Small Biopsy Specimens Reliably Indicate p16 Expression Status of Oropharyngeal Squamous Cell Carcinoma
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Human papillomavirus (HPV)—related oropharyngeal squamous cell carcinoma (SCC) is associated with favorable patient survival. Tumor HPV status at primary diagnosis is critical for proper management, and p16 immunohistochemistry (IHC) has emerged as a reliable, single, surrogate marker. It is not known, however, if small biopsy specimens are completely adequate for p16 evaluation. From a database of oropharyngeal SCC for which p16 IHC and histologic typing were already performed, all patients (32) who had available in-house primary tumor biopsy specimens and also subsequent surgical resections were analyzed. p16 IHC was performed along with histologic typing into: Type 1 keratinizing SCC, Type 2 nonkeratinizing SCC with maturation, and Type 3 nonkeratinizing SCC. Staining was graded on both biopsies and resections as follows: 0 = negative; 1+ = 1–25% of tumor cells positive; 2+ = 26–50%; 3+ = 51–75%; 4+ = 76–100%. Strictly considering p16 score, perfect biopsy-resection correlation was present in 28 of 32 cases (85%), including 6/9 (67%) Type 1, 6/7 (86%) Type 2, and 16/16 (100%) Type 3 cases. Considering p16 expression binarily as 51% tumor cell staining or more (3+ or 4+) being positive and lesser amounts (0, 1+, or 2+) as being negative, there was perfect biopsy-resection correlation for all 32 cases. With p16 expression in resection specimens considered the gold standard, p16 IHC in biopsies was both 100% sensitive and specific. Our results demonstrate that p16 staining in diagnostic biopsies reliably reflects whole tumor staining results, and suggest that biopsies do not suffer from false negatives or positives.
KeywordsHuman papillomavirus p16 immunohistochemistry Squamous cell carcinoma Oropharynx Small biopsy
The authors would like to thank the Anatomic and Molecular Pathology (AMP) Core Lab (specifically, Lab Manager Neha Dahiya, M.D., M.B.A., Senior Research Technician Jianping Li, B.S., Research Lab Supervisor Autumn Watson, B.A., and Research Technician I Vernetta Layton) for their excellent work in preparing the histologic sections and immunohistochemical stains. This study was funded by discretionary research funds of the Department of Pathology and Immunology, Washington University in St. Louis.
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