Does Human Papillomavirus Play a Causative Role in Prostate Cancer? A Systematic Review Using Bradford Hill’s Criteria

SIMPLE SUMMARY: Prostate cancer is a major cause of cancer-related deaths globally, yet its causes remain unclear. While human papillomavirus (HPV) is known to be associated with other cancers, such as cervical cancer and anal cancer, investigation of its connection to prostate cancer has yielded mixed results. This systematic review aimed to assess the relationship between HPV and prostate cancer using Bradford Hill’s criteria. Out of 482 studies screened from PubMed, 60 were included and evaluated. Although the strength of association was not strong and certain criteria were not met, the review identified plausible biological mechanisms and reported the presence of HPV in prostate cancer tissues. However, the overall quality of evidence remains low, and further high-quality studies are needed to establish a definitive link. These findings have implications for understanding prostate cancer and guiding future research efforts. ABSTRACT: Globally, prostate cancer is the fifth most common cause of cancer-related death among men, and metastatic castration-resistant prostate cancer has a high cancer-related mortality rate. However, the aetiology of this disease is not yet fully understood. While human papillomavirus (HPV) has been associated with several types of cancer, including cervical, anal, and oropharyngeal cancers, studies investigating the relationship between HPV and prostate cancer have shown mixed results. This systematic review aimed to evaluate the causative association between HPV and prostate cancer using Bradford Hill’s criteria. A comprehensive search of PubMed was conducted, and 60 out of 482 studies were included in the review. The included studies were evaluated based on nine Bradford Hill criteria, and information on the identification and transmission of the virus and potential oncogenic mechanisms was also extracted. The strength of association criterion was not met, and other criteria, such as consistency and coherence, were not fulfilled. However, biological plausibility was supported, and potential oncogenic mechanisms were identified. While some studies have reported the presence of HPV in prostate cancer tissues, the overall quality of evidence remains low, and the association between HPV and prostate cancer is weak. Nevertheless, the prostate is a potential reservoir for the transmission of HPV, and the HPV E6 and E7 oncoproteins and inflammation are likely to be involved in any oncogenic mechanisms. Further studies with a higher level of evidence are needed to establish a definitive link between HPV and prostate cancer.