p16 Immunohistochemistry Can Be Used to Detect Human Papillomavirus in Oral Cavity Squamous Cell Carcinoma

• Published in: Journal of oral and maxillofacial surgery Vol. 71; no. 8; pp. 1367 - 1375
• Main Authors: Duncan, Lisa D., MD, Winkler, Marcus, DO, Carlson, Eric R., DMD, MD, Heidel, R. Eric, MS, PhD, Kang, Eugene, DMD, Webb, David, DDS
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2013
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Cohort Studies; Cyclin-Dependent Kinase Inhibitor p16; Dentistry; Female; Human papillomavirus 16 - chemistry; Human papillomavirus 16 - genetics; Humans; Male; Middle Aged; Mouth Neoplasms - pathology; Mouth Neoplasms - virology; Neoplasm Proteins - analysis; Neoplasm Proteins - genetics; Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity; Statistics, Nonparametric; Surgery
• ISSN: 0278-2391; 1531-5053
• DOI: 10.1016/j.joms.2013.02.019

Purpose Human papillomavirus (HPV) is of etiologic significance in the development of oral squamous carcinoma and is noted to result in p16 overexpression. Identification of HPV is clinically important because the presence of HPV has prognostic and epidemiologic associations. Detection of HPV by polymerase chain reaction (PCR) is expensive and not widely accessible. The authors examined p16 immunohistochemistry (IHC) as a surrogate marker for high-risk HPV and its use as an alternative test to PCR. Patients and Methods A retrospective cohort of patients with oral squamous cell carcinoma underwent surgery and then analysis with p16 IHC and HPV PCR. The p16 IHC staining intensity was graded from 0 to 3+, and these results were compared with PCR. Descriptive and frequency statistics were performed by comparing HPV PCR results with p16 IHC, patient age, gender, and outcome. Results Eighty-one cases were included in the study. Forty-four study patients were men and 37 were women (mean age, 63.9 yr). Forty-five cases (55.6%) had 0 staining, 22 cases (27.2%) had 1+ staining, and 7 cases (8.6%) had 2+ staining. Seven cases (8.6%) had 3+ staining, all of which were positive for HPV serotype 16 by PCR. Three of 7 HPV PCR-positive cases had keratinization typical of an oral cavity location and not the basaloid growth of HPV oropharyngeal tumors. There was a statistical correlation ( P < .001) among HPV PCR positivity, 3+ staining, and younger age. Conclusion p16 3+ staining correlates with HPV PCR positivity. p16 IHC is a technically simple and widely available test, and this study establishes the use of p16 IHC as an alternative test to HPV PCR. Given the clinical significance of HPV in oral squamous carcinoma, p16 IHC should be performed in all cases and included in the pathology report.