Figure 4.

Model of role of human papillomavirus (HPV) in carcinogenesis. Our model predicts that tumors containing episomal HPV or HPV integrated in intergenic regions are primarily driven by E6/E7 oncogene expression, which are responsive to current therapies. However, tumors with HPV integration into cancer-related genes (or tumors that have integration events that alter expression of microRNAs [Wald et al. 2011]) will be also driven by altered cellular gene expression. These changes in gene expression can have further oncogenic effects, and therefore the tumor will be more aggressive and nonresponsive to therapy. These tumors are still driven by E6/E7 proteins, due to E1/E2 disruption, unregulated expression of E6/E7, and expression of E6* alternate transcripts linked to increased E7 protein expression. In addition, these tumors often have loss of disrupted genes or overexpressed fusion transcripts that contribute to oncogenesis by mechanisms that are still poorly understood.