Wagner Steffen, Wittekindt Claus, Sharma Shachi Jenny, Wuerdemann Nora, Jüttner Theresa, Reuschenbach Miriam, Prigge Elena-Sophie, von Knebel Doeberitz Magnus, Gattenlöhner Stefan, Burkhardt Ernst, Pons-Kühnemann Jörn, Klussmann Jens Peter
Department of Otorhinolaryngology, Head and Neck Surgery, University of Giessen, Giessen DE-35392, Germany.
Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg D-69120, Germany.
Br J Cancer. 2017 Jun 6;116(12):1604-1611. doi: 10.1038/bjc.2017.132. Epub 2017 May 4.
Upfront surgery is a valuable treatment option for oropharyngeal squamous cell carcinoma (OPSCC) and risk stratification is emerging for treatment de-escalation in human papillomavirus (HPV)-related OPSCC. Available prognostic models are either based on selected, mainly non-surgically treated cohorts. Therefore, we investigated unselected OPSCC treated with predominantly upfront surgery.
All patients diagnosed with OPSCC and treated with curative intent between 2000 and 2009 (n=359) were included. HPV association was determined by HPV-DNA detection and p16 immunohistochemistry. Predictors with significant impact on overall survival (OS) in univariate analysis were included in recursive partitioning analysis.
Risk models generated from non-surgically treated patients showed low discrimination in our cohort. A new model developed for unselected patients predominantly treated with upfront surgery separates low-, intermediate- and high-risk patients with significant differences in 5-year OS (86%, 53% and 19%, P<0.001, respectively). HPV status is the most important parameter followed by T-stage in HPV-related and performance status in HPV-negative OPSCC. HPV status and ECOG remained important parameters in risk models for patients treated with or without surgery.
Regardless of treatment strategies, HPV status is the strongest predictor of survival in unselected OPSCC patients. The proposed risk models are suitable to discriminate risk groups in unselected OPSCC patients treated with upfront surgery, which has substantial impact for design and interpretation of de-escalation trials.
upfront手术是口咽鳞状细胞癌（OPSCC）的一种有价值的治疗选择，并且针对人乳头瘤病毒（HPV）相关的OPSCC进行治疗降级的风险分层正在出现。现有的预后模型要么基于选定的、主要是非手术治疗的队列。因此，我们研究了主要接受upfront手术治疗的未选定的OPSCC患者。
纳入2000年至2009年间所有被诊断为OPSCC并接受根治性治疗的患者（n = 359）。通过HPV-DNA检测和p16免疫组化确定HPV相关性。单因素分析中对总生存期（OS）有显著影响的预测因素被纳入递归划分分析。
从非手术治疗患者生成的风险模型在我们的队列中显示出低辨别力。为主要接受upfront手术治疗的未选定患者开发的一种新模型将低风险、中风险和高风险患者区分开来，5年总生存率有显著差异（分别为86%、53%和19%，P<0.001）。在HPV相关的OPSCC中，HPV状态是最重要的参数，其次是T分期；在HPV阴性的OPSCC中，体能状态是最重要的参数。HPV状态和东部肿瘤协作组（ECOG）状态在接受或未接受手术治疗的患者的风险模型中仍然是重要参数。
无论治疗策略如何，HPV状态是未选定的OPSCC患者生存的最强预测因素。所提出的风险模型适用于区分接受upfront手术治疗的未选定OPSCC患者的风险组，这对降级试验的设计和解释有重大影响。
