comprises at least 50 of the cpgs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500 and wherein the sensitivity is at least 58% and the specificity is at least 99%;

b. the set of one or more cpgs comprises the CpG defined by at least SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 60% and the specificity is 100%;

c. the set of one or more cpgs comprises the CpG defined by at least SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 63% and the specificity is 100%; or alternatively

d. The set of one or more cpgs comprises the CpG defined by at least SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and the specificity is 100%;

17. The assay of any one of claims 1 to 13, wherein when the cancer index value of the individual is:

c. about-0.430 or greater and less than about-0.230, the individual is assessed as having a moderate risk of cancer and/or CIN3 development; or alternatively

18. The assay of claim 1 or any one of the preceding claims, wherein the step of determining the methylation status of a group of one or more cpgs comprises determining the methylation status of one or more cpgs represented by a CG identified in a group of one or more DMRs defined by SEQ ID NOs 501 to 808, optionally wherein the group of one or more cpgs comprises two or more cpgs represented by a CG identified in the group of DMRs, three or more cpgs represented by a CG identified in the group of DMRs, four or more cpgs represented by a CG identified in the group of DMRs, or all cpgs represented by a CG identified in the DMR defined by SEQ ID NOs 501 to 808.

19. The assay of claim 18, wherein the step of determining the methylation status of the set of one or more cpgs comprises determining the methylation status of five or more, six or more, seven or more, eight or more, or nine or more or all of the cpgs represented by CG within any one or more of the DMRs defined by SEQ ID NOs 501 to 808.

20. The assay of claim 18 or 19, wherein the step of determining the methylation status of a group of one or more cpgs comprises determining the methylation status of two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, or nine or more or all of the cpgs represented by CG within:

All 237 of dmrs 1 to 308;

d. one DMR defined by SEQ ID No. 501, two DMR defined by SEQ ID nos. 501 to 502, three DMR defined by SEQ ID nos. 501 to 503, four DMR defined by SEQ ID nos. 501 to 504, five DMR defined by SEQ ID nos. 501 to 505, six DMR defined by SEQ ID nos. 501 to 506, seven DMR defined by SEQ ID nos. 501 to 507, eight DMR defined by SEQ ID nos. 501 to 508, or nine DMR defined by SEQ ID nos. 501 to 509;

e. any combination of the following:

one or more DMR defined by SEQ ID NOs 503, 504, 526, 740, 741, 743 and 744, preferably within all of SEQ ID NOs 503, 504, 526, 740, 741, 743 and 744;

one or more DMR defined by SEQ ID NOs 525, 756, 757, 503, 504, 526, 740, 741, 743 and 744, preferably within all of SEQ ID NOs 525, 756, 757, 503, 504, 526, 740, 741, 743 and 744; or alternatively

f. Ten DMRs defined by SEQ ID nos. 501 to 510, twenty DMRs defined by SEQ ID nos. 501 to 520, thirty DMRs defined by SEQ ID nos. 501 to 530, forty DMRs defined by SEQ ID nos. 501 to 540, fifty DMRs defined by SEQ ID nos. 501 to 550, sixty DMRs defined by SEQ ID nos. 501 to 560, seventy DMRs defined by SEQ ID nos. 501 to 570, eighty DMRs defined by SEQ ID nos. 501 to 580, or ninety DMRs defined by SEQ ID nos. 501 to 590. Or alternatively

g. From SEQ ID NO 501 to 510, SEQ ID NO 511 to 520, SEQ ID NO 521 to 530, SEQ ID NO 531 to 540, SEQ ID NO 541 to 550, SEQ ID NO 551 to 560, SEQ ID NO 561 to 570, SEQ ID NO 571 to 580, SEQ ID NO 581 to 590, SEQ ID NO 591 to 600, SEQ ID NO 601 to 610, SEQ ID NO 611 to 620, SEQ ID NO 621 to 630, SEQ ID NO 631 to 640, SEQ ID NO 641 to 650, SEQ ID NO 651 to 660, SEQ ID NO 661 to 670, SEQ ID NO 671 to 680, SEQ ID NO 681 to 690, SEQ ID NO 691 to 700, SEQ ID NO 701 to 710, SEQ ID NO 711 to 720, SEQ ID NO 721 to 730, SEQ ID NO 731 to 731, SEQ ID NO 741 to 750; 751 to 760; 761 to 770; 771 to 780; SEQ ID NOS 781 to 790; ten DMR defined by SEQ ID NOs 791 to 800 or SEQ ID NOs 801 to 808.

