Breast Cancer Risk and Human Papillomavirus Infection: A Bradford Hill Criteria Based Evaluation

Abstract

Background: The association between human papillomavirus (HPV) and human breast cancer (BC) has already been thoroughly studied worldwide with contradictory findings. Although the researchers have tried to minimize the conflict using statistical meta-analysis because of its shortcomings, there is still a need to evaluate the correlation between HPV and BC using any additional method.

Objectives: This study was launched to investigate the correlation between HPV and BC through the application of Bradford Hill criteria postulates.

Methods: Population-wide studies associating HPV with BC were searched using the PubMed database. Then, the information of HPV burden in BC, normal/benign samples was analyzed, and ultimately Bradford Hill criteria postulates were applied on the collected evidence to explore the relationship between HPV and BC. In addition, to make the outcomes more authentic, we also reviewed the methodologies of previous studies to address the propensity of false results.

Results: After a careful evaluation of the obtained data against major Bradford Hill criteria postulates, it was noted that all these postulates, including strength, consistency, biological gradient, temporality, plausibility, experiment, specificity, and analogy were not fulfilled.

Conclusion: The results of the present study have failed to establish a causal association between HPV and BC, but they did suggest HPV as a cause-effective agent or at least a co-participant in the pathogenesis of BC. Because of the weakness of association, particularly the lack of consistency between studies and the lack of effect specificity, more research into Bradford Hill criteria postulates is required.

Keywords: Breast cancer (BC); analogy; biological gradient; bradford hill criteria; human papillomavirus (HPV); temporality.