CE Course. Oral Cancer Detection: The Role of Adjunctive Technology

Transcription

1 Oral Cancer Detection: The Role of Adjunctive Technology CE Course Written by Denis P. Lynch, D.D.S., Ph.D. Educational Objectives 1. Know the incidence of oral cancer in the United States and understand the risk factors 2. Understand screening methods available for the detection of oral cancer 3. Understand the role of chromosomal aberrations in the risk of malignant transformation Abstract In the United States in 2007, over 34,000 new cases of oral cavity and oropharyngeal cancer will be diagnosed. With a fi ve-year relative survival rate estimated at 59.1% overall during Early detection based on diagnoses of suspicious lesions is increased through regular screening of patients. In recent years, screening technologies have become available that supplement the visual examination. The ultimate goals are to reduce mortality and morbidity, and to improve patients quality of life. Introduction/Overview In the United States in 2007, over 34,000 new cases of oral cavity and oropharyngeal cancer will be diagnosed. During the same time period, over 7,000 affected individuals will die of these cancers. 1 In the United States, the most common sites for oral cancer are the tongue and lip. Risk Factors The single greatest risk factor for oral cancer in the United States is the use of tobacco, with combustible and smokeless tobacco being associated with 75% of all cases of oral cancer. Oral cancer is also six times more likely to develop in alcohol drinkers than in non-drinkers. The combination of tobacco use and alcohol abuse is particularly hazardous, posing a fi fteen-fold risk of oral cancer compared to nonusers. 2 Other factors associated with increased oral cancer risk include ultraviolet radiation (lip exposure) and HIV seropositivity (Table 1). A strong association has been found with the presence of HPV in oral tissues, independent of smoking or drinking habits. 3,4,5 One study of 143 patients found HPV-16, present in 16.8% of head and neck squamous cell carcinomas. 6 A reduced risk of oral cancer has been associated with a high dietary fruit and vegetable intake. 7 10

2 Table 1. Risk factors for oral cancer Risk factors Smoking and/or chewing tobacco Drinking alcohol Betel quid chewing Areca nut use HPV HIV seropositivity Use (abuse) of narcotics Cannabis use Sunlight exposure (lower lip) Previous oral or other cancer Predisposing risk factors Increasing age Male gender Genetics Socioeconomic status Negative association High dietary fruit and vegetable intake Morbidity and mortality Oral cancer is associated with signifi cant morbidity and mortality. The fi ve-year relative survival rate for oral and pharyngeal cancer is estimated at 59.1% overall for cases diagnosed during Survival rates vary with the stage of the disease and site. The best prognosis exists for lip cancer, with a 97% fi ve-year relative survival rate if the tumor is localized and completely excised. Oral cancers in other anatomic sites can be clinically occult and asymptomatic. Fifty percent of tongue carcinomas have metastasized by the time they are diagnosed. 9 Early diagnosis signifi cantly improves the patient s long-term survival and reduces morbidity. The excision of an oral cancer, depending on the site and size of the tumor, can severely compromise the patient s quality of life and in some cases may not even be possible. Initial lesions Preventing disease progression relies on early detection, a diagnosis, and appropriate treatment. Early detection of oral cancer is complicated by the fact that many lesions in their earlier stages may be completely asymptomatic. Clinically, cancerous and pre-cancerous lesions may present as ulcers, leukoplakia, erythroplakia, erythroleukoplakia, soft tissue masses, or other lesions that will not heal even after removal of the presumptive etiology (Figures 1 2). 11

