Dentistry is one area of healthcare that has a long history of taking preventive measures to avoid disease, both on a large scale (adding fluoride to drinking water) and a personal one (providing tools and education so people can brush, floss, and maintain optimal oral health). Until recently, these approaches usually shared a “one-size-fits-all” approach. The genomic revolution has made a personalized approach to both prevention and treatment possible, as an understanding of the molecular underpinnings of oral disease informs the industry’s standard of care.
In fact, now patients can use the health and risk assessments from genetic testing as guidance to prevent or mitigate the onset of certain conditions. Dentists, meanwhile, can take into consideration not just a patient’s current oral health, but also the complex interaction of genetic, genomic, and environmental factors affecting patients. In this way, dentistry seems primed to join the personalized medicine revolution.
As with most healthcare industries, the pace of adaption in dentistry to a personalized approach lags the research. In a 2011 review in the journal Oral Diseases, Gene Eng, Annie Chen, Geoffrey Ginsburg, and Tomalei Vess summed up the industry’s lack of advancement in genomic technologies: “While the application of genomic information has been an important part of medical health care for over a decade, the field of dentistry has yet to take full advantage of this newfound technology.”
Slowly, though, change is coming to the dentist’s office. A service called PerioPredict is the industry’s first foray into personalized dentistry. This test can determine which patients are genetically prone to severe periodontitis, an inflammatory disease in which bacteria break down the tissue and bone that support teeth. Symptoms include pain, swollen gums, difficulty chewing, and tooth loss.
Created by Interleukin Genetics, PerioPredict is the pioneer in using genetic testing as part of mainstream dental care. The test, which is administered by a cheek swab, is conducted during a routine dental exam and measures variations in genes for an inflammatory mediator called Interleukin-1. PerioPredict was released in January and is now available in all 50 states.
Kenneth Kornman, Interleukin Genetics’ founder, CEO, and chief scientific officer, suggests that dentists use the test on patients they see regularly and who may be at risk for severe periodontitis, a disease that affects a significant portion of the population. If the test determines that a patient is at risk for severe periodontitis, the dentist can deliver preventive care, including more frequent cleanings to ward off the condition. At the same time, PerioPredict, together with the absence of risk factors like smoking and diabetes, determines those who are at a lesser risk for severe periodontitis. For this population, Kornman says, cleanings and checkups can be administered less frequently than the biannual visits most patients schedule.
Delta Dental, the nation’s largest dental benefits carrier, covers PerioPredict in certain employer groups. In instances where it’s covered, reimbursement is “risk-stratified,” meaning patients who do not already have periodontitis or are not at increased risk are covered for one cleaning per year rather than two, while those at increased risk are covered for more. When PerioPredict is not covered by a patient’s insurance, it costs about $180.
The Delta Dental coverage is part of beta testing launched in 2012 in certain states. As for whether PerioPredict is a success for the insurance company, Jed Jacobson, chief scientific officer and senior vice president for Delta Dental of Ohio and Indiana, says it’s too early to tell. He declined to provide specifics about the locations and parameters of the testing.
While PerioPredict screens for one specific genetic variation, periodontitis has many complicating factors, including smoking, diabetes, and others that may be genetic. Denis Kinane, dean of the University of Pennsylvania School of Dental Medicine, stresses the importance of family history and other risk factors when treating periodontitis. He warns against putting too much stock in one genetic variation when so many other genetic factors could influence the same condition. Nevertheless, among Kinane and others in the field, there is general consensus that PerioPredict is an early sign of a new era in dentistry.
Louis Rose, a Philadelphia-based periodontist who also holds a medical degree and serves as a professor at the University of Pennsylvania and New York University, uses PerioPredict in his practice and feels that it should be used more widely to check for the IL-1 variation, which he considers a significant risk factor. Years ago, before such testing was available, Rose and his colleagues would say that there was an “overriding systemic factor” when a patient had periodontitis that was more severe than their risk factors would normally indicate. With PerioPredict, he can define one of those systemic factors. While other genetic factors may relate to periodontitis, Rose says, “That doesn’t mean you should ignore the one that’s out there, the one that has the most research.”
Rose feels strongly that dentists should take thorough medical histories to understand patients’ risk factors for various diseases because of the connections between periodontal disease and other factors. Periodontitis is associated with diabetes, rheumatoid arthritis, and other inflammation-based conditions. After all, though the mouth is commonly treated as a separate entity, it’s as much a part of the body as any other system or organ.
Periodontitis isn’t the only area where scientists are making progress — albeit slowly — in the quest to make personalized dentistry a routine part of oral healthcare.
David Wong, a professor of oral biology and medicine and an associate dean for research at UCLA, is a leader in saliva-based diagnostics research. Wong’s research focuses on salivary biomarkers of head and neck cancer. He has also conducted promising research on salivary diagnostics for lung cancer.
“The future of personalized medicine in dentistry is tremendous,” Wong says. When it comes to saliva-based diagnostics, “The past decade has built the foundation, the tools, and the credibility [for future clinical application].” The National Institutes of Health has funded much of Wong’s research on biomarkers in saliva.
Such biomarkers could eventually provide an opportunity for early detection and treatment of head and neck cancer. This is especially important, he says, because more people regularly visit the dentist than their primary care doctor.
