Oropharyngeal squamous cell carcinoma: p16/p53 immunohistochemistry as a strong predictor of HPV tumour status

• Published in: Histopathology 2021-09, Vol.79 (3), p.381-390
• Main Authors: Benzerdjeb, Nazim, Tantot, Juliet, Blanchet, Christophe, Philouze, Pierre, Mekki, Yahia, Lopez, Jonathan, Devouassoux‐Shisheboran, Mojgan
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - analysis; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cyclin-Dependent Kinase Inhibitor p16 - analysis; Deoxyribonucleic acid; DNA; DNA, Viral - analysis; DNA-directed DNA polymerase; Female; head and neck; Human papillomavirus; Human papillomavirus 16 - genetics; Human papillomavirus 16 - isolation & purification; Humans; Hybridization; Immunohistochemistry; Infections; INK4a protein; Male; Medical prognosis; Mutagens; Mutants; Mutation; Oropharyngeal Neoplasms - classification; Oropharyngeal Neoplasms - pathology; Oropharyngolaryngeal carcinoma; oropharynx; p16 Protein; p16 staining; p53 Protein; p53 staining; Papillomavirus Infections - complications; Pathology; Polymerase chain reaction; Prognosis; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - classification; Squamous Cell Carcinoma of Head and Neck - pathology; squamous cell carcinoma‐related HPV; Tumor Suppressor Protein p53 - analysis; Tumors
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.14350

Aims Oropharyngeal squamous cell carcinomas (OPSCC) related to human papillomavirus (HPV) infection have a better prognosis than those without HPV infection. Although p16INK4a overexpression is used as a surrogate marker for HPV infection, 5–20% of p16‐positive OPSCC are described as being unrelated to HPV infection, with worse overall survival compared to OPSCC‐related HPV. There is therefore a risk of undertreating a proportion of OPSCC patients falsely considered to be HPV‐driven because of p16 positivity. TP53 mutations are highly prevalent in OPSCC driven by mutagens in tobacco and alcohol. We describe herein a combined p16/p53 algorithm to predict HPV tumour status in OPSCC. Methods and results A total of 110 OPSCC were identified in the database of the pathology department and were studied using p16 and p53 immunohistochemistry. For p16‐positive or p16‐negative/wild‐type patterns‐p53 (WT‐p53) cases (n = 63), DNA in‐situ hybridisation for high‐risk HPV was performed, and if negative the HPV status was controlled by HPV DNA polymerase chain reaction (PCR) (n = 19). A significant association between TP53 mutation and pattern of p53 expression was found (WT‐p53, seven of 16, P