p16INKa immunocytochemistry in fine-needle aspiration cytology smears of metastatic head and neck squamous cell carcinoma.

Objective: Patients with head and neck squamous cell carcinoma (HNSCC) may initially present with neck metastases diagnosed by fine-needle aspiration (FNA). In these patients, it is critical to locate the primary site so that targeted therapy can be administered. Nearly a quarter of HNSCC are associated with human papillomavirus (HPV) infection. The great majority of HPV-related primaries originate in the oropharynx. p16INKa (p16) functions as a surrogate marker of HPV infection. We sought to determine if expression of p16 by immunocytochemistry (ICC) in neck metastases could assist in localizing the primary site to the oropharynx.

Methods: Diagnostic FNA cytology smears of neck metastases from 90 patients with biopsy-proven primary HNSCC were reviewed. Papanicolaou-stained slides were directly subjected to ICC, using p16 antibody.

Results: Twenty-seven (30%) tumors expressed p16 by ICC; 74% of these p16-positive tumors were metastases from oropharynx. There was a significantly higher proportion of p16 expression in patients with primary oropharyngeal carcinoma (47%) versus those whose primary tumor was non-oropharyngeal (15%; p = 0.0013).

Conclusions: p16 expression in FNA cytology smears of metastatic HNSCC is a useful indicator of oropharyngeal origin and can be used to help localize the primary site in cases where this is not clinically evident.