Mutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status.

Patients with HPV-driven (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) have a significantly improved overall survival compared to patients with HPV-negative (HPV-) OPSCC. Nevertheless, 13%-25% of patients with HPV+OPSCC develop local/distant recurrence (LDR) and have a course of disease similar to HPV-OPSCC. We hypothesize that HPV+OPSCCs of patients with LDR have a mutation frequency and pattern similar to HPV-OPSCCs, which is associated with severe outcome. We performed targeted next-generation sequencing using a customized gene panel and compared data from 56 matched HPV+and HPV-OPSCC of patients with/without LDR regarding protein-altering variants. Despite improved overall survival of patients with HPV+OPSCC, those who develop LDR show a strongly reduced survival rate that is similar or even worse compared to HPV-OPSCC patients. Overall, the number of mutations was similar in OPSCC of patients with and without LDR. In total and with respect to TP53, HPV-OPSCC had significantly more protein-altering mutations than HPV+OPSCC. The number of mutations was similar in HPV-OPSCC of patients with and without LDR with the exception of FAT1, which was mutated more frequently in patients without LDR. In HPV+OPSCC, HRAS, PIK3R1, STK11 and TP63 were more frequently mutated in patients with LDR compared to patients without. HPV+OPSCC of patients with LDR have a similar mutation pattern as HPV-OPSCC, except TP53, which was mutated to a significantly lower extent. In conclusion, HPV-and HPV+OPSCC with LDR have similar mutation counts in the analyzed genes. We suspect that the number of mutations is not causal for disease progression, rather specific mutations could be important.