RU2379690C1 - Diagnostic technique for papilloma virus infection - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: there is used for diagnostics of transient and persistent latent papilloma virus infection. The diagnostic technique for papilloma virus infection is ensured by history taking and integrated clinical-laboratory examination. As anamnestic signs, there are assumed compromised oncologic characteristics inheritance, early sexual life, age younger than 20 years old and promiscuity; as clinical - anogenital warts, erosion and ectopic neck of uterus, contact hemorrhagic diathesis, Ovuli nabotti, inflammatory diseases of small pelvis organs and intrauterine spiral. Herewith the laboratory signs are sexually transmitted diseases, mixtinfection, deficient lactic acid bacilli, vaginal disbiosis caused by conditional-pathogenic flora, bacterial vaginosis, virus-virus associations, urogenital herpes, urogenital mycoplasma infection, urogenital ureaplasma infection, urogenital candidiasis, urogenital Chlamidia infection and infection with various genotypes of human papilloma virus. Each sign is scored, and depending the number of points, persistent or transient clinical course of papilloma virus infections, or follow-up examination is performed.

EFFECT: determining tactics of the following management of the patient, forming group of potential risk for development of focal dysontogenetic and malignant transformations of urogenital epithelium.

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Description

The invention relates to medicine, relates to diagnostics in the field of venereology and can be used for the diagnosis and prevention of transient and persistent latent papillomavirus infection.

The high prevalence of urogenital human papillomavirus infection, which has reached the level of an epidemic disease, its proven role in the development of benign and malignant neoplasms of the genital organs, the heterogeneity of the human papilloma virus and the multi-organ pathology caused by it indicate not only the medico-biological relevance of this problem, but also its social significance. Currently, only cases of anogenital (venereal) warts are officially registered [ICD X, A 63.0], the intensive incidence rate of which in the Russian Federation in 2004-2005. amounted to 32.9-32.1 cases per 100 thousand people.

In the last decade, there has been a widespread increase in urogenital papillomavirus infection, one of the most common sexually transmitted viral infections. More than 30 million cases of anogenital warts are recorded annually in the world. These figures reflect only the frequency of clinical manifestations of papillomavirus infection, and not the true extent of infection of the population, since subclinical and latent forms of infection are not recorded. A huge number of young women with an unexpressed clinical picture of vaginal condylomatosis are a reservoir of infection and pose a danger to sexual partners and the unborn child. Given the costs of diagnosing and treating all types of human papillomavirus infection (the cost of investments is $ 1.6-6 billion per year), in the United States it is considered the most “expensive” infection after AIDS (1).

Data on the frequency of human papillomavirus infection of the urogenital tract in Russia are insufficiently complete and are based on statistics from individual medical institutions or doctors involved in this pathology (2, 3).

Diagnosis of human papillomavirus infection presents certain difficulties, especially its latent form, in which, despite the presence of the human papillomavirus, morphological changes in the tissue are not observed (4, 5). The urgency of the problem is increasing due to the fact that the etiological role of the human papillomavirus of high carcinogenic risk in the development of cervical cancer has been established

(6-13).

To date, there is no clear certainty regarding the factors that determine the different rates of progression of human papillomavirus infection, no reliable prognostic signs have been identified that contribute to the long-term persistence of the virus in the human body, while intraepithelial neoplasia develops against the background of a persistent human papillomavirus infection, in 15.0 20.0% of cases leading to carcinoma in situ and invasive cancer

(14-18).

The actual problem is not only the threatening incidence rate of this cancer-associated infection, but also the difficulties associated with its early diagnosis and treatment. Standardized approaches to laboratory verification of the diagnosis of urogenital papillomavirus infection are not well developed. The potential risk of malignancy of the cervical epithelium with a long-existing (persistent) papillomavirus infection dictates the need for mandatory rehabilitation in the detection of human papillomavirus (HPV).

The establishment of factors concomitant with the persistence of the human papillomavirus is also important for the scientific substantiation of the criteria for the formation of dispensary observation groups, the optimization of the diagnostic approach and the development of differentiated management tactics for patients with latent papillomavirus infection of the cervix, due to the 16th and 18th genotypes of the virus, based on anamnestic and laboratory criteria for various variants of the course of infection.

The closest technical solution to the claimed is a method for predicting precancerous diseases of the cervix in women with papillomavirus infection by examining biological material, determining various indices, based on which the correlation proliferation index is calculated. Based on the values of the latter, the degree of development of the disease is predicted (19).

