Multiple mutations – A genetic marker for extracapsular growth in Oropharyngeal Carcinoma

Under the 8th edition of the TNM classification, in addition to HPV status, extracapsular growth (ECS) plays an important role in the classification of the UICC stage of oropharyngeal carcinomas. Both factors could be associated with different mutation profiles. Therefore, the aim of this study was to identify genetic markers for ECS and to identify differences between HPV-positive and HPV-negative patients. We sequenced 99 samples of operable oropharyngeal carcinomas using targeted next-generation sequencing and determined the HPV status. Clinical data including tobacco and alcohol consumption, UICC stage, ECS and overall survival (OS) were analyzed retrospectively. The study included 55 HPV-positive and 44 HPV-negative patients. The groups differed significantly in the distribution of gender (p=0.006), alcohol consumption (p=0.001), UICC stage (p<0.001), TP53 mutation (p<0.001) and tended to differ in FGFR3 (p=0.068). Predictors of survival were young age at initial diagnosis (p=0.026), no invasion of the vein (p=0.048) or perineural region (p=0.008), a small primary tumor (p<0.001), no ECS (p=0.026) and potentially the absence of a TP53 mutation (p=0.088). Grading (p=0.031) and the presence of a residual tumor after surgery (R1; p=0.017) influenced OS only in the HPV-positive group. Multiple mutations occurred in 32% of HPV-positive patients with ECS and only in 9% without ECS (p=0.029). Mutations in PIK3CA were detected in 26 patients. The mutation occurred significantly more frequently in non-smokers (p=0.003). Mutations in PTEN only occurred in HPV-positive tissues, where disease-free survival was significantly reduced (p=0.027). Overall, the presence of multiple mutations in oropharyngeal carcinomas is associated with ECS.

Funding information Supported by the &quot;Berliner Krebsgesellschaft&quot;

Publication History

Article published online:
19 April 2024