Non-keratinizing oropharyngeal squamous cell carcinomas (OPSCC) typically occur in Caucasian males in the 6th decade of life. The majority of these cancers are associated with high-risk human papillomavirus (HPV) infection, typically type 16. As demonstrated by the clinical history in this case, these tumours often present as a metastasis to a cervical lymph node. p16 immunohistochemistry is used as a surrogate marker for high-risk HPV infection and the presentation of a p16+ squamous cell carcinoma within a cervical lymph node is highly suggestive of an occult primary within the oropharynx (i.e. palatine tonsil, base of tongue).

HPV-positive OPSCC differs from HPV-negative OPSCC in terms of demographics, histopathology and prognosis. HPV-negative OPSCC typically presents in a slightly older age group and are more strongly associated with the traditional risk factors for SCC of the oral cavity such as smoking and alcohol use. Microscopically, HPV-negative OPSCC is typically a conventional SCC that shows keratinization, desmoplasia and associated dysplasia of the surface epithelium. The opposite is true of HPV-positive SCC, which is usually non-keratinizing with a basaloid appearance and no overlying dysplasia. The latter feature is in keeping with the notion that HPV-positive SCC arises from the reticulated crypt epithelium, rather than the surface epithelium. Most importantly, HPV-positive OPSCC has a better prognosis with an overall survival rate of 82%.