Advances in understanding the mechanisms of the human papillomavirus oncoproteins

High-risk human papillomaviruses (HPVs) are responsible for almost all cervical cancer cases and a growing number of oropharyngeal and anogenital cancers. The primary HPV oncoproteins, E6 and E7, act together to manipulate multiple cellular pathways that can ultimately result in malignant transformation. This includes the deregulation of several signalling pathways that regulate cell proliferation, cell cycle progression and cell survival. Although multiple functions of HPV E6 and E7 in driving oncogenesis are well known, recent studies have uncovered novel oncogenic functions of the HPV oncoproteins, including the manipulation of emerging mechanisms of cancer development, such as epigenetic modifications, cellular plasticity and genomic instability. This review explores current advances in understanding how the HPV oncoproteins interact with these cellular processes, highlighting potential therapeutic targets in HPV-associated cancers.