HPV’s immune evasion strategies. (A) HPV infects basal epithelial cells and utilises the progressive differentiation of keratinocytes to conceal its viral replication process from the immune system. Immune detection is prevented since the most viral gene expression happens in superficial epithelial layers and since no unexpected cell death or inflammation occurs. (B) HPV E6 and E7 oncogenes reduce secretion of chemokines, CCL20 and CXCL14, which hinders Langerhan’s and dendritic cell recruitment. (C) HPV E5 and E7 oncogenes prevent antigen presentation to cytotoxic T cells by downregulating major histocompatibility complex (MHC) class I expression. (D) HPV E5 and E7 oncogenes inhibit the cGAS-STING (cyclic GMP–AMP synthase, stimulator of interferon genes) pathway, which responds to aberrant DNA from viruses by activating the innate immune system. (E) HPV E5, E6, and E7 oncogenes can also inhibit IFN-stimulated gene expression (e.g., TLR3, RIG-I, MDA5, TRAIL, XAF1, IFIT1, MX1). cGAMP = 2′3′ cyclic GMP–AMP, CTL = cytotoxic T cell, DC = dendritic cell, IFN = Interferon, LC = Langerhan’s cell, MHC-I = major histocompatibility complex-I.