Brush biopsy enables early detection of oral cancer without surgery

 

Reports and Proceedings

UNIVERSITY OF ILLINOIS CHICAGO

A new test invented by University of Illinois Chicago researchers allows dentists to screen for the most common form of oral cancer with a simple and familiar tool: the brush. 

The diagnostic kit, created and patented by Guy Adami and Dr. Joel Schwartz of the UIC College of Dentistry, uses a small brush to collect cells from potentially cancerous lesions inside the mouth. The sample is then analyzed for genetic signals of oral squamous cell carcinoma, the ninth most prevalent cancer globally. 

This new screening method, which is currently seeking commercialization partnerships, improves upon the current diagnostic standard of surgical biopsies — an extra referral step that risks losing patients who sometimes don’t return until the cancer progresses to more advanced, hard-to-treat stages.  

“So many patients get lost; they don’t follow up,” said Adami, associate professor of oral medicine and diagnostic sciences. “We’ve tried to keep our focus mainly on early Stage 1 and 2 cancers, so it actually works with the cancers that you want to detect.” 

The detection system works by looking for small segments of genetic material called microRNA that regulate the expression of genes. Research conducted by Adami and Schwartz found an expression signature of 40 microRNA sequences that can distinguish between a tumor and normal tissue with over 90% accuracy. 

Importantly, their test also worked using epithelial cells, the outermost layer of cells in a patient’s mouth. These cells can be easily collected in less than a minute of gentle brushing — no numbing required — by a dentist or nurse, who then places the brush in a tube of solution and sends it to a lab for microRNA analysis. Results can be returned to the clinic in days with the current version of the diagnostic test. 

“We were the first to observe that brush biopsy samples actually work quite well when you use microRNA,” Adami said. “All you need is a good light and the brushes.” 

In addition to the convenience of the collection method, the brush biopsy also provides several other advantages, the authors said. Surgical biopsies often collect a mixture of cell types, making subsequent analysis more complicated, and risk spreading cancerous cells to other areas of the mouth. And unlike blood tests that survey generally for genetic signals of cancer, the brush method only collects cells from a single site where treatment can be focused if a malignancy is detected. 

“If you compare what we do, which is site-specific targeting of tissue, to the other tests out there, they don’t have a targeting of where the tumors actually are,” said Schwartz, professor of oral medicine and diagnostic sciences. “That makes it harder to start treatment rapidly after detection.” 

The inventors hope that the new test will make screening easier to perform, particularly in patient populations that don’t receive regular dental care or have a higher incidence of oral squamous cell carcinoma. For example, Black men have a dramatically lower survival rate with the disease compared with white, Hispanic and Asian men. Usage of the invention in nonclinical settings would allow earlier cancer detection in high-risk populations.

The technology may also eventually be useful in diagnosing other oral diseases through their own unique microRNA signatures, the authors said. To commercialize the test, Adami and Schwartz formed a company called Arphion Diagnostics that has worked with the UIC Office of Technology Management. But they continue to look for business partners to help take the test into dental clinics. 

“There are 600 different diseases that occur in the mouth, and a number of these have already been characterized with microRNAs,” Schwartz said. “We could use the same approach and really have a profound impact on these kinds of disease.” 

In addition to Adami and Schwartz, research and design of the diagnostic test was conducted by oral and maxillofacial surgeon Dr. Antonia Kolokythas, a key member of the project who helped optimize the methodology and identified and collected brush samples from the first group of patients. The work was supported by grants from the National Science Foundation and the National Cancer Institute. Adami and Schwartz are also members of the University of Illinois Cancer Center.

How gum disease aggravates chronic obstructive pulmonary disease

 

Peer-Reviewed Publication

AMERICAN SOCIETY FOR MICROBIOLOGY

Highlights:

• Previous studies have connected severe gum disease to chronic obstructive pulmonary disease, or COPD.
• Bacteria play a critical role, but the details remain unclear.
• A new study shows how periodontitis, an oral disease, activates immune cells associated with aggravated progression of COPD.
• The findings suggest that periodontitis and COPD together worsen COPD, and point to gum disease management as a potential treatment for COPD.

Washington, D.C.—Severe gum disease has been linked to the progression of chronic obstructive pulmonary disease, or COPD, but an understanding of how the connection plays out in the immune system remains unclear. This week in mSystems, a new study identifies immune system cells that play a critical role in the microbial link between COPD and gum disease.

Researchers from Sichuan University, in China, report that bacteria associated with the gum disease promote COPD through the activation of 2 types of cells, γδ T cells and M2 macrophages, that are important to the immune system. Focusing on this mechanism might offer new, practical strategies for COPD prevention or control, said the researchers, from the West China Hospital of Stomatology at Sichuan University.

“By enhancing periodontal therapy and targeting the inhibition of γδ T cells and M2 macrophages [we] may be able to help control the progression of COPD,” said microbiologist Boyu Tang, Ph.D., who led the study with microbiologist Yan Li, Ph.D. 

According to the World Health Organization, COPD is the sixth-leading cause of death worldwide. It is not curable. In higher-income countries, tobacco smoking is the leading cause of COPD; in low- and middle-income countries, both tobacco smoking and household air pollution are significant risk factors. 

Periodontitis is a gum disease that results from the untreated buildup of plaque, a sticky film made primarily of bacteria. Over time, the plaque can harden into tartar and cause irritation and inflammation of gum tissue, and then produce deep gaps between the teeth and gums where bacteria flourish and may lead to bone loss. Periodontitis is a chronic infectious disease, and previous studies have found that it’s a risk factor for a raft of diseases, including diabetes, hypertension, some cancers, cardiovascular disease and COPD. 

Previous studies, including some led by Li and Tang, have established that the oral bacteria Porphyromonas gingivalis plays an important role in gum disease. For the new work, Li, Tang and their colleagues used mouse models to show how those bacteria could aggravate progression of COPD. In one experiment, they showed that mice infected with both periodontitis and COPD had worse progression of COPD than mice infected with COPD alone. 

In another experiment, they found that in mice orally infected with P. gingivalis, the bacteria migrated to and infected lung tissue, leading to a significant, observable change in the lung microbiota. Further observations using flow cytometry and immunofluorescence revealed that periodontitis promoted the expansion of the immune cells in the lung tissue. Finally, in experiments using mouse lung tissue, the group connected the dots by showing that P. gingivalis could activate the immune cells, promoting their ability to produce cytokines associated with worsening COPD.  

The researchers noted that the decrease in lung function and increase in immune cells was more modest than they’d predicted, but that could be an artifact of the experimental setup. The team created COPD animal models using exposure to cigarette smoke. “If the cigarette smoke exposure could be extended for a longer period of time, these changes might be more pronounced,” Li said. In future studies, Li said that the group plans to investigate how increases in smoke exposure might affect the immune response. 

“We’ll further carry out additional studies on human subjects to confirm the mechanism,” Li said. They plan to recruit patients with both conditions and offer periodontitis treatment, then compare lung function and immune cell counts before and after. “Our finding could lead to a potential new strategy for treating COPD.”