Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Of the more than 100 different human papillomavirus types (HPVs), the "high-risk" HPVs are associated with the vast majority of cervical carcinoma, and a pathologically distinct group of oropharyngeal tumors. In addition, other HPVs are associated with cutaneous tumors, in particular epidermodysplasia verruciformis and non-melanoma skin cancers. In general, HPV-associated cancers arise from a single accidental integration event of the viral genome into a host cell chromosome. Integration is a terminal event for the viral life cycle. Even though integration does not occur at specific chromosomal hot spots in the human genome, it follows a consistent pattern with respect to the viral genome, and expression of the HPV E6 and E7 genes is consistently retained. The normal function of E6 and E7 is to establish and maintain a cellular milieu that allows for viral genome replication. E6 and E7 target important cellular growth regulatory circuits among them the p53 and retinoblastoma tumor suppressors, respectively. Uncontrolled expression of the E6 and E7 proteins, as a consequence of viral integration is paramount to the establishment and maintenance of the tumorigenic state. In addition, expression of E6 and E7 increases genomic instability of the host cell thus accelerating malignant progression. Taken together, there is compelling molecular and epidemiological evidence in support of an oncogenic function of certain HPVs.