Histopathology of human papillomavirus-related oropharyngeal carcinoma: a review of classic and variant forms

Over the past decade, oropharyngeal human papillomavirus-related squamous cell carcinoma has become firmly established as a distinct entity that differs from conventional head and neck cancer in many ways including its epidemiology, genetics, tumor behaviour, and prognosis. While much attention has been given to advanced techniques for genetic profiling and viral detection in these tumors, sometimes overlooked is the fact that human papillomavirus-related oropharyngeal squamous cell carcinomas exhibit characteristic histologic features that can be appreciated by routine microscopy. In addition, there are now variant morphologies of oropharyngeal human papillomavirus-related carcinoma that are well recognized. This review will cover the classic and variant histomorphologic appearances of human papillomavirus-related oropharyngeal carcinoma, with an emphasis on their differences from conventional, human papillomavirus-unrelated cancer. Recognition of these appearances can help facilitate the performance and interpretation of human papillomavirus testing, as well as communication with treating physicians.