A new test invented by researchers at the University of Illinois at Chicago allows dentists to identify the most common form of cancer oral with a simple and familiar tool: the toothbrush.
The diagnostic kit, created and patented by Guy Adami and Dr. Joel Schwartz of the UIC College of Dentistry, uses a small toothbrush 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 common cancer globally.
Oral cancer: some details on the new research
This new screening method, currently seeking commercialization partnerships, improves the current diagnostic standard of surgical biopsies, an additional benchmark step that risks missing patients who sometimes do not return until the cancer progresses to more advanced stages and difficult to treat. .
“So many patients are lost; they don't follow through,” said Adami, associate professor of oral medicine and diagnostic sciences. “We tried to focus primarily on early stage 1 and 2 cancers, so it really works with the cancers you want to detect.”
The detection system works by looking for small segments of genetic material called microRNAs that regulate the expression of genes. Previous research conducted by Adami and Schwartz found an expression signature of 40 microRNA sequences that could distinguish between a tumor and normal tissue with greater than 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, without the need for anesthetization, by a dentist or nurse, who then places the brush in a tube of solution and sends it to a laboratory for microRNA analysis. Results can be returned to the clinic in a few days with the current version of the diagnostic test.
“We were the first to observe that brush biopsy samples work quite well when using microRNAs,” Adami said. “All you need is good light and brushes.”
In addition to the convenience of the collection method, brush biopsy also offers several other advantages, the authors said. Surgical biopsies often collect a mix of cell types, making subsequent analysis more complicated and risking spreading cancer cells to other areas of the mouth. And unlike blood tests that generally detect genetic signals of cancer, the toothbrush 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 tissues, to the other tests available, they don't have a targeting of where the tumors actually are,” said Schwartz, professor of oral medicine and diagnostic sciences. “This makes it more difficult to begin treatment quickly after detection.”
The inventors hope that the new test will make screening easier to perform, particularly in patient populations who do not receive regular dental care or who have a higher incidence of oral squamous cell carcinoma. For example, black men have a significantly lower disease survival rate than white, Hispanic and Asian men. Using the invention in nonclinical settings would enable early cancer detection in high-risk populations.
The technology could eventually also be useful for diagnosing other oral diseases through its unique microRNA signatures, the authors said. To commercialize the test, Adami and Schwartz formed a company called Arphion Diagnostics that partnered with UIC's Office of Technology Management. But they continue to look for commercial partners to help them bring the test to dental clinics.
“There are 600 different diseases that occur in the mouth and some of these have already been characterized with microRNAs,” Schwartz said. “We could use the same approach and really have a profound impact on these types of diseases.”
Surrey scientists have developed a proof-of-concept test called PANDORA which has been shown to be over 92% accurate in identifying patients with oral squamous cell carcinoma (OSCC). The test has also been shown to have an accuracy of over 80% in identifying patients with oral or pre-tumor epithelial dysplasia (OED).
Dr Fatima Labeed, co-author of the study and senior lecturer in human biology at the University of Surrey, said: “Over 300,000 people are diagnosed with oral cancer worldwide, a disease with an alarming mortality rate of around 50%. This suggests that the scientific community does not have the tools available to identify oral cancer early enough and we hope that PANDORA will pave the way for more effective clinical diagnostic tools for this terrible disease.”
The research team took cell samples from 40 people with OSCC and OED, along with 79 people without cancer (including those with other benign lesions), to use as a test group. They used a machine called the DEPtech 3DEP analyzer, with a unique setup protocol, to measure and analyze patients' cells. Samples could be collected at a dentist's office and sent for analysis, allowing them to be used in primary care to identify patients who need specialist care.
Oral squamous cell carcinoma is a common type of cancer that affects the cells lining the mouth and throat and is linked to lifestyle factors such as smoking, poor oral hygiene, or alcohol use. Symptoms may include persistent mouth sores, difficulty swallowing, and changes in speech. OSCC is treatable if identified early, but has a poor survival rate if identified at an advanced stage.
Similar to oral squamous cell carcino
ma, oral epithelial dysplasia is a precancerous condition in which the cells lining the mouth show abnormal changes in shape, size, and arrangement due to smoking, alcohol use, or poor oral hygiene. The condition is precancerous because it can develop into oral cancer over time.
The current five-year survival rate of 60% of individuals with oral squamous cell carcinoma (OSCC), a type of mouth and throat cancer, could be significantly improved if treatments were started as early as possible. In a study published in Natural Sciences, researchers used a technology called polymer spray ionization mass spectrometry to screen blood for metabolic signs of OSCC. The method could accurately distinguish between individuals with and without OSCC.
Additionally, two altered lipid markers discovered in the blood could be traced back to the cancer site to guide surgical margin assessment.
The method, which requires only a single drop of blood, could also distinguish between patients with early and later stages of OSCC.
“This study represents the fruit of research involving the United States and China, in which all participants believed that the results would be a win for both countries and for the world as a whole, an idea that unfortunately seems is disappearing in these times of mutual suspicion and distrust of international collaborations,” said co-corresponding author Richard N, Zare, Ph.D., of Stanford University.
The author of an accompanying paper on the research noted that the study “is a perfect showcase of how mass spectrometry-based metabolomics workflows can be simplified to make them usable in clinical applications.”
Pathogens in the tissues surrounding the teeth contribute to a highly aggressive type of oral cancer, according to a study published Oct. 1 in the open-access journal PLOS Pathogens by Yvonne Kapila of the University of California, San Francisco and colleagues. Furthermore, the study demonstrated that pathogen-mediated oral cancer formation is inhibited by a bacteriocin, an antimicrobial and probiotic peptide produced by bacteria.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world. Oral squamous cell carcinoma (OSCC), a subgroup of HNSCC, accounts for 90% of all oral malignancies and has a poor five-year survival rate that has not changed for decades. Risk factors, including smoking, alcohol consumption, and human papillomavirus infection, alone were not sufficient to explain the incidence and aggressive nature of OSCC.
Other factors such as oral pathogens may play an important role in OSCC tumor development, progression, and metastasis, but this has not been well explored. Kapila and his collaborators tested whether OSCC is promoted by periodontal pathogens (i.e., those that affect the structures that surround and support the teeth).
They found that three types of periodontal pathogens (Porphyromonas gingivalis, Treponema denticola and Fusobacterium nucleatum) enhanced the migration, invasion and tumor formation of OSCC cells in mice. These effects were mediated by interactions between two signaling pathways: integrin/FAK and TLR/MyDD88. Pathogen-mediated processes were inhibited by treatment with nisin, a commonly used bacteriocin and food preservative.
According to the authors, this study offers the first direct evidence that a bacteriocin inhibits periodontal pathogen-mediated oral cancer formation.
Furthermore, the findings suggest that nisin may have broad therapeutic potential as an antimicrobial and anticancer agent and as an inhibitor of pathogen-mediated cancer formation.
The authors conclude: “Because a probiotic bacteriocin peptide, nisin, rescues this pathogen-mediated carcinogenesis, these findings could advance treatment for oral cancer and establish a new paradigm for cancer treatment focused on antimicrobial-based therapies ”.
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