The relationship between p16 expression and high-risk human papillomavirus infection in squamous cell carcinomas from sites other than uterine cervix: a study of 137 cases.

p16 is known to be an excellent surrogate marker of human papillomavirus infection in squamous cell carcinoma of the cervix. Recent studies have demonstrated a link between human papillomavirus infection and a subset of head and neck squamous cell carcinomas, especially from the oropharynx. The aims of this study were to determine the incidence of p16 expression in squamous cell carcinomas of noncervical origin and to assess its utility as a surrogate marker of human papillomavirus infection in various noncervical primary sites. One hundred thirty-seven squamous cell carcinomas from 5 primary sites, including 34 from the oropharynx (tonsil and base of tongue), 43 cases from nonoropharyngeal head and neck sites, and 20 cases each from the lung, esophagus, and skin, were retrieved from our surgical pathology archives. Immunohistochemistry for p16 was performed on each case. All p16-positive cases and 21 p16-negative cases were further tested for both high-risk and low-risk human papillomavirus by in situ hybridization. p16 expression was detected in 54 cases overall, including 25 (74%) of 34 oropharyngeal squamous cell carcinomas, 8 (19%) of 43 nonoropharyngeal head and neck squamous cell carcinomas including 3 of 4 from the sinonasal cavity, 6 (30%) of 20 esophageal squamous cell carcinomas, 7 (35%) of 20 lung squamous cell carcinomas, and 8 (40%) of 20 skin squamous cell carcinomas. Of the 54 p16-positive cases, 30 were positive for high-risk human papillomavirus, including 24 (96%) of 25 from the oropharynx, 5 (63%) of 8 from nonoropharyngeal head and neck sites, and 1 (17%) of 6 from the esophagus. All 7 lung and 8 skin cases tested were negative. All p16-positive cases were negative for low-risk human papillomavirus. In selected head and neck squamous cell carcinomas, mainly from the oropharynx and sinonasal cavity, p16 positivity correlates well with high-risk human papillomavirus infection. p16 is not a reliable indicator of high-risk human papillomavirus infection in squamous cell carcinomas of the lung, skin, and esophagus.