Cervical pathology

Cancer and precancerous lesions of uterine cervix remain one of the most actual issues of oncogynecology worldwide, being not only medical but also social problem. Starting from 1997 slight but constant growth of morbidity rate for cervical cancer is observed in Ukraine, whereas opposite tendency was noticed for the last years in developed countries. 19 cases of new disease per 100 thousand of population are registered in Ukraine today. Moreover, almost 20% of patients can not count on radical treatment due to advanced disease. Cervical intraepithelial neoplasias (CIN) are three consecutive stages of preinvasive lesion of cervix. There is a possibility of development of malignant cervical tumors in case of CIN progression. In most cases cervical cancer is preventable. It is considered, that cancerogenesis in cervical epithelium has step-like pattern and can take up to 10 years, however appropriate treatment on early stages of CIN enables to prevent the development of invasive carcinoma. We have to point to the fact that on every stage this process can be interrupted by activation of immunity, apoptosis or spontaneous regression. In spite of existence of multiple hypotheses, biological properties of CIN which directly determine the likelihood of neoplastic transformation against the background of displastic processes are still unknown.

Well-known and proven is the fact of cervical cancer association with persistence of high risk papillomaviruses (HR-HPV), types 16 and 18 being the most important. These viruses predetermine tumor transformation via activity of 2 viral proteins E6 and E7. More then 300 millions of women worldwide are infected with papillomaviruses nowadays. Nevertheless according to data of different scientists, women who are infected with HR-HPV would develop the progression of displastic lesions only in 3% of cases, invasive carcinoma would developed in less than 0,5% patients. Obviously, HPV is the initial cause of cervical cancer, but infection of epithelial cells causes only a predisposition for malignant transformation. Concomitant conditions are necessary for irreversible development of tumor transformation. Principal part is assigned to hormonal disturbances, associated infections, genital herpes viruses, smoking and type of nutrition.

Pap-test is cytological method which enabled to identify women with asymptomatic courses of precancerous lesions and carcinoma of cervix on earlier stages. Although introduction of screening programs was effective in decrease of mortality and morbidity from cervical cancer in developed countries, utilization of this method is limited because of low specificity and sensitivity. False negative results comprise up to 15-50%, whereas false positive – up to 30%. It mostly depends on subjectivity of cytological diagnoses. In addition, even histological examination of cervical biopsies, which were taken from women with abnormal pap-smears, also was not interpreted unequivocally by different pathologists. That is why today there is a necessity in search of new criteria which can help in earlier and correct diagnostics of CIN and cervical cancer. Analysis of immunohistochemical marker expression significantly gain in importance for the last years, because in this case the quality of information increases dramatically. Determination of tumor or CIN immunophenotypes can be viewed as a basis for selection of the most rational treatment plan or for assignment of risk "groups” (those patients who need more thorough follow-ups owing to probability of subsequent progression of cervical lesions). Studying of molecular biomarkers for detection and interpretation of dysplastic cells also allows to decrease the influence of subjective circumstances, which accompany traditional morphological approach. Due to usage of prognostic markers it is possible to select those patients who have an increased risk of invasive carcinoma development, which can reduce the cost of further diagnostics and therapeutic procedures. Analysis of immunohistochemical marker expression in dysplastic and neoplastic cervical lesions enables to improve diagnostics and prognosis, to predict tumor’s respond to treatment and to form "risk groups”. Thereby, we recommend using the spectrum of most significant and complementary markers while examining patients with cervical cancer or CIN, which would help to ensure maximum efficiency of treatment of each patient with minimal costs.