Role of Cytology in the Diagnosis and Management of HPV-Associated Head and Neck Carcinoma

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) accounts for up to 25% of all HNSCCs. These tumors largely arise from the oropharynx, particularly the tonsil and base of tongue. The first manifestation of HPV-associated HNSCC is frequently as metastasis to cervical lymph nodes that can be documented by fine-needle aspiration. These metastases are often cystic with a predominantly non-keratinizing, basaloid morphology. Knowledge of the HPV status of metastatic HNSCC has significant treatment and prognostic implications as HPV-associated tumors have a more favorable prognosis than conventional HNSCC. Accordingly, HPV testing should be performed on any squamous cell carcinoma of unknown primary identified in neck lymph nodes. HPV detection may be performed using a variety of methods including p16 as a surrogate immunohistochemical marker, in situ hybridization and/or polymerase chain reaction detection of viral DNA or RNA. Further investigation is needed to determine the optimal method for HPV detection in fine-needle aspiration specimens. Cytology screening for HPV-associated HNSCC does not appear to be effective. Greater understanding of the natural history of oral HPV infections is needed before knowing if oral HPV testing may be useful as a screening test.