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

Abstract

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.

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“…Immune correlates of protection against HPV are poorly understood ( 64 , 65 ), preventing optimization of vaccine dosing schedules, such as through multi-cohort vaccination or reduced-dosing strategies ( 66 , 67 ). A better understanding of serological correlates of protection can help define the vaccine dosage needed for protection ( 65 ).…”

“…A better understanding of serological correlates of protection can help define the vaccine dosage needed for protection ( 65 ). In particular, reduced-dose vaccination, either with a single dose or extended interval dosing (at least 12 months between the first and the second dose) ( 66 ), would have significant programmatic implications and allow for increased vaccination coverage in settings with limited healthcare access, infrastructure, personnel, and financial resources ( 68 , 69 ). Among women who did not complete the required number of HPV vaccine doses, one dose induced robust immune responses with comparable decreases in precancerous lesions compared to women who received multiple doses ( 70 , 71 ).…”