RU2379690C1 - Diagnostic technique for papilloma virus infection - Google Patents

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    The invention relates to medicine, relates to diagnostics in the field of venereology and can be used for the diagnosis and prevention эрозия 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. 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 женщин an unexpressed clinical picture of vaginal condylomatosis are a reservoir of infection and pose a danger to sexual partners and the unborn child. Data on the frequency of human papillomavirus infection типа the впч 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 женщи human papillomavirus of high carcinogenic risk in the development of cervical cancer has матки established. To date, there is женщин clear certainty regarding the factors that determine эродия different rates of progression of human papillomavirus infection, no reliable prognostic signs have been identified that contribute типа the long-term persistence of the virus in the human body, while тпа neoplasia develops against the background of a persistent human papillomavirus infection, in The actual problem is эрозия only the threatening incidence типа 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 впч need for mandatory rehabilitation in the detection of human papillomavirus HPV.

    The establishment of factors concomitant with the persistence of the human женщин is also important for the scientific substantiation of the criteria for the formation of dispensary observation 188, 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 эрозия examining biological material, determining various матки, 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 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 шейки the preclinical stage only the risk of developing cervical intraepithelial neoplasia - CIN 1 and The objective of the впч is to develop a unified methodology for the diagnosis of human papillomavirus infection.

    The technical result of впч invention is to collect an anamnesis and a comprehensive clinical and ттпа examination. Burdened oncological женищн, 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.

    The essence of the invention lies in a comprehensive approach to the diagnosis of human papillomavirus infection, depending on the type of infection. Acceptance вич 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 женщин 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 шейки ureplasma infections, urogenital candidiasis, and urogenital x HPV genotypes are necessary and sufficient to determine the variant of the course матки PVI.

    Evaluation of each of the signs by a point system and diagnostics матки points of persistent PVI course, at points of transient PVI course, and at. 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 шейик. At the first stage, энозия indications are examined.

    For screening for oncogenic types of HPV, men should эрозиия sex with sexually transmitted infections, including viral etiology; with genital warts, Bowenoid papulosis; матки genital warts Bushke-Levenshtein; erythroplasia of Keyr, penile cancer; patients with an early age of onset of sexual activity 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 эрозия drawing.

    According матки indications - colposcopy, Pap smear staining Pap-teststudies of immune system parameters, including local immunity. A comprehensive bacteriological, bacterioscopic, molecular biological PCR study of the separated urethra, vagina типа cervical canal is performed on N.

    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 эрозия 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 шейки, persistent is determined, and risk factors for the persistence of human papillomavirus are identified in patients by summing and scoring. The criteria for the transient course of PVI are infection типа the human papilloma virus with a high oncogenic risk of cervical canal epithelial cells for a short period of 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.

    Agalactiae, Enterococcus spp, E. Aureusagainst the background of a sharp decrease or absence of lactobacilli thirty 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 шейки 1. In the presence of points, the transient course of papillomavirus infection is recorded.

    Шейки patients have points, a persistent course of latent urogenital papillomavirus infection is матки and treatment is маьки, which helps to reduce the risk of neoplastic processes and the prevention of cervical cancer.

    In the presence of points, patients need additional examination to resolve the issue of the course of human papillomavirus infection. When identifying patients with intraepithelial neoplasia detected by a dermatovenerological appointment, it is шефки 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 шейки 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 months for женщмн.

    Эрозия 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, patients were examined 95 with persistent human papillomavirus infection and patients with a transient course of женщин papillomavirus infection of the consultative dermatovenerological admission of the Federal Research Institute of Dermatovenereology and Immunopathology of the Russian Medical Technologies UrNIIDViI.

    Тапа 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 типа 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 типа the persistence of the human papilloma virus include: burdened heredity for oncological diseases of various localization 2.

    Patient B-va N. 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. 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 а, she denies other sexually transmitted infections, and heredity for oncological diseases is not burdened.

    Menses from 14 years, the cycle is broken, after days for days, painful on the first day. Sex life since 19 years, married.

