Comparative Safety of AS04- Versus Aluminum-Adjuvanted Human Papillomavirus Vaccines: A Disproportionality Analysis Using World Health Organization VigiBase

Objective: To evaluate whether adverse event reporting patterns differ between AS04adjuvanted and aluminum-adjuvanted Human Papillomavirus (HPV) vaccines using the World Health Organization (WHO) global pharmacovigilance database, VigiBase.Methods: Individual case safety reports for HPV vaccines were extracted from VigiBase.After exclusions, 369,597 vaccine-adverse event pairs were analyzed (57,091 AS04-adjuvanted; 312,506 aluminumadjuvanted).Immune-mediated/autoimmune disorders and hypersensitivity reactions were defined using narrow-scope Standardised MedDRA Queries (SMQ).Disproportionality was assessed using reporting odds ratios (RORs) and Information Component (IC), with the lower bound of the 95% credibility interval of the information component (IC025).Adjusted RORs (aRORs) were estimated controlling for sex, age group, region, notifier type, and report type.Sensitivity analyses included a broader age group, females only, and reports from the European Region.Results: Baseline characteristics differed between groups.Immune-mediated/ autoimmune disorders were reported in 586 AS04 and 3,030 aluminum cases.The prespecified signal criteria did not indicate a disproportionality signal (ROR 1.06, 95% confidence interval [CI]: 0.97-1.16;IC025 -0.05).The adjusted estimate showed only a small increase close to the null (aROR 1.14, 95% CI: 1.04-1.26),interpreted as a supportive, hypothesis-generating finding rather than a robust signal.Hypersensitivity reactions were less frequently reported with AS04 (ROR 0.70, 95% CI: 0.67-0.74;aROR 0.69, 95% CI: 0.66-0.72;IC025 -0.49).Sensitivity analyses by age group and sex showed similar findings, whereas analyses restricted to the European Region demonstrated regional heterogeneity in reporting patterns.Conclusion: No robust or consistent disproportionality signals were identified.Regional sensitivity analyses suggested that differences in reporting patterns may partly reflect regional reporting heterogeneity rather than adjuvant-specific effects.(PeRM 2026;18:159-171)