Poor oral health could lessen survival from head and neck cancer

 

 

IMAGE: “THE INHANCE CONSORTIUM’S PATIENT DATA ALLOWED US TO BE AS THOROUGH AS POSSIBLE AND IDENTIFY ROBUST ASSOCIATIONS BETWEEN ORAL HEALTH AND SURVIVAL,” SAID LEAD AUTHOR JASON TASOULAS MD, DMD, A CURRENT PHD CANDIDATE. “WE ASSEMBLED A DIVERSE AND EXPERIENCED TEAM TO EXAMINE RECORDS OF APPROXIMATELY 2,500 PATIENTS FROM EIGHT COUNTRIES TO CARRY OUT OUR STATE-OF-THE-ART STATISTICAL ANALYSES.” view more 

CREDIT: JASON TASOULAS

An international study has revealed strong associations between oral health and survival among people diagnosed with head and neck cancer. Specifically, better oral health, as evidenced by the number of natural teeth and dental visits prior to the time of diagnosis, was associated with increased survival. Importantly, those who had more frequent dental visits were more likely to have their cancer diagnosed at an earlier, and less deadly, stage of the disease than those who had few or no dental visits.

The study, by researchers at UNC Lineberger Comprehensive Cancer Center and UNC Adams School of Dentistry, Chapel Hill, North Carolina, and Moffitt Cancer Center, Tampa, Florida, in partnership with the International Head and Neck Cancer Epidemiology (INHANCE) consortium, appeared Sept. 19, 2023, in the Journal of the National Cancer Institute.

“The INHANCE consortium’s patient data allowed us to be as thorough as possible and identify robust associations between oral health and survival,” said lead author Jason Tasoulas M.D., DMD, a current Ph.D. candidate. “We assembled a diverse and experienced team to examine records of approximately 2,500 patients from eight countries to carry out our state-of-the-art statistical analyses.”

Head and neck cancer patients were asked to self-report aspects of their oral health and hygiene, including gum bleeding, tooth brushing frequency and mouthwash use, as well as the number of natural teeth and frequency of dental visits they had during a 10-year period prior to their cancer diagnosis.

Those who had frequent dental visits (more than five visits in a reported decade) had higher overall survival at five and 10 years (74% and 60%, respectively) compared to those with no dental visits (54% at five years and 32% at 10 years). This finding was most pronounced among people with cancers of the oropharynx, which consists of the structures in the back of the throat, including the base of the tongue, tonsils and soft palate. Having no natural remaining teeth was associated with a 15% lower five-year overall survival compared to those with more than 20 natural teeth. Survival differences of less than 5%, which were not significant, were found for patient-reported gum bleeding, tooth brushing and mouthwash use.

While survival has improved during the past decades due to treatment advances, head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide and accounts for about 4% of all cancers in the United States. In 2023, an estimated 66,920 people will be diagnosed with the disease in the U.S. The main environmental risk factor for the disease is tobacco use but alcohol consumption and testing positive for the human papillomavirus also increase a person’s risk for the disease.

“This current research effort capitalizes on previous data collection efforts by our team in North Carolina through the Carolina Head and Neck Cancer Epidemiology (CHANCE) study to investigate the role of oral health in patients with head and neck squamous cell carcinoma. The present report is based on a larger-scale study, accounting for geographic variability and capturing more oral health variables,” said Kimon Divaris, DDS, Ph.D., study author and James Bawden Distinguished Professor at the UNC Adams School of Dentistry and UNC Gillings School of Global Public Health.

“Inspired by Dr. Divaris’ previous work, we sought out opportunities to collaborate with a larger network of epidemiologists, surgeons, physicians, dentists and scientists from all over the world to address an important but often overlooked problem for patients with head and neck squamous cell carcinoma,” said corresponding author Antonio L. Amelio, Ph.D., vice chair of research in the Head and Neck Oncology Department and associate member of the Tumor Biology Department at Moffitt Cancer Center, and an adjunct associate professor at the UNC Department of Otolaryngology-Head and Neck Surgery. “Our hope is that these findings become a standard part of guidelines implemented for the prevention and management of head and neck squamous cell carcinomas in the near future.”

Carole Fakhry, M.D., MPH, the Charles W. Cummings M.D. Professor of Otolaryngology at Johns Hopkins School of Medicine, who was not involved in the research, called the findings significant. “This is an important study that highlights the interplay between oral health and head and neck squamous cell carcinoma and overall survival. While we seek biomarkers to predict which patient will do well, this study points out features of a history and examination that are associated with survival. Additionally, this may lead us down the road of prevention of these cancers.”

