CELLULAR AND MOLECULAR PATHOGENESIS OF CE RVICAL-CARCINOMA

There is now substantial evidence that specific human papillomavirus ( HPV) types are probably an etiological factor of cervical cancer and i ts precursors. Virus infection, viral genes expression emerge as neces sary but not sufficient for cell transformation. The E6-E7 oncoprotein s of <<high risk>> (HPV 16-18) papillomaviruses bind specifically, and with high affinity, to cellular tumor suppressor gene products p53 an d pRb, in contrast to <<low risk>> (HPV 6-11) types. This binding dist urbs the cell cycle and results in chromosomal instability, aneuploidy and is likely the starting point of the integration of viral DNA to t he host genome. These endogenous modifications are related to the morp hological and colposcopical events of cervical intraepithelial neoplas ia and seem to be most important in the pathogenesis of cervical cance r precursors lesions and tumor progression.