The role of integration in oncogenic progression of HPV-associated cancers

Persistent infection with a subset of “high oncogenic risk” human papillomaviruses (HPVs) can promote the development of cancer. In these cancers, the extrachromosomal viral genome has often become integrated into the host genome. The integration event is thought to drive oncogenesis by dysregulating expression of the E6 and E7 viral oncogenes, leading to inactivation of critical cell cycle checkpoints and increased genetic instability in the host. This Pearl reviews the evidence that gave rise to the current textbook paradigm of HPV integration events and their consequences and incorporates new findings that demonstrate that stochastic integration events can promote oncogenesis in many ways.