Cleveland researchers are developing a rapid, noninvasive test that could help dentists determine within minutes whether a suspicious lesion in the mouth is likely to require a biopsy. The technology, known as the beta-defensin index fluorescence immunoassay, or BDI-FIA, is being designed to convert a complex laboratory measurement into a compact point-of-care tool that clinicians could use during a routine examination. Instead of removing tissue immediately, a clinician would collect an oral sample with a swab and analyze molecular signals associated with oral squamous cell carcinoma, the most common form of oral cancer.
The project is led by Case Western Reserve University and brings together researchers from its School of Dental Medicine, Case School of Engineering and School of Medicine with Hemex Health Inc., a medical-technology company based in Portland, Oregon. The collaboration is supported by a five-year, $2.93 million award from the National Cancer Institute, part of the National Institutes of Health. The grant is structured as an academic–industrial partnership, a funding model intended to move promising discoveries beyond the laboratory by combining university research with industrial engineering, manufacturing and regulatory expertise.
Aaron Weinberg, professor and chair of the Department of Biological Sciences at Case Western Reserve’s School of Dental Medicine and a member of the Case Comprehensive Cancer Center, is one of the project’s three principal investigators. His team’s work provided the biological foundation for the proposed test. The other principal investigators are Umut Gurkan, the Wilbert J. Austin Professor of Engineering in the Department of Mechanical and Aerospace Engineering and director of the Case Biomanufacturing and Microfabrication Laboratory, and Peter Galen, chief innovation officer and co-founder of Hemex Health and a Case Western Reserve engineering alumnus.
The test focuses on two naturally occurring antimicrobial peptides found in the oral cavity: human beta-defensin-3, known as hBD-3, and human beta-defensin-2, or hBD-2. These short proteins are part of the body’s innate immune defense, helping protect epithelial surfaces from microbes. Weinberg’s laboratory was among the first to characterize human beta-defensins in the mouth. Its research found that, during the early stages of oral cancer, hBD-3 becomes overexpressed while hBD-2 declines. The researchers combine measurements of the two molecules into a ratio called the beta-defensin index, or BDI, which may distinguish cancer-associated biological changes from those found in benign lesions.
In the planned assay, a clinician would collect material from a lesion or nearby oral tissue with a simple swab. The sample would then be processed using antibodies or other molecular recognition components designed to bind specifically to hBD-3 and hBD-2. Fluorescent signals generated by those reactions would be measured, allowing the device to estimate the relative abundance of each peptide. Rather than relying on the concentration of a single biomarker, the BDI-FIA would calculate the relationship between the two signals. This ratio-based approach could help reduce the impact of differences in sample collection and provide a more robust indication of the biological pattern associated with oral squamous cell carcinoma.
The clinical problem is substantial. The American Cancer Society estimates that approximately 60,480 new cases of oral and throat cancers will be diagnosed in the United States this year, with about 13,150 deaths. Oral squamous cell carcinoma is also among the most common cancers worldwide and is particularly challenging in low- and middle-income countries, where pathology laboratories and specialist services may be limited. Delayed diagnosis can allow tumors to progress before treatment begins. A test that can be used near the patient, without the need to immediately transport tissue to a pathology laboratory, could be especially valuable in communities where diagnostic infrastructure is scarce.
At the same time, clinicians in wealthier health systems face a different challenge: deciding which suspicious lesions truly warrant an invasive procedure. Weinberg said that roughly 90% of biopsied oral lesions ultimately prove to be benign. Although biopsy remains essential when cancer is suspected, unnecessary procedures can cause discomfort, anxiety and expense, while also consuming clinical and pathology resources. A chairside result would not replace a definitive diagnosis based on tissue examination, but it could help clinicians prioritize patients, counsel them more quickly and identify people who should proceed urgently to biopsy.
The new project is organized around three technical stages: manufacturing the test, analytically validating its performance and clinically evaluating it in patients. Analytical validation will examine whether the device produces precise and reproducible measurements across repeated tests, sample types and operating conditions. Researchers will also need to establish how accurately the BDI distinguishes malignant disease from benign or premalignant lesions, determine appropriate decision thresholds and assess potential interference from saliva, blood, inflammation or other oral conditions. Clinical validation will then compare the test’s readings with established diagnoses based on biopsy and pathology.
Gurkan’s laboratory will contribute device design, microfabrication and analytical testing, with the goal of creating a system that is reliable, inexpensive and simple enough for use outside a specialized laboratory. Hemex Health will help adapt the technology for manufacturing, regulatory review and eventual distribution. The company’s Gazelle platform, developed in collaboration with Case Western Reserve, has been used in more than 40 countries for blood-disease testing. The team plans to pursue regulatory pathways in both the United States and India, where oral cancer represents a major public-health burden and access to diagnostic services can be uneven.
The investigators include Mireya Diaz-Insua and Rod Rezaee from Case Western Reserve’s School of Medicine, Santosh Ghosh from the School of Dental Medicine and Allesandro Villa from the Miami Cancer Center. Their work builds on earlier support from the Case-Coulter Translational Research Partnership, the NIH Point-of-Care Technologies Research Network, Ohio Third Frontier and the Clinical and Translational Science Collaborative of Northern Ohio. The research described in the project is supported by the National Cancer Institute under Award Number R01CA306044. If the assay performs as hoped, the result could be a new kind of cancer-screening tool: a small, rapid molecular test that gives clinicians actionable information at the moment a suspicious lesion is discovered, while preserving biopsy and pathology as the definitive route to diagnosis.
Subject of Research:
Development of a noninvasive, chairside fluorescence immunoassay for detecting oral squamous cell carcinoma through the beta-defensin index.
Article Title:
Rapid Oral Cancer Test Could Help Dentists Decide Which Lesions Need Biopsy
Web References:
https://case.edu/dental/
https://case.edu/engineering/
https://case.edu/cancer/
https://case.edu/
References:
National Cancer Institute, NIH Award Number R01CA306044; Case Western Reserve University research announcement; American Cancer Society oral and throat cancer estimates.
Keywords:
oral cancer, oral squamous cell carcinoma, beta-defensin index, BDI-FIA, fluorescence immunoassay, point-of-care diagnostics, noninvasive cancer testing, biopsy, biomedical engineering, Case Western Reserve University, Hemex Health, cancer biomarkers
Tags: beta-defensin index fluorescence immunoassaycollaborative university-industry medical researchdental medicine and engineering partnershipdevelopment of oral cancer diagnostic toolsearly detection of oral cancersmedical device innovation for oral healthNIH-funded oral cancer researchnoninvasive oral lesion assessmentoral squamous cell carcinoma diagnosispoint-of-care oral cancer testingquick oral cancer biopsy alternativerapid oral cancer detection technology
