Advances in Precision Oral Health Research

The theme of “Advances in Precision Oral Health Research” for the 2018 American Association for Dental Research (AADR) Fall Focused Symposium (FFS) was spawned from an eloquent and inspiring keynote lecture entitled “From the Human Genome Project to Precision Medicine” presented by Dr. Francis Collins, director of the National Institutes of Health (NIH) on May 8, 2015, at “The Biology of Genomes” meeting held at Cold Spring Harbor Laboratory in Cold Spring Harbor, New York (The Leading Strand 2015). Dr. Collins spoke of progress that was being made in garnering support to develop a large-scale national prospective cohort that could generate a knowledge base needed to move precision medicine into a whole range of diseases, now known as All of Us (National Institutes of Health 2019). As a participant in this meeting, it was apparent that diseases of the oral cavity were not being considered in the context of this important initiative despite advances that were being made in the area of oral health. A previous AADR FFS held in 2013, entitled “Personalized Oral Health Care: Concept Design to Clinical Practice,” had provided an overview of the evolving health care environment empowered by rapid advances in omics technology. Since then, major strides have been made in this area of research due to increasing support from the National Institute of Dental and Craniofacial Research (NIDCR), which has awarded millions of dollars of grants to support the area of precision health with the goal of using data-driven and precision health methods to reduce oral health disparities. NIDCR has recently renewed its commitment to precision oral health in the NIDCR 2030 strategic planning initiative. Based on these developments, plans were put into place to hold the ninth AADR FFS in November 2018 at the Natcher Center on the NIH campus, “Advances in Precision Oral Health Research,” supported in part by the Task Force on Design and Analysis in Oral Health Research and an R13 grant from the NIH. The goal of this FFS was to address the current state of precision oral health research and its clinical application as well as the future of precision oral health and to identify research gaps that need to be filled to realize the full potential of precision oral care.

The proceedings of the FFS “Advances in Precision Oral Health Research,” published in this issue of Advances in Dental Research, an e-supplement to the Journal of Dental Research, captures the spirit of this well-attended 2-d symposium. The initial article on “Precision Health: Bringing Oral Health into the Context of Overall Health” (Tabak et al. 2019) captures the essence of 4 presentations made by distinguished scientists from the NIH, beginning with the importance of the Human Genome Project and technological advances making it cost-effective and relevant to capture genetic information for patients and their families. The recruitment of 1 million volunteers into the All of Us research program has commenced collecting genomic data, lifestyle information, and biological samples linked to electronic health records to be analyzed to accelerate biomedical discoveries. A task force was convened to establish baseline information to be collected from a self-reported oral health survey as determinants of oral health with the hope of discovering important connections between oral and overall health in All of Us participants. During the discussions following this presentation, it was suggested that engagement of the NIDCR-funded Practice Based Research Network for the recruitment of All of Us participants would facilitate the collection of clinical data and oral samples for more accurate and reliable oral health assessments than those measured with self-reported oral health data.

The next article in this issue, entitled “Precision Reengineering of the Oral Microbiome for Caries Management” (Baker et al. 2019), describes the development of a precision oral health therapeutic for the prevention of caries known as specifically targeted antimicrobial peptide (STAMP), providing specificity against Streptococcus mutans. The potential for the development of additional therapeutics through the STAMP platform, which can also be a useful tool in the study of microbial ecology, was discussed. In the following article, which expands beyond caries to include periodontitis, entitled “Searching Deep and Wide: The Molecular Basis of Dental Caries and Periodontitis” (Divaris 2019), the author highlights novel insights that have been gained from studies involving analytical approaches to assess “deep” or “precise” biologically informed disease traits and “wide” collaborative assessments harmonizing the oral health data of thousands of subjects from diverse settings. Subsequent articles focus on oral cancer starting with an article entitled “Oral Cancer: Integration of Studies for Diagnostic and Therapeutic Precision” (D’Silva and Gutkind 2019), which captures 2 presentations addressing precision initiatives for the development of diagnostic criteria that could lead to personalized approaches for treatment selection in people with oral cancer. In addition, novel treatment targets are identified that could enable personalized treatment strategies supporting long-term remission. The final article addressing challenges faced by oral cancer patients and others facing significant oral tissue injuries, entitled “Oral Rehabilitation of Patients Sustaining Orofacial Injuries: UPenn Initiative” (Zhang et al. 2019), describes a precision regenerative medicine initiative integrating multidisciplinary health professionals and translational scientists to develop a patient-centered approach for reconstruction and rehabilitation. An additional session, entitled “Unraveling TMD and Associated Conditions—The Horizon,” is not included in this Advances in Dental Research issue but can be viewed online along with all of the other presentations made at the meeting in the IADR CE On Demand Library (IADR 2019). The meeting closed with a panel discussion reiterating the fact that much progress has been made, emphasizing the need for continued research to support the development of precision oral health, describing challenges regarding third-party reimbursement of new precision health models, and raising concerns about the potential exacerbation of oral health disparities by clinical advances in precision oral health.

