Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2015; 21(1): 342-350
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.342
Human papillomavirus does not have a causal role in colorectal carcinogenesis
Laura Lorenzon, Francesca Mazzetta, Emanuela Pilozzi, Giordana Uggeri, Maria Rosaria Torrisi, Mario Ferri, Vincenzo Ziparo, Deborah French
Laura Lorenzon, Mario Ferri, Vincenzo Ziparo, Surgical and Medical Department of Translational Medicine, Faculty of Medicine and Psychology, University of Rome “La Sapienza”, Sant’Andrea Hospital of Rome, 00189 Rome, Italy
Francesca Mazzetta, Emanuela Pilozzi, Giordana Uggeri, Maria Rosaria Torrisi, Deborah French, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome “La Sapienza”, Sant’Andrea Hospital of Rome, 00189 Rome, Italy
Maria Rosaria Torrisi, Institute Pasteur-Fondazione Cenci Bolognetti, Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, 00185 Rome, Italy
Author contributions: Lorenzon L and French D conceived the idea; Lorenzon L, Mazzetta F, Torrisi MR, Ziparo V and French D designed the clinical study; Lorenzon L, Mazzetta F, Torrisi MR and French D designed the experiments; Lorenzon L, Mazzetta F, Pilozzi E, Uggeri G, Ferri M and Ziparo V collected and analyzed the samples; Lorenzon L, Mazzetta F, Pilozzi E and Ferri M performed data analysis; Lorenzon L and Uggeri G drafted the manuscript; Mazzetta F, Pilozzi E, Uggeri G and Ferri M reviewed the literature; Ziparo V, Torrisi MR and French D critically reviewed the paper; all authors contributed to the manuscript preparation.
Supported by The PhD University Grant program “Clinical and Experimental Research Methodologies in Oncology” provided by the Faculty of Medicine and Psychology University of Rome “La Sapienza” to Lorenzon L; MIUR and AIRC - Associazione Italiana per la Ricerca sul Cancro (IG 10272), Italy
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Laura Lorenzon, MD, PhD, Surgical and Medical Department of Translational Medicine, Faculty of Medicine and Psychology, University of Rome “La Sapienza”, Sant’Andrea Hospital of Rome, Via di Grottarossa 1035-39, 00189 Rome, Italy. laura.lorenzon@uniroma1.it
Telephone: +39-633-775989 Fax: +39-633-775322
Received: April 10, 2014
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
Processing time: 271 Days and 13.7 Hours
Abstract

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.

Keywords: Colorectal cancer; Human papillomavirus; Carcinogenesis; W12

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.