21. The assay of any one of claims 18 to 20, wherein the step of determining the methylation status of a group of one or more cpgs comprises determining the methylation status of one or more cpgs within any one or more DMRs of the group of DMRs consisting of DMRs 1 to 308 defined by SEQ ID NOs 501 to 808, comprising:

a. one or more cpgs within DMR 1 as defined by SEQ ID No. 501 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.911, and more preferably wherein a set of said one or more cpgs comprises said cpgs represented by at least [ [ CG ] ];

b. One or more cpgs within DMR 2 as defined by SEQ ID No. 502 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.903, and more preferably wherein a set of said one or more cpgs comprises said cpgs represented by at least [ [ CG ] ];

c. one or more cpgs within DMR 3 as defined by SEQ ID No. 503 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a set of said one or more cpgs comprises said cpgs represented by at least [ [ CG ] ];

d. one or more cpgs within DMR 4 as defined by SEQ ID NO 504 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a set of said one or more cpgs comprises said cpgs represented by at least [ [ CG ] ];

e. one or more cpgs within DMR 5 as defined by SEQ ID No. 505 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.899, and more preferably wherein a set of said one or more cpgs comprises said cpgs represented by at least [ [ CG ] ];

f. one or more cpgs within DMR 6 as defined by SEQ ID No. 506 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.897, and more preferably wherein a set of said one or more cpgs comprises said CpG represented by at least [ [ CG ] ];

g. One or more cpgs within DMR 7 as defined by SEQ ID NO 507 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.894, and more preferably wherein a set of said one or more cpgs comprises said cpgs represented by at least [ [ CG ] ];

h. one or more cpgs within DMR 8 as defined by SEQ ID No. 508 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.894, and more preferably wherein a set of said one or more cpgs comprises said CpG represented by at least [ [ CG ] ];

i. one or more cpgs within DMR 9 as defined by SEQ ID No. 509 and represented by CG, preferably wherein said assay is characterized by having a ROC AUC of at least 0.892, and more preferably wherein a set of said one or more cpgs comprises said cpgs represented by at least [ [ CG ] ]; or alternatively

j. One or more cpgs within DMR 10 as defined by SEQ ID No. 510 and represented by CG, preferably wherein the assay is characterized by having a ROC AUC of at least 0.891, and more preferably wherein a set of said one or more cpgs comprises said cpgs represented by at least [ [ CG ] ].

22. The assay of any one of claims 18 to 21, wherein:

a. When the cancer index of the individual is about 0.025 or greater, the individual is classified as having cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3; or alternatively

b. Said individual is classified as not having cancer and/or CIN3 when said cancer index of said individual is less than about 0.025;

preferably, wherein the assay has a specificity of 95% or greater, more preferably, wherein the assay comprises determining an average β value for each CpG in the set of one or more cpgs.

23. The assay of any one of claims 18 to 21, wherein:

a. wherein a CpG represented by CG whose cancer index value is determined is at least within DMR 1 defined by SEQ ID NO:501, and wherein when the cancer index of the individual is about 0.209 or greater, the individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 1, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 501;

b. Wherein a CpG represented by CG whose cancer index value is determined is at least within DMR 1 defined by SEQ ID NO:501, and wherein when the cancer index of the individual is less than about 0.209, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 70.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 1, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 501;

c. wherein a CpG represented by CG whose cancer index value is determined is at least within DMR 2 defined by SEQ ID No. 502, and wherein when the cancer index of the individual is about 0.271 or greater, the individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 77.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 2, and more preferably wherein the cancer index value is the average β value of the CpG represented by [ [ CG ] ] in SEQ ID No. 502;

