Maximizing impact: the power of early HPV vaccination for long-term protection―lessons from a systematic review and meta-regression analysis

BACKGROUND: This systematic review and meta-regression analysis assessed the impact of human papillomavirus 16/18 (HPV16/18)-AS04 vaccine (Cervarix®) on advanced cervical lesions, including grade 3 cervical intraepithelial neoplasia or worse (CIN3, CIN3+), or cervical cancer, highlighting age-at-vaccination-dependent vaccine efficacy and effectiveness. METHODS: Studies reporting HPV16/18-AS04 vaccine efficacy or effectiveness were included with an intervention group receiving HPV16/18-AS04 vaccine and comparator group receiving placebo, another vaccine or being unvaccinated. Of 53 articles identified, nine were selected. Meta-analysis and meta-regression models with random effects and data-driven model selection determined vaccine effects (VEs) and impactful covariates. RESULTS: HPV16/18-AS04 vaccine effectively prevented advanced cervical premalignant lesions and cancer in adolescent girls and women vaccinated at 12-25 years. Combined randomized controlled trials and observational studies VEs on CIN3+ ranged between 76.78% (95% CI 28.15-92.49) for HPV16/18 and 56.19% (95% CI 24.76-74.49) irrespective of HPV type. Vaccine effectiveness was greatest in those vaccinated at the youngest ages. CONCLUSIONS: HPV16/18-AS04 vaccine provides long-term protection against cervical premalignant lesions and cervical cancer in both controlled and real-world settings, particularly when administered at younger ages. The evidence urges policymakers and the community to ensure HPV vaccination begins at the youngest recommended ages.