A team of researchers at Case Western Reserve University School of Dental Medicine has discovered a non-invasive, low-cost approach to detecting oral cancer and monitoring precancerous lesions. 

The findings, described in Cell Reports Medicine, can help clinicians determine whether a biopsy—often stressful and costly and not always possible—is needed for certain patients. The team says its approach can reduce biopsies in primary care clinics by 95% and provide results within half an hour.

Beta-defensin index: A functional biomarker for oral cancer detection. Cell.

Case Western Reserve University-led research team discovers new method to test for oral cancer. The Daily.

 

Oral cancer is the sixth most common cancer worldwide. In 2020, it was responsible for 377,713 new cancer cases and 177,757 deaths. However, numbers seem to be on the rise. According to Otolaryngology–Head and Neck Surgery, the incidence of oral squamous cell carcinoma (OSCC) increases with an average annual percentage change of 1.8%, with a 2.3% increase among women, in the US. In approximately 90% of cases, OSCC is the most frequent cause of malignant tumors of the head and neck squamous cell cancer (HNSC).

Tranby EP, Heaton LJ, Tomar SL, et al. Oral cancer prevalence, mortality, and costs in medicaid and commercial insurance claims data. Cancer Epidemiol Biomarkers Prev. 2022;31(9):1849-1857.

Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clinicians. 2021;71(3):209-249.

Stepan KO, Mazul AL, Larson J, et al. Changing epidemiology of oral cavity cancer in the united states. Otolaryngol Head Neck Surg. 2023;168(4):761-768.

 

 

The average five-year survival rate of OSCC in the US is 64.3%, but this is stage-dependent. The average five-year survival rate drops when a patient is diagnosed at later stages, which occurs in approximately 70% of cases. If the cancer has metastasized at the point of diagnosis, this survival rate drops to 38.5%. Compounding the issue, certain kinds of early-stage oral cancer can also be “clinically deceptive” and can be misdiagnosed.

Tranby EP, Heaton LJ, Tomar SL, et al. Oral cancer prevalence, mortality, and costs in medicaid and commercial insurance claims data. Cancer Epidemiol Biomarkers Prev. 2022;31(9):1849-1857.

Sujir N, Ahmed J, Pai K, Denny C, Shenoy N. Challenges in early diagnosis of oral cancer: cases series. Acta Stomatologica Croatica. 2019;53(2):174.

Home: Cell press. (n.d.).

 

The new detection method is a game changer, the study’s lead researcher, Aaron Weinberg, DMD, PhD, Chair of the Department of Biological Sciences at the Case Western Reserve University’s School of Dental Medicine, tells MDLinx.

The team’s findings are based on the discovery of two proteins: human beta-defensin 3 (hBD-3) and human beta-defensin 2 (hBD-2). In early-stage cancer, hBD-3 is expressed at high levels while hBD-2 remains unchanged or is low. 

The hBD-3 protein plays a useful role in wound healing. However, in OSCC, it can exhibit pro-tumorigenic properties.

“The ratio of hBD-3 to hBD-2 in the lesion site—over the ratio of the two proteins on the opposite, normal site—generates a score, called the beta defensin index (BDI),” the authors write.

Case Western Reserve University-led research team discovers new method to test for oral cancer. The Daily.

 

“​​Our initial study showing that overexpressed hBD-3 and underexpressed hBD-2 accompany the carcinoma in situ (CIS) phenotype25 prompted us to conduct a human observational study to determine whether the ratio of hBD-3/hBD-2 correlated with the diagnosis of OSCC,” they continue.

Home: Cell press. (n.d.).

 

 

When using this method, a value of or above a predetermined threshold would indicate cancer. Anything beneath the threshold would not. 

Dr. Weinberg says that he and his colleagues have been exploring the two proteins for nearly 17 years: “We’ve been publishing on these two proteins—one of which is a ‘good guy’ in the context of wound healing, but becomes a ‘bad guy’ in cancer—for a long time. It’s a Dr. Jekyll and Mr. Hyde story.”

 

What does this approach mean for clinicians? 

 

Dr. Weinberg says that he sees this method playing a major role in healthcare in two key ways: First, he says, it can reduce biopsy prevalence (and all the stressors and costs involved) in a major way, which is helpful in that most results turn out to be negative for cancer. “This will empower clinicians to really say, ‘You gotta go get a biopsy’ or, ‘You don't need it,’” he says.

Furthermore, Dr. Weinberg says that he envisions the method being used in countries where oral cancer is an epidemic—in parts of Asia, for example, where the use of carcinogenic products, such as betel quid, is widespread.

Oral cancer in asia - a systematic review. Advances in Oral and Maxillofacial Surgery. 2022;8:100366.

NCI Dictionary of Cancer terms. National Cancer Institute. (n.d.).

 

 

He says that betel quid—used by adults and kids alike, sold at roadside kiosks, and often made with other ingredients, including tobacco—is highly addictive. “The World Health Organization in 2020 estimated that 700 million are using betel quid. 20% of that 700 million will develop a lesion in the oral cavity, and 5% of that 20% will succumb to squamous cell carcinoma (oral cancer),” Dr. Weinberg says. 

“We think this can be used to monitor and screen easily in a way that is cost-effective in these countries,” he continues. 

Beyond financial costs and lost jobs, some patients with oral cancer experience serious trauma and often need rehabilitation in order to swallow or speak again. For this reason, “I can envision the health departments in these countries wanting a cost-effective, non-invasive screening process to check people,” Dr. Weinberg says. 

For remote and rural areas in Asia, he adds, the goal is to develop a point-of-care device that can be used chairside in a village by a field nurse. “Having a lab is good in the big city, but you need them in the villages,” he says. 

The next step? To complete a clinical trial with a demographically diverse group of people, as the original findings were based on data from 100 people from the Midwestern US.