Pathogenic TP53 mutations influence chemotherapy response and survival rate of patients with HPV-negative oral carcinomas

Background/Aim. Oral squamous cell carcinoma (OSCC) is the most common tumor type of head and neck carcinomas, characterized by a high recurrence rate and patients' poor survival. Further elucidation of the function and regulation of the TP53, a pivotal tumor suppressor gene, would provide advances in predicting the clinical behavior, prognosis, and chemotherapy re-sponse of OSCC patients. Thus, we investigated the as-sociation of TP53 gene mutations with survival and re-sponse to cisplatin chemotherapy in human papilloma vi-rus (HPV)-negative OSCC patients. Methods. The po-tential clinical relevance of TP53 mutations was analyzed in 82 patients with HPV-negative OSCC. All patients underwent radiotherapy, and 25 patients received cispla-tin chemotherapy. A negative HPV status was deter-mined by type-specific polymerase chain reaction (PCR) for high-risk HPV 16, 18, 31, and 33. Targeted sequenc-ing of TP53 exons 4-8 was assessed by Sanger sequenc-ing. Results. Of 82 HPV-negative OSCC patients, 49 (59.79%) had TP53 mutations, and 26 patients (31.7%) carried pathogenic TP53 mutations. Patients with patho-genic TP53 mutations had significantly reduced overall survival (p = 0.009). Recurrence status, but not TP53 mu-tations, was an independent marker of poor survival in our cohort [hazard ratio (HR) = 4.733, 95% confidence interval (95% CI): 2.027-11.053, p = 0.0001]. In the sub -cohort of patients who underwent cisplatin-based chem-otherapy, pathogenic TP53 mutations were predictors of poor response to chemotherapy (p = 0.026). Conclu-sion. Our findings indicate that pathogenic TP53 muta-tions in HPV-negative OSCC tumors could be a prog-nostic marker of patients' reduced overall survival. In addition, pathogenic TP53 mutations in HPV-negative OSCC could be a marker of poor chemotherapy re-sponse of OSCC patients.