1. Module 4: Screening and Diagnosis

2. Diagnosis Definitive diagnosis of oral cancer must be confirmed by scalpel biopsy and histological assessment Without a biopsy, many lesions cannot be assessed as dysplasia, precancer, cancer, or something else

3. Types of Biopsy Scalpel biopsy –Excisional biopsy –Incisional biopsy Fine-needle aspiration biopsy

4. Screening Tools Assist in decision to proceed with scalpel biopsy Tools available include: –tolonium chloride (toluidine blue) –exfoliative cytology ® –OralCDx ® brush biopsy ® –ViziLite ®

5. OralCDx ® brush biopsy Computer-assisted analysis of oral brush biopsy Evaluate benign appearing lesions High accuracy ADA “Seal of Acceptance” Does not replace scalpel biopsy

6. OralCDx ® brush biopsy Image used with permission from Dr. Jane Eisen, DDS, OralCDx, CDx Laboratories, 2004

7. OralCDx ® Kit Kit contents: Oral brush biopsy instrument Precoded glass slide Matching coded test requisition form Alcohol/carbowax fixative pouch Prepaid mailer

8. OralCDx ® brush biopsy Steps: –Place brush against lesion –Rotate brush 10 times (bleeding) –Transfer cellular material to slide –Immediately apply fixative –Allow slide to air dry –Place slide in prepaid mailing container –Mail specimen to laboratory

9. Brush placement Image used with permission from Dr. Jane Eisen, DDS, OralCDx, CDx Laboratories, 2004

10. Slide Preparation Immediately spread on slide Rotate brush- spread material along entire slide Use all fixative Air dry 20 minutes Image used with permission from Dr. Jane Eisen, DDS, OralCDx, CDx Laboratories, 2004

11. OralCDx ® Results No cellular abnormalities Definitive cellular evidence of epithelial dysplasia or carcinoma Abnormal epithelial changes warranting further investigation Negative: Positive: Atypical:

12. OralCDx ® Report Atypical or positive reports include color images of cellular abnormalities and written pathologist’s report Image used with permission from Dr. Jane Eisen, DDS, OralCDx, CDx Laboratories, 2004

13. OralCDx ® study Data from 150,000 patients 100 harmless appearing lesions that would not have been tested 1 positive lesion; 14 atypical lesions All 14 atypical lesions underwent scalpel biopsy, of which 8-10 were negative Resulted in 15 early referrals for lesions that would otherwise have been watched or ignored. Svirsky et al. General Dentistry 2002

14. Positive Predictive Value ®Probability that patient with OralCDx ® atypical result will be confirmed with precancer or cancer by scalpel biopsy = positive predictive value ®PPV of OralCDx ® = 38% in this study PPV of atypical mammogram = 2.6-16% PPV of atypical Pap smear = 7-20% Svirsky et al. General Dentistry 2002

15. ViziLite ® ®ViziLite ® is an oral cancer screening tool marketed by Zila Pharmaceuticals ®ViziLite ® is NOT a diagnostic tool It is a screening device that may help the clinician more easily visualize suspicious lesions

16. ViziLite ® Kit Kit contents: –Chemiluminescent device –30 ml acetic acid –Light stick holder/retractor Image used with permission from Dr. Mark Bride, DDS, ViziLite, Zila Pharmaceuticals, 2004

17. ViziLite ® Procedure Steps: –Patient rinses with 1% acetic acid for 1 minute –Activate device by bending outer capsule to break inner vial –Shake capsule to mix contents –Insert capsule into retractor unit –Dim room lighting –Visually inspect oral cavity using device –Discard materials

18. How ViziLite ® Works Normal epithelium absorbs the light and appears dark Abnormal tissue reflects light and appears bright white Images used with permission from Dr. Mark Bride, DDS, ViziLite, Zila Pharmaceuticals, 2004

19. Tolonium Chloride Toluidine blue Phenothiazine Metachromatic dye Stains nuclear DNA 1% aqueous solution followed by 1% acetic acid to decolorize lesion Abnormal tissue retains the blue dye

20. Tolonium Chloride A large study by Epstein, Feldman, Dolor and Porter found tolonium chloride to be more sensitive than clinical examination alone in detecting carcinoma or carcinoma in situ. They did not find an excessive number of false positives, as has been raised by other researchers. Epstein, Feldman, Dolor & Porter (2003) Head & Neck 25(11): 911-921.

21. OraTest ® Zila Pharmaceuticals, Inc.

22. Exfoliative Cytology Microscopic examination of cells Spread on slide Fixed Stained

23. Exfoliative Cytology Image used with permission from Dr. Mark Bride, DDS, ViziLite, Zila Pharmaceuticals, 2004

24. Imaging Diagnosis of oral cancer usually by surgical or fine needle biopsy. Imaging techniques are used to determine the extent of the disease and detect recurrent disease following therapy

25. Imaging Techniques CT: Computed tomography MRI: Magnetic resonance imaging PET: Positron emission tomography

26. Referral Sites Where do you refer a patient if oropharyngeal cancer is suspected? –Oral surgeons –Oral pathologists –Otolaryngologists –Head and neck cancer centers

27. National Cancer Institutes Cancer Centers Illinois: University of Chicago Cancer Research Center Comprehensive Cancer Center Chicago, IL Robert H. Lurie Cancer Center Comprehensive Cancer Center Northwestern UniversityMissouri: Washington University School of Medicine Siteman Cancer Center – Clinical Cancer Center St. Louis, MO **accepts Illinois Medicaid patients

28. National Cancer Institutes Cancer Centers Indiana: Purdue University Cancer Center West Lafayette, IN Indiana University Cancer Center Clinical Cancer Center Indianapolis, INWisconsin: University of Wisconsin Comprehensive Cancer Center Madison, Wisconsin

29. Summary Diagnosis must be by scalpel biopsy Tools can assist in detection Tools can help determine when a scalpel biopsy is warranted Referral to head and neck cancer centers is critical