This invention allows to determine individual adequate tactics of patient management, and the method of calculating the correlative proliferation index is not difficult and can be feasible in any institution of practical health care, however, this method is suitable to determine at the preclinical stage only the risk of developing cervical intraepithelial neoplasia - CIN 1 and 11.

The objective of the invention is to develop a unified methodology for the diagnosis of human papillomavirus infection.

The technical result of the invention is to collect an anamnesis and a comprehensive clinical and laboratory examination. Burdened oncological heredity, early onset of sexual activity, age up to 20 years and promiscuity are taken as anamnestic signs. Clinical signs include anogenital warts, cervical erosion and ectopia, contact bleeding, Ovuli nabotti, pelvic inflammatory diseases and the presence of an intrauterine device. Laboratory signs include sexually transmitted infections, mixed infection, lactobacillus deficiency, vaginal dysbiosis caused by opportunistic flora, bacterial vaginosis, virus-virus associations, urogenital herpes, urogenital mycoplasma infection, urogenital ureplasma infection, urogenital candidiasis and infection with various HPV genotypes. Then, each of the signs is evaluated according to a scoring system according to the table 1 “Differential signs of transient and persistent latent papillomavirus infection” described in the description, and if the patient has 55-86 points, the persistent course of papillomavirus infection is diagnosed, in the presence of 0-31 points, the transient course of papillomavirus is diagnosed infections (PVI), and at 32-54 points, patients are subjected to additional examination.

To improve the diagnosis, laboratory signs such as the average concentration of oncoprotein, IFN-α, TNF-α, the average level of prolactin in blood serum, the average level of interferon α and γ in the secret of the cervical canal and the average level of secretory immunoglobulins A can be taken into account.

The essence of the invention lies in a comprehensive approach to the diagnosis of human papillomavirus infection, depending on the type of infection.

Acceptance as anamnestic signs of burdened oncological heredity, early onset of sexual activity, age up to 20 years and promiscuity; as clinical - anogenital warts, cervical erosion and ectopia, contact bleeding, Ovuli nabotti, pelvic inflammatory diseases and the presence of an intrauterine device; as laboratory - sexually transmitted infections, mixed infection, lactobacillus deficiency, vaginal dysbiosis caused by opportunistic flora, bacterial vaginosis, virus-virus association, urogenital herpes, urogenital mycoplasma and ureplasma infections, urogenital candidiasis, and urogenital x HPV genotypes are necessary and sufficient to determine the variant of the course of PVI.

Evaluation of each of the signs by a point system and diagnostics at 55-86 points of persistent PVI course, at 0-31 points of transient PVI course, and at

32-54 points additional examination of patients reveals a variant of the course of persistent PVI.

The additional use as laboratory signs of an average level of concentration of oncoprotein, IFN-α, TNF-α, an average level of prolactin in blood serum, an average level of interferon α and γ in the secret of the cervical canal and an average level of secretory immunoglobulins of class A allows you to clarify the course of PVI of the cervix and thereby increase the accuracy of diagnosis.

From the analysis of scientific, technical and patent literature of the claimed combination of features is not revealed, which allows us to conclude that the claimed technical solution meets the criteria of "novelty" and "inventive step".

The invention is as follows.

At the first stage, epidemiological indications are examined. For screening for oncogenic types of HPV, men should have sex with sexually transmitted infections, including viral etiology; with genital warts, Bowenoid papulosis; giant genital warts Bushke-Levenshtein; erythroplasia of Keyr, penile cancer; patients with an early age of onset of sexual activity (14-16 years); faces of promiscuity.

Then examine the laboratory signs. The latent form of human papillomavirus infection is diagnosed only using molecular biological research methods - the detection of high-risk HPV by the method of polymerase chain reaction (PCR) in the absence of clinical, colposcopic and cytological changes in the cervix.

Next, the oncogenic genotype of the human papilloma virus is determined in the urogenital tract, combined infection with human papilloma viruses of different genotypes (see drawing).

According to indications - colposcopy, Pap smear staining (Pap-test), studies of immune system parameters, including local immunity.

