Effect of HPV-Associated p16INK4A Expression on Response to Radiotherapy and Survival in Squamous Cell Carcinoma of the Head and Neck
Effect of HPV-Associated p16INK4A Expression on Response to Radiotherapy and Survival in Squamous Cell Carcinoma of the Head and Neck
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DOI：
10.1200/jco.2008.20.2853
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发表时间：
2009-04-20
影响因子：
45.3
通讯作者：
Overgaard, Jens
中科院分区：
文献类型：
--
作者：
Lassen, Pernille;Eriksen, Jesper G.;Overgaard, Jens
目的头颈癌的一个亚型与人乳头瘤病毒（HPV）有关。病毒感染与p16（INK4A）在这些肿瘤中的表达密切相关。在丹麦头颈癌组（DAHANCA） 5试验中，我们对p16（INK4A）作为治疗反应和生存的预后标志物进行了评估，这是一项明确且前瞻性收集的仅接受常规放疗的患者队列。方法分析156例单纯常规放射治疗的石蜡包埋肿瘤块预处理组织中p16（INK4A）的免疫组化表达。评估p16（INK4A）状态对放疗后局部肿瘤控制、疾病特异性生存和总生存的影响。结果35例肿瘤中INK4A阳性，占22%。p16（INK4A）肿瘤阳性与改善局部区域肿瘤控制（5年精算值58% vs 28%， P = 0.0005）、改善疾病特异性生存率（72% vs 34%, P = 0.0006）和改善总生存率（62% vs 26%, P = 0.0003）显著相关。在多变量分析中，p16（INK4A）仍然是局部区域失败（风险比[HR]， 0.35; 95% CI， 0.19至0.64）、疾病特异性死亡（HR, 0.36; 95% CI， 0.20至0.64）和总死亡（HR, 0.44; 95% CI， 0.28至0.68）的一个强有力的独立预后因素。结论p16（INK4A）的表达对常规放疗头颈癌患者的治疗反应和生存有重要影响。中华临床杂志27(2):1992-1998。(C) 2009年美国临床肿瘤学会
PurposeA subset of head and neck cancers is associated with the human papillomavirus (HPV). Viral infection is closely correlated with expression of p16(INK4A) in these tumors. We evaluated p16(INK4A) as a prognostic marker of treatment response and survival in a well-defined and prospectively collected cohort of patients treated solely with conventional radiotherapy in the Danish Head and Neck Cancer Group (DAHANCA) 5 trial.Patients and MethodsImmunohistochemical expression of p16(INK4A) was analyzed in pretreatment paraffin-embedded tumor blocks from 156 patients treated with conventional primary radiotherapy alone. The influence of p16(INK4A) status on locoregional tumor control, disease-specific survival, and overall survival after radiotherapy was evaluated.Resultsp16(INK4A) positivity was found in 35 tumors (22%). Tumor-positivity for p16(INK4A) was significantly correlated with improved locoregional tumor control (5-year actuarial values 58% v 28%; P = .0005), improved disease-specific survival (72% v 34%; P = .0006), and improved overall survival (62% v 26%; P = .0003). In multivariate analysis, p16(INK4A) remained a strong independent prognostic factor for locoregional failure (hazard ratio [HR], 0.35; 95% CI, 0.19 to 0.64), disease-specific death (HR, 0.36; 95% CI, 0.20 to 0.64), and overall death (HR, 0.44; 95% CI, 0.28 to 0.68).ConclusionExpression of p16(INK4A) has a major impact on treatment response and survival in patients with head and neck cancer treated with conventional radiotherapy. J Clin Oncol 27: 1992-1998. (C) 2009 by American Society of Clinical Oncology