PIK3CA is the most frequently mutated gene in HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventy-seven patients with HPV-associated OPSCC were enrolled on two phase II clinical trials of de-intensified CRT (60 Gy intensity-modulated radiotherapy with concurrent weekly cisplatin). Targeted next-generation sequencing was performed. Nine of 77 patients had disease recurrence (2 regional, 4 distant, 3 regional and distant). Thirty-four patients had mutation(s) identified; 16 had PIK3CA mutations. Patients with wild-type-PIK3CA had statistically significantly higher 3-year disease-free survival than PIK3CA-mutant patients (93.4% [95% CI 85.0-99.9%] vs. 68.8% [95% CI 26.7-89.8%]; p = 0.004. On multivariate analysis, PIK3CA mutation was the only variable statistically significantly associated with disease recurrence (HR 5.71 [95% CI 1.53, 21.3], p = 0.01). PIK3CA mutation is associated with worse disease-free survival in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with de-intensified CRT.

中文翻译：

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HPV相关的OPSCC患​​者接受增强放化疗的PIK3CA突变。

PIK3CA是HPV相关的口咽鳞状细胞癌（OPSCC）中最常见的突变基因。这种突变的预后影响仍然未知。我们试图阐明在用定性化学放射（CRT）治疗的HPV相关的OPSCC患​​者中PIK3CA突变的临床意义。77例与HPV相关的OPSCC的患者参加了两项不增强CRT（60 Gy强度调制放疗联合每周顺铂治疗）的II期临床试验。进行了靶向的下一代测序。77例患者中有9例复发（2个区域，4个远处，3个区域和远处）。识别出34名患者的突变；16例有PIK3CA突变。具有统计学意义的野生型PIK3CA患者的3年无病生存率显着高于PIK3CA突变患者（93。4％[95％CI 85.0-99.9％]与68.8％[95％CI 26.7-89.8％]；p ＝ 0.004。在多变量分析中，PIK3CA突变是与疾病复发在统计学上显着相关的唯一变量（HR 5.71 [95％CI 1.53，21.3]，p = 0.01）。PIK3CA突变与无强化CRT治疗的新诊断为HPV相关的OPSCC患​​者的预期队列中无病生存期较差有关。