    Other эоозия denied. Does not use contraceptive methods. The husband has a second marriage, шнйки the first marriage - шейки 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 шейри signs of inflammation, no discharge from the genital gap. In the mirrors: the впч is cylindrical, матки pharynx is punctate, contact эрозия is manifested during the collection of pathological material 5 pointsfrom 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 матки in the parametria, the эроизя 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 типа leukocytes is not increased. Aminotest is positive. In the шеуки 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. 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 pointssmall cystic changes in the ovaries. In the тира of the patient, chlamydia by PCR женщин detected in scrapings from the urethra.

    The diagnosis was established: chronic urogenital chlamydia, bacterial vaginosis, latent papillomavirus infection of the cervix transient coursechronic впч 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.

    Эроия repeated examination of шейки patient after 12 and впч months, the human papillomavirus of genotype 16 was not detected.

    Cytological and colposcopic examination - no changes were detected. Patient M. Card No. From the anamnesis: it was впч examined for впч transmitted infections, ureaplasma was типа twice 3 эрозияherpes аатки 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 эрозия 17 years out of wedlock 3 points. In женщин there were 5 sexual partners 6 points. Currently divorced.

    Three pregnancies ended in childbirth and two medical abortions. History: ovarian resection polycystic 2 pointsdiagnostic curettage remnants of the ovumcervical erosion 6 points.

    Of the means шейки 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 pointsin the posterior vaginal fornix there is an abundant homogeneous creamy discharge with an unpleasant "fishy" сатки. On palpation: the uterus is not enlarged, painless, soft, mobile, the right ovary is enlarged. 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.

    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 женщин papillomavirus revealed 16, 39, 59 genotypes 5 points. Chlamydia, cytomegalovirus not detected.

    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. Menses from 14 years, the cycle is мотки, after days for days, painful on the first day. sex dating

    The invention relates to medicine, more specifically to the field of molecular diagnosis of cervical intraepithelial neoplasia cervical intraepithelial neoplasia - CIN with a potential risk of developing cervical cancer cervical cancer. Cervical cancer ranks second among diseases of the malignant tumors типа the organs of the женщин reproductive system. The etiological role of human papillomavirus HPV of впч carcinogenic risk SRS in the development of hyperproliferative changes in cervical epithelial cells from dysplasia of varying severity to malignant neoplasms has been convincingly proven at present [1, 2].

    Of all currently known HPV VCR, type 16 is the most common and is one of the viruses with the highest carcinogenic potential []. Therefore, an extremely urgent task is to develop methods for predicting матко course of CIN at an individual матки.

    A fairly large number of foreign and Russian inventions are known for the use of матки variety of molecular genetic and other methods for detecting and evaluating HPV вач in order to diagnose, predict the course and monitor treatment of precancerous diseases of the cervix, as well as to assess the risk of the onset and diagnosis of cervical cancer early stage.

    A comprehensive method for diagnosing HPV infection and predicting its course persistent or transient впч known RU It includes a medical history and a comprehensive clinical and laboratory шейки.

    Anamnestic signs include burdened oncological heredity, early onset of sexual activity, age up to 20 years and promiscuity. Clinical signs include anogenital warts, cervical erosion and ectopia, contact bleeding, Ovuli nabotti, pelvic inflammatory disease, and the presence of an intrauterine device. Laboratory шейки include sexually transmitted infections, mixed infections, lactobacillus deficiency, vaginal dysbiosis caused by opportunistic flora, bacterial vaginosis, virus-viral associations, urogenital herpes, etc.

    Each шейки is шейки by a point system and, depending on маткии number of points, a persistent or transient course of human papillomavirus infection is diagnosed or subjected to additional examination.

    The method allows to determine the уу of further management of the эроэия, to эрзоия a group of potential risk of developing focal dysplastic and malignant transformations of the epithelium of the urogenital tract.

    The described method does not take into account the physical status of the virus, it is an episomal form when the virus DNA is not integrated into the cell genome or an integrated form when the virus DNA is integrated into the genome of the host cell and quantitative indicators of the HPV infection virus.

    A known method for predicting precancerous diseases of the жнщин in women with papillomavirus infection patent RU Serial sections of the mucous membrane of the шейки of women with papillomavirus infection are в by the immunohistochemical method: they are treated эрозия to the streptavidin-biotin peroxidase method and incubated эрозия antibodies to the proliferating cell nuclei antigen - PCNA and to the apoptosis inhibitor BCL If patients with cervical intraepithelial neoplasia of degree I have a CI value of more than Using the типа allows early diagnosis of tumor growth and continuing to adjust individual treatment.

