The purpose of this initiative is to encourage studies aimed at understanding biological factors that mediate the increased prevalence and severity of Dental, Oral, and Craniofacial (DOC)-related diseases and conditions in oral health disparities populations. It is long recognized that there are racial and ethnic differences in DOC diseases and conditions, such as oral/oropharyngeal cancers, early childhood caries (ECC), dental caries, and periodontitis. For each of these diseases, substantial racial and ethnic differences exist in prevalence, severity, persistence and/or disease progression. However, because critical scientific gaps remain in our understanding of underlying biological mechanisms that could contribute to these differences, it is difficult to develop targeted therapeutic regimens for those in greatest need.
Recent studies of other diseases demonstrating racial/ethnic disparities in prevalence and severity have identified biological factors as possible reasons for differences in disease outcomes. African American women are as likely to get breast cancer as white American women, yet they have a higher breast cancer death rate. Tumor analyses indicate that the disparity in death rates may be due in part to an increased risk of triple-negative breast cancer in African American women as compared to women from other racial/ethnic groups in the US (DeSantis, Newman). Biologic factors may contribute to other cancer health disparities, such as colorectal cancer and prostate cancer in African-Americans (National Cancer Institute).
African-Americans who develop oral cavity and oropharyngeal cancers (OPC) have consistently had poorer survival than whites. An analysis of SEER data from 1973 to 2008 found that the 5-year relative survival of whites with squamous cell carcinoma of the tongue, base of tongue and tonsils was close to 57%, while blacks had a survival rate of close to 33% (Saba). More recent estimates indicate that there has been a slight improvement in 5-year relative survival for oral cancers; however, African-Americans continue to experience much poorer survival (Howlader). Whites are more likely to have human papillomavirus (HPV)-positive OPC, which is associated with better survival and may account for some of the long-term differences in outcomes; however, other biological factors have not been explored in detail.
ECC is much more prevalent in African-American, Hispanic and American Indian / Alaska Native children (Dye). Investigations have focused on whether these children harbor more virulent strains of Streptococcus mutans, whether humoral responses differ by racial/ethnic group, and whether varying concentrations of selected salivary innate immunity proteins are associated with different caries outcomes. To date, transmission patterns of Streptococcus mutans from mother to child and between family members have been characterized, but no distinct biological differences in caries pathways have been documented for different racial or ethnic groups.
There are multiple reports that African-Americans and other minority populations exhibit increases in the prevalence and severity of destructive periodontal disease as compared to US whites. Loe & Brown analyzed data from over 11,000 adolescents and found African-Americans were at higher risk for all forms of early onset periodontal diseases, Differences in disease prevalence by race were also found in studies of young adult Naval recruits (Melvin), and in analysis of NHANES III data after adjustment for age and gender (Albander). Microbial studies suggest differences in subgingival bacterial profiles are associated with this increased prevalence and severity in African-Americans, while ethnic/racial differences in host response to bacterial colonization, including serum antibody levels, have also been found in small cohort studies.
Gaps and Opportunities
While African-Americans tend to be diagnosed with later stage OPC tumors that may contribute to poorer survival as compared to whites, tumor characteristics of the two groups have not been compared extensively. Existing tumor bio-repositories with matched clinical data can be used to accelerate this area of research.
To date, biological factors such as highly virulent S. mutans strains that could account for the higher caries burden in children with oral health disparities have not been identified (Argimón), though children with more S. mutans genotypes had higher levels of caries (Momeni). However, few studies have examined the microbial flora other than S. mutans and Lactobacillus and few have used comprehensive methods of comparing salivary proteins (Johansson; Colombo). Research aimed at understanding how the trajectory of a cariogenic microbiota can be modified once established is also sparse. Preliminary findings from several studies suggest the existence of mechanisms that may account for the increased destructive periodontal disease prevalence and severity observed in African-Americans (Craig), but these initial findings need further exploration.