A comprehensive bacteriological, bacterioscopic, molecular biological (PCR) study of the separated urethra, vagina and cervical canal is performed on N..gonorrhoeae, T.vaginalis, C.trachomatis, U.urealyticum, M.hominis, M.genitalium, G.vaginalis, yeast-like fungi of the genus Candida, Herpes simplex virus type I, II, Cytomegalovirus, determination of the microflora of the urogenital tract, taking into account the number, type of microorganisms and the sensitivity of microflora to antibiotics, detection of mixed infection with sexually transmitted infections. During verification of concomitant sexually transmitted infections and conditionally pathogenic microflora in diagnostically significant credits, treatment of the patient and her sexual partner is prescribed in accordance with sensitivity to antibiotics. Sexually transmitted infections associated with the human papilloma virus lengthen the duration of treatment and increase the risk of relapse. With dysbiotic processes against the background of changes in the pH of the vaginal environment and tissue hypoxia, the risk of activation of viral and other infections increases.

At the second stage, a variant of the course of human papillomavirus infection (transient, persistent) is determined, and risk factors for the persistence of human papillomavirus are identified in patients by summing and scoring.

Criteria for the persistent course of PVI are considered to be three or more cases of isolation of human papilloma virus of high oncogenic risk (16/18 genotypes) in scrapings of the cervical canal by PCR for a long time when taking material with an interval of 3-6 months, regardless of the change in the sexual partner. The criteria for the transient course of PVI are infection of the human papilloma virus with a high oncogenic risk of cervical canal epithelial cells for a short period of 3-6 months, when the human papilloma virus was detected once, with subsequent negative research results.

Gradation of symptoms is presented by the significance and frequency of occurrence in patients with different course of PVI (Table 1). The table below shows the maximum possible values of the scoring characteristics.

Table 1 Differential signs of transient and persistent latent papillomavirus infection No. Sign Patients with persistent PVI [n = 95] Patients with transient PVI [n = 112] abs % points abs % Anamnestic signs one Burdened oncological heredity 42 44,2 5 24 21,4 2 Early onset of sexual activity (14-17 years old) 28 29.5 3 22 19.6 3 Under 20 years old 12 12.6 one 3 2.7 four Promiscuity 61 64,2 6 48 42.9 Clinical signs 5 Anogenital Warts thirty 31.6 3 26 23,2 6 Cervical erosion and ectopia 59 62.1 6 42 37.5 7 "Contact" bleeding 51 53.7 5 36 32.1 8 Ovuli nabotti 22 23,2 2 9 8.0 9 Pelvic inflammatory disease 16 16.8 2 12 10.7 10 Intrauterine device 12 12.6 one 2 1.8 Laboratory signs eleven Sexually transmitted infections 84 88.4 9 80 71,4 12 Mixed infection (infectious index of 3 or more pathogens) 63 66.3 7 46 41.1 13 Lactobacillus Deficiency 69 72.6 7 48 42.9 fourteen Vaginal dysbiosis caused by opportunistic microflora (Str. Agalactiae, Enterococcus spp, E. coli, Proteus spp, Staph. Aureus), against the background of a sharp decrease or absence of lactobacilli thirty 31.6 3 29th 25.9 fifteen Bacterial vaginosis 38 40,0 four 24 21,4 16 Virus-virus associations 45 47.4 5 32 28.6 17 Urogenital Herpes 17 17.9 2 7 6.3 eighteen Urogenital mycoplasma infection (Mycoplasma hominis, Mycoplasma gemtalium) 22 23,2 2 17 15,2 19 Urogenital ureaplasma infection thirty 31.6 3 24 21,4 twenty Urogenital candidiasis twenty 21.1 2 3 2.7 21 Urogenital Chlamydia Infection 26 27.4 3 23 20.5 22 Infection with various HPV genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) with a range of infection index from 2 to 6 52 54.7 5 9 8.0 Additional laboratory symptoms 23 The average concentration of oncoprotein E7 16 HPV, ng / g protein 7.95 ± 0.47 0.89 ± 0.07 24 IFN-α, PCG / ml serum levels 12.7 ± 2.9 26.4 ± 3.1 25 TNF-α, PCG / ml in blood serum 24.9 ± 6.4 53.8 ± 10.9 26 The average level of prolactin in serum, mIU / ml 553.9 ± 36.29 321.3 ± 26.03 27 The average level of α-interferon, PCG / ml 2311 ± 500 486 ± 237 28 The average level of γ-interferon, PCG / ml 2379 ± 701.5 1218 ± 432 29th The average level of secretory immunoglobulins class A (sIgA), μg / ml 348.9 ± 4.2 175.6 ± 6.4

If a patient has a high oncogenic risk of a human papillomavirus, after clarification of complaints, medical history, examination and clinical and laboratory examination of the patient, all points are summed up in accordance with the gradation of the symptoms presented in table 1. In the presence of 0-31 points, the transient course of papillomavirus infection is recorded.

