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

点击翻译按钮获取中文摘要

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.