3544 Background: There have been some reports of an association between human papilloma virus (HPV) and colonic neoplasms, but large scale investigations of this subject are particularly lacking. In this study we examined a cohort of colorectal adenocarcinomas for the presence of HPV 16 and 18 E6 viral protein expression.
METHODS
A tissue microarray including specimens from 447 patients with primary colorectal adenocarcinoma was employed. Using a novel quantitative protein analysis system (AQUA), expression levels of HPV 16/18 E6 oncoprotein were determined. This system uses an anti-cytokeratin antibody conjugated to Cy3 to define pixels as tumor within the tissue spot. The intensity of HPV 16/18 E6 expression is then measured using Cy5 conjugated antibody with signal amplification. Scores were divided into quartiles and correlated with clinical and pathological variables.
RESULTS
The primary sites were rectum/sigmoid (237), descending/transverse (84), ascending colon/cecum (61) and colon, not specified (65). Tumors were stage I (97), II (121), III (162), IV (46) and not specified (21). A significant relationship was found between high-risk HPV E6 protein expression and distal tumor location (p=0.007). High HPV E6 expression was also associated with lower stage (p<0.001). Analysis of a colon adenocarcinoma tumor with Real-Time PCR confirmed HPV16 presence.
CONCLUSION
To our knowledge this is the largest cohort of colorectal adenocarcinomas examined specifically for HPV oncoprotein expression. Our findings indicate a possible association of HPV 16/18 types with colorectal adenocarcinoma. Specimens expressing higher levels of E6 protein were associated with lower stage and distal location. HPV-associated tumors of the head and neck area are also associated with a lower stage. The association of HPV with distal colonic location may be explained by retrograde viral transmission from the perineum to the lower gastrointestinal tract. No significant financial relationships to disclose.