Human papilloma virus related squamous cell carcinomas of the head and neck: diagnosis, clinical implications and detection of HPV

High-risk human papillomavirus (HPV) positive squamous cell carcinoma (SCC) of the head and neck is reported most commonly in the oropharynx but can also uncommonly be found in other sites such as the anterior oral cavity and sinonasal tract. While HPV positive oropharyngeal squamous cell carcinoma (HPV-OPSCC) has been shown to have a more favourable prognosis than conventional smoking- and alcohol-related anterior oral cavity squamous cell carcinoma (OSCC), HPV positive SCC arising elsewhere in the head and neck region does not carry the same favourable prognosis. HPV-OPSCC often tends to present with large cystic metastases in the cervical lymph nodes, with a clinically and radiologically occult primary. Correct diagnosis of the initial biopsy/cytology specimen is critical for directing further investigations and management. In recognition of its distinct biological behaviour, the 8th edition of the American Joint Commission on Cancer (AJCC 8) has proposed a separate clinical and pathological staging system for HPV-OPSCC compared to that for a conventional primary OSCC or neck metastasis of similar size. The new AJCC staging does not apply to other HPV positive SCC of the head and neck. This review examines the current biology of HPV positive SCC, focusing on HPV-OPSCC. The value and pitfalls of current detection methods of HPV are discussed with an emphasis on the role of the pathologist in the diagnosis and management of HPV positive SCC of the head and neck.