Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.342
Peer-review started: April 11, 2014
First decision: May 29, 2014
Revised: June 24, 2014
Accepted: July 16, 2014
Article in press: July 16, 2014
Published online: January 7, 2015
AIM: To investigate the presence of human papillomavirus (HPV) DNA along with the integration, the quantification and the expression of the HPV16 in colorectal cancers.
METHODS: A prospective series of colorectal tumors were genotyped for HPV DNA. The clinical and pathological variables of the HPV-positive tumors were compared to those of HPV-negative samples. The integration status of HPV16 was evaluated by calculating E2/E6 ng ratios. HPV16-positive tumors were also evaluated for (1) E2, E4, E5, E6 and E7 viral gene ng quantification; (2) relative quantification compared to W12 cells; and (3) viral E2, E4, E5, E6 and E7 mRNA transcripts by real-time polymerase chain reaction.
RESULTS: HPV infection was detected in 16.9% of all tumors examined, and HPV16 was the most frequent type detected (63.6% of positive tissues). Notably, the clinical and pathological features of HPV-positive colorectal cancers were not significantly different than those of HPV-negative cancers (χ2 and t-test for all clinical and pathological features of HPV-positive vs HPV-negative colorectal cancers: p ns). HPV16 DNA was present exclusively in episomal form, and the HPV16 E2, E4, E5, E6 and E7 genes were detected in trace nanogram quantities. Furthermore, the HPV16 genes ranged from 10-3 to 10-9 compared to W12 cells at an episomal stage. Although the extractions were validated by housekeeping gene expression, all the HPV16 positive tissues were transcriptionally inactive for the E2, E4, E5, E6 and E7 mRNAs.
CONCLUSION: Based on our results, HPV is unlikely involved in colorectal carcinogenesis.
Core tip: The burden of human papillomavirus (HPV)-associated cancers is not limited to the cervix, but includes the oropharynx and the ano-genital area. Moreover, emerging studies have reported the detection of HPV DNA in the tumoral mucosae of several epithelia, including the colorectum. This is the first study aimed to investigate the presence of HPV in specimens using clinically validated methodology, and it is the first to apply the molecular basis of HPV-related carcinogenesis. Because we only detected episomal HPV16s in low quantities, and it was transcriptionally inactive, we conclude that the virus unlikely plays a role in colorectal carcinogenesis.