Once again about HPV and cervical neoplasia: biology and pathogenesis

Human papillomavirus (HPV) is the main risk factor for developing cervical cancer (CC). About 70–75 % of all invasive CC cases worldwide are associated with HPV 16 and 18 genotypes, 20–25 % cases being related to HPV 31, 33, 35, 45, 52, and 58 genotypes. Currently, there are more than 100 tests for HPV diagnostics, but up to now, it has been difficult to establish and evaluate sensitivity of cytological examination for detecting pre-invasive and invasive cervical squamous and glandular lesions. The use of biomarkers for a more objective diagnostics of squamous intraepithelial lesions (SIL) was investigated in numerous studies. The most widely used biomarker is the p16INK4a (p16) antibody that flags E7-induced high-risk HPV-caused cell proliferation. The diagnosis of SIL upon cervical biopsy is also highly variable convincingly supported by the documented evidence. The intermediate category, cervical intraepithelial neoplasia grade 2 (CIN2), provides the least reproducible results. The use of immunohistochemistry p16, alone or in combination with the proliferation marker Ki-67, increases the effectiveness of differentiation between SIL and its benign imitators. Thus, a high degree of variability still is observed between the data of cervical cytology and biopsy due to both sampling errors and the expertise of medical works involved in data interpretation. Atypical squamous cells of undetermined significance (ASC-US) represent the primary source of such variability.