Immune Landscape of Papillomavirus Infections: Innate Recognition, Adaptive Immunity, and Immune Evasion

Human papillomavirus (HPV) infection remains a major global health concern due to its strong association with cervical and other anogenital and oropharyngeal cancers. The outcome of HPV infection is largely determined by complex interactions between the virus and host immune responses. This review summarizes current knowledge on the immune landscape of HPV infection, focusing on innate immune recognition, adaptive immune responses, and viral immune evasion strategies. HPV is sensed by host pattern recognition receptors, yet it efficiently suppresses interferon signaling and cytokine responses to establish persistent infection. Adaptive immunity, including HPV-specific CD4⁺ and CD8⁺ T-cell responses and neutralizing antibodies, plays a critical role in viral clearance, while defects in these responses contribute to persistence and disease progression. The virus employs multiple immune evasion mechanisms, such as downregulation of antigen presentation and modulation of cytokine signaling, facilitating immune escape and oncogenesis. The review also highlights immune correlates of protection, vaccine-induced immunity, and emerging immunotherapeutic strategies targeting HPV-associated diseases. A comprehensive understanding of HPV–host immune interactions is essential for optimizing vaccine design, improving therapeutic interventions, and reducing the global burden of HPV-related malignancies.