ROC analysis of p16 expression in cell blocks of metastatic head and neck squamous cell carcinoma

• Published in: Journal of the American Society of Cytopathology JASC Vol. 10; no. 4; pp. 423 - 428
• Main Authors: Wilson, Bennett L., Israel, Anna-Karoline, Ettel, Mark G., Lott Limbach, Abberly A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2021
• Subjects: Alphapapillomavirus - metabolism; Biomarkers, Tumor - metabolism; Biopsy, Fine-Needle - methods; Carcinoma; Cell block; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Cytology; Female; Fine-needle aspiration; Human papillomavirus; Humans; Immunohistochemistry - methods; In Situ Hybridization - methods; Lymph Nodes - pathology; Lymphatic Metastasis - diagnosis; Lymphatic Metastasis - pathology; Male; Middle Aged; Neck; Oropharyngeal cancer; Oropharyngeal Neoplasms - diagnosis; Oropharyngeal Neoplasms - metabolism; Oropharyngeal Neoplasms - pathology; Oropharyngeal Neoplasms - virology; p16; Papillomavirus Infections - diagnosis; Papillomavirus Infections - metabolism; Papillomavirus Infections - pathology; Papillomavirus Infections - virology; RNA, Viral - metabolism; ROC Curve; Sensitivity and Specificity; Squamous cell; Squamous Cell Carcinoma of Head and Neck - diagnosis; Squamous Cell Carcinoma of Head and Neck - metabolism; Squamous Cell Carcinoma of Head and Neck - pathology; Squamous Cell Carcinoma of Head and Neck - virology; Human papillomavirus; Fine-needle aspiration; Carcinoma; Cell block; Squamous cell; p16; Oropharyngeal cancer; Cytology
• ISSN: 2213-2945; 2213-2945
• DOI: 10.1016/j.jasc.2021.03.004

Oropharyngeal squamous cell carcinoma is associated with human papillomavirus (HPV) and often presents with early metastasis to cervical neck lymph nodes that are amenable to fine-needle aspiration (FNA). The most common method of HPV status determination is p16 immunohistochemistry (IHC). The literature suggests that a lower threshold is needed for p16 positivity on cell block. We examined and quantified p16 IHC staining on cell block and used receiver operating characteristics (ROC) curve analysis to determine an optimal cutoff value with high sensitivity and specificity. Thirty-six FNAs of metastatic squamous cell carcinoma from cervical lymph nodes with p16 IHC were evaluated. The p16 stain was quantified in 5% increments and high-risk HPV mRNA in situ hybridization was performed as a gold standard test. Statistical analysis was performed. Interobserver variability was evaluated and was shown to be low with an intraclass correlation coefficient of 0.857. ROC analysis was performed and showed that a cell block p16 IHC cutoff of 15% yielded the highest sensitivity (80%) and specificity (81.8%). Our data show that a threshold of 15% p16 staining in cell block maximizes sensitivity and specificity.