Molecular classification identifies a subset of human papillomavirus-associated oropharyngeal cancers with favorable prognosis
Molecular classification identifies a subset of human papillomavirus-associated oropharyngeal cancers with favorable prognosis
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DOI：
10.1200/jco.2004.00.3335
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发表时间：
2006-02-10
影响因子：
45.3
通讯作者：
Psyrri, A
中科院分区：
文献类型：
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作者：
Weinberger, PM;Yu, ZW;Psyrri, A
目的探讨人乳头瘤病毒（HPV）在口咽鳞状细胞癌（OSCC）中的感染情况。HPV E7下调视网膜母细胞瘤（Rb）导致p16上调。我们假设，p16过度表达在口腔鳞癌定义HPV诱导的肿瘤，预后良好。方法使用实时聚合酶链反应HPV 16，我们确定了HPV 16病毒载量在一个队列的79 OSCC注释与长期患者随访。包括这些病例的组织微阵列也分析了p53，p16和Rb利用原位定量蛋白表达分析。77例肿瘤被分为三级模型的基础上p16表达和HPV-DNA的存在：I类，HPV-，p16低; II类，HPV+，p16低;和III类，HPV+，p16 high.Results 61%的OSCC是HPV 16 +; HPV状态本身是没有预后价值的局部复发和生存时间几乎没有显着。III类患者的总生存率（79%）高于其他两类患者（20%和18%; P = 0.0095）。同一类别的无病生存率分别为75%、15%和13%（P = 0.0025）。III级患者的5年局部复发率为14%，而III级患者为45%和74%（P = 0.03）。只有III级患者的p53和Rb表达显著较低（分别为P = 0.017和0.001）。结论利用该系统进行分类，我们确定了HPV+ OSCC预后良好的分子特征，即HPV+/p16高（111类）。这项研究定义了一种新的分类方案，可能对HPV靶向治疗临床试验的患者分层有价值。
Purpose We sought to determine the prevalence of biologically relevant human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC). Retinoblastoma (Rb) downregulation by HPV E7 results in p16 upregulation. We hypothesized that p16 overexpression in OSCC defines HPV-induced tumors with favorable prognosis.Methods Using real-time polymerase chain reaction for HPV16, we determined HPV16 viral load in a cohort of 79 OSCCs annotated with long-term patient follow-up. A tissue microarray including these cases was also analyzed for p53, p16, and Rb utilizing in situ quantitative protein expression analysis. Seventy-seven tumors were classified into a three-class model on the basis of p16 expression and HPV-DNA presence: class I, HPV-, p16 low; class II, HPV+, p16 low; and class III, HPV+, p16 high.Results Sixty-one percent of OSCCs were HPV16+; HPV status alone was of no prognostic value for local recurrence and was barely significant for survival times. Overall survival was improved in class III (79%) compared with the other two classes (20% and 18%; P =.0095). Disease-free survival for the same class was 75% versus 15% and 13% (P =.0025). The 5-year local recurrence was 14% in class III versus 45% and 74% (P =.03). Only patients in class III had significantly lower p53 and Rb expression (P =.017 and .001, respectively). Multivariable survival analysis confirmed the prognostic value of the three-class model.Conclusion Using this system for classification, we define the molecular profile of HPV+ OSCC with favorable prognosis, namely HPV+/p16 high (class 111). This study defines a novel classification scheme that may have value for patient stratification for clinical trials testing HPV-targeted therapies.