Table 1.

Biological functions of HPV oncoproteins.

HPV Protein	Function	References
E1	Initiates viral genome replication.	[51]
E2	Induces viral DNA replication and transcription.Modulates viral gene expression.	[52]
E3	Not known.	[53]
E4	Facilitates the encapsidation and maturation of viral particles.	[53]
E5	Disrupts the v-ATPase-dependent endosomal acidification process, reducing EGFR degradation.	[56,57]
	Increases both EGFR and pEGFR expression on cell surface.	[54,55,58]
	Downregulates the MHC-I, disrupting the host immune response.	[59]
E6	Protects cells from apoptosis inducing p53, Bak, FADD, and caspase-8 degradation.	[60,61,62]
	Activates MAPK and mTORC1 signaling.	[63,64]
	Disrupts the activation of Th1 CD4+ T cells by means of pro-IL-1ꞵ degradation.	[65]
	Downregulates MHC-I expression, targeting STAT1.	[66]
E7	Induces cell cycle progression by means of Rb degradation.	[67,68]
	Decreases INFs production targeting STING.	[69]
	Activates AKT activity and EGFR expression.	[70]
E6 and E7	Interact with c-myc, inducing hTERT activation and cell immortalization.	[72,73]
	Induce EMT, upregulating N-cadherin, Fibronectin, and Vimentin.	[74]
	Inhibit INFs and IL-1β production, contributing to immune evasion.	[75]

EGFR, epidermal growth factor receptor; MHC-I, major histocompatibility complex class I; FADD, Fas-associated protein with death domain; MAPK, mitogen-activated protein kinase; mTORC1, rapamycin complex 1; IL, interleukin; STAT1, signal transducer and activator of transcription 1; STING, stimulator of interferon genes; INF, interferon; AKT, protein kinase B; hTERT, human telomerase reverse transcriptase; EMT, epithelial-to-mesenchymal transition.