d. Wherein a CpG represented by CG whose cancer index value is determined is at least within DMR 2 defined by SEQ ID No. 502, and wherein when the cancer index of the individual is less than about 0.271, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 77.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least one CpG from DMR 2, and more preferably wherein the cancer index value is the average β value of the CpG represented by [ [ CG ] ] in SEQ ID No. 502;

e. wherein a CpG represented by CG whose cancer index value is determined is at least within DMR 3 defined by SEQ ID NO:503, and wherein when the cancer index of the individual is about 0.123 or greater, the individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 3, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 503;

f. Wherein a CpG represented by CG whose cancer index value is determined is at least within DMR3 defined by SEQ ID NO:503, and wherein when the cancer index of the individual is less than about 0.123, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR3, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 503;

g. wherein a CpG represented by CG whose cancer index value is determined is at least within DMR 4 defined by SEQ ID No. 504, and wherein when the cancer index of the individual is about 0.123 or greater, the individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 4, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 504;

h. Wherein a CpG represented by CG whose cancer index value is determined is at least within DMR 4 defined by SEQ ID No. 504, and wherein when the cancer index of the individual is less than about 0.123, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 73.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least three cpgs from DMR 4, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID No. 504;

i. wherein a CpG represented by CG whose cancer index value is determined is at least within DMR5 defined by SEQ ID NO:505, and wherein when the cancer index of the individual is about 0.105 or greater, the individual is classified as suffering from cancer and/or CIN3 or having a high risk of developing cancer and/or CIN3, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR5, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 505; or alternatively

j. The CpG represented by CG whose cancer index value is determined is at least within DMR5 defined by SEQ ID NO:505, and wherein when the cancer index of the individual is less than about 0.105, the individual is classified as not suffering from cancer and/or CIN3 or having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 71.00%, and the specificity of the assay is at least 95.00%, preferably wherein the set of one or more cpgs comprises at least five cpgs from DMR5, and more preferably wherein the cancer index value is the average β value of the cpgs represented by [ [ CG ] ] in SEQ ID NO: 505.

24. The assay of claim 1 or any one of the preceding claims, wherein the step of determining the methylation status of the one or more cpgs in the set further comprises or additionally comprises determining the methylation status of each CpG within one or more sequences identified by SEQ ID NOs 809 to 919.

25. The assay of claim 24, wherein the step of determining the methylation status of the one or more cpgs in the group comprises determining each CpG within:

a. SEQ ID NO 809 and/or SEQ ID NO 846 and/or SEQ ID NO 883, and wherein when the cancer index value is about 0.282 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 809 and/or SEQ ID NO 846 and/or SEQ ID NO 883;

SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884, and wherein when the cancer index value is about 0.212 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 55.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884;

e.seq ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885, and wherein when the cancer index value is about 0.002 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885;

f. SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885, and wherein when the cancer index value is less than about 0.002, the individual is classified as not having endometrial cancer or having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885;

SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887, and wherein when the cancer index value is about 0.003 or greater, the individual is classified as having endometrial cancer or having a high risk of endometrial cancer developing, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.97, preferably wherein the cancer index value is the methylation reference percentage of the sequence defined by SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887; and/or

26. The assay of any one of claims 1 to 25, wherein the step of determining the methylation status of each CpG in the set of one or more cpgs in the population of DNA molecules in the sample comprises:

a. performing a sequencing step to determine the sequence of each CpG;

b. hybridizing DNA to a chip comprising probes capable of distinguishing between methylated and unmethylated forms of said cpgs, and applying a detection system to said chip to determine said methylation status of each CpG; and/or

c. The PCR step is performed using methylation specific primers, wherein the methylation status of the CpG is determined by the presence or absence of a PCR product.

27. The assay of any one of claims 1 to 26, wherein the step of determining the methylation status of each CpG in the set of one or more cpgs comprises:

a. bisulfite converts the DNA; or alternatively

b. The following steps are carried out: a step of oxidizing the 5-methylcytosine base (5 mC) to a 5-carboxycytosine base (5 cat), preferably by 10-11 translocation (TET), and/or oxidizing the 5-hydroxymethylcytosine base (5 hmC) to a 5-carboxycytosine base (5 cat), preferably by 10-11 translocation (TET); the 5-carboxycytosine base (5 caC) is then optionally reduced to a dihydrouracil base (DHU) with pyridine borane.

