Next-generation human papillomavirus (HPV) vaccines encompass newly licensed and emerging formulations that employ alternative production platforms, expanded valency, or novel antigenic targets beyond conventional L1-based vaccines. These vaccines aim to address affordability challenges, supply limitations, and suboptimal vaccination coverage, particularly in low- and middle-income countries. This review aggregates current clinical, immunological, and programme-related evidence on newly licensed vaccines, including the World Health Organization (WHO)-prequalified bivalent formulations (Cecolin® and Walrinvax®), the quadrivalent Cervavac®, and the Escherichia coli-derived nonavalent Cecolin 9®, which received national licensure in 2025. Additionally, emerging high-valency candidates in Phase I–III trials—9-valent, 11-valent, and 14-valent formulations—are critically assessed. Clinical trials demonstrate that next-generation HPV vaccines provide robust protection; for example, Cecolin® showed 100% efficacy against HPV-16/18-associated high-grade squamous intraepithelial lesions (HSIL) and up to 97.8% efficacy against persistent HPV infection, while Walrinvax® demonstrated 78.6% protection against CIN2+ lesions. Cervavac® showed non-inferior immunogenicity compared with established vaccines. While comparative analyses of efficacy, immunogenicity, and safety indicate that these vaccines are strong alternatives to established products, robust long-term effectiveness and real-world impact data remain essential before full clinical equivalence can be definitively established. Advances in L2-based platforms further aim to broaden cross-type protection, simplify manufacturing, and enable thermostable formulations, thereby enhancing applicability in resource-limited settings. Economic evaluations demonstrating favorable cost-effectiveness emphasize the essential role of next-generation vaccines in improving access and reducing inequity. Overall, innovations in valency, technology, and delivery strategies have the potential to significantly expand global HPV prevention coverage and accelerate progress toward cervical cancer elimination.
Akgör et al. (Thu,) studied this question.