Opportunities and Barriers to HPV Vaccination Among Men Who Have Sex with Men and Related Sexual and Gender Minority Populations: A Systematic Review and Exploratory Clustering Analysis Using a Socio-Ecological Framework

Background: Men who have sex with men (MSM) experience a disproportionate burden of human papillomavirus (HPV)-related disease, yet vaccination uptake remains uneven. With MSM as the key population of interest, this review synthesized evidence on uptake, willingness, multilevel barriers and opportunities, and vaccine-oriented outcomes among MSM and related sexual and gender minority populations when MSM-relevant findings could be extracted. Methods: Six databases were searched for original English- or Chinese-language studies published from 1 January 2010 to 31 December 2025. Findings were synthesized narratively. Barriers and opportunities were mapped using a five-level socio-ecological model; study-level willingness–uptake patterns were explored using K-means clustering as an exploratory analysis among the nine studies reporting both outcomes; and genotype-specific and immunogenicity findings were summarized separately. Results: Fifty-three studies involving 169,241 participants were included; 87.2% of participants were MSM, and 79% of studies were cross-sectional. Barriers and opportunities occurred across individual, provider-related interpersonal, organizational/institutional, community, and policy/societal levels. Recurrent paired mechanisms involved knowledge and trust, provider recommendation and communication, service accessibility, community support, and eligibility and affordability. Nine studies contributed data to the exploratory clustering analysis; seven fell into low-uptake clusters, including three with high willingness but low uptake, which may indicate a possible study-level implementation gap. Two studies reporting genotype prevalence and antibody responses provided limited biological context supporting vaccination before exposure and suggesting potential benefit from catch-up vaccination. Discussion: Among MSM and related sexual and gender minority populations, HPV vaccination is shaped by interacting individual and structural conditions, with MSM remaining the principal focus of the evidence base. Improving uptake is likely to require complementary strategies: universal, gender-neutral routine vaccination in adolescence before their sexual debut, and targeted catch-up for MSM who missed routine vaccination, supported by trusted provider endorsement, convenient service delivery, community engagement, and inclusive, affordable policy. The thematic counts were study-level and unweighted, and the nine-study clustering analysis was exploratory rather than definitive.