Does human papillomavirus cause human colorectal cancer? Applying Bradford Hill criteria postulates

The role of human papillomavirus (HPV) in human colorectal cancer (CRC) has already been widely investigated worldwide with conflicting results. Although researchers have tried to establish the link between HPV and CRC through a statistical meta-analysis of the previous studies associating HPV with CRC, they failed to establish a more reliable link due to the shortcomings of the statistical meta-analysis. In the present study, we identified population-wide studies relating HPV with CRC through the PubMed search engine. Then, we examined the available data of HPV prevalence in CRC and normal/benign samples and applied the postulates of Bradford Hill criteria on the available evidence to investigate the association between HPV and CRC. The Bradford Hill criteria are very old, reliable and widely accepted for establishing a link between the cause and disease. In addition, to further enhance the reliability of the outcomes, we have also evaluated the methodologies of the previous studies to address the possibility of false-negative and false-positive results. After a careful evaluation of the extracted data against the postulates of Bradford Hill criteria, it was observed that none of the studies fulfil all the major postulates of Bradford Hill criteria for causation including temporality, consistency, biological gradient, experiment, coherence, specificity and analogy. Hence, no causal relationship has been suggested between HPV and CRC patients of the any included population. The results failed to prove the causal relationship between HPV and CRC and suggested HPV as a coparticipant in the pathogenesis of CRC.