Pre-cancer and cervical cancer have a common etiology and pathogenesis. Currently, the etiological role of HPV in the occurrence of this pathology has been proven. The virus and its genetic material are found in 98% of cases in epithelial cells with moderate, severe dysplasia and cervical cancer. Among the HPV that can affect the genitals, are serotypes associated with low (3,6,11,13,32,42, 43,44,72,73) and high (16, 18, 31, 33, 35, 39 45, 51, 52, 56, 58) oncological risk. Serotypes 16 and 18 in Europe and Russia cause about 80% of cervical cancer and severe dysplasia, the remaining serotypes are responsible for approximately 20% of precancerous and cancerous processes of the cervix.
The virus has a tropism for epithelial cells and has a productive (papilloma, condyloma) and transforming effect (CIN, cancer). Human papillomavirus infection (PVI) can be latent (carriage), subclinical (examination reveals koilocytosis, dysplasia, iodine negative zone) and clinically severe (endophytic, exophytic condylomas, cancer). In most cases, HPV infection goes unnoticed, during the life of the PVI suffers 80% of the sexually active population. HPV infection is asymptomatic, it is diagnosed according to PCR or microscopic detection of koilocytosis, less often – by the method of hybridization in solution (Digene-test). Serodiagnosis of PVI is not performed, since antibodies are formed in less than 30% of infected HPV.
The peculiarities of the course of PVI are such that in 95% of those infected, spontaneous elimination of the virus occurs over a period of 9-15 months. Approximately 5% of patients with HPV elimination does not occur; This is associated with susceptibility of the epithelium, hereditarily caused by defects in antiviral and antitumor protection. In such patients, the viral infection persists, the degree of dysplasia increases, and later, in 2–15 years, cervical cancer can form.
HPV is a DNA-containing virus, its DNA contains 9 genes, 2 of which encode structural proteins L1 and L2, the rest are functional proteins, including the E6 and E7 genes responsible for the tumor transformation of epithelial cells. HPV infection has an episomal stage, when viral particles are assembled in the cell, and integrative, in which part of the viral DNA is inserted into the genome of the ion exchanger, and then the tumor transformation of the host cell begins.
By dysplasia, or cervical intraepithelial neoplasia (CIN), is meant the processes of structural and cellular atypia (impaired cell differentiation) with a change in the epithelium layering without involving the basement membrane. According to the WHO classification (1995), mild, moderate and severe dysplasia (CIN) is isolated. If a violation of the structure of the epithelium, polymorphism of cells, an increase in mitoses, and dyskaryosis of the nuclei are observed in the lower third of the epithelial layer, then they speak of mild dysplasia, if there are changes in the lower and middle thirds, of its average degree, if the above changes seize the entire layer dysplasia.
Dysplasia is asymptomatic, more often it exists with background processes (90%), less often with visually unchanged cervix (10%). In almost all countries, screening programs have been adopted to detect precancer and cervical cancer, according to which a cytological examination of cervical smears and colposcopy should be carried out to all women every 1 time every 1 year, including those who have no complaints. The feasibility of including PCR screening for HPV in screening programs is currently being studied.
Cytological examination does not allow to make an accurate diagnosis, its sensitivity fluctuates within 60–0%, the information content of the method increases with an increase in the degree of dysplasia. It must be remembered that inflammation of the cervix can cause a cytological picture characteristic of dysplasia; after appropriate treatment, the picture is normalized.
A colposcopic picture of dysplasia may include opathological vessels (dilated, improperly branched) in the zone of transformation, punctuation, mosaics, whitish epithelium. Dysplasia causes local whitening of the epithelium in the case of acetoaceous test and iodine negative zones in Schiller’s test.
However, neither colposcopy nor cytology can determine the degree of dysplasia and exclude pre-invasive and micro-invasive cancer. The final diagnosis is established on the basis of a histological examination, for which material can be obtained, a targeted knife biopsy of the cervix with scraping of the cervical canal. It is not recommended to perform a biopsy with a conchotome (special forceps), since this technique does not allow to evaluate the underlying stroma. There should also be no electric loop biopsy, since coagulative tissue damage obscures pathological changes. It is necessary to avoid undue biopsy of the cervix and to strive for complete removal of the pathological focus, followed by histological examination, since the biopsy disrupts the integrity of the epithelial basement membrane, and cancer can proceed to the next stage.
Current data on the course of PVI and dysplasia indicate that CIN I spontaneously regresses in 75% of cases without any treatment, CIN II – in 40%, CIN III – in 5% of cases, and more often than not young contingent of patients. Therefore, when determining the management tactics, the degree of dysplasia, the age of the patient and reproductive function are taken into account. It is known that the surgical treatment of cervical dysplasia increases the risk of subsequent premature labor by 4 times.
In young women with infant dysplasia, a dynamic observation is shown during a year; in the absence of regression or deterioration, cervix is made conizable. In moderate and severe dysplasia, the cervical canal is scraped and the cervix is conized (radiosurgical, laser, electroconization), followed by histological examination of the removed tissues.
In postmenopausal patients with mild and moderate dysplasia, conization with curettage of the cervical canal is permissible, however, the indications for hysterectomy should be expanded.