多重突变——人乳头瘤病毒/p16阳性口咽癌包膜外扩散的遗传标志物
Multiple Mutations-A Genetic Marker for Extracapsular Spread in Human Papillomavirus/p16-Positive Oropharyngeal Carcinoma.
作者信息
Graessle Raphaela, Piwonski Iris, Husemann Cora, Kleo Karsten, Sabtan Deema, Franzen Achim, Olze Heidi, Erben Ulrike, Hummel Michael, Coordes Annekatrin
机构信息
Department of Otorhinolaryngology - Head and Neck Surgery University Hospital Ruppin-Brandenburg, Brandenburg Medical School Theodor Fontane (MHB) Neuruppin Germany.
Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam Brandenburg University of Technology Cottbus-Senftenberg and Brandenburg Medical School Potsdam Germany.
出版信息
Laryngoscope Investig Otolaryngol. 2025 Feb 4;10(1):e70094. doi: 10.1002/lio2.70094. eCollection 2025 Feb.
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 ( < 0.001). Among other things, a small primary tumor ( < 0.001), no ECS ( = 0.026) were identified as predictors for survival. Multiple mutations were associated with an increased incidence of ECS, especially in HPV+/p16+ cases ( = 0.017). A mutation in PIK3CA occurred more frequently in nonsmokers, especially in HPV-/p16- patients ( = 0.027). A PTEN mutation-which only occurred in HPV+/p16+ tissues-reduced disease-free survival (DFS, = 0.026).
CONCLUSION
The presence of multiple mutations in HPV+/p16+ OPSCC was associated with a higher risk of ECS.
LEVEL OF EVIDENCE
背景
在第8版TNM分类中，包膜外扩散（ECS）成为口咽癌（OPSCC）国际抗癌联盟（UICC）分期的一个因素。我们旨在寻找ECS的遗传标志物，并确定HPV/p16阳性和HPV/p16阴性病例之间的差异。
方法
我们对99例可手术的OPSCC样本进行了靶向二代测序，并对临床数据进行了回顾性分析。
结果
我们纳入了55例HPV/p16阳性和44例HPV/p16阴性患者。我们发现两组之间存在显著差异，尤其是在TP53突变方面（<0.001）。除此之外，小的原发肿瘤（<0.001）、无ECS（=0.026）被确定为生存的预测因素。多种突变与ECS发生率增加相关，尤其是在HPV+/p16+病例中（=0.017）。PIK3CA突变在非吸烟者中更频繁发生，尤其是在HPV-/p16-患者中（=0.027）。仅在HPV+/p16+组织中发生的PTEN突变降低了无病生存期（DFS，=0.026）。
结论
HPV+/p16+ OPSCC中多种突变的存在与ECS的较高风险相关。
证据级别
3级。
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