Effectiveness, immunogenicity and safety of human papillomavirus vaccination in non-HIV immunocompromised individuals: a systematic review.

Background: Immunocompromised individuals may be at an increased risk for human papillomavirus (HPV)-related diseases and cancers, but the protective benefit of HPV vaccination remains unclear. In this systematic review and meta-analysis we assessed the efficacy, effectiveness, immunogenicity, and safety of HPV vaccination in non-HIV immunocompromised individuals. Methods: We searched MEDLINE, Embase and CENTRAL (26 November 2025) for randomised and non-randomised studies comparing vaccinated immunocompromised individuals to unvaccinated immunocompromised individuals (comparison 1). Additionally, we considered studies comparing vaccinated immunocompromised individuals to vaccinated individuals with a different disease or condition (comparison 2) or vaccinated healthy individuals (comparison 3). We assessed the risk of bias (ROBINS-I) and the certainty of evidence (CoE; GRADE) for prioritised outcomes including cervical precancer or cancer, HPV types 16 and 18 immunogenicity, and serious adverse events. We pooled studies using the random-effect meta-analyses model. This study is registered in PROSPERO, CRD42024554574. Findings: We identified 24 non-randomised studies, comprising various immunocompromised populations (e.g. solid organ transplant recipients or autoimmune diseases). One case-control study compared vaccinated immunocompromised with unvaccinated immunocompromised individuals (comparison 1), reporting rate ratios near the null effect for effectiveness against cervical intraepithelial neoplasia (CIN) 2+ (0.96, 95% CI 0.68-1.37) and CIN 3+ (0.96, 95% CI 0.54-1.70), although the CoE was very low. Most studies assessed immunogenicity, generally showing high seropositivity rates (median at 7 months 95.8%, IQR 89.2-99.7; 13 studies) in immunocompromised individuals compared to other immunocompromised or healthy individuals, with a CoE ranging from low to very low (comparisons 2 and 3). Antibody titres were generally high but varied across immunocompromised populations. Serious adverse events were rare and deemed unrelated to vaccination. Interpretation: HPV vaccination appears immunogenic and safe for non-HIV immunocompromised individuals, but the CoE is low to very low and heterogeneity across populations limits generalisability of the findings and pooled analyses. Given the unclear correlate of protection and lack of standardisation of assays for antibody measurement, immunogenicity data should be interpreted cautiously. Future studies should assess HPV-associated precancerous lesions and cancers, and explore subgroups effects, including differences in sex, age, immunosuppressive treatments, and dosing. Funding: EU4Health Programme - European Health and Digital Executive Agency, European Commission. Service Contract HaDEA/OP/2021/0011.