“The holy grail of personalized medicine is noninvasiveness,” Wong says. When it comes to personalized medicine, the more information that can be gathered from the surface, the better. With an increasing body of research, the knowledge available to healthcare providers (without invasive procedures) is remarkable.
Tooth decay, formally known as dental caries, is another example of an oral disease with a link to genetics. “It’s the most common disease in humans,” says J. Timothy Wright, a distinguished professor of pediatric dentistry at the University of North Carolina. “And in children, it’s more common than asthma, more common than most everything else.”
Walter Bretz, a professor at New York University College of Dentistry, has conducted several studies on the heritability of factors that relate to the formation of caries. He focused on a remote area of Brazil where there was a significant population of twins (to test genetics with a control), limited access to dental care, and not a lot of fluoride in the water. One of his studies, published in 2005, examined 314 sets of twins (some identical, some fraternal) ranging from 1.5 to 8 years old. It tested the hypothesis “that incident dental caries has a heritable component in very young children, and that environmental factors play a more pronounced role in dental caries onset and development with increasing age.”
The future of personalized medicine in dentistry is tremendous.
The study found that heritability played a more significant role in caries formation in children at the younger and older ends of the age range. This is because the role of genetics is greatest in new teeth (both when children first get them and when their second teeth grow in). Years later, environmental factors tend to overpower genetics in caries formation.
While the role of genetics is significant, it is more difficult to pin down the exact genes that cause tooth decay. Adding to the challenge, Bretz says, is that “dental caries is a multifactorial disease” affected by saliva production, the oral microbiome, diet, behavioral issues, and tooth composition, among other things. Cavities could be linked to genes that determine a variety of factors, including enamel formation. Further complicating matters, Wright of UNC says, “We know that there are over 100 influencers on enamel formation.”
Mapping this complicated genetic terrain is the next frontier in caries study. With much future progress, it is conceivable that children will visit the dentist and undergo genetic screening to determine their caries risk.
In addition to genetics, a complicating factor of oral disease, including caries and periodontitis, is the oral microbiome, the ecosystem of various types of bacteria found on teeth, gums, and throughout the oral cavity. The composition and balance of the oral microbiome are currently — and literally — under the microscope of the dental profession. Many types of bacteria in the mouth have been identified and are known to influence disease progression. Some have been recently discovered; others remain unknown. Dental researchers believe that the composition of the oral microbiome can vary — in some people it may be healthy, but in others, disease-prone. And it can shift over time.
The University at Buffalo recently received a $4 million grant from the National Institute of Dental and Craniofacial Research to study the oral microbiome and its relation to periodontal disease in postmenopausal women. This study adds another layer to a previous study of this population, throughout which researchers collected and froze oral microbiome samples after five and 10 years. With the recent grant, and with newly accessible technology, researchers are bringing the subjects back for a 15-year oral microbiome sample. The goal is to examine whether and how the populations of oral bacteria have shifted and how this shift relates to disease prevalence.
“The new paradigm now is to study the interaction of the human microbiome with the human genome. I don’t think we can study one in isolation,” says Robert Genco of the University at Buffalo School of Dental Medicine. For example, a person’s genome may make him more prone to a certain condition that can be exasperated (or treated) by changes in the microbiome. The body is connected in more ways than once imagined.
A prime example of a healthcare system concerned with the interactions between the microbiome and the genome, as well as oral health and overall health, is the Marshfield Clinic in Wisconsin. The clinic has a nonprofit research division dedicated to human genetics and maintains an electronic database of genetic and health-related information for 20,000 participants. Murray Brilliant leads the Center for Human Genetics and is attuned to the connections between dental care and systemic disease.
In recent years, the Marshfield Clinic has opened dental clinics in rural Wisconsin. These locations use electronic records that can be easily cross-referenced with patients’ medical records. Patients can opt in to the clinic’s growing database of biological samples to aid in ongoing genetic research. Dental plaque samples are part of the biological materials collected in order to track the makeup of a patient’s oral microbiome.
“The important thing we keep in mind is that the mouth is an integral part of the body and that oral health really influences systemic health,” Brilliant says. “The bacteria we encounter in our oral cavity — that plays a role in disease processes that are not limited to dental problems. … In reality, inflammation caused by periodontal disease, that inflammatory signal does affect the whole body.”
The Marshfield Clinic is leading the charge of connecting dental care more closely to overall healthcare. “By a more holistic approach, we hope to prove that we’ve made a very positive impact not only on patients’ dental care, but on their systemic health.” On the research side, building a database of thousands of patients’ microbiomes is a huge undertaking, but a priceless resource. As the base of knowledge grows, personalized medicine becomes more intertwined with clinical practice.
“The mouth is now understood as a diagnostic goldmine for identifying diseases of the body,” periodontist Rose says. Over the years, he has pushed for more collaboration between dentists and physicians. He says there are initial signs of progress, especially in medical schools like the University of Pennsylvania, which now include oral health in their curricula.
“I think, as people would expect, there’s a major education process that needs to take place. And I don’t think this is unique to dentists,” Interleukin’s Kornman says. “This is really where healthcare is going. There is absolutely tremendous technology out there in a broad range of disease areas that is thrilling and exciting. The potential benefits for patients are tremendous.”