TERT promoter mutations in head and neck squamous cell carcinoma: A systematic review and meta-analysis on prevalence and prognostic significance

Objectives: To estimate the prevalence of two most common and mutually exclusive -124 C > T and -146 C > T TERT promoter mutations in HNSCC and analyse their prognostic role. Materials and methods: The databases Medline (via Ovid), Embase (via Ovid), Cochrane Library, Scopus, and Web of Science (Core Collection) were searched from inception to December 2022 to identify studies analysing TERT promoter mutations in HNSCC. Pooled prevalence of TERT promoter mutations and hazard ratio (sHR) of death/progression, with corresponding confidence intervals (CI), were estimated. Results: The initial search returned 6416 articles, of which 17 studies, including 1830 patients, met the criteria for prevalence meta-analysis. Among them, 8 studies fitted the inclusion criterion to analyse the prognostic impact of TERT promoter mutations. Overall, 21% (95% CI: 12%-31%) of HNSCCs harboured TERT promoter mutation. TERT promoter mutations were more commonly found in oral cavity cancer (prevalence = 47%, 95% CI: 33%-61%), followed by laryngeal/hypopharyngeal cancer (prevalence = 12%, 95% CI: 4%-25%), while they were quite rare in oropharyngeal cancer (prevalence = 1%, 95% CI: 0%-4%). TERT promoter mutation -124 C > T was associated with a higher risk of death (sHR = 2.01, 95% CI: 1.25-3.23) and progression (sHR = 2.79, 95% CI: 1.77-4.40), while -146 C > T TERT promoter mutation did not show any significant correlation neither to overall nor progression-free survival. Conclusion: TERT promoter mutations were mainly topographically restricted to oral cavity cancer. -124 C > T was the most common TERT promoter mutation and was significantly associated to worse outcome in HNSCC.