Intratumoral Human Papillomavirus in Advanced Prostate Cancer: Systematic Review, Meta-Analysis, and Real-World Evidence from the Largest Cohort to Date.

The etiopathogenesis of prostate cancer (PCa) is complex and involves multiple hormonal and environmental factors. Among these, the role of infectious agents remains controversial. Human papillomavirus (HPV) is known to promote carcinogenesis in epithelial tumors and has also been detected, albeit inconsistently, in PCa tissues. This systematic review, meta-analysis, and real-world cohort study aimed to clarify the prevalence and the prognostic role of intratumoral (IT)-HPV detection in locally advanced and metastatic PCa. We performed a systematic literature search including studies reporting IT-HPV detection in locally advanced (LA-PCa) and metastatic PCa (mPCa). Pooled prevalence estimates were calculated using random-effects models. In parallel, HPV DNA was analyzed using archival tissue in a single-center real-world retrospective cohort of 196 metastatic PCa patients. Twenty-three records met the inclusion criteria, comprising 22 full-text publications and one abstract. Nineteen datasets, encompassing 837 patients, contributed to the quantitative synthesis of stage III-IV disease. Pooled IT-HPV prevalence in mPCa was 18.5% (95% CI, 6.4-34%), while including also LA-PCa was 14.6% (95% CI, 5.2-26.8). Eastern countries showed higher IT-HPV prevalence in both mPCa and LA-PCa (40% and 34.3%, respectively) compared with Western regions (0.8% and 0.3%;