Research in Focus
The NYU Oral Cancer RAAHP Center: An Update After Seven Years of NIH Funding Featuring Clinically Relevant Findings

Dr Ralph Katz
Ms. Emile Godfrey

Dr. Doug Morse

Dr. Gustavo Cruz

The dentist thoroughly examines all sides of the tongue and the floor of the mouth.

Dr. David Sirois

By Ralph V. Katz, DMD, MPH, PhD
Professor and Chair, Department of Epidemiology & Health Promotion
NYU College of Dentistry

Emile Godfrey, MS, RD
Research Administrator
Department of Epidemiology & Health Promotion
NYU College of Dentistry

In 2001, as part of a national effort to redress disparities in our nation's health, the National Institute for Dental and Cranio-facial Research (NIDCR) at NIH awarded an $8.3M, seven-year grant to the NYU College of Dentistry to establish the NYU Oral Cancer RAAHP (Research for Adolescent and Adult Health Promotion) Center, one of five national Oral Health Disparities Centers funded by NIDCR/NIH. The four additional centers, which all focused on early childhood caries as their disease target, were at the dental schools at the University of California at San Francisco, University of Washington, University of Michigan, and Boston University.

The NYU RAAHP Center focused on oral cancer since, like many other diseases in the US, oral cancer takes a disproportionate toll on minorities. African-American males, a subgroup in the US, suffer both the highest incidence of and highest mortality from oral cancer with the next highest oral cancer rates being found in Puerto Rican males residing in Puerto Rico. The goal of the NYU Oral Cancer RAAHP Center has been to provide information that will change the behavior of both the public and the profession with regard to lifestyle and healthcare habits that lead to oral cancer occurrence and death.

The project has also had the related goal of providing training and career development opportunities for scientists in underrepresented groups and others interested in establishing careers in oral cancer disparities research.

Since its inception, the NYU Oral Cancer RAAHP Center has been engaged in a number of research initiatives that can properly be described as 'firsts':

  • determining why minorities do not get oral cancer screening exams that might pick up the earliest signs of this deadly disease by studies of the behaviors of both community residents and practicing dentists,
  • studying whether there are differences in willingness to participate in both cancer screening exams and biomedical research studies among African-Americans, Whites, and Puerto Rican Hispanics (both on the US mainland and in Puerto Rico),
  • using a dental practice setting to deliver effective smoking cessation interventions,
  • conducting a "first-ever" study directly comparing the diagnostic capability of five currently available-to-dentists, non-invasive, oral cancer detection methods, to the gold standard of a tissue biopsy, and
  • conducting the first comprehensive, in-depth study of risk factors both for the precancerous condition of oral epithelial dysplasia and for oral cancer in a Hispanic population.

The NYU Oral Cancer RAAHP Center has been led administratively by Dr. Ralph Katz, an oral epidemiol-ogist who has served as Director since its inception, and Ms. Emile Godfrey, a Research Administrator with many years of prior experience coordinating NIH-funded, multi-site clinical studies. The activities over the past seven years have involved investigators from 15 universities and agencies geographically spread from Puerto Rico to Boston, from New York to Texas.

The Center included four major studies: 1) an epidemiologic study on environmental and genetic risk factors for Oral Epithelial Dysplasia in Puerto Rico (PI: Dr. Doug Morse, NYU College of Dentistry); 2) a dental practice-based smoking cessation Randomized Clinical Trial (RCT) using Personalized Risk Feedback (PI: Dr. Jamie Ostroff, Memorial Sloan-Kettering Cancer Center, with Dr. Gustavo Cruz as the NYU-site Director); 3) a study of factors related to willingness to participate in oral cancer screening and in biomedical research studies (PI: Dr. Ralph Katz, NYU College of Dentistry); and 4) a clinical study directly comparing the screening and diagnostic validity of five current oral cancer detection technologies against the gold standard of surgical biopsy (PI: Dr. David Sirois, NYU College of Dentistry).

