Virtually all cases of cervical cancer are associated with persistent infection with a restricted set of high-risk human papillomaviruses (HPV). The majority of HPV infections induce low grade squamous epithelial lesions that in more than 90% of cases spontaneously regress and in about 10% eventually progress to high grade lesions and even less frequently evolve to invasive cancer. Tumor progression is characterized by (1) increased expression of viral E6 gene and E6-dependent degradation of p53, and increased expression of E7, known to bind and inactivate pRb; and (2) integration of viral DNA into host genome with the consequent disruption of E2 viral gene. Molecular markers able to identify viral infections associated with progressing cervical neoplasia are strongly needed for cervical cancer screening and triage. We have recently performed the expression profile analysis of p53-related genes in HPV16- positive carcinomas along with autologous non-tumor tissue, and identified significant differences in the expression levels of genes involved in regulation of apoptosis, cell cycle, proliferation and DNA repair pathways. In particular, BRCA1, CDKN2A (p16), CASP2 and TNFRSF10B genes were significantly up-regulated (P < 0.05) in cancer lesions. Validation of these candidate biomarkers is currently in progress on a larger number of cases, including different grades of HPV-related neoplastic lesion (CIN1-3 and invasive cervical cancer). Such studies will contribute to the development of new tools for the identification of premalignant lesions at high risk of progession to invasive cervical carcinoma.
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