Abstract 5359: HPV 16 infection and physical status in Hispanic patients with colorectal cancer: A case-control study

Abstract

Abstract Purpose: The association between human papillomavirus (HPV) infection and the development of cervical cancer and anogenital cancer has been established. In addition, molecular studies have detected HPV DNA in tumor tissues of head and neck cancer, oral cancer, esophageal cancer, and some skin cancers as well as lung cancer. 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. 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 HPV16 infection in patients with CRC and to probe the viral integrations status of HPV 16 in CRC and its adjacent normal colonic mucosa. Experimental Designs: To determine the association of HPV 16 and CRC, we conducted a case-control study using tumor and tumor-adjacent colorectal tissues from patients with CRC (cases), and compared the prevalence of HPV 16 with normal colorectal mucosa from individuals without CRC (controls). Detection of L1, E2, and E6 genes, which cover the two ends and middle part of the virus genome, we were able to analyze whether a full-length HPV genome existed in the tissue samples. Head-to-tail junctions of HPV genomes were analyzed to determine the physical status the HPV genome in the HPV (+) cases. Hypothesis testing was performed using Fisher exact and analysis of proportions using STATA 10.0. Results: A total of 21 (ß-actin+) CRC patients (mean age 63 ±11 years, 8 males) and 20 controls (mean age was 63 ± 9 years, 3 males) were evaluated. Tumors were located in rectum (n=3), sigmoid (n=6), descending (n=7) and ascending (n=5) colon. HPV 16 DNA was identified in 13 of 21 (62%) patients with CRC and in none of 20 (0%) controls (p = 0.0002). HPV 16 DNA was observed in the all rectal cancer cases and in 10 (55.5%) of colon cancer cases. Among the 9 cases where both tumor and adjacent tissue was available, 2 of the 9 (22%) exhibited HPV16 DNA in both tumor and tumor-adjacent tissues. Nine of the ten (90%) tumors and all adjacent normal colonic mucosa (5/5) contained the HPV integrated form. Conclusion: These results suggest that colorectal HPV16 infection is common among patients with CRC. Furthermore, our finding of frequent integration of viral DNA in the host genome suggests that integration HPV 16 could be a common event in CRC patients. The presence of HPV 16 in tumors located proximal to the rectum suggests that this infection might not result from direct spread from anogenital sites. Taken together our findings suggest that HPV 16 oncoproteins may play a role in the pathogenesis of colorectal carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5359.