Immunogenicity of Alternative Dosing Schedules for HPV Vaccines among Adolescent Girls and Young Women: A Systematic Review and Meta-Analysis

Alternative dosing schedules for licensed human papilloma virus (HPV) vaccines, particularly single dose and extended intervals between doses (>12 months), are being considered to address vaccine shortages and improve operational flexibility. We searched PUBMED/MEDLINE for publications reporting immunogenicity data following administration of one of the licensed HPV vaccines (2vHPV, 4vHPV, and 9vHPV) to females aged 9-26 years. We conducted non-inferiority analyses comparing alternative to standard schedules using mixed effects meta-regression controlling for baseline HPV status and disaggregated by vaccine, subtype, time point, and age group (9-14 and 15-26 years). Non-inferiority was defined as the lower bound of the 95% confidence interval (CI) for the geometric mean titer (GMT) ratio being greater than 0.5. Our search returned 2464 studies, of which 23 were included in data analyses. When evaluated against standard schedules, although robust immunogenicity was demonstrated across all multi-dose groups, non-inferiority of extended interval dosing was mixed across vaccines, subtypes, and time points. Single dose did not meet the criteria for non-inferiority in any comparisons. Sparse data limited the number of possible comparisons, and further research is warranted.