A Case Western Reserve University–led research team is developing a noninvasive oral cancer test to help clinicians decide-chairside and within minutes- whether a suspicious lesion in the mouth needs a biopsy.

The project pairs a discovery made in the university's School of Dental Medicine with device-engineering and microfabrication expertise from the Case School of Engineering and the commercialization capabilities of industry partner Hemex Health Inc. of Portland, Oregon.

The work is supported by a new five-year, $2.93 million grant from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). 

The type of grant is an NIH award structured as an academic–industrial partnership: It teams university researchers with a company to advance technology from the lab to a commercial, point-of-care product.

Our goal is to take a sophisticated laboratory measurement and engineer it into a simple, affordable device that works reliably at the chairside. Manufacturing and validating that device to a commercial standard is exactly the kind of translational engineering challenge our collaboration was built to solve."

Aaron Weinberg, professor and chair of the Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University

Weinberg, also a member of the NCI-designated Case Comprehensive Cancer Center, is one of the project's three principal investigators. The team spanning dentistry, engineering and industry also is led by:

• Umut Gurkan, the Wilbert J. Austin Professor of Engineering in the Department of Mechanical and Aerospace Engineering at the Case School of Engineering and director of the Case Biomanufacturing and Microfabrication Laboratory. Gurkan's group contributes point-of-care device design, microfabrication and analytical validation to turn the lab work into a manufacturable, easy-to-use test.

• Peter Galen, chief innovation officer and co-founder of Hemex Health and a Case Western Reserve engineering alumnus. Hemex Health's Gazelle point-of-care platform, developed in collaboration with CWRU, has been used in more than 40 countries for blood-disease testing. The company will help advance the oral cancer test toward regulatory clearance and manufacturing.

The research team also includes: CWRU's Mireya Diaz-Insua and Rod Rezaee, from the School of Medicine, and Santosh Ghosh, from the School of Dental Medicine; and Allesandro Villa, from the Miami Cancer Center.

Simpler test for a difficult decision

The American Cancer Society estimates about 60,480 new cases of oral and throat cancers and 13,150 deaths nationally this year.

Oral squamous cell carcinoma (OSCC) is among the most common cancers worldwide and is especially prevalent in low- and middle-income countries, where pathology services are often scarce and diagnoses can be delayed or inaccurate.

In higher-income settings, the opposite problem is common: Clinicians often biopsy suspicious lesions even though roughly 90% turn out to be benign, Weinberg said. While reassuring for patients, those biopsies add cost, discomfort and anxiety.

The test being developed, called the BDI fluorescence immunoassay, or BDI-FIA, offers a non-invasive alternative. It measures the ratio of two naturally occurring peptides-human beta-defensin-3 (hBD-3) and human beta-defensin-2 (hBD-2)-from a simple oral swab.

That ratio, which the research team calls the beta-defensin index (BDI), corresponds with the presence of OSCC. A reading available at the chairside in minutes could help clinicians advise patients immediately, identify who actually needs a biopsy and serve as a screening tool in communities with limited pathology services.

Weinberg's lab was among the first to characterize human beta-defensins in the oral cavity and showed that hBD-3 becomes overexpressed, while hBD-2 declines, in the early stages of oral cancer. That observation is the biological basis for the BDI.

From bench to chairside

The project has three aims: manufacturing the test, analytically validating its precision and accuracy and then clinically validating it in patients. The team plans to pursue commercialization through both U.S. and Indian regulatory agencies to reach communities where oral cancer is common but diagnostic services are limited.

By combining a CWRU discovery with a commercial partner's manufacturing and distribution capacity, the academic–industrial structure is designed to more quickly get a promising product into clinicians' hands to treat patients-an approach of growing importance as federal research budgets tighten and funders prioritize work with a clear path to real-world and commercial impact.

The project also received funding from the Ohio Third Frontier, managed through the Ohio Department of Development, and was supported by the Clinical and Translational Science Collaborative of Northern Ohio, which is funded by the National Center for Advancing Translational Sciences of the NIH, UM1TR004528.