The effectiveness of gender-neutral HPV vaccination programmes in preventing HPV-associated oral cancers: a systematic review.
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BACKGROUND: Human papillomavirus infections are a significant risk factor for the development of oral cancers. While HPV vaccines have proven effective in preventing cervical cancers, their impact on oral cancers remains insufficiently examined. This systematic review assesses the effectiveness of gender-neutral HPV vaccination in reducing oral HPV rates, a key precursor to HPV-associated oral cancers, focusing exclusively on studies including gender-neutral samples. METHODS: Following PRISMA 2020 guidelines, a comprehensive search strategy was implemented, covering multiple databases, including MEDLINE and Embase, as well as grey literature and ongoing trials sources via WHO ICTRP, EUCTR and ClinicalTrials.gov. Inclusion criteria encompassed studies published between 2009 and 2025 with gender-neutral samples, oral HPV prevalence data, and vaccination status information. Quality of the included studies was assessed using the JBI Critical Appraisal Checklists. RESULTS: Nine observational studies were included, with sample sizes ranging from 394 to 9,437 participants and age ranges spanning from 18 to 70 years across multiple countries, including the United States, Australia, and Italy. Six studies reported lower prevalence of oral vaccine-type HPV (VT-HPV) among vaccinated individuals, with relative reductions ranging from 57.5% to 93.2% and an overall mean reduction of 78.5%. Lower prevalence was observed even after a single vaccine dose. In sex-stratified analyses, females showed a mean reduction of 86.8%, while males showed a mean reduction of 69.1%, with two studies reporting 100% protection among vaccinated males. Heterogeneity in outcome definitions, reporting formats, and sample overlap precluded meta-analysis. CONCLUSIONS: This is the first systematic review focusing exclusively on gender-neutral samples. The findings suggest that gender-neutral HPV vaccination programmes, which are associated with lower oral prevalence of vaccine-type HPV, may contribute to reducing the burden of HPV-associated oral cancers. Including males in national immunisation strategies is essential to promote equity and maximize public health impact, particularly given the higher burden of HPV-associated oropharyngeal cancers in men. Further research is required to better understand this effect, including the influence of dose number and the potential role of sex in vaccine response. REGISTRATION: PROSPERO (CRD420251144148).