Clinical research progress and challenges of vaccine for human papillomavirus-associated cancers

As a major cause of cancer-related morbidity in women, cervical cancer is strongly related to chronic infection by high-risk human papillomavirus (HPV). This viral persistence also underpins the pathogenesis of a broad spectrum of cancers. In this review, we summarize the research progress of prophylactic and therapeutic HPV vaccines in clinical trials. Furthermore, we present a critical analysis of future challenges, specifically discussing the type replacement phenomenon and its potential implications for long-term vaccine efficacy. We also expand the discourse to a pan-gender and pan-cancer scope, rigorously evaluating the necessity of gender-inclusive vaccination in the context of rising HPV-related oropharyngeal cancers. To overcome real-world implementation barriers, next-generation design strategies, such as chimeric virus-like particles, HPV L2-based vaccines, and heterologous prime-boost immunotherapy regimens for therapeutic HPV vaccines, should be expedited into clinical trials. In summary, this review provides a comprehensive perspective and a forward-looking roadmap for the immunotherapy of HPV-related malignancies.