Infections with specific high-risk of human papillomavirus constitute a major risk factor in the development of precancerous and cancerous lesions of the uterine cervix. Laboratory studies suggest that the human papillomavirus has a mechanistic role in development of these lesions. The two viral proteins consistently expressed in cervical carcinomas functionally abrogate critical cell cycle regulatory pathways, including those governed by the p53 tumor suppressor protein and the product of the retinoblastoma susceptibility gene, pRB. Subversion of these pathways by viral proteins causes genomic instability, resulting in the accumulation of chromosomal abnormalities followed by clonal expansion of malignant cells. Since continued expression of the papillomavirus proteins is critical for maintenance of the transformed state, they are attractive targets for prevention and therapy of precursor as well as cancerous lesions of the cervix.