The genetic program of genital human papillomaviruses in infection and cancer.

Human papillomavirus (HPV) infection has been recognized as the major cause of cervical cancer. This article summarizes the functions of HPV gene products that cause abnormal cell growth--E6 and E7--and reviews how cellular and viral factors influence their synthesis. E6 and E7 inactivate two cellular tumor-suppressor gene products, p53 and RB. In cervical cancer, E6-E7 gene control is deranged by mutations in viral control sequences and in integrated HPV fragments by the disruption of the viral repressor E2. Elimination of this sequence makes E6-E7 mRNAs unstable, and deranges cellular regulation at the integration site. It is apparent that an intricate interplay of cellular and viral factors determines whether the outcome is active papillomavirus infection, viral latency, or ultimately, genital cancer.