28. A method of treating or preventing cancer in an individual, the method comprising:

a. assessing the presence, absence or progression of cancer in the individual by performing the assay of any one of claims 1 to 27, thereby assessing the cancer status of the individual;

b. administering one or more therapeutic or prophylactic treatments to the individual based on the evaluation.

29. The method of claim 28, wherein the individual is assessed as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, and wherein the cancer index value is about-0.660 or greater and less than about-0.430, and preferably wherein the assay comprises determining a methylation β value for each CpG in the set of one or more cpgs, the individual receiving one or more treatments according to their cancer index value, the one or more treatments comprising:

a. Evaluating endometrium and ovary via vaginal ultrasound;

b. the repeat assay of any one of claims 1 to 27, preferably wherein the repeat assay is performed about two years after the previous assay.

30. The method of claim 28, wherein the individual is assessed as having a moderate risk of cancer and/or CIN3 or having a moderate risk of cancer and/or CIN3 development, and wherein the cancer index value is about-0.430 or greater and less than about-0.230, and preferably wherein the assay comprises determining a methylation β value for each CpG in the set of one or more cpgs, the individual receiving one or more treatments according to their cancer index value, the one or more treatments comprising any one of:

a. evaluating endometrium and ovary via vaginal ultrasound;

i. colposcopy;

HPV test;

cervical cytology test;

testing for ca 125, preferably wherein the test is repeated every six months;

testing for methylation of cell-free tumor DNA in plasma/serum, preferably wherein the testing is repeated annually;

Testing for methylation of cell-free tumor DNA in vaginal fluid, preferably wherein the testing is repeated annually;

the repeat assay of any one of claims 1 to 27, preferably wherein the repeat assay is performed about one year after the previous assay;

31. The method of claim 30, wherein when the colposcopy, HPV, and cytologic test is negative, the enhanced screening further comprises hysteroscopy and endocervical and endometrial biopsies.

32. The method of claim 31, wherein when both transvaginal ultrasound and intensive screening are negative:

a. the transvaginal ultrasound, the test of CA125, the test of cell-free tumor DNA methylation in the plasma/serum, and the test of cell-free tumor DNA methylation in the vaginal fluid were repeated about six months after the previous assay; and

b. The colposcopy, HPV test and cervical cytology test are repeated about one year after the previous assay.

33. The method of claim 28, wherein the individual is assessed as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, and wherein the cancer index value is about-0.230 or higher, and preferably wherein the assay comprises determining a methylation β value for each CpG in the set of one or more cpgs, the individual receiving one or more treatments according to their cancer index value, the one or more treatments comprising any one of:

a. evaluating endometrium and ovary via vaginal ultrasound;

i. colposcopy;

HPV test;

cervical cytology test;

testing for ca 125, preferably wherein the test is repeated every six months;

testing of cell-free tumor DNA methylation in vaginal fluid, preferably wherein the test is repeated annually

c. administering one or more of a progestin, aspirin, metformin, an aromatase inhibitor, and a weight loss regimen, particularly wherein the progestin is delivered locally or systemically;

d. total hysterectomy and bilateral tubal ovariectomy.

34. The method of claim 33, wherein when the colposcopy, HPV, and cytologic test is negative, the enhanced screening further comprises hysteroscopy and endocervical and endometrial biopsies.

35. The method of claim 34, wherein when the transvaginal ultrasound and enhanced screening are both negative:

a. the transvaginal ultrasound, the test of CA125, the test of cell-free tumor DNA methylation in the plasma/serum, the test of cell-free tumor DNA methylation in the vaginal fluid, the colposcopy, the HPV test and the cervical cytology test are repeated about six months after the previous assay; and

b. The pelvic MRI scan is repeated approximately one year after the previous assay.

36. The method of any one of claims 33-35, wherein the progestin is delivered locally via an intrauterine contraceptive.

37. The method of any one of claims 28-36, wherein the one or more treatments received by the individual are repeated on a monthly, three month, six month, yearly, or two year basis following initial administration.

