Figure 3.

Mechanism of action of the human papillomavirus (HPV) on cell cycle regulation. To progress from G1 to S cell cycle phase, cells have to pass the G1 restriction point that is under the control of the retinoblastoma protein (pRb). pRb binds and represses E2F transcriptional factors. Mitogenic signalling through CyclinD1/CDK4 or CyclinD1/CDK6 phosphorylates pRb, promoting E2F release. CyclinE/CDK2 completes pRb phosphorylation, allowing S-phase entry. HPV affects the cell cycle by using two viral oncoproteins, E6 and E7. The E6 protein binds p53 and promotes its degradation, whereas E7 protein binds and inactivates pRb. These viral oncoproteins determine cell cycle entry and inhibition of p53-mediated apoptosis. HPV-dependent inhibition of pRb promotes p16 accumulation. p16 represents a surrogate marker of HPV-positive HNSCC