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BRUSH BIOPSY ‘SAVES LIVES'
L E T T E R S
LETTERS ADA welcomes letters from readers on topics of current interest in dentistry. The Journal reserves the right to edit all communications and requires that all letters be signed. The views expressed are those of the letter writer and do not necessarily reflect the opinion or official policy of the Association. Brevity is appreciated.
J
BRUSH BIOPSY ‘SAVES LIVES’
Dr. Tyler Potter and colleagues’ March JADA letter to the editor was highly critical of the most comprehensive, nationwide oral cancer campaign ever conducted in the United States and used the opportunity to disparage the brush biopsy technique. In the past year alone, dentists have used the brush biopsy to detect well over 2,000 oral dysplasias and carcinomas among lesions that would not have aroused sufficient suspicion to biopsy prior to the advent of this test. The emphasis on lives saved as a result of the oral cancer campaign was recently communicated by the ADA president and executive director to all ADA members. The many comparisons made by the authors between incisional biopsy and brush biopsy suggest that they mistakenly view the two biopsy modalities as competitive methods for testing the same spectrum of abnormality. The authors fail to appreciate the fact that the brush biopsy is utilized to test the spectrum of benign-appearing lesions that have been either “watched” or ignored in the past and that this use has already 688
saved many lives. The authors suggest that all five articles on the brush biopsy technique,1-5 published in peerreviewed journals by oral pathologists from prestigious universities, were written by academicians who had a financial interest in the company providing the brush biopsy service. None of the authors who has participated in clinical studies or published articles on the brush biopsy technique has any financial interest in, commercial associations with, stock in or other equity ownership in CDx Laboratories. This insinuation is outrageous. The authors contend that the multicenter trial,2 published as the cover story in the October 1999 JADA, contained design flaws and statistical errors. They obviously are unaware that independent statisticians reviewed the design of the study and all of the results, and that statisticians and scientists at the ADA, before granting OralCDx the Seal of Acceptance, analyzed the raw data rigorously. Additionally, the CDx technology is currently in clinical trials for the early detection of laryngeal, pharyngeal and esophageal cancer, and clinical protocols identical to the OralCDx protocol have been approved by review committees at more than 15 U.S. medical schools. The authors’ suggestion that the “sensitivity and specificity data [are] incomplete” is totally unfounded since, as is clearly stated in the publication of the clinical trial and confirmed by statisticians, only those brush biopsies with matching scalpel biopsies were used to determine OralCDx sensitivity and specificity.
To suggest that the brush biopsy is painful and may be as painful as an incisional biopsy also is incorrect, since every publication based on clinical experience with the brush biopsy technique describes it as painless.1-5 Although they claim that the brush biopsy is “a variation of the cytologic smear technique,” the authors overlook the fact that studies employing oral cytology resulted in false negative rates of 30 percent to 50 percent,6,7 compared with the 96 percent sensitivity demonstrated with the OralCDx computerassisted brush biopsy. The letter writers’ greatest misunderstanding is revealed in their statements that “mucosal abnormalities are clinically recognizable” and that the brush biopsy is, therefore, “a test that confirms what is clinically visible.” The literature is replete with documentation of the fact that precancers and early oral cancers often appear clinically identical to commonly encountered benign lesions.8-10 In fact, the oral brush biopsy was developed to enable dentists to evaluate countless such lesions seen in their patients on a routine basis. Indeed, in the multicenter trial, 29 benignlooking lesions judged harmless in appearance by experienced academic clinicians were identified as precancers and cancers only as a result of the use of the brush biopsy test. In contrast to the numerous oral pathologists, oral surgeons and oral medicine specialists who have presented hundreds of lectures in which they have explained the value of the brush biopsy to thousands of dentists, these authors fail to understand that the brush biopsy is intended
JADA, Vol. 133, June 2002 Copyright ©2002 American Dental Association. All rights reserved.
