Heterogeneity of p16 immunohistochemistry and increased sensitivity of RNA in situ hybridization in cytology specimens of HPV-related head and neck squamous cell carcinoma.

p16 is heterogeneous in cell blocks of metastatic HPV-HNSCC, suggesting that any p16 positivity should prompt confirmatory HPV studies. RNA ISH appears to demonstrate high sensitivity, and laboratories even may consider using RNA ISH as a first-line HPV test in cytologic specimens.