If patients have 55-86 points, a persistent course of latent urogenital papillomavirus infection is diagnosed and treatment is prescribed, which helps to reduce the risk of neoplastic processes and the prevention of cervical cancer.

In the presence of 32-54 points, patients need additional examination to resolve the issue of the course of human papillomavirus infection.

In case of a doubtful result of papillomavirus infection, additional laboratory signs are used: the level of interferon (IFN-α), tumor necrosis factor (TNF-α in blood serum), the level of prolactin in blood serum, the level of α- and γ-interferon in the secretion of the cervical canal, the level of secretory class A immunoglobulins (sIgA).

When identifying patients with intraepithelial neoplasia detected by a dermatovenerological appointment, it is recommended that they be referred to a gynecologist with constant monitoring by a dermatovenerologist: at high risk once every 3 months and once every six months - at low risk. With a transient variant of the course of papillomavirus infection of the cervix, in the absence of manifest manifestations, a follow-up is necessary in a gynecological institution with periodic examination for the human papillomavirus once every 3-4 months for 1.5 years.

In the latent course of human papillomavirus infection, observation and regular examination in gynecological institutions (cytological examination of smears and fingerprints and colposcopy) is necessary.

According to the presented algorithm, 207 patients were examined (95 with persistent human papillomavirus infection and 112 patients with a transient course of human papillomavirus infection) of the consultative dermatovenerological admission of the Federal Research Institute of Dermatovenereology and Immunopathology of the Russian Medical Technologies (UrNIIDViI).

The level of HPV infection and the nature of the course of human papillomavirus infection largely depend on the impact of a combination of risk factors. The use of a staged examination algorithm made it possible to identify signs accompanying the persistence of the human papillomavirus, which made it possible to differentiate a persistent human papillomavirus infection and to begin treatment at earlier stages.

The signs accompanying the persistence of the human papilloma virus include: burdened heredity for oncological diseases of various localization (2.1 times more often with persistent human papillomavirus infection compared with the transient course of infection), anamnesis of the pelvic organs in history (1.6 times ), the presence of background, pre-tumor and benign neoplasms of the reproductive system (erosion and ectopia of the cervix) (1.7 times), manifest manifestations of papillomavirus infection in the form of acute of condylomas (1.4 times), signs of chronic inflammation of the cervix, such as contact bleeding (1.7 times) and obstruction of the nabott glands (2.9 times), the use of intrauterine devices as a contraceptive method (7 times) ), mixed infection with other sexually transmitted infections (1.6 times) with a predominance of virus-virus associations (herpes simplex virus type I-II, cytomegalovirus) (1.7 times); Lactobacillus deficiency (1.7 times); disorders of the microbiocenosis of the urogenital tract (1.2 times); bacterial vaginosis (1.9 times); urogenital herpes (2.8 times); mycoplasma infection (1.5 times); urogenital candidiasis (7.8 times); urogenital chlamydia (1.3 times); expression of the human papillomavirus E7 oncogen (diagnostic criterion for potential neoplastic risk) (10.4 times), infection with various human papilloma virus genotypes (6.8 times), expressed intensity of local α- and γ-interferonogenesis in cervical secretion (α- interferon 1.9 times, γ-interferon 3.8 times higher), a high level of prolactin in the blood serum; increased secretory sIgA in vaginal secretion.

The following are clinical examples with extracts from outpatient records.

Patient B-va N.G., 33 years old (outpatient card No. 2145). I complained about the absence of pregnancy for 2 years. During the examination in the antenatal clinic, the diagnosis was established: primary infertility, cystic changes in the ovaries, chronic adnexitis.

For additional examination and treatment, the patient was referred to UrNIIDViI.

From the anamnesis, it is known that a woman was repeatedly examined for sexually transmitted infections, a human papillomavirus of high oncogenic risk (genotype 16) was detected, she denies other sexually transmitted infections, and heredity for oncological diseases is not burdened.

