Module 4:
Screening and
Diagnosis
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
Types of Biopsy
• Scalpel biopsy
–Excisional biopsy
–Incisional biopsy
• Fine-needle aspiration biopsy
Screening Tools
• Assist in decision to proceed with
scalpel biopsy
• Tools available include:
– tolonium chloride (toluidine blue)
– exfoliative cytology
– OralCDx® brush biopsy
– ViziLite®
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
OralCDx® brush biopsy
Image used with permission from Dr. Jane Eisen, DDS, OralCDx, CDx Laboratories, 2004
®
OralCDx
Kit contents:
• Oral brush biopsy
instrument
• Precoded glass slide
• Matching coded test
requisition form
• Alcohol/carbowax
fixative pouch
• Prepaid mailer
Kit
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
Brush placement
Image used with permission from Dr. Jane Eisen, DDS, OralCDx, CDx Laboratories, 2004
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
OralCDx® Results
Negative:
No cellular abnormalities
Positive:
Definitive cellular evidence of
epithelial dysplasia or
carcinoma
Atypical:
Abnormal epithelial changes
warranting further investigation
®
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
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
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
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
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
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
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
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
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.
OraTest®
Zila Pharmaceuticals, Inc.
Exfoliative Cytology
•
•
•
•
Microscopic examination of cells
Spread on slide
Fixed
Stained
Exfoliative Cytology
Image used with permission from Dr. Mark Bride, DDS, ViziLite, Zila Pharmaceuticals, 2004
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
Imaging Techniques
• CT: Computed tomography
• MRI: Magnetic resonance imaging
• PET: Positron emission tomography
Referral Sites
• Where do you refer a patient if
oropharyngeal cancer is suspected?
– Oral surgeons
– Oral pathologists
– Otolaryngologists
– Head and neck cancer centers
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 University
Missouri:
Washington University School of Medicine
Siteman Cancer Center – Clinical Cancer Center
St. Louis, MO
**accepts Illinois Medicaid patients
National Cancer Institutes Cancer
Centers
Indiana:
Purdue University Cancer Center
West Lafayette, IN
Indiana University Cancer Center
Clinical Cancer Center
Indianapolis, IN
Wisconsin:
University of Wisconsin
Comprehensive Cancer Center
Madison, Wisconsin
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