Clinicopathologic features associated with human papillomavirus/pl6 in patients with metastatic squamous cell carcinoma of the anal canal

Background. The incidence of anal carcinoma in the U.S. continues to increase steadily, and infection with the human papillomavirus (HPV) is an established risk factor for the development of anal carcinoma. However, the clinicopathologic characteristics of patients with metastatic squamous cell carcinoma of the anal canal according to HPV status have not yet been defined. Materials and Methods. The records of patients treated for metastatic squamous cell carcinoma of the anal canal at the MD Anderson Cancer Center from June 2005 to August 2013 were reviewed. The patients were tested for the presence of HPV DNA by in situ hybridization and/or the p16 oncoprotein by immunohistochemistry. Associations between the presence of HPV and clinicopathologic attributes were measured. Results. Of the 72 patients reviewed, 68 tumors (94%) had detectable HPV. Patients with HPV-negative tumors were more likely to be of nonwhite ethnicity (odds ratio, 8.7) and have a strong (>30 pack-year) tobacco history (odds ratio, 8.7). A trend toward improved survival from the time of diagnosis of metastatic disease was noted among patients with HPV-positive tumors. Conclusion. Most patients with metastatic anal cancer had detectable HPV, with differences in tobacco history and ethnicity detected according to HPV status. The high frequency of HPV positivity for patients with metastatic anal cancer has important implications for novel immunotherapy treatment approaches, including ongoing clinical trials with immune checkpoint blockade agents using antibodies targeting the programmed death-1 receptor.