New at-home test for gingivitis protects oral health

 

 

IMAGE: UNIVERSITY OF CINCINNATI ENGINEERS HAVE DEVELOPED A TEST THAT USES SALIVA TO WARN CONSUMERS ABOUT PERIODONTAL DISEASE, WHICH IF LEFT UNTREATED CAN LEAD TO TOOTH LOSS, STROKE, HEART DISEASE AND OTHER ILLNESSES. view more 

CREDIT: ANDREW STECKL AND DAEWOO HAN

Engineers at the University of Cincinnati have developed a new device that can warn consumers about early risks of tooth decay from diseases such as gingivitis and periodontitis.

Gingivitis, the earliest form of gum disease, is caused by bacteria. But not just any bacteria.

The problem for researchers was getting a device to single out the particular type responsible for the disease, said Andrew Steckl, an Ohio Eminent Scholar and distinguished research professor in UC’s College of Engineering and Applied Science.

“It’s been quite the challenge to get to the point where we can detect this toxin created by the bacteria responsible for gingivitis,” he said.

Steckl and UC Senior Research Associate Daewoo Han collaborated with Sancai Xie, a principal scientist at Procter & Gamble Co., and described their results in a paper published in the Royal Society of Chemistry journal Sensors and Diagnostics.

Steckl’s research team has been exploring biosensing for various applications. They studied stress hormones in sweat in collaboration with the Air Force Research Lab at Wright-Patterson Air Force Base. Now they are studying saliva.

“There are good reasons to use saliva,” he said. “It’s relatively plentiful and easy to obtain through noninvasive methods. And saliva has a lot of important elements that can act as indicators of your health.”

Bacteria from gingivitis can travel through the bloodstream, leading to cardiovascular disease and other serious health problems, Steckl said.

But saliva is a complicated biofluid, said Han, the study's lead author.

Researchers pretreated the sample using potato starch to remove a protein called amylase that could interfere with the test results. Their test uses antibodies that react to the endotoxins found in the bacteria.

“Daewoo worked very hard on many dead-ends before he had success,” Steckl said. “I tell my students that research is search, search and re-search until you find the answer.”

At-home health testing has been available for generations in niche uses such as detecting pregnancy. But the COVID-19 pandemic introduced a wide audience of consumers to the concept of monitoring their health with new technology.

The at-home testing industry is expected to generate $45 billion annually by 2031, according to Allied Market Research.

Steckl said he sees a lot of opportunity for new consumer products.

“Our results definitely show promise,” Steckl said. “Sometimes it comes easy. Most of the time you have to persevere.”

New guideline details dental pain management strategies for pediatric patients

 

Acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen are recommended as first-line treatments for managing short-term dental pain in children under age 12, according to a new clinical practice guideline developed by the American Dental Association Science & Research Institute (ADASRI), the University of Pittsburgh School of Dental Medicine and the Center for Integrative Global Oral Health at the University of Pennsylvania School of Dental Medicine. The guideline has been endorsed by the American Dental Association.

A guideline panel determined that, when used as directed, acetaminophen alone, NSAIDs (like ibuprofen) alone or acetaminophen in combination with NSAIDS can effectively manage a child’s pain after a tooth extraction or during a toothache when dental care is not immediately available. These and other recommendations are now available in the September issue of The Journal of the American Dental Association. 

The guideline evaluated doses of acetaminophen and NSAIDs that may differ from the dosing printed on the over-the-counter packages of these medications. According to the guideline, when acetaminophen or NSAIDs are administered as directed by a dentist or other health care provider, the risk of harm to children from either medication is low. 

Guideline senior author Paul Moore, D.M.D., Ph.D., M.P.H., is professor emeritus at the University of Pittsburgh’s School of Dental Medicine. He said the recommendations align with previous guidance from the U.S. Food and Drug Administration (FDA), which contraindicated the use of codeine and tramadol in children under age 12 in 2017.

“While prescribing opioids to children has become less frequent overall, this guideline ensures that both dentists and parents have evidence-based recommendations to determine the most appropriate treatment for dental pain,” Dr. Moore said. “Parents and caregivers can take comfort that widely available medications that have no abuse potential, such as acetaminophen or ibuprofen, are safe and effective for helping their children find relief from short-term dental pain.”

