Fig. 2

HPV-driven carcinogenesis: a multistep molecular mechanism of host-viral interaction. The initial outcome of carcinogenesis is modulated by both viral (high-risk versus low-risk HPV types, HPV integration) and host factors (inflammatory response, oxidative stress). Inflammatory response upon initial infection such as IFN response plays role in reducing episomal HPV resulting clearance of infection. Integration of HPV is initiated with DNA damage. The IFN induced loss of episomal HPV and down-regulation of E2 leads to the selection of cells with integrated HPV genomes expressing higher levels of E6 and E7. Once the early genes E6 &E7 are expressed, TLR9 downregulated and IFN response impaired, resulting a conducive milieu for immune evasion and persistent infection. Upregulation of E6/E7 increases genetic instability and chromosomal rearrangements that increase the risk of integration. Overexpression of E6/E7 leads to deregulation of the cell cycle via p53 & Rb degradation, deregulation of oncogenes and miRNAs expression. Epigenetic and genetic modification in viral and host genome leads to the deregulation of E6 &E7 oncogenes, and host tumor suppressor genes that lead to carcinogenesis. Oxidative modification of TFs also leads to altered gene expression and carcinogenesis