Department of Medical Oncology, Peter MacCallum Cancer Centre, A'Beckett St, Locked Bag No 1, Melbourne 8006, Australia.
J Clin Oncol. 2010 Sep 20;28(27):4142-8. doi: 10.1200/JCO.2010.29.2904. Epub 2010 Aug 9.
To determine the prognostic importance of p16 and human papillomavirus (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial.
Patients with stage III or IV head and neck squamous cell cancer were randomly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine. In this substudy, analyses were restricted to patients with oropharyngeal cancer. p16 was detected by immunohistochemistry, and HPV was detected by in situ hybridization and polymerase chain reaction.
Slides were available for p16 assay in 206 of 465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172 patients. One hundred six (57%) of 185 were p16-positive, and in patients evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also HPV-positive. Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group (ECOG) performance status. p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74; P = .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P = .003). p16 was a significant prognostic factor on multivariable analysis (HR, 0.45; 95% CI, 0.21 to 0.96; P = .04). p16-positive patients had lower rates of locoregional failure and deaths due to other causes. There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients (HR, 0.33; 95% CI, 0.09 to 1.24; P = .13).
HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.
在一项 III 期同期放化疗试验中，确定 p16 和人乳头瘤病毒（HPV）在接受治疗的口咽癌患者中的预后重要性。
将 III 期或 IV 期头颈部鳞状细胞癌患者随机分配接受顺铂同期放化疗加或不加替拉扎胺。在这项亚研究中，分析仅限于口咽癌患者。通过免疫组织化学检测 p16，通过原位杂交和聚合酶链反应检测 HPV。
在 465 例患者中，有 206 例的幻灯片可用于 p16 检测，其中 185 例符合条件，172 例患者可评估 p16 和 HPV。185 例中有 106 例（57%）为 p16 阳性，在可同时评估 p16 和 HPV 的患者中，102 例 p16 阳性患者中有 88 例（86%）HPV 也呈阳性。p16 阳性患者的 T 分期较低，N 分期较高，东部肿瘤协作组（ECOG）表现状态较好。与 p16 阴性肿瘤相比，p16 阳性肿瘤的 2 年总生存率（91%比 74%；风险比[HR]，0.36；95%置信区间[CI]，0.17 至 0.74；P =.004）和无失败生存率（87%比 72%；HR，0.39；95% CI，0.20 至 0.74；P =.003）均更好。多变量分析显示 p16 是一个显著的预后因素（HR，0.45；95% CI，0.21 至 0.96；P =.04）。p16 阳性患者局部区域复发和其他原因导致的死亡率较低。在 p16 阴性患者中，替拉扎胺组有改善局部区域控制的趋势（HR，0.33；95% CI，0.09 至 1.24；P =.13）。
与接受顺铂为基础的放化疗的 HPV 阴性口咽癌相比，HPV 相关口咽癌是一种预后较好的独特实体瘤。
