Host cell regulation of HPV transforming gene expression.

Infections with specific types of human pathogenic papillomaviruses, most notably HPV 16 and 18, appear to be necessary but not sufficient factors in the etiology of anogenital cancer. Recently their role in the induction of genital intraepithelial neoplasias became evident. The expression of specific HPV genes (E6-E7) emerges as an important prerequisite for the proliferative phenotype of cervical carcinoma cells. Increasing evidence points to the existence of a host-mediated intracellular control which down-regulates these HPV genes in replicating normal cells. This control appears to be interrupted in HPV-positive carcinoma-cells, probably due to structural modifications of the respective host cell genes acquired during the period of viral DNA persistence. Factors affecting genes seem to be responsible for geographic differences in anogenital cancer incidence, since HPV infections appear to occur worldwide at similar frequency.