L E T T E R S
to evaluate benign-appearing oral lesions and not those distinguished by signs and symptoms of malignancy, which are clear signals for immediate incisional biopsy. Tens of thousands of U.S. dentists who have adopted the brush biopsy as a diagnostic aid have understood clearly both the message of early detection publicized by the ADA and the potential benefits to their patients. It is unfortunate that Dr. Potter and his colleagues have not appreciated the positive impact that the brush biopsy already has had on the health of the thousands of patients diagnosed with oral precancers and cancers. The care and diligence exercised by dentists in using this tool to evaluate a spectrum of lesions whose benign appearance previously would not have directed them for biopsy serves the public well. Drore Eisen, M.D., D.D.S. Medical Director CDx Laboratories Suffern, N.Y. 1. Felefli S, Flaitz CM. The oral brush biopsy: it’s as easy as 1, 2, 3. Tex Dent J 2000; 117(6):20-4. 2. Sciubba JJ. Improving detection of precancerous and cancerous oral lesions: computer-assisted analysis of the oral brush biopsy. U.S. Collaborative OralCDx Study Group. JADA 1999;130(10):1445-57. 3. Svirsky JA, Burns JC, Page DG, Abbey LM. Computer-assisted analysis of the oral brush biopsy. Compend Contin Educ Dent 2001;22:99-106. 4. Drinnan AJ. Screening for oral cancer and precancer: a valuable new technique. Gen Dent 2000;48(6):656-60. 5. Zunt SL. Transepithelial brush biopsy: an adjunctive diagnostic procedure. J Indiana Dent Assoc 2001;80(2):6-8. 6. Banoczy J. Exfoliative cytologic examinations in the early diagnosis of oral cancer. Int Dent J 1976;26(4):398-404. 7. Folsom TC, White CP, Bromer L, Canby HF, Garrington GE. Oral exfoliative study: review of the literature and report of a threeyear study. Oral Surg Oral Med Oral Pathol 1972;33(1):61-74. 8. Silverman S Jr. Early diagnosis of oral cancer. Cancer 1988;62(8 supplement):1796-9. 9. Shugars DC, Patton LL. Detecting, diagnosing, and preventing oral cancer. Nurse Pract 1997;22(6):105, 109-10, 113-5 passim. 10. Mashberg A, Feldman LJ. Clinical criteria for identifying early oral and oropharyngeal carcinoma: erythroplasia revisited. Am J
Surg 1988;156(4):273-5.
BRUSH BIOPSY ‘BRIDGES THE GAP’
In reading the March JADA letter to the editor from Dr. Tyler Potter and colleagues regarding the ADA’s recent oral cancer campaign, it becomes clear that they “just don’t get it.” While the entire profession would agree with the final statement in their letter advocating earlier diagnosis of oral mucosal abnormalities using improved methodologies, they fail to acknowledge the wellknown fact that techniques exist to accomplish exactly that, including the scalpel biopsy. Historically, dental and medical practitioners have been encouraged and admonished relative to performance of a thorough oral examination on all patients with any follow-up care or treatment as needed. In spite of these efforts, the large number of undetected early oral cancer cases persists, ultimately presenting as late-stage disease. Their letter, on the other hand, fails to recognize that many early-stage cancers we seek to identify are often mistaken for or considered as benign lesions1,2 and thus go undefined. Their criticism of the billboard featuring a young attractive woman with a “photographically superimposed” tongue cancer seems unwarranted. The message, which Dr. Potter and colleagues apparently missed, relates, in part, to the documented sharp upward trend in tongue cancer in young Americans3 and that attention be directed to all patients relative to oral cancer. Furthermore, the statement that the original study design4 was flawed reflects a lack of
comprehension of the statistical analysis. A review of the protocol at institutional review boards before performance of the study and the data generated afterward by independent statisticians did not indicate such “flaws.” The letter writers seem to dismiss the grassroots acceptance, utilization and impact of this diagnostic approach within the dental community, in particular with reference to identifying oral mucosal alterations of uncertain potential. While a substantial proportion of lesions evaluated will be of a benign nature, as noted in the multicenter trial, the significant number of unexpected dysplastic lesions identified and verified (by scalpel biopsy) speaks directly to early diagnosis. As clinicians, we are all too aware of the large number of mucosal alterations that are observed only with no sense of their biological nature. The brush biopsy is such a modality that bridges the gap between visual acknowledgment and scalpel biopsy, the latter being arguably the “gold standard.” Finally, the statement that nine authors who have previously published in peerreviewed journals, including JADA, are “associated with the company that offers the service” is patently untrue. Blatantly implied is a relationship in which there was financial incentive in place in the form of an honorarium for authoring these publications. Lectures across the country have been given by many of my esteemed and respected colleagues in which the rationale and basis for the use of the brush biopsy as a clinical tool has been explained in updates on mucosal diseases/leuko-
JADA, Vol. 133, June 2002 Copyright ©2002 American Dental Association. All rights reserved.
