Sexual behavior-related exposures, sexually transmitted infections, and viral markers in relation to prostate cancer risk: a systematic review and meta-analysis

Background Sexual behavior, sexually transmitted infections (STIs), and viral markers have been investigated in relation to prostate cancer, but heterogeneous exposure definitions and ascertainment methods complicate interpretation. We synthesized observational evidence separately across biologically and methodologically distinct exposure domains. Methods We followed PRISMA 2020 and searched PubMed/MEDLINE, Embase.com , and Web of Science Core Collection from inception through 27 May 2026. Eligible studies were comparative observational studies evaluating sexual behavior-related exposures, STI history or serology, or viral markers in relation to prostate cancer. Random-effects meta-analysis was performed for sufficiently comparable estimates. Risk of bias was assessed using Newcastle-Ottawa Scale domains, supplemented by design-specific epidemiological considerations. GRADE was used as a post-registration evidence-certainty assessment. Results Of 121 reports assessed for eligibility, 57 primary observational reports were included after final eligibility reconciliation. Twenty-five reports entered at least one pooled model and three additional reports appeared only in descriptive forest plots. For tissue- or PCR-based HPV detection, the observed pooled association was OR 3.01 (95% CI 1.97-4.61; I²=36.2%; prediction interval 1.15-7.91; 13 studies). HPV16 and HPV18 tissue/PCR subtype estimates were also elevated, whereas HPV serology showed no clear association. Estimates for Trichomonas vaginalis serology and history-based STI exposure were imprecise or heterogeneous, and sexual-behavior exposures were too heterogeneous for pooling. Certainty was very low across all evaluated exposure domains. Conclusions Tissue- or PCR-based HPV detection was more frequent among prostate cancer cases in the available comparative studies, but the evidence is very uncertain because of risk of bias, limited temporal clarity, sampling and comparator differences, and other methodological limitations. These findings should not be interpreted as establishing an etiologic or causal effect and do not support prostate-cancer prevention recommendations based on HPV vaccination, STI screening, or sexual-behavior modification. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1334823 , identified: CRD420261334823.