HPV infection causes benign lesions of the skin and mucous membranes and many malignant tumors such as cervical cancer and oropharyngeal tumors. HPV infection stimulates the host immune system (intrinsic and adaptive immunity) to produce a certain immune response; HPV also evades surveillance and clearance by the host immune system through various immune escape mechanisms. The interaction between HPV and the host immune system determines the different clinical manifestations of HPV infection (clinically asymptomatic or persistent lesions or even cancer). In this paper, we will review the progress of research on the host immune response and HPV immune escape mechanisms after HPV infection. HPV infection and the intrinsic immune response Intrinsic immunity, also known as natural immunity, is the body’s first barrier against microbial infection, clearing approximately 90% of invading pathogens and activating a modest adaptive immunity. The initiation and activation of innate immunity depends on the role of pattern recognition receptors such as Toll-like receptor (TLR) signaling pathways, dendritic cells (DCs), phagocytes, and various cytokines. The HPV life cycle and the initiation of innate immunity HPV infects basal keratinocytes (KCs) through microscopic breaks in the epithelium (without invading the basement membrane), and the intraepithelial life cycle of HPV allows it to evade recognition and immune response by the host innate immune system. HPV gene expression and protein synthesis are restricted to KC, and viral assembly and maturation occur in well-differentiated cells of the squamous epithelium. Therefore, HPV viral antigens are difficult to contact and be recognized by antigen-presenting cells in the infected area, and are less likely to initiate an intrinsic immune response and activate adaptive immunity, allowing HPV to multiply and persist in the infected area. HPV infection and TLR Three pattern recognition receptors have received particular attention: the TLR, NOD-like receptors, and RIG-I-like receptors. Studies have shown that the TLR signaling pathway can be altered during HPV infection, but the mechanism and significance of this is unclear. the HPV11 E7 peptide does not effectively activate monocyte-derived DCs, but TLR agonists contribute to the activation of this DC, and it is hypothesized that the TLR signaling pathway plays an important role in the activation of DCs by the E7 peptide. However, the results of studies on TLR expression in HPV infection-associated cervical disease are inconsistent. hpv E6 and E7 proteins may delay host immune response by downregulating KC, cervical cancer cell TLR9 expression through the ubiquitin-proteasome pathway. yu et al. showed that TLR4 and TLR9 expression were both downregulated in cervical intraepithelial neoplasia (CIN) and squamous epithelial invasive carcinoma, and It is speculated that HPV proteins may cause downregulation of TLR transcription and expression, thus suppressing the intrinsic immune response. However, it has also been suggested that TLR5 and TLR9 expression is upregulated in CIN grade 2/3 and cervical cancer cell lines. Therefore, the expression of TLR in HPV infection-associated diseases and its role in the pathogenesis of HPV infection-associated diseases still need to be further investigated. HPV infection and DC Studies have shown a significant decrease in the number of specialized antigen-presenting cells-Langerhans cells (LC) at the site of HPV infection, and suggested that this may be related to certain factors: (i) insufficient chemokine MIP-3α produced by KCs expressing HPV E6 and E7 proteins, so fewer LC precursor cells are recruited to the HPV-infected region; (ii) LC surface adhesion molecules such as E-cadherin expression was downregulated, resulting in impaired adhesion between LC and KC. In addition, LC co-incubated with HPV16 L1 virus-like particles (VLP) did not trigger L1 antigen epitope-specific immune responses, suggesting that LC function was inhibited during HPV infection, and the mechanism may be related to abnormal activation of LC PI3-K signaling pathway. The abnormal expression of the LC may be associated with abnormal expression of prostaglandin E2, TGF-β, CD207 and TRAIL. HPV infection and adaptive immunity Adaptive immunity, also known as acquired immunity, includes T-lymphocyte immune responses and antibody-mediated humoral immunity, which can clear infected cells and avoid reinfection. Cellular immune responses The host cellular