Advances in Precision Oral Health Research: Opportunities for the Future!

The American Association for Dental Research (AADR) created the Fall Focused Symposium (FFS) Series in 2009, providing the dental, oral, and craniofacial research community with a forum for in-depth exploration of critical and emerging scientific topics. Previous FFSs held since then have focused on Nanotechnology, Tissue Engineering, Salivary Diagnostics (Wong 2011), Oral Health Disparities (Ebersole et al. 2012), Translational Genetics (D’Souza et al. 2013), Translational Research, Personalized Oral Health Care held in the fall of 2013, and Pain Management.

Much progress has occurred since the 2013 FFS on personalized oral health care, a rapidly advancing field, prompting the AADR to organize the ninth FFS on “Advances in Precision Oral Health Research,” which was held on the National Institutes of Health (NIH) campus in November of 2018. This most recent FFS was supported in part by funding from the NIH/National Institute of Dental and Craniofacial Research (NIDCR) and the Task Force on Design and Analysis in Oral Health Research.

A goal of the NIDCR 2014 to 2019 Strategic Plan is to “enable precise and personalized oral health care through research.” NIDCR has renewed its commitment to precision oral health in NIDCR 2030, the Institute’s most recent strategic planning initiative. AADR hosted a 2 day symposium on “Advances in Precision Oral Health Research” to address the current state of research in this area and its clinical application, the future of personalized oral health, and the research gaps that need to be filled to realize the full potential of personalized oral care. Papers of presentations from this well-attended symposium are published in a special issue of Advances in Dental Research.

The introductory session sets the stage for precision oral health research, defines precision medicine, and outlines the promise of precision medicine approaches for both individual and population health (Ryan and Garcia 2019). At the same time, it is acknowledged that despite the promise of precision oral health to reduce costs and improve oral care, an unintended consequence may be an exacerbation of oral health disparities. These ethical and social issues must be addressed.

The next session brought oral health into the context of overall health (Tabak et al. 2019). Unprecedented advances in genomics, data science, and biotechnology are presented in light of their contributions to a new era of health care in which interventions and treatment are increasingly tailored to individual patients. These precision-based approaches extend to oral health. The NIH “All of Us” Research Program, launched in 2018, is a large-scale prospective study that aims to gather data from 1 million or more participants living in the United States across life span, race, sex, ethnicity, and socioeconomic status to reflect the diversity of the American population. A self-report of oral health will be part of this research program and will provide researchers with an unprecedented, large-scale data set of oral health and general health information.

A session on the oral microbiome and dental caries described the development of a precision-engineered peptide to better control caries, the most common chronic disease affecting the population (Baker et al. 2019). Using precision approaches to specifically target the cariogenic species Streptococcus mutans could have the potential to dramatically reduce the prevalence and severity of dental caries. Specifically targeted antimicrobial peptides (STAMPs) were engineered to target S. mutans by combining a segment of an antimicrobial peptide with a targeting domain from a S. mutans pheromone. After successful phase I clinical trials, several formulations are currently in phase II clinical trials. This exciting advance in precision oral health research could pave the way for additional therapeutics.

Another session highlighted novel insights into the molecular basis of dental caries and chronic periodontitis using “deep” and “wide” analytic approaches (Divaris 2019). “Deep” refers to the identification and interrogation of biologically informed disease traits, and “wide” refers to the formation of international consortia with oral health data of thousands of individuals. Combining these 2 analytic approaches, with the engagement of systems biology and team science models, has the potential to dramatically advance precision oral health. A prime example of using this approach for periodontitis is described with the identification of a novel genetic locus encoding for the regulatory cytokine interleukin 37 (IL37).

Head and neck cancers are among the 10 most common cancers in the world and include cancers of the oral cavity, hypopharynx, larynx, nasopharynx, and oropharynx. At least 90% of head and neck cancers are squamous cell carcinomas (SCCs). A session discussed the integration of clinical and mechanistic studies in achieving diagnostic and therapeutic precision in the context of oral cancer (D’Silva and Gutkind 2019). Emerging precision therapeutic options for SCC prevention and treatment are described leveraging our biologic understanding of the activation of the P13K/mTOR pathway in SCC. Precision immunotherapies are based on the ability to reactivate the antitumor response of the patient’s own immune system. Immunotherapeutic agents that inhibit PD-1 are demonstrating potent antitumor activity in a subset of oral cavity and oropharyngeal SCC patients.

Finally, orofacial injuries, whether from trauma, warfare, cancer, congenital defects, or other causes, pose significant reconstruction and rehabilitation challenges. A unique program at the University of Pennsylvania is described that integrates multidisciplinary health professions and translational/clinical scientists in medicine, dentistry, stem cell biology, tissue engineering, and regenerative medicine with the aim to develop comprehensive, patient-centered approaches for precision and personalized reconstruction for patients with orofacial injuries (Zhang et al. 2019) Although this approach is acknowledged to be in its infancy, it certainly holds great promise.

It should also be noted that the FFS was recorded and IADR members are able to access this conference as part of their membership benefits (IADR 2019). In addition to the excellent presentations described in the Advances in Dental Research issue, there was an additional session on temporomandibular disorders (TMDs) and orofacial pain that is not included in this special issue but is well worth viewing.

In summary, precision oral health research and its clinical applications have demonstrated great progress since the first AADR FFS on the topic just 5 y earlier. These advances would not have been possible without significant NIH and NIDCR investments, from Office of the Director for trans-NIH initiatives like the All of Us Research Program to the NIDCR prioritization of precision oral health in their strategic planning documents, including individual investigator-initiated R01s. The AADR would like to acknowledge and thank the NIDCR and the Task Force on Design and Analysis in Oral Health Research for their financial and scientific support of this FFS.