Advances in HPV Vaccine Development: Toward Combined Prevention and Treatment Strategies

Human papillomavirus (HPV) causes cervical and other cancers, but first-generation L1 vaccines are underused and cannot treat existing infections. Research shows that the activities of p53 and pRb can be inhibited by proteins E6 and E7, promoting cancer development. These insights have led to new vaccine platforms that aim to both prevent and treat HPV infection. Clinical trials are testing L2-based, DNA, peptide, and mRNA vaccines. However, no single vaccine yet offers broad protection, treatment effectiveness, low cost, and stability in field settings. This review describes HPV biology, explains how E6 and E7 drive cancer, and assesses the strengths and weaknesses of current L1 vaccines. It also reviews next-generation approaches such as L2 vaccines with broader coverage, DNA and peptide vaccines that reduce lesions, and mRNA vaccines showing tumour clearance in early studies. Examples include VGX-3100, imiquimod-based regimens, and first-in-human mRNA vaccines. The review outlines a combined prevention-and-treatment strategy for HPV-related diseases. Future work should focus on large global trials, combinations with checkpoint inhibitors, and affordable, heat-stable vaccines for use in resource-limited areas. Success in these areas could greatly reduce world impact of HPV-related diseases.