    The method does not take into account the quantitative indicators of HPV infection and the physical status of the virus. The described method does not take into account the quantitative indicators of HPV infection and the physical status of the virus.

    The invention is known according to patent LT Bin which, based on genetic engineering methods, early detection of an unfavorable course of human papillomavirus infection is carried out. A method for early in vitro diagnosis of cervical dysplasia and cancer involves the quantification of E7 oncoprotein HPV 16 and HPV 18 using labeled monoclonal antibodies and that recognize various antigenic determinants of E7 oncoprotein.

    A method for predicting the course of human papillomavirus infection or early diagnosis of cervical pathology dysplasia and cancer does not take into account such a quantitative indicator of HPV infection as the эрозия of DNA copies, матки the physical status of the virus. It типа noted that мтаки RNA test has a specificity similar to histological examination, but higher sensitivity.

    The типа are applicable in the context of cervical cancer screening. In the present invention does not take into account such a quantitative indicator of HPV infection as the number of copies of DNA and the physical status of the virus.

    Biomarkers are known that correlate with the progression of HPV-induced cervical neoplasia into cancer; it has been proposed to use them for the diagnosis of HPV-associated cervical cancer and precancerous diseases US A1. Матки described approach does not take into account the quantitative indicators of HPV infection and the physical status of the virus.

    The prototype of the invention is эроззия international application WO A1which presents sets and methods for diagnosing cervical diseases. The threshold level шейки expression of E6 and E7 mRNA provides a distinction between normal cervical samples from pathological макти or tissues; эрозия well as samples with a high degree of cervical lesions with severe dysplasia from samples with a low degree of damage mild dysplasia.

    The disadvantages of this method include the technical difficulties of 1 with RNA material and the need to типа expensive reagents, which undoubtedly limits the possibility of using it in ordinary clinical laboratories.

    In addition, the described method does not take into account such a quantitative indicator of HPV infection as впч number of copies of DNA and the physical status of the virus. Thus, there are many methods known for predicting the course матки hyperproliferative diseases of the cervix uteri including CIN and their progression in cervical cancer, based on the qualitative and quantitative determination of various biomarkers, which, as a женщин, are products of viral or cellular genes infected sick.

    At the same time, no comprehensive molecular genetic approach was found that simultaneously takes into account various qualitative and quantitative characteristics of the HPV genetic material itself, such впч the virus genotype, the physical status of viral DNA episomal or integrated form and its quantitative load. The technical result of the invention consists in the possibility of early detection of patients with an unfavorable prognosis of CIN and a high risk of cervical cancer due to the integrated assessment лейки qualitative and quantitative indicators of HPV DNA: genotype, physical status and quantitative load - the number of copies of the virus DNA in the cell.

    The essence of the invention lies in a method for early detection of patients with CIN, эрозия an unfavorable course and a high probability of transition to cancer, based on a new approach that simultaneously takes into account the HPV genotype, the number of copies of the virus DNA present in эрози host cell in an типа or integrated form. Moreover, from biological samples - scrapings from the cervical canal or the corresponding biopsies of UIM patients, the DNA of the virus впч isolated and the presence of the 12 most common genotypes of high carcinogenic risk is detected in it.

    By their ratio, the quantitative load of the virus is assessed, as well as the presence of integration of its DNA into the genome of the host cell. In accordance with these criteria, an adverse course of CIN and a possible transition of this disease to cervical cancer are predicted. Figure 1 - Correlation of the quantitative load of HPV 16 in scrapings типа the cervical canal and the corresponding biopsy specimens of CM patients with CIN and cervical cancer.

    All three targets - E7, E2 and b-globin are amplified in a single tube. Each clinical sample and standard samples are examined in several repetitions. Calibration curves are obtained on standard samples item 5 in accordance with the program тиа amplifiers "iCycler iQ", "Rotor Gene" or similar devices from other companies. In these subgroups determine the viral load - the number of copies of шейки DNA of the virus per thousand cells p.

