Negative Prognostic Implication of TERT Promoter Mutations in Human Papillomavirus-Negative Tonsillar Squamous Cell Carcinoma Under the New 8th AJCC Staging System

Abstract

Telomerase reverse transcriptase gene promoter (TERTp) mutation is a potential candidate for pathogenesis and therapeutic target of tonsillar squamous cell carcinomas (TSCCs) in association with human papillomavirus (HPV). Their clinical relevance has not been validated under the new 8th American Joint Committee on Cancer (AJCC) staging system. We analyzed real-time peptide nucleic acid-mediated PCR and sequencing methods (TERTpmutation) and real-time PCR-based assay (HPV) in 80 surgically resected TSCCs. The 8th edition staging system improved the stratification of the early and advanced stages and between T or N categories for overall survival over the 7th edition.TERTpmutation was found in 7.5%, and HPV in 80.0% of the patients. The majority (83.3%) ofTERTpmutation cases were HPV-positive TSCCs. Applying the 8th edition staging system,TERTpmutation was an independent factor of poor prognosis for disease-free survival (DFS) in TSCC patients, supporting the clinical significance ofTERTpmutation in tonsil cancer.TERTpmutations were also negatively correlated with overall survival and DFS in HPV-negative TSCCs. Conclusively,TERTpmutation provides negative prognostic impact on survival of surgically managed tonsil cancers staged with the AJCC 8th edition.