Background. Human papillomavirus (HPV) infection is a necessary cause of cervical cancer and a major contributor to other anogenital and oropharyngeal cancers. Although effective prophylactic vaccines are available and the World Health Organization has set a target of achieving 90% HPV vaccination coverage among girls by 2030, uptake remains suboptimal globally. 
Objectives. This umbrella review aims to synthesize evidence from systematic reviews and meta-analyses on determinants influencing HPV vaccination uptake and on the effectiveness of interventions to improve vaccination outcomes, while assessing methodological quality and identifying key evidence gaps.
Methods. The study protocol was prospectively registered in the Open Science Framework (https://osf.io/z8pj9). We conducted an umbrella review of systematic reviews with meta-analyses published between 2006 and 2025, following established guidance. PubMed, Scopus, Web of Science, and PsycINFO were searched. Eligible studies included meta-analyses of observational studies assessing determinants of HPV vaccination uptake and meta-analyses of randomized controlled trials (RCTs) evaluating interventions targeting initiation, completion, uptake, or coverage. Study selection and data extraction were performed independently by two reviewers. Methodological quality will be assessed using AMSTAR-2. Credibility will be appraised using quantitative, rule-based criteria tailored to study design. For observational meta-analyses (and mixed designs), associations will be graded from weak to convincing based on random-effects significance (p<0.05, p<10?³, p<10??), adequate sample size (≥1,000 cases), significance of the largest study, prediction intervals excluding the null, low heterogeneity (I²<50%), and absence of small-study effects and excess-significance bias (Egger’s p>0.10; excess-significance p>0.10). For RCT meta-analyses, evidence will be rated (high to very low) via downgrades for risk of bias, inconsistency (I²), indirectness, imprecision, and publication bias, with upgrades for large/very large effects.?
Results. The database search identified 2,499 records, of which 30 systematic reviews were included (17 reviews of RCT and 13 reviews of observational studies). Reviews often targeted multiple populations: adolescents were included in 18 reviews (60.0%), young adults in 6 (20.0%), parents or caregivers in 7 (23.3%), and healthcare providers in 4 (13.3%). Most reviews included both females and males (22/30; 73.3%), while fewer focused exclusively on females (7/30; 23.3%) or males (1/30; 3.3%). Vaccine uptake was the most frequently examined outcome (n = 11; 36.7%), followed by initiation (n = 4; 13.3%) and completion (n = 2; 6.7%).
A total of 207 meta-analyses of observational studies examined associations between determinants and HPV vaccination outcomes; the most frequently investigated factors were race/ethnicity (n=33; 15.9%), region of residence (n=18; 8.7%), and health insurance status (n=12; 5.8%). In the intervention evidence, 39 meta-analyses of RCTs evaluated strategies to increase vaccination outcomes, most commonly reminder/recall interventions (n=16; 41.0%), followed by educational or communication-based (n=11; 28.2%), multi-component (n=8; 20.5%), and incentive-based interventions (n=4; 10.3%). Methodological quality and credibility assessments will be completed prior to the conference.
Conclusions. This umbrella review maps current evidence on determinants and interventions related to HPV vaccination.  Ongoing analyses will clarify evidence strength and help identify priority gaps to inform more effective, context-specific strategies to increase HPV vaccination coverage globally.