Table 1:

The Role of HPV Proteins in Cervical Cancer Inflammation

HPV type	Viral protein	Target	Effect on Inflammation	Note	Ref
16 18	E6	CD40	Induction	The expression level of CD40 was increased in E6 positive CC suggesting the presence of CD40 is related to lymph node metastasis and neovascularization.	90
16	E7	IL-32 COX-2/PGE2	Induction	The high-risk variant of HPV promotes IL-32 expression by E7-mediated COX-2 stimulation.	91
16	E2	NF-kB STAT3	Induction	E2 enhanced STAT3 and NF-kB gene expression and potentiated NF-kB activation via inflammatory mediators.	92
16	E2	NF-kB	Induction	Re-expression of E2 combined with TNF-α in cervical cells affected NF-kB and and increased IL-6, IL-8, HMGB1, cyclin D1, hTERT, Bcl2 and survivin, promoting cell proliferation and survival.	93
16 18	-	IL-1α TNF-α	Induction	HPV virus stimulated IL-1α and TNF-α. Proinflammatory cytokines enhanced amphiregulin expression and proliferation through an EGFR-dependent pathway.	94
16	E6+E7 E7	NF-kB	Inhibition	E7 and/or E6 inhibited NF-kB activity in cervical epithelial cells and induced immortalization and cell growth	95
16	E2	IL-10	Inhibition	The expression of IL-10 was regulated by E2 protein; over-expressed IL-10 may be related to virus persistence, cancer development and cervical epithelial cell transformation.	96
16	E6	IL-1β	Inhibition	E6 altered the release of IL-1β in NALP3 inflammasomes and decreased lysosomal or autophagy activity.	97
16	E6 E7	TGF-β1	Inhibition	HPV-E6/E7 induced activation of TGF-beta1	98
16	E7	NF-kB Bp50–p65 Erα	Inhibition	E7 protein induced TLR9 down-regulation affecting IFN responses that negatively regulate viral infection.	99
16	E6 E7	IFN-γ	-	The level of IFN-γ was significantly associated with HPV viral load	100
16	E5	COX-2	Induction	E5 protein mediated cervical carcinogenesis least in part by over-expression of COX-2 via AP-1 and NF-kB.	101
16 18	E6	STAT3	Induction	Over-expression of HPV-E6 activated STAT3, elevated IL-6 expression and increased tumor burden in mice with ME180 and C33A tumors.	102