Abstract
BACKGROUND: In the 8th edition of the TNM classification, extracapsular spread (ECS) became a factor in classifying the UICC stage of oropharyngeal carcinomas (OPSCC). We aimed to find genetic markers for ECS and to identify differences between HPV/p16-positive and HPV/p16-negative cases. METHODS: We performed targeted next-generation sequencing on 99 samples of operable OPSCC and a retrospective analysis of clinical data. RESULTS: We included 55 HPV/p16-positive and 44 HPV/p16-negative patients. We found a significant difference between both groups, particularly in TP53 mutation (p < 0.001). Among other things, a small primary tumor (p < 0.001), no ECS (p = 0.026) were identified as predictors for survival. Multiple mutations were associated with an increased incidence of ECS, especially in HPV+/p16+ cases (p = 0.017). A mutation in PIK3CA occurred more frequently in nonsmokers, especially in HPV-/p16- patients (p = 0.027). A PTEN mutation-which only occurred in HPV+/p16+ tissues-reduced disease-free survival (DFS, p = 0.026). CONCLUSION: The presence of multiple mutations in HPV+/p16+ OPSCC was associated with a higher risk of ECS. LEVEL OF EVIDENCE: 3.