Prognostic Significance of p16INK4A and Human Papillomavirus in Patients With Oropharyngeal Cancer Treated on TROG 02.02 Phase III Trial
Prognostic Significance of p16INK4A and Human Papillomavirus in Patients With Oropharyngeal Cancer Treated on TROG 02.02 Phase III Trial
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DOI：
10.1200/jco.2010.29.2904
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发表时间：
2010-09-20
影响因子：
45.3
通讯作者：
McArthur, Grant A.
中科院分区：
文献类型：
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作者：
Rischin, Danny;Young, Richard J.;McArthur, Grant A.
目的探讨p16和人乳头状瘤病毒(HPV)在III期同期放化疗中对口咽癌患者预后的影响。在这项子研究中，分析仅限于口咽癌患者。结果465例患者中有206例P16阳性，其中185例阳性，172例P16和HPV阳性。在185名患者中，106名(57%)p16阳性，在p16和HPV均可评估的患者中，102名p16阳性患者中有88名(86%)也是HPV阳性。P16阳性的患者有较低的T和较高的N分类，以及较好的东部合作肿瘤组(ECOG)表现状态。与p16阴性肿瘤相比，p16阳性肿瘤的两年总生存率(91%比74%；风险比0.36；95%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=0.003)更好。多因素分析显示P16是显著的预后因素(HR，0.45；95%CI，0.21~0.96；P=0.04)。P16阳性患者的局部区域失败率和因其他原因死亡的比率较低。在p16阴性的患者中，替拉帕扎明有改善局部区域控制的趋势(HR，0.33；95%CI，0.09~1.24；P=.13)。结论HPV相关性口咽癌是一个独立的实体，与HPV阴性的口咽癌相比，以顺铂为基础的放化疗具有更好的预后。
Purpose 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 and Methods 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.Results 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).Conclusion HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.