Clinicopathologic Features Associated With Human Papillomavirus/p16 in Patients With Metastatic Squamous Cell Carcinoma of the Anal Canal

Oncologist. 2015 Nov;20(11):1247-52. doi: 10.1634/theoncologist.2015-0091. Epub 2015 Sep 17.


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.

Implications for practice: Previous studies investigating the clinical features of patients with anal cancer focused on those with early-stage disease. The present study characterizes, for the first time, clinical and pathological features according to human papillomavirus (HPV) status for patients with metastatic anal cancer. A high frequency of HPV-positive tumors and correlations between HPV status and both ethnicity and tobacco history was found. No standard-of-care therapy is available for patients with metastatic anal cancer, and most receive cytotoxic chemotherapy. The high prevalence of HPV in the current population generates optimism for ongoing clinical trials investigating the role of immune checkpoint blockade agents as a novel treatment approach for this disease.

Keywords: Anal canal; Anus neoplasms; Human papillomavirus; Immunohistochemistry; In situ hybridization; p16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anal Canal / metabolism
  • Anal Canal / pathology
  • Anal Canal / virology
  • Anus Neoplasms / genetics*
  • Anus Neoplasms / pathology
  • Anus Neoplasms / virology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / pathogenicity
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / pathogenicity
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis*