High-Risk Human Papillomaviruses and DNA Repair

Human papillomaviruses (HPVs) are small DNA viruses that infect basal epithelial cells and are the causative agents of cervical, anogenital, as well as oral cancers. High-risk HPVs are responsible for nearly half of all virally induced cancers. Viral replication and amplification are intimately linked to the stratified epithelium differentiation program. The E6 and E7 proteins contribute to the development of cancers in HPV positive individuals by hijacking cellular processes and causing genetic instability. This genetic instability induces a robust DNA damage response and activating both ATM and ATR repair pathways. These pathways are critical for the productive replication of high-risk HPVs, and understanding how they contribute to the viral life cycle can provide important insights into HPV's role in oncogenesis. This review will discuss the role that differentiation and the DNA damage responses play in productive replication of high-risk HPVs as well as in the development of cancer.