Table 1.

HPV gene expression influencing neoplastic transformation and immune control [28]

Epithelial cell behaviour	HPV gene: Targets
Sustained proliferation & signalling	E7: ↓RB/HDAC; E7: ↑KDM6A/B; E5: ↑EGFR
Enabling replicative immortality	E6: ↑Telomerase
Resisting cell death	E6: ↓p53/BAK; E6: ↑BCL-2
Deregulating cellular energetics	E6: ↑ mTORC1/MYC
Genome instability & mutation	E7: ↑dsDNA breaks
Inducing angiogenesis	E7: ↑ HIF1α; E6/E7: ↑VEGF & IL8
Activating invasion & metastasis	E6: ↓PDZ proteins
Evading growth suppression	E6: ↓p53; E7: ↑RB
Impacts on immune control
Avoiding immune destruction	E5: ↓MHCI/II/TAP; E7: ↓CXCL14; IFNk E7: ↓IRF1 & cGAS-STING; E6: ↓IRF3
Tumour promoting inflammation	E6/E7: ↓CCL20/& local APC E6/E7: ↑IL6 & monocyte CCL2 & MMP9

Abbreviations: RB, RetinoBlastoma tumour suppressor protein; HDAC, Histone DeACetylase; KDMA/B, Lysine DeMethylases; EGFR, Epithelial Growth Factor Receptor; p53, DNA-binding transcription factor; Bcl-2, apoptosis suppressor protein; BAK, Bcl-2 homologous antagonist/killer protein; mTORC1, Mammalian Target of Rapamycin Complex-1; MYC, proto-oncogene; ds, double stranded; HIF1α, Hypoxia-Inducible Factor-1-alpha; VEGF, Vascular Endothelial Growth Factor; IL8, InterLeukin 8 cytokine; PDZ domain binding proteins; MHC, Major Histocompatibility Complex I/II; TAP, Transport associated with Antigen Processing; IFN, Interferon; IRF, Interferon Regulatory Factor; cGAS, cyclic GMP-AMP and STING, cyclic GMP-AMP receptor of interferon genes; CXCL14, Chemokine (C-X-C motif)-14; CCL20, Chemokine (C–C motif)-20; APC, Antigen Presenting Cell; CCL2, Chemokine (C–C motif)-2 or Monocyte Chemoattractant Protein-1 (MCP-1); MM9, Matrix Metallopeptidase-9.