As described by Meyer (2019), “The broad adoption of precision medicine into clinical care promises to reduce unnecessary medical treatment and costs, improve outcomes, and increase innovation in health care.” This shift is facilitated by the development of large-scale biomedical databases and powerful computational tools for characterizing patients, including proteomics, metabolomics, genomics, and mobile health technology (Meyer 2019). Although precision medicine focuses on individualized care, its success truly requires a population-based approach (Khoury et al. 2015). To customize treatment, data on each individual need to be compared with data from large, diverse numbers of people to identify population subgroups likely to respond differently to interventions. A priority is to focus more attention on prevention and early detection with precision public health providing the right intervention to the right population at the right time (Khoury et al. 2015). At the same time, we must keep in mind that most human disease results from gene-environment interactions. From a public health perspective, risks are “framed as the consequence of structural factors, including social class, ethnic background, gender and sexual identity, and physical environment, among others” (Chowkwanyun et al. 2018). While the growth of genomics science will continue to yield important insights into better ways to treat and to prevent disease, research on the role of epigenetics and gene-environment interactions, as well as on the social and behavioral determinants of disease, needs to remain a high priority in our nation’s research agenda. As Khoury et al. (2018) have noted, “Genomics is only one approach to improving health, and for the most part cannot be used in isolation from other factors or determinants of health and disparities including socioeconomic factors such as housing, education and access to care.”

Dental researchers along with the broader biomedical research community recognize the variation that exists between individuals in their risk of developing disease and response to therapy based on genetic, environmental, social, and lifestyle factors. On a broader scale, stratification of people into different risk categories informing different preventive and treatment strategies will lead the way to precision oral health care. It must also be recognized that one of the unintended consequences of precision oral health may be an exacerbation of oral health disparities (Gansky and Shafik 2019), as access to such novel oral health care services may be more difficult to attain by those from population groups that, for example, have limited oral health literacy and that lack adequate insurance coverage and a usual source of oral health care. The detailed genomic data being collected from individuals, which may identify persons at higher risk for chronic medical conditions, also have the potential to be used to discriminate against individuals and thereby limit their ability to obtain and retain affordable high-quality health insurance coverage. Similarly, absent stringent legal protections being enacted, individuals whose genomic data indicate high disease risks may also suffer discrimination in employment, as employers may be reluctant to hire such high-risk and thus costly employees. Thus, as stated by Khoury et al. (2015), “Various ethical and social issues should be addressed, such as privacy, protection of genomic data from being used against employment and health insurance, and informed consent on storing and using genetic and non-genetic information for research and development. Precision healthcare will also require human capital, infrastructure, and education of the healthcare workforce, as well as empowering the general public with accurate information. Moreover, a more effective balance needs to be achieved in the research and implementation of both precision medicine and precision public health.”

There is no doubt that advances being made in precision oral health research will provide practitioners and insurers with new strategies to achieve optimal oral and overall health. As stated by Ryan (2018) at the opening ceremonies of the 2018 AADR Annual Meeting, “Based on technological achievements in genomics, proteomics, metabolomics, bioinformatics, systems biology, and in so many other areas, we are poised to make tremendous strides enabling us to advance the four Ps of health care in this century describing our ability to be: predictive, preventative, personalized and participatory, a term coined by the biologist Leroy Hood” (Hood 2013; Ryan 2018). Dr. Hood was the initial speaker for the IADR Distinguished Lecture Series presenting “21st Century Medicine is Transforming Healthcare” to an attentive audience at the 2019 IADR/AADR/CADR meeting held in Vancouver, British Columbia. He described his work to develop dense personal data clouds around individuals based on biometric and medical data as well as his collaborations with dental researchers to couple health data with oral exams and samples to allow for long-term prospective studies of oral and overall health. Translation of rapidly growing scientific and technological advances relies on strong partnerships across multiple disciplines. As a follow-up to the successful FFS in 2018, a follow-up AADR FFS has been scheduled for the fall of 2019 at the J. Craig Venter Institute in La Jolla, California, entitled “Integrating Omic Datasets towards Translation.” Topics in this upcoming FFS include an introduction to multiomic approaches, advanced analysis of metagenomes and metatranscriptomes in caries, clinical relevance of multiomics in periodontal treatments, omics in clinical oral health disparities, and more.