Prophylactic and therapeutic immunization strategies are an effective method to control human papillomavirus (HPV)-associated diseases and
cancers. Current protective virus-like particle and capsid-based
vaccines are highly protective against
vaccine-matched HPV types, and continued improvements in second-generation
vaccines will lead to broader protection and cross-protection against the
cancer-associated types. Increasing the effectiveness of broadly cross-protective L2-based immunogens will require adjuvants that activate innate immunity to thus enhance adaptive immunity. Therapeutic immunization strategies are needed to control and cure clinical disease and HPV-associated
cancers. Significant advances in strategies to improve induction of cell-mediated immunity to HPV early (and
capsid) proteins have been pretested in preclinical animal papillomavirus models. Several of these effective protocols have translated into successful therapeutic immune-mediated clearance of clinical lesions. Nevertheless, there are significant challenges in activating immunity to
cancer-associated lesions due to various immune downregulatory events that are triggered by persistent
HPV infections. A better understanding of immune responses to HPV lesions in situ is needed to optimize immune effector T cells that efficiently locate to sites of
infection and which should lead to an effective immunotherapeutic management of this important human viral pathogen. The most effective immunization strategy may well require combination
antiviral and immunotherapeutic treatments to achieve complete clearance of
HPV infections and associated
cancers.