Role of human papillomavirus in squamous cell metaplasia-dysplasia-carcinoma of the rectum.

Primary colorectal squamous cell carcinoma (SCC) and squamous dysplasia are uncommon and little is known about their pathogenesis. Most have been reported in association with ulcerative colitis and other chronic disease states. Although cervical and anal SCC have been strongly linked to human papillomavirus (HPV) infection, the role of HPV in rectal squamous carcinoma has not been well-examined. We evaluated 3 cases of primary rectal SCC for the presence of high-risk HPV by immunohistochemistry for p16(INK4A), in situ hybridization, and polymerase chain reaction. HPV type 16 was detected by polymerase chain reaction in all cases. In addition, all cases exhibited diffuse strong reactivity for p16(INK4A) and punctate nuclear staining by Ventana HPVIII in situ hybridization. The presence of HPV 16 in all three cases suggests that high-risk HPV infection is a risk factor for rectal SCC, particularly in patients with underlying chronic inflammatory disease processes or altered immune status. Further studies are warranted to determine if SCC occurring more proximal in the colon are also HPV-dependent or occur via another, HPV-independent pathway.