Menses from 14 years, the cycle is broken, after 25-35 days for 4-7 days, painful on the first day. Sex life since 19 years, married. Other sex denied. Does not use contraceptive methods. The husband has a second marriage, in the first marriage - two children.

On examination: peritoneal symptoms are negative, the external genitalia are formed correctly, female-type hair, the inguinal lymph nodes are painless, not enlarged, elastic. The mucous membrane of the vestibule of the vagina and sponge of the urethra without signs of inflammation, no discharge from the genital gap. In the mirrors: the cervix is cylindrical, the pharynx is punctate, contact bleeding is manifested during the collection of pathological material (5 points), from the cervical canal there is a clear discharge, in the back arch there is an abundant, homogeneous creamy discharge with an unpleasant "fishy" smell. On palpation: the uterus is not enlarged, painless, soft, mobile; ovaries on both sides - not enlarged, painless, dense. The vaults are free, there are no infiltrates in the parametria, the perianal region is not changed.

On examination: gonococci, trichomonads, yeast-like fungi of the genus Candida were not found in smears from the urethra, cervical canal and vagina; identified "key cells", the number of leukocytes is not increased. Aminotest is positive. In the study of scraping material from the urethra and cervical canal by PCR, the human papillomavirus of genotype 16 was detected; chlamydia, herpes simplex virus and cytomegalovirus not detected. Bacteriological examination of ureaplasma and mycoplasma was not detected. When sowing vaginal discharge at 5% blood agar, an increase in Lactobacillus spp was noted. 10 ³ (7 points), Staphylococcus epidermidis 10 ³ , Gardnerella vaginalis 10 ⁴ (4 points). An ELISA test revealed blood-specific Ig M in titer 1/200, species-specific Ig G in titer 1/40, species-specific Ig G to Chlamydia trachomatis in titer 1/20, species-specific Ig A to Chlamydia trachomatis in titer 1/20, antibodies to lipopolysaccharide antigens (RNGA) in the titer 1/320 (3 points).

The study of immunological parameters revealed a decrease in the relative content of T-lymphocytes, in particular T-helpers / inducers, an imbalance of immunoregulatory cells, an increase in the level of immunoglobulins of class G (white blood cells 5.4, lymphocytes 38% - 2.1, CD 3 + 42% - 0 , 86, CD 4 + 13% - 0.27,

CD 8 + 18% - 0.37, CD 16 + 15% - 0.31, CD 19 + 20% - 0.41, CD4 + / CD8 + 0.72, IgA 1.6 g / l, IgM 1.5 g / l, IgG 18.0 g / l, TNF-α 1.5 pcg / ml, IFN-α 0 pcg / ml.

Colposcopy revealed signs of cervical inflammation. When cytological examination of morphological changes were not detected. Ultrasound examination of the pelvic organs: signs of chronic inflammation of the ovaries on both sides (2 points), small cystic changes in the ovaries.

In the husband of the patient, chlamydia by PCR was detected in scrapings from the urethra.

The diagnosis was established: chronic urogenital chlamydia, bacterial vaginosis, latent papillomavirus infection of the cervix (transient course), chronic adnexitis outside the acute stage, cystic changes in the ovaries.

We used the developed score for the variant of the course of urogenital papillomavirus infection by the combination of aggravating signs. In this clinical case, the amount was 21 points (<31 points), which indicates a transient course of human papillomavirus infection. Upon repeated examination of the patient after 12 and 18 months, the human papillomavirus of genotype 16 was not detected. Cytological and colposcopic examination - no changes were detected.

Patient M., 34 years old (amb. Card No. 812). I went to the gynecologist for a preventive examination and was sent to the UrNIIDViI with suspected intrauterine infection.

From the anamnesis: it was repeatedly examined for sexually transmitted infections, ureaplasma was detected twice (3 points), herpes simplex virus type II (5 points). Treatment was prescribed. Oncological heredity is burdened by lung cancer (5 points).

Menses from 12 years, painful, cycle after 26 days for 5 days. Sex life from 17 years out of wedlock (3 points). In total there were 5 sexual partners (6 points). Currently divorced.

Three pregnancies ended in childbirth and two medical abortions. History: ovarian resection (polycystic) (2 points), diagnostic curettage (remnants of the ovum), cervical erosion (6 points). Of the means of individual prevention of sexually transmitted infections, uses a condom.