3 Figure 1. Erythroplakia Figure 2. Erythroleukoplakia Leukoplakia, erythroplakia, and erythroleukoplakia (speckled leukoplakia) are clinical terms for white, red, or mixed red/white lesions, respectively, that cannot be wiped off, do not have an obvious clinical diagnosis, and have an unclear etiology. 10 An estimated 85% of oral premalignant and malignant lesions present clinically as leukoplakias 11 and the rate of malignant transformation of leukoplakia is estimated to be 7%, occurring on average seven years following initial diagnosis. 12 Non-homogenous leukoplakia has been found to have a seven times greater risk of malignant degeneration than homogenous leukoplakia. Lesions greater than 2 cm in size had a 5.4 times greater risk of developing malignancy than smaller lesions. 13 In the case of erythroplakias, 70% 14 to 90% 15 have been found to be severely dysplastic or frankly malignant at the time of initial biopsy. The defi nitive diagnosis of oral cancer can only be determined by histopathologic examination of a biopsy specimen and ranges from normal, through varying degrees of dysplasia, to carcinoma-in-situ to invasive malignancy. The detection of suspicious lesions is increased through routine, regular screening of patients. 16 Early detection will result in earlier diagnosis, less aggressive treatment, and decreased need for complicated post-treatment management. Early detection and technology Historically, unaided visual examination, palpation, and radiographs were available for oral cancer screening. Supplemental screening technologies now available that help the clinician identify suspicious lesions include the use of special wavelength lights and chemiluminescence, as well as dyes that selectively stain lesions. Standalone screening devices include the Microlux/DL (AdDent), VELScope (LED Dental, Inc.), and ViziLite and ViziLite Plus (Zila Pharmaceuticals, Inc.). Microlux/DL Microlux/DL is a hand-held device that uses light-emitting diodes (LEDs) as the illumination source. The patient rinses for seconds with 1% acetic acid, and upon illumination the abnormal tissue will appear white ( aceto-white ). 12

4 VELScope VELScope is a hand-held device that emits a blue light to fl uoresce the mucosa. No pre-rinse is required. When exposed to the blue light, normal mucosa emits a pale green autofl uorescence, while abnormal tissue appears dark green to black (Figures 3a, b). Highly infl amed mucosa results in a loss of fl uorescence which may result in a false positive. 17 The VELScope has been found to help delineate the extent of visible lesions, as well as to identify lesions that were diffi cult to appreciate with unaided visual examination. 18 In one study, 12 of 19 VELScope-positive lesions were biopsied and found to exhibit loss of heterozygocity. 19 Figure 3a. Lesion prior to use of VELScope Figure 3b. Appearance following autofl uorescence ViziLite and ViziLite-Plus ViziLite is a hand-held device that emits chemiluminescent light. The patient rinses for seconds with 1% acetic acid and the ViziLite device is used to illuminate the oral cavity. Abnormal areas will appear white ( aceto-white ). The light increases both the brightness and the sharpness of lesions. 20 Chemiluminescence has been found to signifi cantly assist the clinician in identifying white and erythroleukoplakic lesions. In one study of 134 patients, use of ViziLite identifi ed two lesions that were not found by unaided visual examination, one of which was a squamous cell carcinoma of the tongue. 21 Kerr et al. studied 501 patients and ninety-eight lesions found in when ViziLite was used with 77 of these considered suspicious, including six that had been missed with unaided visual examination. 22 The adjunctive use of T-Blue 630 is a feature specifi c to the ViziLite-Plus system. This is the only FDA-cleared device and in-vivo staining system for the marking and identifi cation of oral lesions. After using the ViziLite to identify abnormal aceto-white areas, T-Blue 630 can be used to mark suspicious areas for further evaluation (Figures 4a, b). 23 Figure 4a. Lesion prior to use of T-Blue Figure 4b. Lesion after use of T-Blue 13

5 T-Blue 630 is the brand name for pharmaceutical-grade tolonium chloride, a toluidine blue dye. Generic toluidine blue is not FDA-cleared for human use. Screening protocol Early detection of oral cancer and related premalignancy requires an appropriate screening and diagnosis protocol (Figure 5). All oral structures must be thoroughly examined, and any abnormalities should be recorded on a mouth map. If suspicious lesions are found, the lesion must be biopsied or the patient referred to a specialist for further evaluation. It has been recommended that all adult patients 18 and over be screened annually, 24 even if medical and dental histories elicit no risk factors. Known-risk patients should be screened every six months. Figure 5. Screening and biopsy protocol Medical and Dental History Extra-oral Examination: Visual and Palpation Intra-oral Examination: Unaided Visual Radiographs Palpation Chemiluminescence Autofluorescence T-Blue Clinically Suspicious Lesion No Staining By T-Blue Clinically Suspicious Lesion Staining By T-Blue No Clinically Suspicious Lesion Clinically Suspicious Lesion Biopsy Known Risk: Semi-Annual or More Frequent Screening No Known Risk: Routine Annual Screening Biopsy Malignant Non-Malignant Malignant Treat Non-Malignant Frequent Follow-Up Risk Prediction Treat Frequent Follow-Up Risk Prediction Biopsy protocol The two basic biopsy techniques for defi nitive diagnosis of oral mucosal lesions are incisional biopsy and excisional biopsy. The brush biopsy (CDx) is a less-invasive, preliminary diagnostic tool and may also be useful as an intermittent preliminary diagnostic technique in patients under observation, 25 but is insuffi cient to provide a defi nitive diagnosis. Incisional or excisional biopsy is the standard-of-care for defi nitive diagnosis. 14

