HPV vaccination in people living with HIV : A network meta‐analysis highlighting safety, immunogenicity, and evidence gaps

Abstract Background HPV infection is a major contributor to cervical and other anogenital cancers, with people living with HIV (PLWH) at particularly high risk due to persistent infection. Although prophylactic HPV vaccines are widely used and generally safe, their efficacy and safety in PLWH remain uncertain. Objective To evaluate the efficacy and safety of HPV vaccination in PLWH through an overview and network meta‐analysis (NMA). Search Strategy An electronic search was conducted in several databases up to August 12, 2025, without date or language restrictions, using keywords related to HPV vaccines, efficacy, and safety. Selection Criteria We included systematic reviews of randomized controlled trials (RCTs) involving PLWH with HIV who received bivalent (bHPV), quadrivalent (qHPV), or nonavalent (9vHPV) HPV vaccines. Data Collection and Analysis Study selection (Rayyan software) and data extraction were conducted by two independent researchers, and discrepancies were resolved by a third author. Quantitative synthesis was performed using R software. Risk of bias was assessed using AMSTAR 2. The certainty of the evidence was assessed using the Confidence in Network Meta‐Analysis (CINeMA). Main Results NMA identified that the qHPV vaccine showed significant immunological efficacy, with a significant increase in seroconversion for anti‐HPV 6 (odds ratio OR: 17.72; 95% confidence interval CI: 2.55, 123.19) and anti‐HPV 18 (OR: 22.81; 95% CI: 2.31, 225.32) antibodies, compared to the control group. No significant differences were observed for types 11 and 16. Regarding safety, qHPV demonstrated the best profile regarding pain outcomes at all doses analyzed, with a P score greater than 0.98. Conclusions The qHPV vaccine presented the best safety profile regarding pain, including at all doses. Regarding immunological efficacy, significant differences were only found between patients vaccinated with qHPV for anti‐HPV 6 and 18. No trials directly evaluated the 9vHPV in PLWH, limiting the applicability of these findings to current vaccination programs.