689
LETTERS ADA welcomes letters from readers on topics of current interest in dentistry. The Journal reserves the right to edit all communications and requires that all letters be signed. The views expressed are those of the letter writer and do not necessarily reflect the opinion or official policy of the Association. Brevity is appreciated.
J
BRUSH BIOPSY ‘SAVES LIVES’
Dr. Tyler Potter and colleagues’ March JADA letter to the editor was highly critical of the most comprehensive, nationwide oral cancer campaign ever conducted in the United States and used the opportunity to disparage the brush biopsy technique. In the past year alone, dentists have used the brush biopsy to detect well over 2,000 oral dysplasias and carcinomas among lesions that would not have aroused sufficient suspicion to biopsy prior to the advent of this test. The emphasis on lives saved as a result of the oral cancer campaign was recently communicated by the ADA president and executive director to all ADA members. The many comparisons made by the authors between incisional biopsy and brush biopsy suggest that they mistakenly view the two biopsy modalities as competitive methods for testing the same spectrum of abnormality. The authors fail to appreciate the fact that the brush biopsy is utilized to test the spectrum of benign-appearing lesions that have been either “watched” or ignored in the past and that this use has already 688
saved many lives. The authors suggest that all five articles on the brush biopsy technique,1-5 published in peerreviewed journals by oral pathologists from prestigious universities, were written by academicians who had a financial interest in the company providing the brush biopsy service. None of the authors who has participated in clinical studies or published articles on the brush biopsy technique has any financial interest in, commercial associations with, stock in or other equity ownership in CDx Laboratories. This insinuation is outrageous. The authors contend that the multicenter trial,2 published as the cover story in the October 1999 JADA, contained design flaws and statistical errors. They obviously are unaware that independent statisticians reviewed the design of the study and all of the results, and that statisticians and scientists at the ADA, before granting OralCDx the Seal of Acceptance, analyzed the raw data rigorously. Additionally, the CDx technology is currently in clinical trials for the early detection of laryngeal, pharyngeal and esophageal cancer, and clinical protocols identical to the OralCDx protocol have been approved by review committees at more than 15 U.S. medical schools. The authors’ suggestion that the “sensitivity and specificity data [are] incomplete” is totally unfounded since, as is clearly stated in the publication of the clinical trial and confirmed by statisticians, only those brush biopsies with matching scalpel biopsies were used to determine OralCDx sensitivity and specificity.
To suggest that the brush biopsy is painful and may be as painful as an incisional biopsy also is incorrect, since every publication based on clinical experience with the brush biopsy technique describes it as painless.1-5 Although they claim that the brush biopsy is “a variation of the cytologic smear technique,” the authors overlook the fact that studies employing oral cytology resulted in false negative rates of 30 percent to 50 percent,6,7 compared with the 96 percent sensitivity demonstrated with the OralCDx computerassisted brush biopsy. The letter writers’ greatest misunderstanding is revealed in their statements that “mucosal abnormalities are clinically recognizable” and that the brush biopsy is, therefore, “a test that confirms what is clinically visible.” The literature is replete with documentation of the fact that precancers and early oral cancers often appear clinically identical to commonly encountered benign lesions.8-10 In fact, the oral brush biopsy was developed to enable dentists to evaluate countless such lesions seen in their patients on a routine basis. Indeed, in the multicenter trial, 29 benignlooking lesions judged harmless in appearance by experienced academic clinicians were identified as precancers and cancers only as a result of the use of the brush biopsy test. In contrast to the numerous oral pathologists, oral surgeons and oral medicine specialists who have presented hundreds of lectures in which they have explained the value of the brush biopsy to thousands of dentists, these authors fail to understand that the brush biopsy is intended
JADA, Vol. 133, June 2002 Copyright ©2002 American Dental Association. All rights reserved.