6 The ability to predict risk of a benign lesion undergoing malignant transformation could help determine the frequency of follow-up and/or earlier intervention. Risk differentiation and prediction Dysplasia and risk prediction The conventional wisdom is that the more severe a lesion s dysplasia, the more likely it is that it will undergo malignant transformation. A number of recent studies do not support this presumption. 26,27 While dysplasia can be predictive, that is not always the case. 28 Rosin et al. found that forty-seven percent of leukoplakias classifi ed as having either no dysplasia or mild dysplasia developed into a secondary oral malignancy. Primary tumor stage, grade, and location were not signifi cantly associated with the outcome. 29 Chromosomal abnormalities and risk prediction Recent microscopic studies have investigated loss of heterozygocity (LOH) in tumor cells and its potential role as a risk predictor for malignant transformation. LOH has been found to indicate high risk of transformation or conversion to malignancy. In particular, aberrations in the 3p, 9p, and 17p chromosomal arm sites have been implicated as high-risk predictors. 30,31,32,33,34 LOH in multiple chromosome arms, and in particular in 3p and 9p sites, has also been found to be predictive of a secondary malignancy. 35 Summary The importance of routine screening to improve early diagnosis of oral malignancies cannot be overemphasized. It is incumbent upon the clinician to screen all adult patients for oral cancer. Available screening technologies include the use of LED lights, autofl uorescence, chemiluminescence, and the combined use of chemiluminescence and T-Blue 630. Recent advances have shown that the risk of malignant transformation is associated with chromosomal aberrations. The ability to identify lesions and to predict which lesions will undergo malignant transformation would facilitate early diagnosis and subsequent disease management. References 1 American Cancer Society. Available at: Accessed June 15, Oral Cancer Facts. Available at: Accessed July Gillison ML, Shah KV. Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers. Curr Opin Oncol. 2001;13: D Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):