In 2020, the FDA awarded the University of Pittsburgh and ADASRI a three-year $1.5 million grant to develop a clinical practice guideline for the management of acute pain in dentistry in children, adolescents and adults. A group of researchers and methodologists from ADASRI, the University of Pittsburgh School of Dental Medicine, the Center for Integrative Global Oral Health at the University of Pennsylvania School of Dental Medicine, McMaster University and the Art of Democracy worked together to develop the guideline.

“This clinical prescribing guideline is a critical step in supporting appropriate treatment of pediatric acute dental pain through the use of acetaminophen and NSAIDs," said Patrizia Cavazzoni, M.D., director of the FDA Center for Drug Evaluation and Research. “Not only will this advice allow for better treatment of this kind of pain, but it will help prevent unnecessary prescribing of medications with abuse potential, including opioids.” 

This is the first of two guidelines on acute dental pain management. A second set of recommendations for adolescents and adults is in development. The new acute pediatric pain management guideline can be found at ada.org/painmanagement.

For more information on how the ADA is working to combat opioid misuse, while continuing to help patients manage dental pain, visit ada.org/opioids.

The contents of the guidelines are those of the author(s) and do not necessarily represent the official views of, nor an endorsement by, FDA, HHS or the U.S. government.

Metformin is ameliorating hmgb1-mediated oxidative stress in periodontitis

 

 

IMAGE: PERIODONTITIS INCREASE THE EXPRESSION OF PROINFLAMMATORY CYTOKINE HMGB1. HMGB1 AFFECTS THE EXPRESSION OF INFLAMMATION-RELATED CYTOKINES (IL-6, IL-8) AND AGGRAVATES PERIODONTAL TISSUE DESTRUCTION AND OXIDATIVE STRESS. METFORMIN ACTIVATES AUTOPHAGY THROUGH MTOR PATHWAY, REGULATE THE EXPRESSION, TRANSLOCATION AND RELEASE OF HMGB1, AND THEN REDUCE THE OXIDATIVE STRESS AND TISSUE DESTRUCTION OF PERIODONTAL TISSUE. view more 

CREDIT: GENES & DISEASES

Periodontitis, a prevalent global health concern, results in the gradual destruction of tooth-supporting tissues and is often exacerbated by oxidative stress conditions and bacterial changes. Current treatment methodologies include mechanical debridement, anti-inflammatory drugs, and regenerative surgery.

The research published in the journal of Genes & Diseases, conducted detailed examinations on cellular interactions with Metformin, investigating its role in relation to HMGB1 during the progression of periodontitis. It was observed that Metformin could inhibit oxidative stress, and activate autophagy via the AMPK/mTOR pathway. Experimental periodontitis was induced in a murine model, and Metformin was found to attenuate alveolar bone resorption, a major hallmark of the disease.

A notable discovery from this study is that Metformin not only decreases oxidative stress in periodontal ligament cells but also activates autophagy, a cellular waste removal and recycling process, through the AMPK/mTOR pathway. This pathway has been shown to inhibit HMGB1-mediated oxidative stress in periodontal tissues.

The study concludes that Metformin can mitigate periodontal tissue damage through its anti-inflammatory effects, which involve reducing the expression and translocation of HMGB1, a key pro-inflammatory factor. These results align with previous studies demonstrating Metformin's capabilities in reducing oxidative stress.

HMGB1's pivotal role in inducing oxidative stress in periodontal cells adds further credence to this protein being a potential target for periodontal intervention. This opens up a promising avenue for future research and the development of drugs aimed at HMGB1.

"While our study presents compelling evidence on the protective role of Metformin in periodontitis, further research is needed," the research team stated. "We are optimistic that our findings will pave the way for more comprehensive studies on the relationship between Metformin and HMGB1 in periodontitis, ultimately leading to more effective treatment options."

The potential role of Metformin in managing periodontitis could be transformative, especially for patients suffering from both diabetes and periodontitis. The study's results offer hope for an affordable, well-tolerated, and readily available therapeutic option, building on Metformin's known antidiabetic effects. This aligns with the broader medical goal of developing targeted treatments that manage the disease's symptoms while also addressing its root cause.