38. A method of monitoring the cancer status of an individual according to the individual's cancer index value, the method comprising: (a) Assessing the presence, absence or progression of cancer in an individual by performing the assay of any one of claims 1 to 27 at a first time point; (b) Assessing the presence, absence or progression of cancer in the individual by performing the assay according to any one of claims 1 to 27 at one or more additional time points; and (c) monitoring the individual for any change in the cancer index value and/or cancer status and/or CIN3 status between time points.

39. The method of claim 38, wherein the additional point in time after initial assessment is monthly, trimester, hexa month, yearly, or bi-yearly.

40. The method of claim 38 or 39, wherein one or more treatments of any one of claims 28-35 are administered to the individual depending on the cancer index value and/or cancer status and/or CIN3 status of the individual, or no treatment is administered to the individual when the cancer index value of the individual is less than about-0.660.

41. The method of any one of claims 38 to 40, wherein an increase in the cancer index value is indicative of a negative response to the one or more treatments.

42. The method of claim 41, wherein the one or more treatments are altered if a negative response is identified.

43. The method of any one of claims 38-40, wherein a decrease in the cancer index value is indicative of a positive response to the one or more treatments.

44. The method of claim 43, wherein the one or more treatments are altered if a positive response is identified.

45. The assay according to any one of the preceding claims, wherein the sample is obtained from a tissue comprising epithelial cells, preferably wherein the sample is not obtained from ovarian or endometrial tissue.

46. The assay according to claim 45, wherein said sample is obtained from:

a. cervical tissue;

b. vaginal tissue;

c. cervical vaginal tissue;

d. cheek tissue;

preferably, wherein the sample is obtained from cervical tissue, most preferably wherein the sample is obtained from tissue from a cervical smear, and optionally wherein the sample is self-collecting.

47. The assay according to any one of the preceding claims, wherein the assay is used to assess the presence, absence or development of:

a. endometrial cancer, preferably wherein the endometrial cancer is endometrioid cancer, uterine sarcoma, squamous cell carcinoma, small cell carcinoma, transitional cell carcinoma, serous carcinoma, clear cell carcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma or serous adenocarcinoma;

b. ovarian cancer, particularly wherein the ovarian cancer is a severe cancer, a mucinous cancer, an endometrioid cancer, a clear cell cancer, a Low Malignant Potential (LMP) tumor, a borderline epithelial ovarian cancer, a teratoma, a asexual cell tumor, an endoembryo sinooma, choriocarcinoma, a granulosa-follicular tumor, an ovarian support-stromal cell tumor, a granulosa cell tumor, an ovarian small cell cancer, or a primary peritoneal cancer;

48. A chip capable of distinguishing between methylated and unmethylated forms of CpG; the chip comprises oligonucleotide probes specific for the methylated form of each CpG in the set of CpG and oligonucleotide probes specific for the unmethylated form of each CpG in the set; wherein the panel consists of at least 50 cpgs selected from the cpgs identified in SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62 and identified in SEQ ID NOs 501 to 808 and represented by CG.

49. The chip of claim 48, provided that the chip is not a Infinium MethylationEPIC BeadChip chip or Infinium HumanMethylation chip, and/or provided that the number of CpG-specific oligonucleotide probes of the chip is 482,000 or less, 480,000 or less, 450,000 or less, 440,000 or less, 430,000 or less, 420,000 or less, 410,000 or less, or 400,000 or less.

50. The chip of claim 48 or 49, wherein the set comprises any set of cpgs defined in the assay of any one of claims 1 to 27.

51. The chip of any one of claims 48 to 50, further comprising one or more oligonucleotides comprising any set of CPGs as defined in the assay of any one of claims 1 to 27, wherein the one or more oligonucleotides hybridize to corresponding oligonucleotide probes of the chip.

52. A hybridization chip, wherein said chip is obtainable by hybridizing a set of oligonucleotides to a chip according to any one of claims 48 to 50, said oligonucleotides comprising any set of cpgs as defined in the assay of any one of claims 1 to 27.

53. A method for preparing a hybridization chip according to claim 52 comprising contacting the chip according to claims 45 to 48 with a set of oligonucleotides comprising any set of cpgs as defined in the assay of any one of claims 1 to 27.