7 5 Rosenquist K. Risk factors in oral and oropharyngeal squamous cell carcinoma: a populationbased case-control study in southern Sweden. Swed Dent J Suppl. 2005;(179): Braakhuis BJM, Snijders PJF, Keune W-JH, Meijer CJLM, Ruijter-Schippers HJ, et al. Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. JNCI J Nat Cancer Inst. 2004;96(13): Pavia M, Pileggi C, Nobile CG, Angelillo IF. Association between fruit and vegetable consumption and oral cancer: a meta-analysis of observational studies. Am J Clin Nutr. 2006;83(5): National Cancer Institute. SEER Cancer Statistics Review Available at: seer.cancer. gov/csr/1975_2004/results_merged/sect_20_oral_cavity. Accessed June 19, Landis S, Murray T, Bolden S, et al. Cancer Statistics, CA Cancer J for Clin. 1998;48(1): Axell T, et al. Oral white lesions with special reference to precancerous and tobacco-related lesions: conclusions of an international symposium held in Uppsala, Sweden, May International Collaborative Group on Oral White Lesions. J Oral Pathol Med. 1996;25(2): Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 2nd ed. Philadelphia: WB Saunders; Silverman S. Oral Cancer. 5th ed. 13 Holmstrup P, Vedtofte P, Reibel J, Stoltze K. Long-term treatment outcome of oral premalignant lesions. Oral Oncol. 2006;42(5): Oral Cavity and Oropharyngeal Cancer. American Cancer Society. Available at: documents.cancer.org/ / pdf. Accessed June 27, Neville B, Damm D, Allen C, Bouquot J. Oral and Maxillofacial Pathology. 2nd ed. Philadelphia: WB Saunders; Carvalho AL, Nishimoto IN, Cali-fano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specifi c analysis of the SEER database. Int. J. Cancer 2005;114: Kois JC, Truelove E. Detecting oral cancer: a new technique and case reports. Dent Today. 2006;25(10):94, Poh CF, Ng SP, Williams PM, Zhang L, Laronde DM, Lane P, Macaulay C, Rosin MP. Direct fl uorescence visualization of clinically occult high-risk oral premalignant disease using a simple hand-held device. Head Neck. 2007;29(1): Poh CF, Zhang L, Anderson DW, Durham JS, Williams PM, Priddy RW, Berean KW, Ng S, Tseng OL, MacAulay C, Rosin MP. Fluorescence visualization detection of fi eld alterations in tumor margins of oral cancer patients. Clin Cancer Res. 2006;12(22): Huber MA, Bsoul SA, Terezhalmy GT. Acetic acid wash and chemiluminescent illumination as an adjunct to conventional oral soft tissue examination for the detection of dysplasia: a pilot study. Quintessence Int. 2004;35(5): Epstein JB, Gorsky M, Lonky S, Silverman S Jr, Epstein JD, Bride M. The effi cacy of oral lumenoscopy (ViziLite) in visualizing oral mucosal lesions. Spec Care Dentist. 2006;26(4): Kerr AR, Sirois DA, Epstein JB. Clinical evaluation of chemiluminescent lighting: an adjunct for oral mucosal examinations. J Clin Dent. 2006;17(3): Epstein JB, Scully C, Spinelli J. Toluidine blue and Lugol s iodine application in the assessment of oral malignant disease and lesions at risk of malignancy. J Oral Pathol Med. 1992;21(4): Joseph BK. Oral cancer: prevention and detection. Med Princ Pract. 2002;11(1S): Kosicki DM, Riva C, Pajarola GF, Burkhardt A, Gratz KW. OralCDx brush biopsy a tool for early diagnosis of oral squamous cell carcinoma. Schweiz Monatsschr Zahnmed. 2007;117(3): Holmstrup P, Vedtofte P, Reibel J, Stoltze K. Long-term treatment outcome of oral premalignant lesions. Oral Oncol May;42(5): Holmstrup P, Vedtofte P, Reibel J, Stoltze K. Oral premalignant lesions: is a biopsy reliable? J Oral Pathol Med. 2007;36(5):

8 28 Scully C, Sudbø J, Speight PM. Progress in determining the malignant potential of oral lesions. J Oral Pathol Med. 2003;32(5): Rosin MP, Lam WL, Poh C, Le ND, Li RJ, et al. 3p14 and 9p21 loss is a simple tool for predicting second oral malignancy at previously treated oral cancer sites. Cancer Res. 2002;62: Tabor MP, Brakenhoff RH, van Houten VMM, Kummer JA, Snel MHJ, et al. Persistence of genetically altered fi elds in head and neck cancer patients: Biological and clinical implications. Clin Cancer Res. 2001;7: Partridge M, Pateromichelakis S, Phillips E, Emilion GG, Ahern RP, Langdon JD. A casecontrol study confi rms that microsatellite assay can identify patients at risk of developing oral squamous cell carcinoma within a fi eld of cancerization. Cancer Res. 2000; 60: Mao L, Lee JS, Fan YH, Ro JY, Batsakis JG, Lippman S. et al. Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment. Nat. Med. 1996;2: Guo Z, Yamaguchi K, Sanchez-Cespedes M, Westra WH, Koch WM, Sidransky D. Allelic losses in OraTest-directed biopsies of patients with prior upper aerodigestive tract malignancy. Clin Cancer Res. 2001;7(7): Nawroz H, van der Riet P, Hruban RH, Koch W, Ruppert JM, Sidransky D. Allelotype of head and neck squamous cell carcinoma. Cancer Res. 1994;54: Rosin MP, Lam WL, Poh C, Le ND, Li RJ, et al. 3p14 and 9p21 loss is a simple tool for predicting second oral malignancy at previously treated oral cancer sites. Cancer Res. 2002;62: Author Profile Denis P. Lynch, D.D.S., Ph.D. Dr. Lynch received his Doctor of Dental Surgery degree from the University of California at San Francisco in He subsequently completed a residency in oral and maxillofacial pathology at the University of Alabama at Birmingham, as well as a Ph.D. in Experimental Pathology. Dr. Lynch is currently Professor of Oral and Maxillofacial Pathology and Associate Dean for Academic Affairs at Marquette University School of Dentistry in Milwaukee, as well as Professor of Dermatology at the Medical College of Wisconsin. He is the author of numerous scientifi c articles and book chapters, as well as the coauthor of The Mouth: Diagnosis and Treatment. Disclaimer Dr. Lynch lectures on oral cancer for Zila Pharmaceuticals, Inc. Acknowledgement Thanks to Dr. Joel Epstein for providing clinical images for use in this article. Reader Feedback We encourage your comments on this or any ADTS course. For your convenience, an online feedback form is available at 17

