Abstract 552: Characterization of HPV infection in Hispanic colorectal cancer patients

Abstract

Abstract Purpose: The association between Human Papillomavirus (HPV) infection and the development of cervical cancer and anogenital cancer has been established. Moreover, molecular studies have detected HPV DNA in tumor tissues of head and neck cancer, esophageal cancer, and some skin cancers. Viral genes expression and multiplication occur exclusively in the nuclei of the infected cells and are tightly linked to the state of differentiation of the cells. Integration of viral DNA into host genome is essential for carcinogenesis since it promotes disruption of HPV E2 gene, leading to abnormal expression of E6 and E7 oncoproteins. Both E6 and E7 can form specific complexes with tumor suppressor gene p53 and pRB respectively. However, the role of HPV infection in colorectal cancer (CRC) and its mechanisms of carcinogenesis have not been properly elucidated. Our objectives were to evaluate the presence of HPV infection in patients with CRC; to probe the viral integrations status of HPV 16 in CRC and its adjacent normal colonic mucosa, and to determine the mRNA expression levels of the viral oncogenes HPV-16 E6 and HPV-16 E7. Experimental Designs: To determine the association of HPV and CRC, we conducted an age-and-gender matched case-control study using tumor and tumor-adjacent colorectal tissues from patients with CRC (cases) and without CRC (controls). Presence of L1, E2, and E6 genes was analyzed to determine whether a full-length HPV genome existed in tumor and normal tissue samples. Head-to-tail junctions of HPV-16 genomes were analyzed to determine the integration the HPV-16 genome in the HPV-16 (+) cases. Moreover, we determined the mRNA expression levels of E6 and E7 in the HPV-16 (+) cases. Hypothesis testing was performed using Pearson Chi-square analysis of proportions using SPSS 17. Results: A total of 45 (ß-actin+) CRC patients (mean age 61 ±11 years, 24 males) and 47 controls (mean age was 60 ± 9 years, 18 males) were evaluated. Tumors were located in proximal colon (n=7) and distal colon (n=38). HPV DNA was identified in 19 of 45 (42.2%) patients with CRC and in 2 of 47 (4.3%) controls (OR = 16.4; 95% CI 3.5-76.3, p < 0.001). HPV-16 was identified in 12 of 19 (63.2%) HPV (+) CRC patients and in none (0%) HPV(+) controls. The twelve HPV-16 CRC cases showed integration of HPV-16. Three of 12 (25%) HPV16 (+) cases expressed E6 and E7 mRNA. Among the 12 CRC cases where both tumor and adjacent tissue was available, 2 of 9 (16.7%) exhibited HPV-16 DNA in both tumor and tumor-adjacent tissues.Conclusion: These results suggest that colorectal HPV infection is common among patients with CRC. The presence of HPV in tumors located proximal to the rectum suggests that this infection might not result from direct spread from anogenital sites. Moreover, our finding of highly frequent integration of viral DNA and the active expression of E6 and E7 viral oncogenes in the host strongly suggests that HPV oncoproteins may play a role in the pathogenesis of colorectal carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 552. doi:1538-7445.AM2012-552