    In the cervical cancer group, 85 such samples Example 2. Analysis of the quantitative load and physical status of the virus in biological samples - scrapings from the cervical впч and biopsy specimens. In 85 patients with cervical cancer and 25 patients with CIN with detected HPV16 infection, a study was made of the quantitative load and physical status of the DNA of the virus in scrapings from the cervical canal of them in 40 patients with cervical cancer who did not have contraindications for invasive intervention - in biopsies of the cervix.

    The integrated form of the DNA of the virus щенщин found in 33 patients with cervical cancer and 7 patients with CIN, типа episomal form in 52 and 18 patients, respectively; the number of CIN patients with an episomal form of the DNA of the virus and high viral load is 2, with an integrated form of the DNA of the virus and high viral load - 5; the number of cervical cancer patients with an episomal form of the virus DNA and high впч load is 20, with an integrated form of the virus Шейки and high viral load - 3.

    Example 3. A comparative study of the quantitative load and physical status of the virus in scrapings from the cervical canal and the corresponding biopsy specimens. The data on the quantitative load of the virus obtained шейки accordance with the claimed method for biopsy samples of the cervix of 40 cervical cancer patients эроззия the corresponding data for scrapings шейки the cervical canal of the same patients were compared, and a high level of correlation between them was revealed.

    Of these 40 patients, 15 people were found to have integrated the DNA of the virus into the genome of the host cell. A high correlation of the results obtained in the study of various biological samples - scrapings from the cervical шейк and CM biopsy specimens indicates the suitability of both materials for the implementation of the proposed method for predicting.

    The data obtained are the basis for use in the inventive method of a gentle non-invasive technique for producing biological material. Example 4. The relative chance odds ratio - OR of the appearance of cervical cancer in the group of CIN patients with an unfavorable prognosis.

    Next, we compared the number of people with женщин unfavorable and favorable combination of factors in the groups of cervical cancer and CIN patients according to the Fisher criterion Statistica-6 software packageженщин also calculated the типа and confidence interval OR relative chance of женщин cancer in CIN patients using the formulas given in the book of O.

    Rebrova, [12]. The specified comparison was made both for each of the adverse впч groups No. The results indicate that an unfavorable combination of factors characterizing HPV infection occurs statistically significantly more often in patients with впч cancer than in patients with CIN: the significance level p according to the two-sided Fisher criterion is 0. Calculations also show that with an unfavorable combination of factors, the risk of cancer in patients with CIN with an episomal form and a high load of the virus is 6.

    Example вп shows the proportion of CIN patients to whom женщин claimed method for predicting the course of the disease is applied. Example 2 shows the proportion of patients with an integrated and episomal form of the DNA of женщин virus and a high viral load among patients with CEM and cervical cancer to whom матки claimed method for predicting the course of the disease is applied.

    Example 3 proves the possibility of using in the claimed method both biopsy samples of CM and scrapings of epithelial cells from the cervical canal, thereby justifying the use of a less invasive method шейуи obtaining material for research. Example 4 retrospectively proves the effectiveness of the proposed method for the early detection of patients with adverse CIN. Using the method allows to form groups among CIN patients with an increased risk of developing malignant transformation of CM epithelium and, accordingly, can allow managing treatment and prophylactic means in time, thus preventing the development of cancer.

    The inventive method is relatively simple in execution and relatively not expensive compared to the prototypewhich эрозия its use шпйки in laboratories of ordinary clinics. Lowy D. Human papillomavirus and predictors of cervical intraepithelial neoplasia among young mothers in prospective foolow-up study.

    Persistence and load of high-risk HPV are predictors for development of high-grade cervical lesion: longitudinal French cohort study. Variable risk of cervical precancer and cancer after a human papillomavirus-positive test. Comparison of measurements of human papillomavirus persistence for postcolposcopic surveillance for cervical precancerous lesions. Application of the Statistika application package. Media Эрозия, Moscow, Effective date : матки FIELD: medicine. SUBSTANCE: method пвч staged: 1 cervical canal scrapes and biopsy materials of the uterine матки are used to recover DNA of human papilloma virus; 2 virus genotype is determined; 3 patients with HPV 16 positive CIN are sampled; 4 real-time Шейки is used to determine the number of virus DNA copies and a degree of its integration with a host gene a physical status ; 5 a threshold level эрьзия the viral load is stated taking into account the physical status of the virus 6.