9 1. In the United States, more than new cases of oropharyngeal cancer will be diagnosed in a. 17,000 b. 26,000 c. 34,000 d. 42, The most common site for oral cancer in patients in the United States is. a. the tongue b. the cheek c. the lip d. a and c 3. The single greatest risk factor for oral cancer in the United States is. a. drinking b. use of tobacco c. use of narcotics d. a and c 4. A reduced risk of oral cancer has been associated with a high dietary fruit and vegetable intake. 5. The overall five-year relative survival rate for oral and oropharyngeal cancer diagnosed between 1996 and 2003 is estimated to be. a. 51.1% b. 59.1% c. 62.3% d. none of the above 6. Leukoplakia is estimated to. a. be found in approximately 15% of adults b. be the clinical presentation in 85% of oral premalignant and malignant lesions c. have a 7% rate of malignant transformation d. b and c 7. Non-homogenous leukoplakia has a greater risk of malignant degeneration than homogenous leukoplakia. Questions 8. The definitive diagnosis of oral cancer can be determined by. a. brush biopsy b. incisional or excisional biopsy c. visual and clinical examination d. all of the above 9. The detection of suspicious lesions is increased through regular screening. 10. Stand-alone oral cancer screening devices currently available include. a. ViziLite Plus b. VELScope c. Ultrascope d. a and b 11. is cleared by the FDA as a stain for the marking of oral lesions. a. Toluidine blue b. Methylene blue c. T-Blue630 d. all of the above 12. Studies have shown that use of ViziLite aids identification of lesions not found with unaided visual examination. 13. Adjunctive use of T-Blue630 can. a. help identify abnormal lesions b. stain tissue pink c. provide a defi nitive diagnosis d. none of the above 14. If a lesion does not stain with toluidine blue and remains clinically suspicious after two weeks,. a. it should still be biopsied b. it does not need to be biopsied c. it should be biopsied if it is still present in six months d. none of the above 15. Known-risk patients should be screened more often than patients with no known risk. 16. A screening protocol should include. a. a medical and dental history b. visual examination c. palpation d. all of the above 17. Rosin et al. found that of leukoplakias in previously treated sites with either no dysplasia or mild dysplasia developed into a secondary oral malignancy. a. 25% b. 38% c. 47% d. 53% 18. Aberrations on certain chromosomal arms have been found to be high-risk predictors of malignant transformation. 19. The clinician should screen all adult patients for oral cancer. 20. The ability to predict lesions at high risk of malignant transformation would. a. facilitate disease management b. be relatively unimportant c. facilitate early diagnosis d. a and c* 18

