p16INK4a expression, human papillomavirus, and survival in head and neck cancer
p16INK4a expression, human papillomavirus, and survival in head and neck cancer
复制标题
DOI：
10.1016/j.oraloncology.2007.01.010
复制
发表时间：
2008-02-01
期刊：
影响因子：
4.8
通讯作者：
Turek, Lubomir P.
中科院分区：
文献类型：
--
作者：
Smith, Elaine M.;Wang, Donghong;Turek, Lubomir P.
头颈癌（HNC）的发生与人乳头瘤病毒高危型（HPV-HR）有关。HPV E7癌蛋白使pRB蛋白失活，增加p16（INK 4a）的表达。p16表达和HPV状态与HNC临床结局的差异相关。本研究探讨了当这些生物标志物作为个体或联合分子效应进行检查时，HNC预后是否不同。对301例HNC患者的肿瘤组织进行HPV类型分析和测序。免疫组化法检测p16蛋白表达。p16蛋白阳性率为35%，HPV-HR阳性率为27%。校正年龄、吸烟和饮酒后，p16+肿瘤与HPV-HR（OR = 13.3，7.1-24.9）、组织学、分期、分级、肿瘤部位和淋巴结受累在统计学上显著相关。与p16+ HNC病例相比，不表达p16的患者的疾病特异性（DS）生存率显著更差（风险比，调整HR = 2.0）。1.0-3.9）和复发（调整HR = 3.6，1.6-8.2）;与HPV-HR患者相比，HPV-病例的DS生存率（调整HR = 2.8，1.1-7.1）和复发率（调整HR = 2.0，0.8-4.8）更差。每个p16/HPV组有不同的生存结局：p16+/HPV-HR病例（参考）的DS生存率最好，p16-/HPV-病例的DS生存率最差（调整HR = 3.6; 53% vs 13%，p = 0.004），而p16+/HPV-和p16-/HPV-HR的DS生存率相似（调整HR = 2.7/2.8）。p16-/HPV-HR病例的复发率（adj.HR = 7.0; 60% vs 0%，参考，p = 0.08）比p16-/HPV-（adj.HR = 4.5）或p16+/HPV-（adj.HR = 1.8）病例更差。与单独评估的每种标志物相比，组合的p16/HPV生物标志物数据与HNC的不同生存结局相关，表明一起评估的两种分子机制可能提供更准确的临床结局预测。(c)2007年由Elsevier Ltd.出版
Development of head and neck cancer (HNC) is associated with human papillomavirus high-risk (HPV-HR) types. The HPV E7 oncoprotein inactivates the pRB protein increasing expression of p16(INK4a). p16 Expression and HPV status have been associated with differences in clinical outcomes for HNC. This study examined whether HNC prognosis was different when these biomarkers were examined as individual or joint molecular effects. Tumor tissue from 301 HNC patients were analyzed and sequenced for HPV types. p16 was evaluated by immunohistochemical staining. p16 was expressed in 35% and HPV-HR was detected in 27% of HNC patients. After adjustment for age, tobacco, and alcohol, p16+ tumors were statistically significantly associated with HPV-HR (OR = 13.3, 7.1-24.9), histology, stage, grade, tumor site, and node involvement. Compared to p16+ HNC cases, those who did not express p16 had significantly worse disease-specific (DS) survival (Hazards Ratio, adj.HR = 2.0. 1.0-3.9) and recurrence (adj.HR = 3.6, 1.6-8.2); and HPV- cases had worse DS survival (adj.HR = 2.8, 1.1-7.1) and recurrence (adj.HR = 2.0, 0.8-4.8) compared to HPV-HR patients. Each of the p16/HPV groups had different survival outcomes: p16+/HPV-HR cases (referent) had the best and p16-/HPV- cases had the worst DS survival, (adj.HR = 3.6; 53% versus 13%, p = 0.004) whereas p16+/HPV- and p16-/HPV-HR had similar DS survival (adj.HR = 2.7/2.8). p16-/HPV-HR cases had a worse recurrence rate (adj.HR = 7.0; 60% versus 0%, referent, p = 0.08) than p16-/HPV- (adj.HR = 4.5) or p16+/HPV- (adj.HR = 1.8) cases. The combined p16/HPV biomarker data are associated with different survival outcomes of HNC compared to each marker evaluated separatety, indicating that the two molecular mechanisms evaluated together may provide a more accurate prediction of clinical outcomes. (c) 2007 Published by Elsevier Ltd.