For successful clinical translation of therapeutic human papillomavirus (HPV) vaccines, optimizing antigen selection is key to enhancing efficacy. Traditional E6/E7 targets are limited by heterogeneous tumor expression. This review advocates expanding the antigen repertoire to include tumor-specific neoantigens in next-generation vaccines. We systematically evaluate established HPV therapeutic antigens and vaccine platforms, and comprehensively explore the frontier of novel antigens, advanced screening technologies, and recent vaccine innovations. Central is a bioinformatics-guided antigen selection framework spanning multi-omics analysis, immunogenicity prediction, and vaccine design. Key selection parameters - including antigen clonality, expression level, major histocompatibility complex (MHC) binding affinity and stability, and immunogenic potential - are critically assessed alongside state-of-the-art computational tools. By proposing standardized selection criteria and optimization strategies, this review aims to provide a roadmap for developing more potent and broadly effective therapeutic vaccines, ultimately bridging the gap between the molecular etiology of HPV-associated cancers and successful therapeutic discovery.
Zhang et al. (Thu,) studied this question.