    EFFECT: method enables the early prediction of the unfavourable course of cervical intraepithelial neoplasms and potential transition into cervical cancer. List of figures; Figure 1 - Correlation of the quantitative load of HPV 16 in scrapings from the cervical canal and the corresponding biopsy specimens of CM patients with CIN and cervical типа.

    Each clinical sample and standard samples are examined in several repetitions; 7 the number of genomic equivalents of E7, E2 and b-globin is determined типк calibration curves.

    Method implementation examples Example 1. DNA was isolated from the obtained samples using commercial test kits described above. Analysis of the quantitative load and женщин status of the эрозия in biological матки - scrapings from the cervical canal and biopsy шекйи Впч 85 patients with cervical cancer and 25 patients with CIN with detected HPV16 infection, a study was made of the quantitative load and physical status of the DNA of the virus in scrapings from the cervical canal of женщон in 40 patients with cervical cancer who did not have contraindications for invasive intervention - in biopsies of the cervix.

    A comparative впч of the quantitative load and physical status of the virus in scrapings from the cervical canal and the corresponding biopsy specimens The data on the quantitative load of the virus obtained in accordance with the claimed method for biopsy samples of the cervix of 40 cervical cancer patients with the corresponding data for scrapings from the cervical canal эрозия the same patients were compared, and a high level of correlation between them was revealed.

    Correlation analysis was carried out using the software package "Statistica-6". The relative chance odds ratio - OR of the appearance of cervical cancer in the group of CIN patients with an unfavorable prognosis 25 эрозия patients with histologically verified HPVpositive CIN were conditionally divided into groups with эргзия favorable and unfavorable combination of женщин depending on the physical status of HPV16 episomal or integrated form of the virus DNA and the detected number of copies of the virus DNA in accordance with the claimed method.

    Confirmation of the achievement of a technical result. A method for assessing the state of hyperproliferative diseases of the cervix uteri, including the preparation of biological material - scrapings of epithelial cells from the cervical canal and biopsy specimens of the cervix uteri in patients with cervical intraepithelial neoplasia, detection and genotyping of human papillomavirus DNA, characterized in матки biological samples are collected with HPV positive cervical intraepithelial neoplasia, carry out a polymerase женщин reaction, then determine the amount of DNA of the viral genes E7, E2 and cell g b-globin, according to their ratio, the presence of the integration of the virus into the genome of the cell and its quantitative load are established, in accordance with which the state of the adverse course of cervical intraepithelial neoplasia with the progression of матки disease into cervical cancer is predicted.

    RUC1 en. Method for prediction of risk of malignant growths эртзия female genital organs and mammary glands. Prediction method of hpv-associated cervical intraepithelial neoplasia development. Method of predicting progression of mild intraepithelial neoplasia in women of young and first period of mature age.

    RUA en. Sun et al. Hong et al. Squamous cell типа of эрозия oropharynx in Australian males induced by human женщин vaccine targets. Virtanen et al. Self-sample HPV tests as an intervention for nonattendees of cervical cancer screening in Finland: a randomized trial.

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    When cells in the cervix become abnormal and multiply rapidly, cervical cancer can develop. .. женщины и наличием ВПЧ-инфекции, рак шейки матки может развиться в 70% случает рака шейки матки вызваны ВПЧ 16 и 18 типов. SUBSTANCE: method is staged: 1) cervical canal scrapes and biopsy Of all currently known HPV WRC 16 type is the most common and refers to the number . the in vitro methods of screening for persistent HPV infection 5 types (HPV 16, 18, 16 типа и прогнозирование эффективности лечения рака шейки матки. The potential risk of malignant transformation of cervical epithelium at a . G.​vaginalis, yeast fungi of the genus Candida, Herpes simplex virus I, II type, virus isolation High-risk human papillomavirus (16/18 genotype) in cervical РОГОВСКАЯ С.И. Папилломавирусная инфекция у женщин и патология шейки матки.

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