Figure 1.

HPV Patho-oncogenesis. The HPV virion invades the epithelium of the oropharynx, infecting the basal layer of cells. Within these cells, E6 and E7 inhibit p53 (tumour protein 53) and pRb (retinoblastoma protein) respectively, affording the cell the ability to replicate without regulation by these Tumor Suppressor Genes (TSGs). Further to this E6, promotes carcinogenesis in several ways: firstly, through inhibition of pro-apoptotic proteins (namely, GADD34/PP1 (growth arrest and DNA damage induced transcript 34/serine/threonine protein phosphatase), Procaspase 8, FADD (FAS-associated death domain protein), or Bak) [85,86,87,88]; secondly, by suppressing host–IFN (interferon) antiviral response by downregulating IRF3 (interferon regulatory factor 3) and Tyk2 (Tyrosine kinase 2); thirdly, by disrupting tissue integrity through degradation of PDZ proteins (PDZ proteins play an important role in anchoring receptor proteins in the cell membrane to cytoskeletal components; these proteins also play an integral role in signal transduction complexes. Interaction with certain proteins promotes oncogenic potential) via expression of a PDZ protein binding motif (PSD-95/D1g/ZO-1) [89]; and finally, by promoting cellular immortalisation by targeting NFX1-91, which is an endogenously expressed transcriptional regulator of human telomerase reverse transcription (hTERT) (active in stem cells) that promotes telomerase induction and cellular immortalisation [90].