immune response induced by viral infection relies on two types of effector cells: CD4+ helper T lymphocytes (Th) and cytotoxic T lymphocytes (CTL). The balance of Th1/Th2 ratio is exceptionally important to maintain an appropriate intensity of immune response. In recent years CD4+CD25+ Foxp3+ regulatory T cells (Treg) are considered to be the third class of CD4+ T cells. treg secrete IL-10 and TGF-β and have immunosuppressive functions. The incidence of HPV infection is high and severe in hosts in a state of cellular immunosuppression, e.g. HIV-infected patients often have recurrent cervical HPV infection and a high incidence of skin and genital tract warts. Follow-up of CIN grade 1 patients revealed common HPV16 E2-specific Th1 cell responses at lesion clearance; whereas Th1-type immune responses against HPV16 E2 and E6 proteins were detected in HPV-infected patients without clinical manifestations. These results suggest that the CD4+ Th1 cell-dominant cellular immune response plays an extremely important role in the fight against HPV infection, and the presence of impaired Th1 immune response and imbalance of Th1/Th2 cell subsets in the direction of Th2 in persistent HPV infection results in a state of cellular immunosuppression that is detrimental to virus clearance. In patients with CIN grade 2/3, there is only an occasional Th1 cell immune response; in patients with cervical cancer, Th1 cell immunity is impaired; in cervical cancer, Th2 cell infiltration is predominant in the progressive stage and the proportion of Treg cells in the regional draining lymph nodes is higher. In vitro studies have also shown that HPV16 E5 protein interferes with the formation of MHC-II-antigenic peptide complexes thereby inhibiting the recognition of HPV-infected KCs by CD4+ T cells and is one of the mechanisms by which HPV evades host Th cell immunity. Humoral immune response Genital HPV infection was found to produce HPV-type-specific neutralizing antibodies to the major coat protein L1; while no antibodies to the minor coat protein L2 were detected in animals or humans with natural infection. yang et al. showed that HPV16 L1 VLP induced humoral immune response by activating B cells through TLR4-MyD88-dependent signaling pathway. l1-neutralizing antibodies protected host uninfected cells from HPV invasion and block HPV transmission, making it an ideal candidate for HPV prophylactic vaccines. The mechanism of protective effect of serum neutralizing antibodies is still unknown. Binding of neutralizing antibodies to HPV capsid proteins prevents their spatial conception from changing so that HPV particles cannot bind to the corresponding receptors and enter the KC is the most likely mechanism. Seroconversion most often occurs 6-18 months after the first detection of HPV DNA. However, not all HPV-infected patients present with seronegative antibodies. About 20-50% of women with HPV DNA (+) do not develop serum HPV type-specific antibodies, which may be related to the poor sensitivity of currently applied serologic tests. Human serum HPV antibody titers are generally only moderately elevated, or may be related to the fact that viral antigens rarely reach regional lymph nodes via the vascular and lymphatic systems during HPV infection. It has been reported that approximately 20-25% of women with initially detected HPV DNA remain seropositive 10 years later. However, it is controversial whether low titers of L1 antibodies are protective against reinfection with the same type of HPV. The clinical manifestations of HPV infection are highly variable and may be the result of the interaction between HPV and the host’s innate and adaptive immunity. The study of HPV immunopathogenesis, immune escape mechanisms and their intervention strategies is of great significance and is one of the current hot spots in the field of HPV research. The development and application of HPV L1 VLP prophylactic vaccines and therapeutic vaccines targeting HPV E6 and E7 have provided new tools for the immunological prevention and treatment of HPV infection in the past 20 years. However, there are still many questions about the mechanisms of HPV immunopathogenesis and immune escape that need to be addressed, such as: the receptors that mediate HPV entry into KC have not been identified; how HPV triggers an effective immune response, especially the intrinsic immune response, during natural infection; how HPV achieves immune escape; and the mechanisms of HPV-induced host immune tolerance.