Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination.
Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination.
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DOI：
10.1158/1078-0432.ccr-11-0388
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发表时间：
2011-10-01
期刊：
影响因子：
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通讯作者：
Shaw RJ
中科院分区：
文献类型：
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作者：
Schache AG;Liloglou T;Risk JM;Filia A;Jones TM;Sheard J;Woolgar JA;Helliwell TR;Triantafyllou A;Robinson M;Sloan P;Harvey-Woodworth C;Sisson D;Shaw RJ
人乳头瘤病毒16型（HPV 16）是口咽鳞状细胞癌（OPSCC）的一个生物学上独特的亚群的病原体，具有高度有利的预后。在临床试验中，HPV 16状态是一个重要的入选或分层参数，突出了准确检测的重要性。来自108例OPSCC病例的固定和新鲜冷冻组织进行了8种可能的检测/检测组合：p16免疫组织化学（p16 IHC）;高危HPV的原位杂交（HR HPV ISH）;病毒E6 RNA（RNA qPCR）和DNA（DNA qPCR）的定量PCR;以及上述组合。HPV 16阳性OPSCC出现在吸烟较少的年轻患者中（平均年轻7.5岁，p=0.003），而HPV阴性患者（p=0.007）。1988年至2009年期间，HPV 16阳性病例的比例从15%增加到57%（p=0.001）。与RNA qPCR“金标准”相比，p16 IHC / DNA qPCR的组合表现出可接受的灵敏度（97%）和特异性（94%），并且是有利结果的最佳选择（OS p=0.002）。p16 IHC / HR HPV ISH也具有可接受的特异性（90%），但其敏感性（88%）的大幅降低影响了其预后价值（p=0.02）。当单独使用时，p16 IHC、HR HPV ISH和DNA qPCR均不具有足够的特异性，不推荐用于临床试验。在应用HPV 16诊断测试时必须谨慎，因为以前发表的技术在准确性和预后价值方面存在显着差异。
Human Papillomavirus-16 (HPV16) is the causative agent in a biologically distinct subset of oropharyngeal squamous cell carcinoma (OPSCC) with highly favourable prognosis. In clinical trials, HPV16 status is an essential inclusion or stratification parameter, highlighting the importance of accurate testing. Fixed and fresh frozen tissue from 108 OPSCC cases were subject to eight possible assay/assay combinations: p16 immunohistochemistry (p16 IHC); in-situ hybridisation for high risk HPV (HR HPV ISH); quantitative PCR for both viral E6 RNA (RNA qPCR) & DNA (DNA qPCR); and combinations of the above. HPV16 positive OPSCC presented in younger patients (mean 7.5 years younger, p=0.003) who smoked less than HPV negative patients (p=0.007). The proportion of HPV16 positive cases increased from 15% to 57% (p=0.001) between 1988 and 2009. A combination of p16 IHC / DNA qPCR demonstrated acceptable sensitivity (97%) & specificity (94%) compared with the RNA qPCR “gold standard”, as well as being the best discriminator of favourable outcome (OS p=0.002). p16 IHC / HR HPV ISH also had acceptable specificity (90%) but the substantial reduction in its sensitivity (88%) impacted upon its prognostic value (p=0.02). Neither p16 IHC, HR HPV ISH nor DNA qPCR were sufficiently specific to recommend in clinical trials when used in isolation. Caution must be exercised in applying HPV16 diagnostic tests due to significant disparities in accuracy and prognostic value in previously published techniques.