The role of human papillomavirus in anogenital cancer

More than 30 types of HPV infect the anogenital skin and mucosa, causing condylomas and intraepithelial neoplasia of different severity. On a worldwide basis, HPV 16, 18, and 45 are distinguished by a strong association with high-grade intraepithelial neoplasia and the greatest prevalence in anogenital malignancy. Genetic experiments have assigned oncogenic activity to the viral genes E6, E7, and E5. The encoded proteins interact with and disturb the physiologic functions of cellular proteins that are involved in cell cycle control. The proteins of HPV 16, 18 or related types are most efficient in this regard. Some of these activities lead to genetic instability of the persistently infected human cell. This enhances the probability of mutations in cellular proto-oncogenes and tumor suppressor genes and thus contributes to tumor progression. Mutations in cellular genes devoted to the intracellular surveillance of HPV infections, integration of viral DNA, and deletions or mutations of viral transcription control sequences lead to a significantly increased expression of the E6/E7 genes, which is a consistent characteristic of high-grade intraepithelial neoplasia and cancers. The genetic instability caused by viral oncoproteins and the autocatalytic increase in oncoprotein expression caused by mutations in the viral and cellular genome identify the virus as a major driving force of progression.