In addition to the Administrative Core, the Biostatistical Core (PI: Dr. Judy Goldberg, NYU School of Medicine) and the Informatics Core (PI: Dr. Titus Schleyer, University of Pittsburgh School of Dental Medicine) were critical resources for the investigators working within the RAAHP Center.

Key Findings:
The following are the key findings to date with clear and direct clinical relevance from the four major studies conducted over the past seven years by the scientists at the NYU Oral Cancer RAAHP Center.

Clinically Relevant Findings from the Environmental and Genetic Risk Factors for Oral Epithelial Dysplasia Study
(PI: Dr. Doug Morse)

Findings: Based on a thorough review of biopsy tissue specimens submitted to the major pathology laboratories in Puerto Rico, the ratio of practitioner-submitted precancerous lesions to cancer lesions was a very surprising: 1:4; i.e., for every one precancerous lesion (early lesion), there were 4 times as many cancer lesions (late lesions). [Notably, on the US mainland, this ratio was completely reversed with about six precancerous biopsies for each cancer lesion biopsy.] This was especially surprising given that Puerto Rico is known to have high rates of oral cancer; i.e., Puerto Rico has an oral cancer incidence rate that is 30% higher, and a mortality rate that is 50% higher, than that found on the US mainland.

Clinical Interpretation: These data suggest that a significant factor in the 50% higher mortality rate is related to the simple observation that biopsies, in Puerto Rico, are not being done frequently enough by practitioners, and when they are done, they are being done only at advanced stages of disease. This leads to the conclusion that if dentists were more aware of the need to take surgical biopsies, and/or if patients were more demanding of or receptive to getting oral lesions biopsied, the high mortality rate from oral cancers could likely be significantly reduced.

Clinically Relevant Findings from the Smoking Cessation RCT
(PI: Dr. Jamie Ostroff and NYU-site PI: Dr. Gustavo Cruz)

Findings: A Randomized Clinical Trial (RCT) on smoking cessation interventions on 929 patients who were heavy smokers with high nicotine dependence demonstrated that smoking cessation advice from dental office personnel proved to be effective in achieving clinically significant levels of smoking cessation. Participants were randomized to one of three interventions: Arm 1) Standard Care only (SC) received standard care defined as dentist-provided smoking cessation advice, brief counseling, a nicotine reduction patch and follow-up; Arm 2) received standard care plus motivational smoking cessation counseling (SC + MC) provided by a trained dental hygienist; and Arm 3) received standard care and motivational counseling plus personalized risk counseling based on a tobacco-related oral exam (SC + MC + PTRC). After 1 year, the smoking cessation rates for the three intervention levels ranged from 18%-24%, and even subjects who did not cease smoking had similar levels of reduction in smoking; i.e., an average of 18 cigarettes/day down to 11 cigarettes/day (~ 66% reduction) for each of the three arms of the RCT.

Clinical Interpretation: These data suggest that dentists, within the context of their normal dental practice, can indeed be effective agents of change (acting either alone, or in partnership with reinforcement by their dental hygienist) to aid patients seeking smoking cessation, and thereby make a substantial contribution to the overall health of their patients and to protection against oral cancer.

Key Clinically Relevant Findings for the Willingness to Participate in Cancer Screening Exams and as Research Subjects Study
(PI: Dr. Ralph Katz)

I. Key Relevant Cancer Screening Findings

Of 10 site-specific cancers (e.g., lung, liver, skin, stomach, colon, prostate, breast, etc.), willingness to participate in community-based cancer screenings was lowest for oral cancer with about 70% indicating willingness to participate in oral cancer screenings, based upon 1,148 questionnaire interviews with randomly selected households in three US cities. Comparatively, the highest rated cancer screening rates were for breast and prostate cancer screenings (about 90% indicated willingness to participate), while the other site-specific cancers willingness levels ranged from 71-77%.

Clinical Interpretation: Even with willingness to participate in oral cancer screenings being the lowest among 10 site-specific cancers, 70% of respondents indicated a positive attitude toward participation in oral cancer screenings. Thus, active participation by dentists in dental society and/or community group-sponsored oral cancer screenings has the potential to be a valuable professional service to one's community.