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Gum disease linked to buildup of Alzheimer’s plaque formation

Oral bacteria traveling to the brain causes brain cells to become dysfunctional, promoting neuroinflammation

Peer-Reviewed Publication

FORSYTH INSTITUTE

Cambridge, Mass. - Although most people don’t associate oral disease with serious health problems, increasing evidence shows that oral bacteria play a significant role in systemic diseases like colon cancer and heart disease. Now, new research from the Forsyth Institute shows a link between periodontal (gum) disease and the formation of amyloid plaque, a hallmark of Alzheimer’s disease.

In their paper, “Microglial cell response to experimental periodontal disease,” published in the Journal of Neuroinflammation, Forsyth scientists and their collaborators at Boston University demonstrate that gum disease can lead to changes in brain cells called microglial cells, which are responsible for defending the brain from amyloid plaque. This plaque is a type of protein that is associated with cell death, and cognitive decline in people with Alzheimer’s. The study provides important insight into how oral bacteria makes its way to the brain, and the role of neuroinflammation in Alzheimer’s disease.

“We knew from one of our previous studies that inflammation associated with gum disease activates an inflammatory response in the brain,” said Dr. Alpdogan Kantarci, senior member of staff at Forsyth and a senior author of the study. “In this study, we were asking the question, can oral bacteria cause a change in the brain cells?”

The microglial cells the researchers studied are a type of white blood cell responsible for digesting amyloid plaque. Forsyth scientists found that when exposed to oral bacteria the microglial cells became overstimulated and ate too much. “They basically became obese” Dr. Kantarci said. “They no longer could digest plaque formations.”

The finding is significant for showing the impact of gum disease on systemic health. Gum disease causes lesions to develop between the gums and teeth. The area of this lesion is the size of your palm. Dr. Kantarci explained, “It’s an open wound that allows the bacteria in your mouth to enter your bloodstream and circulate to other parts of your body.” These bacteria can pass through the blood/brain barrier and stimulate the microglial cells in your brain.

Using mouse oral bacteria to cause gum disease in lab mice, the scientists were able to track periodontal disease progression in mice and confirm that the bacteria had traveled to the brain.  

They then isolated the brain microglial cells and exposed them to the oral bacteria. This exposure stimulated the microglial cells, activated neuroinflammation and changed how microglial cells dealt with amyloid plaques.

“Recognizing how oral bacteria causes neuroinflammation will help us to develop much more targeted strategies,” said Dr. Kantarci. “This study suggests that in order to prevent neuroinflammation and neurodegeneration, it will be critical to control the oral inflammation associated with periodontal disease. The mouth is part of the body and if you don’t take care of oral inflammation and infection, you cannot really prevent systemic diseases, like Alzheimer’s, in a reproducible way.”

This study is the first time that scientists caused periodontal disease with mouse-specific bacteria and could study the effects of same-species oral microbiome on the brain. Having same-species bacteria and cells brings the test closer to replicating what the process looks like in humans.

Taking good care of your teeth may be good for your brain

 

 Taking good care of your teeth may be linked to better brain health, according to a study published in the July 5, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study found that gum disease and tooth loss were linked to brain shrinkage in the hippocampus, which plays a role in memory and Alzheimer’s disease. The study does not prove that gum disease or tooth loss causes Alzheimer’s disease; it only shows an association.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” said study author Satoshi Yamaguchi, PhD, DDS, of Tohoku University in Sendai, Japan. “Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth.”

The study involved 172 people with an average age of 67 who did not have memory problems at the beginning of the study.

Participants had dental exams and took memory tests at the beginning of the study. They also had brain scans to measure volume of the hippocampus at the beginning of the study and again four years later.

For each participant, researchers counted the number of teeth and checked for gum disease by looking at periodontal probing depth, a measurement of the gum tissue. Healthy readings are from one to three millimeters.

Mild gum disease involves probing depths of three or four millimeters in several areas, while severe gum disease involves probing depths of five or six millimeters in several areas as well as more bone loss and can cause teeth to become loose and eventually fall out.

Researchers found that the number of teeth and amount of gum disease was linked to changes in the left hippocampus of the brain.

For people with mild gum disease having fewer teeth was associated with a faster rate of brain shrinkage in the left hippocampus.

However, for people with severe gum disease having more teeth was associated with a faster rate of brain shrinkage in the same area of the brain.

After adjusting for age, researchers found that for people with mild gum disease, the increase in the rate of brain shrinkage due to one less tooth was equivalent to nearly one year of brain aging. Conversely, for people with severe gum disease the increase in brain shrinkage due to one more tooth was equivalent to 1.3 years of brain aging.