L E T T E R S
to evaluate benign-appearing oral lesions and not those distinguished by signs and symptoms of malignancy, which are clear signals for immediate incisional biopsy. Tens of thousands of U.S. dentists who have adopted the brush biopsy as a diagnostic aid have understood clearly both the message of early detection publicized by the ADA and the potential benefits to their patients. It is unfortunate that Dr. Potter and his colleagues have not appreciated the positive impact that the brush biopsy already has had on the health of the thousands of patients diagnosed with oral precancers and cancers. The care and diligence exercised by dentists in using this tool to evaluate a spectrum of lesions whose benign appearance previously would not have directed them for biopsy serves the public well. Drore Eisen, M.D., D.D.S. Medical Director CDx Laboratories Suffern, N.Y. 1. Felefli S, Flaitz CM. The oral brush biopsy: it’s as easy as 1, 2, 3. Tex Dent J 2000; 117(6):20-4. 2. Sciubba JJ. Improving detection of precancerous and cancerous oral lesions: computer-assisted analysis of the oral brush biopsy. U.S. Collaborative OralCDx Study Group. JADA 1999;130(10):1445-57. 3. Svirsky JA, Burns JC, Page DG, Abbey LM. Computer-assisted analysis of the oral brush biopsy. Compend Contin Educ Dent 2001;22:99-106. 4. Drinnan AJ. Screening for oral cancer and precancer: a valuable new technique. Gen Dent 2000;48(6):656-60. 5. Zunt SL. Transepithelial brush biopsy: an adjunctive diagnostic procedure. J Indiana Dent Assoc 2001;80(2):6-8. 6. Banoczy J. Exfoliative cytologic examinations in the early diagnosis of oral cancer. Int Dent J 1976;26(4):398-404. 7. Folsom TC, White CP, Bromer L, Canby HF, Garrington GE. Oral exfoliative study: review of the literature and report of a threeyear study. Oral Surg Oral Med Oral Pathol 1972;33(1):61-74. 8. Silverman S Jr. Early diagnosis of oral cancer. Cancer 1988;62(8 supplement):1796-9. 9. Shugars DC, Patton LL. Detecting, diagnosing, and preventing oral cancer. Nurse Pract 1997;22(6):105, 109-10, 113-5 passim. 10. Mashberg A, Feldman LJ. Clinical criteria for identifying early oral and oropharyngeal carcinoma: erythroplasia revisited. Am J
Surg 1988;156(4):273-5.
BRUSH BIOPSY ‘BRIDGES THE GAP’
In reading the March JADA letter to the editor from Dr. Tyler Potter and colleagues regarding the ADA’s recent oral cancer campaign, it becomes clear that they “just don’t get it.” While the entire profession would agree with the final statement in their letter advocating earlier diagnosis of oral mucosal abnormalities using improved methodologies, they fail to acknowledge the wellknown fact that techniques exist to accomplish exactly that, including the scalpel biopsy. Historically, dental and medical practitioners have been encouraged and admonished relative to performance of a thorough oral examination on all patients with any follow-up care or treatment as needed. In spite of these efforts, the large number of undetected early oral cancer cases persists, ultimately presenting as late-stage disease. Their letter, on the other hand, fails to recognize that many early-stage cancers we seek to identify are often mistaken for or considered as benign lesions1,2 and thus go undefined. Their criticism of the billboard featuring a young attractive woman with a “photographically superimposed” tongue cancer seems unwarranted. The message, which Dr. Potter and colleagues apparently missed, relates, in part, to the documented sharp upward trend in tongue cancer in young Americans3 and that attention be directed to all patients relative to oral cancer. Furthermore, the statement that the original study design4 was flawed reflects a lack of
comprehension of the statistical analysis. A review of the protocol at institutional review boards before performance of the study and the data generated afterward by independent statisticians did not indicate such “flaws.” The letter writers seem to dismiss the grassroots acceptance, utilization and impact of this diagnostic approach within the dental community, in particular with reference to identifying oral mucosal alterations of uncertain potential. While a substantial proportion of lesions evaluated will be of a benign nature, as noted in the multicenter trial, the significant number of unexpected dysplastic lesions identified and verified (by scalpel biopsy) speaks directly to early diagnosis. As clinicians, we are all too aware of the large number of mucosal alterations that are observed only with no sense of their biological nature. The brush biopsy is such a modality that bridges the gap between visual acknowledgment and scalpel biopsy, the latter being arguably the “gold standard.” Finally, the statement that nine authors who have previously published in peerreviewed journals, including JADA, are “associated with the company that offers the service” is patently untrue. Blatantly implied is a relationship in which there was financial incentive in place in the form of an honorarium for authoring these publications. Lectures across the country have been given by many of my esteemed and respected colleagues in which the rationale and basis for the use of the brush biopsy as a clinical tool has been explained in updates on mucosal diseases/leuko-
JADA, Vol. 133, June 2002 Copyright ©2002 American Dental Association. All rights reserved.
689