THE ONCOGENIC ROLE OF HUMAN PAPILLOMAVIRUS PROTEINS

Each human papillomavirus (HPV) type is genotypically distinct and inf ects epithelial cells at unique anatomic sites. Among the HPV types de scribed, a subgroup is associated with genital disease and a subset of these is found in 90% of genital cancers. Although in benign infectio ns the viral genome is present as an episome, in cancers it is integra ted. The integration event invariably results in the expression of two viral proteins, E6 and E7. These two proteins are capable of transfor ming cells individually and cooperate to immortalize primary human epi thelial cells. Molecular analysis has revealed that the E6 protein enc oded by the HPV ''high risk'' types prevalent in cancers forms a tripa rtite complex with the p53 tumor suppressor protein and a cellular pro tein termed E6-AP, resulting in the degradation of p53. The E7 protein encoded by ''high-risk'' HPV types shows high-affinity association wi th the retinoblastoma tumor suppressor, pRb. The E7 protein associates also with other cellular factors known to play a role in cell cycle r egulation. This review discusses the evidence, molecular and biologica l, in vitro and in vivo, supporting a direct role for the ''high-risk' ' HPV type encoded E6 and E7 proteins in cervical carcinogenesis.