Human papillomavirus and colorectal cancer: evidences and pitfalls of published literature

The aim of this study is to review published literature regarding a possible role of human papillomavirus (HPV) infection in colorectal cancer in order to understand if HPV infection plays an active role in colorectal carcinogenesis and to highlight evidences and pitfalls of published studies. We reviewed literature by searching PubMed, Ovid, and the Cochrane databases for published series investigating HPV and colorectal cancer from 1988 to date. Twenty-one studies investigating a possible correlation between HPV infection and colon cancer have been published. We reviewed 15 case-control studies and six studies investigating a possible role for HPV virus in colorectal carcinogenesis. HPV was detected in the majority of reported series with a significant difference in HPV infection between tumors and disease-free controls or tumor-adjacent tissue; the HPV mean detection rate within carcinomas was 41.7%, comparing to a mean detection rate of 32.8% in adjacent colic mucosae, and 5.8% in disease-free controls (Chi-square test, p = 0.001). The correlation between HPV infection and c-myc amplification, k-ras mutation, and p53 polymorphism or mutations has been investigated; however, the possible role of HPV in colorectal carcinogenesis was not defined. HPV has been detected in the majority of reported series, but published literature lacks in definitive data regarding standard methods of investigation and stratification of groups and population. These data encourage further studies with the aim to investigate the presence of the virus in larger series, its possible role in oncogenesis, the integration in host genome, the expression of viral oncoproteins, the mutations in HPV positive cancers and routes of colon infection (hematologic/lymphatic spreading or perineal diffusion).