Professional Documents
Culture Documents
and Cytology
Joel L. Schwartz, D.M.D., D.M.Sc.
Director of Oral Maxillofacial Pathology
University of Illinois at Chicago
College of Dentistry
New Directions
The future of oral and pharyngeal cancers
is prevention
New screening techniques are progressing
that allow researchers to evaluate the risk
prior to developing lesions
Oral cytology testing using cells from the
tongue is both cost-effective and accurate
Researchers from UCLA report early
success using saliva to detect oral cancer
Damage to DNA
DNA Repair
Oral Cancer
Cell
Laboratory
Studies
Pre-Clinical
Oral Cancer
Model
Clinical
Translational
Early
Screening
Studies
Approach:
Test hypothesis for initial markers following
exposure to carcinogen in human oral
keratinocytes
Further evaluate markers during low dose oral
carcinogenesis and inhibition
Investigate expression of markers in at risk
populations for oral cancer (e.g., smokers)
Human Papillomavirus
Estimated: 35-55% of
oral cancers positive for
HPV
70 subtypes documented
High Risk
Types:
16,18
Lower Risk:
6,11,31
No Cancer
Oral Cancer
Finger-like
projections with
fibrovascular core
No oral cancer
formation
HPV
HPV
PAH
PAH
PAH
PAH
Conclusions
The combination of HPV 16,18
infection and treatment with low doses
of environmental and/or tobacco
carcinogens is capable of changing a
non-cancer cell into a cancer cell
Pre-Clinical Oral
Cancer Model
and Inhibition of Oral
Carcinogenesis
Tobacco Carcinogens
Later Events
Promotion
Cancer Formation
Clinical Translational
Early Screening Studies
We need to:
Screen before a lesion is observed
Change behavior
Provide prevention treatment
cytology smear
-42% were ever taught how to do a smear
-96.9 % of dental offices lack necessary
materials
Horowitz, et. al. JADA:131: 453-462, 2000
Determination of Malignancy
Evaluation of current lesion for malignancy
-analysis dependent on nuclear staining, pap
stain, toluidine blue, feulgen stain
-morphology-nuclear cytoplasmic ratio, bizarre
mitoses, micronuclei
Lack of specific genetic and molecular markers
NEED TO:
Combine current genetic and molecular
markers with the advantages of oral
cytology.
Screen for the risk for cancer before the
presence of a lesion.
Oral Cells
From Brush
Flow Cytometric
Analysis
1. DNA
Content-Ploidy
2. Cell Cycle,Apoptosis,
etc.
SIGNIFICANCE TO EXTENDED
ORAL CYTOLOGY METHODS
Non-invasive
Low cost
Sensitive
Reliable
Consistent
HIGH CORRELATION TO RISK (requires more
study)
Relevant to risk for other tobacco cancers (e.g.,
Lung, bladder, etc.)
Non-smoker
8-OHdG Detection
(60-70%Nucleated)
Smoker
(90-95%Nucleated)
(3)Smoker
(3) Non-smoker
Mean %
44.26
3.14
Conclusion
Oral cytology which is relatively noninvasive, and low cost can provide a
genetic and molecular survey approach
of various markers linked to increased
risk for oral cancer
A base line of genetic and molecular
status can be obtained before a lesion is
observed. This information can be
associated with disease risk.
Prevention methods such as tobacco
control and chemoprevention can be
tested
Future Studies
Oral cytology validation requires further
study with a larger population of smokers,
former smokers, and non-smokers.
Development of novel approaches to regulate
tobacco carcinogen metabolism by controlling
oral bacteria
Synthesize novel chemoprevention agents
Molecular manipulation of proteins that block
carcinogen DNA damage
Future Studies
UCLA researchers report they can
measure elevated levels of four distinct
cancer-associated molecules in saliva and
distinguish with 91% accuracy between
healthy individuals and those diagnosed
with SCC using mRNA
Highlights the potential clinical value of
saliva as a diagnostic biofluid
http://www.nidcr.nih.gov/NewsAndReports/NewsRelease12202004.htm