II. Key Relevant Racial Findings on "being a subject in a biomedical research study"

The phrase "legacy of the Tuskegee Syphilis Study" has been used to denote the widespread belief that Blacks are more reluctant than Whites to participate in biomedical research studies because of the infamous US Public Health Service's Tuskegee Syphilis Study conducted on 399 Black sharecroppers from 1932-72. The Tuskegee Legacy Project Study conducted within the NYU Oral Cancer RAAHP Center - the first to assess directly the accuracy of this belief within a multi-city, multi-racial, large-scale detailed random survey - found that: 1) Blacks self-reported to be as willing as Whites to participate in biomedical research, despite being more wary about such participation (as measured by the Guinea Pig Fear Factor Scale); and 2) there was no association between either awareness or detailed knowledge of the Tuskegee Syphilis Study and willingness to participate in biomedical studies in either Blacks or Whites; i.e., the study found no support for the long and widely held belief in the so-called "legacy" of the Tuskegee Syphilis Study.

Societal Benefits Interpretation: These clear-cut findings from the Tuskegee Legacy Project (TLP) Study, in which all findings were observed - and then confirmed and validated - in repeat random surveys conducted in 7 US cities in two distinct surveys consisting of over 2,200 interviews, allow clinical researchers to focus on the development of active recruitment plans for the inclusion of minorities into biomedical studies that address the real issues involved in obtaining racially diverse study samples within biomedical studies, to ensure that those studies address the needs of our whole population, as mandated by the federal government since 1994.

Key Clinically Relevant Findings for the Comparative Diagnostic Capability of Non-invasive Oral Cancer Diagnostic Tests vs Biopsy Findings
(PI: Dr. David Sirois)

Findings In-Development: The critically important findings from our other major study (which compared the diagnostic agreement between today's gold standard of surgical biopsy with the five non-invasive oral cancer detection techniques readily available to all dental practitioners) having completed its data collection on the enrolled 270 patients, are currently in the data analysis stage. The five non-invasive oral cancer detection techniques were: 1) visual clinical examination; 2) salivary molecular markers for oral cancer; 3) application of toluidine blue; 4) oral speculoscopy; and 5) brush biopsy. The findings from this long overdue, comparative study (which surprisingly had never been investigated previously) will be published within the year, once the data analysis is completed.

Clinical Interpretation: These findings will inform dentists as to whether any of the five "non-invasive" oral cancer detection techniques, alone or in combination, are accurate enough (i.e., have a high specificity and high sensitivity) to replace the current gold standard of surgical biopsy with a high degree of confi-dence in the diagnostic accuracy. Being non-invasive, these techniques might well prove to be highly attractive to patients, as well as to dentists, as a diagnostic alternative for early lesions.

A Solid Foundation for Future Research

Since 2001, the NYU Oral Cancer RAAHP Center has built a solid foundation for future research and implementation of successful clinical, research, and public health oral cancer initiatives in a community-based setting toward the goal of reducing oral health disparities. This is reflected in the scientific productivity of the NYU Oral Cancer RAAHP Center and its investigators over the past seven years, which has included to date, publication of 59 scientific articles and three book chapters on health disparities, plus 64 scientific abstracts presented at national or international scientific meetings, with more to unfold over the next two years as the latest data continue to be analyzed and interpreted.

In addition, the RAAPH Center has fulfilled its related goal of training the next cohort of health disparities researchers by providing support and productive training opportunities to eight NIH NRSA Postdoctoral Fellows and six junior faculty members. Finally, over the past seven years, the RAAHP Center funded and supported a total of 14 scientific and bioethics pilot studies related to the four major studies, including an innovative set of bioethics pilot studies via a partnership with Tuskegee University's National Center for Bioethics in Research and Health Care. All together, these initiatives bode well for the creation in the near future of an oral cancer prevention and early detection model that can be replicated at the national level.