“These results highlight the importance of preserving the health of the teeth and not just retaining the teeth,” Yamaguchi said. “The findings suggest that retaining teeth with severe gum disease is associated with brain atrophy. Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices.”

Yamaguchi said future studies are needed with larger groups of people. Another limitation of the study is that it was conducted in one region of Japan, so the results may not be generalizable to other locations.

The study was supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology; Keio University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teikyo University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astellas Pharma; Takeda Pharmaceutical; Health Care Science Institute; Health Science Center; and Takeda Science Foundation.

Learn more about Alzheimer’s disease at BrainandLife.org, home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life® on Facebook, Twitter and Instagram.

When posting to social media channels about this research, we encourage you to use the hashtags #Neurology and #AANscience.

The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with over 40,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.

For more information about the American Academy of Neurology, visit AAN.com or find us on Facebook, Twitter, Instagram, LinkedIn and YouTube.

Artificial intelligence for early detection of gum inflammation

 

IMAGE: THREE CASES ILLUSTRATING DENTIST'S VISUAL EXAMINATION (B) AND AI'S DETECTION (C) OF GUM PROBLEMS (A) INTRAORAL PHOTOGRAPH (B) HEALTH STATUS LABELLED BY A CALIBRATED DENTIST (GREEN=HEALTHY, RED=DISEASED, YELLOW=QUESTIONABLE) (C) AI DETECTION RESULTS view more 

CREDIT: FACULTY OF DENTISTRY, THE UNIVERSITY OF HONG KONG

A groundbreaking study led by researchers at the Faculty of Dentistry of the University of Hong Kong (HKU), in collaboration with multiple international institutions has successfully demonstrated the use of artificial intelligence (AI) in detecting gum inflammation, also known as gingivitis, from intraoral photographs.

This cutting-edge technology can revolutionise early detection and prevention of oral and systemic diseases linked to gum inflammation, such as tooth loss, cardiovascular diseases, and diabetes.

The study, published in the prestigious International Dental Journal, an official journal of the World Dental Federation (FDI), shows that AI algorithms can analyse patients' intraoral photographs to detect signs of inflammation like redness, swelling, and bleeding along the gum margin with over 90% accuracy, matching the visual examination of a dentist. This innovative technology enables population-wide monitoring of gum health and paves the way for more personalised dental care.

The study was conducted by researchers from the HKU Faculty of Dentistry, the Department of Computer Science at Hong Kong Chu Hai College, the School of Information Engineering at Guangdong University of Technology, and the Faculty of Dentistry at The National University of Malaysia. It involved developing and testing an AI model using a dataset of over 567 images of gums with varying degrees of inflammation and is one of the first to explore the use of AI in detecting gum inflammation.

Dr Walter Yu-Hang Lam, the study’s leading HKU researcher, emphasises the significance of the findings for the early detection and management of gum disease.

"Many patients do not attend regular dental check-ups, and they only seek dentists to alleviate pain when their teeth are at the end stage of dental diseases, in which tooth loss is inevitable, and only expensive rehabilitative treatments are available. Our study shows that AI can be a valuable screening tool in detecting and diagnosing gum disease, one of the key indicators of periodontal disease, allowing earlier intervention and better health outcomes for the population." He said.

The use of AI in dentistry has been gaining momentum in recent years, with researchers exploring various applications of the technology, from detecting cavities to predicting treatment outcomes to biomimetic design of artificial teeth. The use of AI in gum inflammation detection is a promising development that could revolutionize how gum disease is detected, treated, and even prevented.

Dr. Reinhard Chun-Wang Chau, an HKU co-investigator of the team, pointed out the benefits of using intraoral photographs in conjunction with AI technology and said: “Based on these intraoral photographs, patients can address the area that they did not clean well and seek dentist’ help at an earlier stage.”

The collaborative nature of this study is a testament to the power of interdisciplinary research and knowledge exchange. By bringing together experts from different fields and regions, the researchers can develop an AI model that could accurately detect gum inflammation, with important implications for public health and wellbeing.

For the project’s next stage, Dr Lam plans to utilize the AI system for community services, making the technology more accessible to elderly and underserved communities, with the aim of improving oral health outcomes and reducing health disparities.

The study, Accuracy of Artificial Intelligence-Based Photographic Detection of Gingivitis, is available on the International Dental Journal
(https://doi.org/10.1016/j.identj.2023.03.007).