On examination: peritoneal symptoms are negative, the external genitalia are formed correctly, female-type hair growth, inguinal lymph nodes are painless, not enlarged, elastic, the mucous membrane of the vestibule and urethral sponge without signs of inflammation, no discharge from the genital gap. On examination in the mirrors: the cervix is cylindrical in shape, contact bleeding is manifested during the collection of pathological material (5 points), in the posterior vaginal fornix there is an abundant homogeneous creamy discharge with an unpleasant "fishy" smell.

On palpation: the uterus is not enlarged, painless, soft, mobile, the right ovary is enlarged. The vaults are free, there are no infiltrates in the parametria, the perianal region is not changed.

During bacterioscopic examination of material from the urethra, cervical canal and vagina, gonococci, Trichomonas, yeast-like fungi of the genus Candida were not detected; identified "key cells", the number of leukocytes is not increased. Aminotest is positive. In the study of scraping material from the urethra and cervical canal by PCR, a human papillomavirus of genotype 16 was detected. Molecular genotyping of the human papillomavirus revealed 16, 39, 59 genotypes (5 points). Chlamydia, cytomegalovirus not detected. Bacteriological examination of ureaplasma and mycoplasma was not detected. When sowing the vaginal discharge, growth of Gardnerella vaginalis 10 ⁵ (4 points), Streptococcus agalactiae 10 ⁵ (3 points), absence of lactobacilli (7 points) was noted.

When examining the level of oncoprotein E7, an increase in its concentration to 10.16 ng / g of protein was revealed. An elevated serum prolactin level was noted - 553.9 ± 36.3 mIU / ml.

Clinical diagnosis: Bacterial vaginosis, persistent papillomavirus infection of the cervix, aerobic vaginitis, genital herpes (7 points).

When evaluating the course of the urogenital papillomavirus infection, the sum of aggravating signs was 61 points (> 56 points), which indicates a persistent course of papillomavirus infection. Upon repeated examination of the patient, the human papillomavirus of genotype 16 was again detected, and repeated cytological and colposcopic examination revealed signs of atypia (intraepithelial neoplasia - CIN grade I).

The cost of introducing early molecular genetic screening for human papillomavirus is 25% lower than the cost of treating patients with developing complicated forms of human papillomavirus infection.

Thus, the basic principles of the differential diagnosis of the persistent and transient course of papillomavirus infection of the urogenital tract in the early stages are determined, based on clinical and medical history, laboratory: molecular genetic, bacteriological, immunological features of the course of human papillomavirus infection, and factors for the persistence of human papillomavirus have been established, which made it possible to develop stage examination algorithm, tactics of further patient management, form potential groups ceiling elements the risk of focal dysplastic and malignant transformation of the epithelium of the urogenital tract, early treatment in 95.8% of patients, to optimize the prevention of formation of persistent forms of genitourinary papillomavirus infections.

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19. Patent RU No. 2310197, IPC G01N 33/483, G01N 33/55, publ. November 10, 2007

Claims (2)

1. A method for the diagnosis of papillomavirus infection by collecting an anamnesis and a comprehensive clinical and laboratory examination, characterized in that the anamnestic signs are aggravated oncological heredity, early onset of sexual activity, age up to 20 years and promiscuity; as clinical - anogenital warts, erosion and ectopia of the cervix, contact bleeding, Ovuli nabotti, inflammatory diseases of the pelvic organs and the presence of an intrauterine device; as laboratory - sexually transmitted infections, mixed infections, lactobacillus deficiency, vaginal dysbiosis caused by opportunistic flora, bacterial vaginosis, virus-virus associations, urogenital herpes, urogenital ureaplasma infection, urogenital candidiasis, urogenital candidiasis infection with various genotypes of human papillomavirus, after which each of the signs is evaluated using a point system, as described in the description table 1 "Differential signs of transient and persistent latent papillomavirus infection" and if the patient has 55-86 points, the persistent course of papillomavirus infection is diagnosed, in the presence of 0-31 points, the transient course of papillomavirus infection is diagnosed, and at 32-54 points the patients are subjected to additional examination. 2. The method according to claim 1, characterized in that in addition as laboratory signs, the average concentration level of oncoprotein, IFN-α, TNF-α, the average level of prolactin in blood serum, the average level of interferon α and γ in the secretion of the cervical canal and the average level of secretory immunoglobulins of class A.

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