title: Genomic Instability Induced By Human Papillomavirus Oncogenes.
abstract: Cervical cancer is one of the leading causes of cancer death in women worldwide. Human papillomavirus (HPV) infection is necessary but not sufficient for the development of cervical cancer. Genomic instability caused by HPV allows cells to acquire additional mutations required for malignant transformation. Genomic instability in the form of polyploidy has been implicated in a causal role in cervical carcinogenesis. Polyploidy not only occurs as an early event during cervical carcinogenesis but also predisposes cervical cells to aneuploidy, an important hallmark of human cancers. Cell cycle progression is regulated at several checkpoints whose defects contribute to genomic instability.The high-risk HPVs encode two oncogenes, E6 and E7, which are essential for cellular transformation in HPV-positive cells. The ability of high-risk HPV E6 and E7 protein to promote the degradation of p53 and pRb, respectively, has been suggested as a mechanism by which HPV oncogenes induce cellular transformation. E6 and E7 abrogate cell cycle checkpoints and induce genomic instability that leads to malignant conversion.Although the prophylactic HPV vaccine has recently become available, it will not be effective for immunosuppressed individuals or those who are already infected. Therefore, understanding the molecular basis for HPV-associated cancers is still clinically relevant. Studies on genomic instability will shed light on mechanisms by which HPV induces cancer and hold promise for the identification of targets for drug development.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Chen