HPV-related squamous cell carcinoma of oropharynx: a review

In early 1930, R. E. Shope paved the way for the recognition of human papillomavirus (HPV) as a causative agent of some types of cancers. In early 2000, the relationship between HPV and a subset of head and neck cancers, mostly located in the oropharynx, was discovered. In the last 20 years, we have made great progress in the recognition and treatment of HPV-positive head and neck cancers. However, there are still grey areas that leave room to subjective interpretation and need to be addressed. The majority of high risk (HR) HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) shows a 'basaloid' morphology, and despite the variegated morphological spectrum of this malignancy, highlighted by some very recent publications, there is a lack of consensus on a universal morphological classification of HPV-OPSCC. The advent of immunohistochemistry with p16 ^ink4a (p16) protein made the diagnosis of HPV-related OPSCC more straightforward; currently patients with OPSCC are stratified in p16-positive and p16-negative. Although p16 is an excellent surrogate of HR HPV infection, it is not the direct demonstration of the presence of virus. At present, there is no univocal 'gold-standard' technique for the detection of oncogenic HPV infection. It is well known that HR HPV-related (OPSCC) bear significantly better survival outcome than HPV-negative cases. Consequently, the eighth edition of the American Joint Committee on Cancer and the Union for International Cancer Control now have separate staging systems for these two distinct malignancies. The present review discusses the salient features of HR HPV-driven OPSCC.