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HLA Class I and II Expression in Oropharyngeal Squamous Cell Carcinoma in Relation to Tumor HPV Status and Clinical Outcome

机译:口咽鳞状细胞癌中HLA I和II类表达与肿瘤HPV状况和临床结果的关系

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摘要

HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16INK4a and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16INK4a overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.
机译:HPV-DNA阳性(HPVDNA +)口咽鳞状细胞癌(OSCC)的临床疗效优于HPV-DNA阴性(HPVDNA-)OSCC。对于大多数HPV + OSCC,当前的治疗可能不必要地广泛,但是在降级之前,需要额外的标记物以及HPV状态以更好地预测治疗反应。在这里探讨了HLA I类/ HLA II类表达的影响。对来自2000/2009年诊断并经过治疗的439/484名OSCC患者的治疗前活检进行了HLA I和II表达,p16 INK4a 和HPV DNA的分析。在单变量和多变量分析中,与高水平的HLA I类强度相比,缺失/弱与HPVDNA + OSCC中非常有利的无病生存期(DFS),疾病特异性生存期(DSS)和总体生存期(OS)相关II类没有影响。值得注意的是,当单独使用诱导化学放疗(CRT)或放疗(RT)进行治疗时,HLA I级缺乏/弱的HPVDNA + OSCC的反应同样好。在患有HPVDNA-OSCC的患者中,高HLA I类/ II类表达通常与更好的临床预后相关。 p16 INK4a 的过表达与HPVDNA + OSCC的较好临床预后相关。 HPVDNA + OSCC中不存在HLA I类强度,这表明独立于治疗的生存率非常高,并且可以在临床上用于选择患者以进行逐步降级的随机试验。

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