Substantial experimental evidence accumulated over the past 8 years has indicated an etiological role for specific human papillomavirus (HPV) types in anogenital cancer and its premalignant precursors. Virus infection and viral gene expression emerge as necessary but obviously not sufficient factors for cancer induction. Additional modifications of host cell genes appear to be required for malignant progression of infected cells. The expression of viral oncoproteins in cells infected by "high-risk" types (e.g., HPV 16, HPV 18), in contrast to "low-risk" types (e.g., HPV 6, HPV 11), results in chromosomal instability and apparently in accumulation of mutational events. These "endogenous" modifications seem to be most important in the pathogenesis of premalignant lesions and tumor progression. Exogenous mutagens should act as additional cofactors.