10 ANSWER SHEET Oral Cancer Detection: The Role of Adjunctive Technology Name: Title: Specialty: Mailing Address: Address: City: State: ZIP: Telephone: Home ( ) Office ( ) Requirements for successful completion of the course and to obtain dental continuing education credits: 1) Read the entire course.2) Complete all information above. 3) Complete answer sheets in either pen or pencil. 4) Mark only one answer for each question. 5) A score of 70% on this test will earn you 2 CE credits. 6) Complete the Course Evaluation below. 7) Make check payable to The Academy of Dental Therapeutics and Stomatology OR PennWell Corp. Educational Objectives 1. Know the incidence of oral cancer in the United States and understand the risk factors 2. Understand screening methods available for the detection of oral cancer 3. Understand the role of chromosomal aberrations in the risk of malignant transformation Course Evaluation Please evaluate this course by responding to the following statements, using a scale of Excellent = 5 to Poor = Were the individual course objectives met? Objective #1: Yes No Objective #3: Yes No Objective #2: Yes No 2. To what extent were the course objectives accomplished overall? Please rate your personal mastery of the course objectives Mail completed answer sheet to Academy of Dental Therapeutics and Stomatology P.O. Box 116, Chesterland, OH or fax to: (440) For IMMEDIATE results, go to and click on the button Take Tests Online. Answer sheets can be faxed with credit card payment to (440) , (216) , or (216) Payment of $24.00 is enclosed. (Checks and credit cards are accepted.) If paying by credit card, please complete the following: MC Visa AmEx Discover Acct. Number: Exp. Date: Charges on your statement will show up as Pennwell 4. How would you rate the objectives and educational methods? How do you rate the author s grasp of the topic? Please rate the instructor s effectiveness Was the overall administration of the course effective? Do you feel that the references were adequate? Yes No 9. Would you participate in a similar program on a different topic? Yes No 10. If any of the continuing education questions were unclear or ambiguous, please list them. 11. Was there any subject matter you found confusing? Please describe. 12. What additional continuing dental education topics would you like to see? AGD Code 734, 739 PLEASE PHOTOCOPY ANSWER SHEET FOR ADDITIONAL PARTICIPANTS. AUTHOR DISCLAIMER Dr. Lynch lectures on oral cancer for Zila Pharmaceuticals, Inc. SPONSOR/PROVIDER This course was made possible through an unrestricted educational grant. No manufacturer or third party has had any input into the development of course content. All content has been derived from references listed, and or the opinions of clinicians. Please direct all questions pertaining to the ADTS or the administration of this course to Machele Galloway, 1421 S. Sheridan Rd., Tulsa, OK or macheleg@pennwell.com. COURSE EVALUATION and PARTICIPANT FEEDBACK We encourage participant feedback pertaining to all courses. Please be sure to complete the survey included with the course. Please all questions to: macheleg@pennwell.com. INSTRUCTIONS All questions should have only one answer. Grading of this examination is done manually. Participants will receive confirmation of passing by receipt of a certificate. Certificates will be mailed within two weeks after taking an examination. EDUCATIONAL DISCLAIMER The opinions of efficacy or perceived value of any products or companies mentioned in this course and expressed herein are those of the author(s) of the course and do not necessarily reflect those of the ADTS. Completing a single continuing education course does not provide enough information to give the participant the feeling that s/he is an expert in the field related to the course topic. It is a combination of many educational courses and clinical experience that allows the participant to develop skills and expertise. COURSE CREDITS/COST All participants scoring at least 70% (answering 14 or more questions correctly) on the examination will receive a certificate verifying 2 CE credits. The formal continuing education program of this sponsor is accepted by the AGD for Fellowship/Mastership credit. Please contact ADTS for current term of acceptance. Participants are urged to contact their state dental boards for continuing education requirements. The cost for courses ranges from $24.00 to $ Many ADTS self-study courses have been approved by the Dental Assisting National Board, Inc. (DANB) and can be used by dental assistants who are DANB Certified to meet DANB s annual continuing education requirements. To find out if this course or any other ADTS course has been approved by DANB, please contact DANB s Recertification Department at FOR-DANB, ext RECORD KEEPING The ADTS maintains records of your successful completion of any exam. Please contact our offices for a copy of your continuing education credits report. This report, which will list all credits earned to date, will be generated and mailed to you within five business days of receipt. CANCELLATION/REFUND POLICY Any participant who is not 100% satisfied with this course can request a full refund by contacting the Academy of Dental Therapeutics and Stomatology in writing by the Academy of Dental Therapeutics and Stomatology 19