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Colorectal Papillomavirus Infection in Patients with Colorectal Cancer

Authors' Affiliations: ¹ HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; ² Pathology and Internal Medicine, University of Texas Medical Branch, Galveston, Texas; and ³ Department of Medicine, University of California, San Francisco, San Francisco, California

Requests for reprints: Zhi-Ming Zheng, HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute/NIH, 10 Center Drive, Room 10 S255, MSC-1868, Bethesda, MD 20892-1868. Phone: 301-594-1382; Fax: 301-480-8250; E-mail: zhengt{at}exchange.nih.gov.

Purpose: Infection with human papillomaviruses (HPV) is associated with the development of cervical cancer, but whether HPVs have a role in colorectal cancer remains controversial.

Experimental Designs: To determine the relationship between HPV and colorectal cancer, we did a retrospective, controlled study using tumor and tumor-adjacent colorectal tissues dissected from patients with colorectal cancer, as well as colorectal tissues from control individuals with no cancer. The samples were processed in a blinded fashion for nested PCR and in situ PCR detection of HPV DNAs. The PCR products were gel-purified and sequenced for HPV genotyping.

Results: We found that colorectal tissues from 28 of 55 (51%) patients with colorectal cancer were positive for HPV DNA. Colorectal tissues from all 10 control individuals were negative for HPV DNA (P = 0.0034). Of the 107 usable (GAPDH⁺) samples collected as paired colorectal tissues (tumor and tumor-adjacent tissues) from the patients, 38 (36%) had HPV16 (n = 31), HPV18 (n = 5), or HPV45 (n = 2), with HPV DNA in both tumor and tumor-adjacent tissues of 10 paired samples, 13 in only the tumor, and 5 in only tumor-adjacent tissues. In situ PCR detection of the tumor tissues confirmed the presence of HPV DNA in tumor cells.

Conclusion: Our results suggest that colorectal HPV infection is common in patients with colorectal cancer, albeit at a low DNA copy number, with HPV16 being the most prevalent type. HPV infection may play a role in colorectal carcinogenesis.

Key Words: Human papillomavirus type 16 • Viral oncogenesis • Tumor virus infection • PCR

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