Print

Bentz, Jessica Leigh

Pathology

2007

MS

Human papillomavirus (HPV) is a 8000 bp DNA virus that infects humans through small microabrasions in the epithelium. Its ability to transform benign lesions in the cervix into maIignant carcinomas has given WV recognition as a necessary cause of cervical cancer. There is also evidence that HPV may play a role in the etiology of other tumors including esophageal, head and neck, and anal carcinomas. Studies have also been conducted on the involvement of HPV with colon cancers, with reports having identified HPV in 0%-83% of colon carcinomas. This study was conducted to better assess the etiological role of HPV in colorectal cancer. Formalin-fixed, paraffin-embedded (FFPE) colon (ascending, descending, transverse, sigmoid, and rectal) carcinomas and normal adjacent tissue (NAT) samples were obtained for 48 recent patients. In addition, 43 FFPE normal non-neoplastic (NNT) colon tissue samples from patients treated for constipation, diverticulitis, or ulcerative colitis were collected. DNA was extracted from blocks and amplified through two different GP5+/6+ PCR protocols of differing sensitivities. Cervical carcinoma samples were used as positive controls. HPV-negative samples of tonsil and thyroid were used as negative controls. Biotinyl-tyramide based chromogenic in situ hybridization (CISH) and L1 Immunohistochemistry (IHC) were performed on selected samples that tested HPV positive with both PCR tests to identify biological activity of the virus.
Twelve of 49 (24%) colon carcinomas and 8/48(23.5%) associated NAT tested positive for HPV DNA (Types 16, 18,35 or 40) following a hgh sensitivity PCR GP5+/6+ assay. These results were compared to 17/43 (40%) of NNT samples (types 16, 18,45) that were positive for the high sensitivity protocol (p=0.007). The low sensitivity GP5+/6+ assay produced 5/49 (10%) colon carcinomas, and 3/48 (7%) NAT, and 5143 (12%) NNT positive for HPV DNA. There was no significant difference in the prevalence of HPV in cancer tissues compared to NAT and NNT samples; (p=0.222). HPV was not detectable by CISH or IHC in PCR HPV positive colon tissues (carcinoma, NAT, or NNT); whereas HPV was readily detectable in positive control cervical carcinomas and lesions, respectively. These data support recent findings that HPV is commonly present in the colorectal tract as identified by PCR assays. However, the prevalence of high risk types of HPV that was found in carcinoma, NAT, and NNT samples did not show integrated or episomal DNA with CISH. This suggests the virus is present in low copy numbers. Additionally, IHC results did not show biological activity of the L1 capsid protein, and further suggests the infection is latent and not producing virions. These results implicate that HPV is a bystander in the lower digestive tract and unlikely to have causal significance in colorectal disease progression.