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

Abstract

Oral squamous cell carcinoma (OSCC) is the most common tumor type of head and neck carcinomas, characterized by a high recurrence rate and 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 response of OSCC patients. Thus, we investigated the association of TP53 gene mutations with survival and response to cisplatin chemotherapy in HPV-negative OSCC patients. Methods. The potential clinical relevance of TP53 mutations was analyzed in 82 patients with HPV-negative OSCC. All patients underwent radiotherapy and 25 patients received cisplatin chemotherapy. A negative HPV status was determined by type-specific PCR, for high-risk HPV 16, 18, 31, and 33. Targeted sequencing of TP53 exons 4-8 was assessed by Sanger sequencing. Results. Of 82 HPV-negative OSCC patients, 49 (59.79%) had TP53 mutation, and 26 patients (31.7%) carried pathogenic TP53 mutations. Patients with pathogenic TP53 mutations had significantly reduced overall survival, p=0.009. Recurrences status, but not TP53 mutations, was an independent marker of poor survival in our cohort, HR=4.733, [2.027-11.053], p=0.0001. In the subcohort of patients who underwent cisplatin-based chemotherapy, pathogenic TP53 mutations were predictors of poor response to chemotherapy, p=0.026. Conclusions. Our findings indicate that pathogenic TP53 mutations in HPV-negative OSCC tumors could be a prognostic marker of patients’ reduced overall survival. In addition, pathogenic TP53 mutations in HPV-negative OSCC could be a marker of poor chemotherapy response.