New in vitro technologies to examine the oral microbiome, inflammatory mediators of periodontal disease, genetic risk/protective factors and salivary proteins could be employed to advance research to explore biological factors underlying oral health disparities.
The scope of this initiative includes but is not limited to, research on:
- Microbial and inflammatory mediators of oral diseases in different racial/ethnic groups, and their contribution to racial/ethnic differences in disease prevalence and/or severity.
- Biologic responses to conventional therapy for dental, oral, and craniofacial diseases that may explain the persistence of these diseases in different racial/ethnic minority populations.
- Genetic/genomic risk or protective factors that might contribute to racial/ethnic differences in dental, oral, and craniofacial diseases, and the interplay with other factors.
This initiative will build on recent advances in the definition of the oral microbiome, evidence of inflammatory proteins and the microbiome mediating periodontal diseases, and findings that certain genetic markers confer a higher risk for caries and periodontal disease.
Current Portfolio Overview
R01 DE023414, Exome sequencing for head and neck cancer susceptibility genes
U01 DE025046, Genome-Wide Association Study of Early Childhood Caries
R01 DE014899, Factors Contributing to Oral Health Disparities in Appalachia
Individuals and Groups Whose Input was Solicited for This Initiative
Program officials at National Heart, Lung and Blood Institute and National Cancer Institute discussed this topic with NIDCR. Public comments specific for this concept were solicited on NIDCR website from August 4-September 5, 2017.
Alignment with Institute Goals and Strategic Plan
This initiative is aligned with the NIDCR Strategic Plan 2014-2019, Goals II and III, “Enable precise and personalized oral health care through research” and “Apply rigorous, multidisciplinary research approaches to overcome disparities and inequalities in dental, oral, and craniofacial health”, respectively.
Albandar JM, Brunelle JA, Kingman A. Destructive periodontal disease in adults 30 years of age and older in the United States, 1988–94. J Periodontol 1999;70:13–29.
Argimón S, Konganti K, Chen H, Alekseyenko AV, Brown S, Caufield PW. Comparative genomics of oral isolates of Streptococcus mutans by in silico genome subtraction does not reveal accessory DNA associated with severe early childhood caries. Infect Genet Evol. 2014 Jan;21:269-78.
Colombo NH, Ribas LF, Pereira JA, Kreling PF, Kressirer CA, Tanner AC, Duque C. Antimicrobial peptides in saliva of children with severe early childhood caries. Arch Oral Biol. 2016 Sep;69:40-6.
Craig RG, Boylan R, Yip J, Mijares D, Imam M, Socransky SS, Taubman MA, Haffajee AD. Serum IgG antibody response to periodontal pathogens in minority populations: relationship to periodontal disease status and progression. J Periodont Res 2002; 37: 132–146.
DeSantis CE, Siegel RL, Sauer AG, Miller KD, Fedewa SA, Alcaraz KI, Jemal A. Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities. CA Cancer J Clin 2016;66:290-308.
Dye BA, Arevalo O, Vargas CM. Trends in paediatric dental caries by poverty status in the United States, 1988-1994 and 1999-2004. Int J Paediatr Dent. 2010 Mar;20(2):132-43.
Howlader N, Ries LAG, Mariotto AB, et al. Improved estimates of cancer-specific survival rates from population-based data. J Natl Cancer Inst . 2010;102(20):1584–1598.
Johansson I, Witkowska E, Kaveh B, Holgerson L, Tanner ACR. The Microbiome in Populations with a Low and High Prevalence of Caries. J Dent Res. 2016 Jan;95(1):80-6.
Löe H, Brown LJ. Early onset periodontitis in the United States of America. J Periodontol 1991;62:608–616.
Melvin WL, Sandifer JB, Gray JL. The prevalence and sex ratio of juvenile periodontitis in a young, racially mixed population. J Periodontol 1991;62:330–334.
Momeni SS et al. Genetic Diversity and Evidence for Transmission of Streptococcus mutans by DiversiLab rep-PCR. J Microbiol Methods. 2016 Sep;128:108-17.