Validation of a saliva test using methylated microRNAs for head and neck cancer recurrence

项目总结 这种UH2/UH3组合应用的目标是开发一种非侵入性、准确和成本效益高的 唾液检测用于头颈部鳞状细胞癌(SCCHN)复发的早期检测。 SCCHN包括来自口腔、舌、咽和喉部的鳞状细胞癌。今天是7号 按发病率计算，美国和全球最常见的癌症，5年内在美国排名第3，在全球排名第4 流行率。SCCHN是一种生物学侵袭性癌症，其复发率(局部、局部或局部)较高 远距离)对患者的生存状况有很大的影响。目前临床实践中常见的检测方法 SCCHN复发具有主观性、侵袭性、难以触及、不能及时发现复发等特点 方式或昂贵。对客观的、非侵入性的、易于获取的检测的医疗需求尚未得到满足 能够及时、经济有效地检测到SCCHN复发。我们的解决方案是“HNKlear”，一个非 基于唾液的侵入性候选试验用于SCCHN复发的早期检测。HNKlear采用了7- 甲基化的microRNA生物标志物面板。我们测试的实时特性将提供更及时和更准确的 SCCHN复发的检测。在我们发表的概念验证研究中，HNKlear展示了92% 在~300个SCCHN和对照组织样本中的敏感性和98%的特异性，以及在 ~200个SCCHN和对照唾液样本使用连续变量，这支持临床翻译 这个测试。我们建议将UH2/UH3联合应用于HNKlear的临床翻译。在UH2中 在这一阶段，我们将在一项临床前研究和新的患者队列中分析验证测试和算法。 这一阶段的成功将让我们锁定测试，并在达到里程碑时终止测试。然后我们将进行 HNKlear治疗SCCHN复发的UH3期临床研究 将HNKlear纳入当前临床实践的观察性临床随访研究。这一阶段的成功 将产生强有力的证据，证明HNKlear在早期发现SCCHN复发方面的临床有效性，以及 将进一步使HNKlear作为实验室开发的测试能够在临床上应用。

PROJECT SUMMARY The objective of this combined UH2/UH3 application is to develop a non-invasive, accurate, and cost-effective saliva-based test for early detection of squamous cell carcinoma of the head and neck (SCCHN) recurrence. SCCHN includes squamous cell carcinomas derived from oral cavity, tongue, pharynx and larynx. It is the 7th most common cancer in US and worldwide by incidence, and the 3rd in US and 4th worldwide by 5-year prevalence. SCCHN is a biologically aggressive cancer in which high rates of recurrence (local, locoregional or distant) contribute significantly to poor patient survival. Current clinical practice methods for detection of SCCHN recurrence are either subjective, invasive, hard to access, not able to detect recurrence in a timely manner or expensive. There is an unmet medical need for an objective, non-invasive, easy to access test that is able to detect SCCHN recurrence in a timely and a cost-effective way. Our solution is “HNKlear”, a non- invasive, saliva-based candidate test for early detection of SCCHN recurrence. HNKlear incorporates a 7- methylated microRNA biomarker panel. The real-time nature of our test will provide more timely and precise detection of SCCHN recurrence. In our published proof of concept studies, HNKlear demonstrated 92% sensitivity and 98% specificity in ~300 SCCHN and control tissue samples and 85% sensitivity and 95% in ~200 SCCHN and control saliva samples using continuous variables, which supports the clinical translation of the test. We propose a combined UH2/UH3 application for the clinical translation of HNKlear. In the UH2 phase, we will analytically validate the test and algorithm in a pre-clinical study and in a new patient cohort. Success of this phase will let us lock down the test and cut-off when the milestone is met. We will then conduct a clinical study in the UH3 phase to demonstrate the clinical validity of HNKlear for SCCHN recurrence in an observational clinical follow-up study incorporating HNKlear into current clinical practice. Success of this phase will generate robust evidence of the clinical validity of HNKlear for early detection of SCCHN recurrence, and will further enable clinical application of HNKlear as a Laboratory Developed Test.