Background: This study compared survival outcomes between upfront surgery +/−radiotherapy (RT) and definitive RT with or without chemotherapy (RT/CRT) in HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). Methods: A retrospective matched-pair analysis included 150 patients treated between 1990 and 2020. Fifty (RT/CRT) cases (2009–2020) were matched 2:1 to 100 surgical cases (1990–2009) by sex, subsite, T/N classification, and AJCC 8th stage. Sixty-six percent of surgically treated patients received adjuvant RT. Only HPV-negative tumors confirmed by p16 and HPV DNA testing were analyzed. Survival was assessed with Kaplan–Meier and Cox regression. Results: RT/CRT achieved significantly higher 5-year overall survival (59% vs. 28%) and disease-specific survival (69% vs. 45%) compared with surgery. Matched-pair analysis showed increased overall mortality (HR 1.91;p= 0.008) and disease-specific mortality (HR 2.05;p= 0.022) in surgical patients. In stage III disease, RT/CRT provided markedly superior DSS (87% vs. 42%). No significant differences were found in local control or recurrence-free survival, but metastasis-free survival was significantly worse in the surgical cohort, and the incidence of second primary tumors was significantly lower in the RT/CRT group. Conclusions: These findings indicate that RT/CRT provides superior survival outcomes and better control of distant metastasis and second primary tumors compared with surgery in HPV-negative OPSCC, particularly in stage III disease. RT/CRT should be considered an effective organ-preserving option for this population.
背景：本研究比较了人乳头瘤病毒（HPV）阴性口咽鳞状细胞癌（OPSCC）患者接受前期手术联合或不联合放疗（RT）与根治性放疗联合或不联合化疗（RT/CRT）的生存结局。方法：通过回顾性配对分析纳入1990年至2020年间治疗的150例患者。将50例（2009-2020年）接受RT/CRT治疗的患者与100例（1990-2009年）接受手术治疗的患者按性别、原发部位、T/N分期及AJCC第8版分期进行1:2配对。手术患者中66%接受了辅助放疗。仅对经p16及HPV DNA检测确认为HPV阴性的肿瘤进行分析。采用Kaplan-Meier法和Cox回归模型评估生存情况。结果：与手术相比，RT/CRT组5年总生存率（59% vs. 28%）和疾病特异性生存率（69% vs. 45%）显著更高。配对分析显示手术组总体死亡率（HR 1.91；p=0.008）和疾病特异性死亡率（HR 2.05；p=0.022）显著增加。在III期患者中，RT/CRT组的疾病特异性生存率显著更优（87% vs. 42%）。两组在局部控制率或无复发生存率方面无显著差异，但手术组无转移生存率显著更差，且RT/CRT组第二原发肿瘤发生率显著更低。结论：研究结果表明，对于HPV阴性OPSCC患者，尤其是III期患者，RT/CRT相较于手术能提供更优的生存结局，并更好地控制远处转移和第二原发肿瘤。RT/CRT应被视为该人群有效的器官保留治疗方案。
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