Module 2:
Risk Factors and
Prevention
Major Risk Factors for
Oral Cancer are:
 Tobacco use
 Alcohol use
 Age over 40
Additional Risk Factors Linked
To Oral Cancer Include:









Exposure to UV radiation
Human Papilloma Virus (HPV)
Nutritional deficiencies
Oral lichen planus
Immuno-supression
Syphilis
Marijuana use
Chronic irritation
Chronic candidiasis
Tobacco Use
The risk of oral cancer increases with the
amount of tobacco used and the
duration of the habit.
All tobacco types are associated with oral
cancer, for example:
-cigarettes
-cigars
-pipes
-quid
-snuff
-chew
Tobacco Risks
 90% of patients with oral cancer use tobacco
 Smokers have 6 times greater risk of developing
oral cancer than nonsmokers.
 Tobacco users who regularly use alcohol are at
greatest risk
Tobacco and Cancer Recurrence
According to the ACS (2004):
 37% of patients who smoke after a first oral
cancer will develop another in the
oropharyngeal area.
 Chances are that only 6% of these patients will
develop another cancer if they stop smoking
 Illinois Department of Public Health (IDPH) Toll
Free Tobacco Quit Line is 1-866-QUIT-YES or
1-800-784-8937
Statistics Of The Adult
Population Who Smoke
DISTRIBUTION OF THE ADULT
POPULATION BY GENDER
Women
80%
 The percentage of
women who smoke has
increased 300% in the
last 50 years.
60%
40%
Men
20%
WOMEN
MEN
DISTRIBUTION OF ADULT
POPULATION
Smoke
0%
SMOKE
23%
DO NOT
Male to female ratio in 1950
was 6 to 1; today the ratio is
2 to 1.
Smoke
Do Not
Do Not
77%
Current* Cigarette Smoking Prevalence
(%), by Gender and Race/Ethnicity, High
School Students, US, 1991-2001
50
1991
40
Prevalence (%)
40
32
40
39
40
37
1995
1997
30
2001
38
33
31
1999
33
35 36 34
32 32
30
28
28 28
26
22
20
17
18
23
16
13
11 12
27
14
10
0
White, nonHispanic Female
White, nonHispanic Male
African
African
Hispanic Female
American, non- American, nonHispanic Female Hispanic Male
*Smoked cigarettes on one or more of the 30 days preceding the survey.
Source: Youth Risk Behavior Surveillance System, 1991, 1995, 1997, 1999, 2001, National Center for
Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 2002.
Hispanic Male
Risks From
Smokeless Tobacco
 Long term snuff users face 50 times
the risk of cheek and gum cancer.
 ¾ of the daily users of moist snuff and
chewing tobacco have non-cancerous
or pre-cancerous lesions in the mouth.
 Smokeless tobacco (8-10 times a
day) are exposed to the same nicotine
as 30-40 cigarettes a day (ACS, 2004)
Cigars Not A Safer Alternative
 Cigar smoking has increased among young and middle-aged
white men (18-44) (higher than average incomes and
education.)
 CDC reports cigar use among adolescents is higher than
smokeless tobacco.
 Risk of laryngeal, oral or esophageal cancer is 4-10 times
higher than non smokers.
 Cigar smokers who inhale deeply are 6 times more likely to
die from oral cancer and 39 times more likely to die from
laryngeal cancer (ACS, 2004).
Alcohol And Oral Cancer
 75 – 80% of all patients with oral cancer drink
alcohol frequently
Alcohol may act as a solvent and allow
carcinogens from tobacco to more easily enter
oral tissues
Alcohol produces acetaldehyde as a byproduct, which is an animal carcinogen (NIDCR,
2004)
A
combination of both alcohol and
tobacco provides the greatest risk of
oral cancer.
Tobacco And Alcohol:
Deadly Combination
 It is estimated that
tobacco smoking and
alcohol drinking
combined account for
approximately ¾ of all
oral and pharyngeal
cancers in the U.S.
(ACS, 2004)
Age And Oral Cancer

95% of oral cancers occur in individuals over age
40, and the average age of diagnosis is in the 60s
 Because
1/3 of the U.S. population is now over
age 45, oral cancer will be a significant problem in
upcoming years

Changes in biochemical and biophysical
processing occur in aging cells

Chemicals, viruses, hormones, nutrients, and
physical irritants further affect aging cells, and may
contribute to the development of oral cancer
Silverman, 1999
Race And Genetics
 Link unclear
 African-Americans have higher rates than other groups
 Genetic factors may be at work
 Differences in lifestyles and habits also have an impact
 Differences in
access to care,
tendency to seek medical and dental care, and
education levels most likely contribute to higher rates
of later diagnosis of oral cancer (Silverman, 1999)
 Mutation of the p53 gene under investigation (damage to
cell’s DNA, growth and division)
Gender And Oral Cancer
 Oral cancer occurs more than twice as often in
males
 The ratio of male to female cases was 6:1 in
1950; today is about 2:1
 One reason for the reduced ratio is the
enormous increase during the past 50 years in
females who smoke
Gender And Oral Cancer
 The lifespan of women is
longer and may contribute
to the increase in oral
cancer among women
 The number of women
over age 65 exceeds that
of men by nearly half
Ultraviolet Light
& Lip Cancer
 UV exposure contributes to lip cancer
 Fair skinned individuals at higher risk
 30% of lip cancers occur in those with prolonged exposure
to sunlight
 Lip cancer decreasing due to lip balm w/ sun screen
 Lip cancer is also seen in pipe smokers at the site where the
pipe stem is held
 Lip cancers readily seen
 More likely to be diagnosed at earlier, treatable stage
Diet And Oral Cancer
 Nutritional deficiencies implicated as risk
factor
 Diet low in fruits & vegetables implicated in
cancers of mouth, larynx, and esophagus
 Diet low in vitamin A has been linked to oral
cancer in some studies
 Iron deficiency associated with PlummerVinson syndrome causes an elevated risk for
squamous cell carcinoma of the esophagus,
oropharynx and posterior mouth (Regezi &
Scuiba, 1999).
Viruses
 Human papilloma virus (HPV) and herpes simplex
(HSV) may play a role in oral cancer development
 2/3rds of oral cancers have HPV DNA in their cells
 DNA from Epstein-Barr, cytomegalovirus, herpes
simplex, and HVP detected in oral cancer
biopsies (NIDCR, 2004)
 Viruses contribute to the oral cancer
transformation in the presence of other
contributing factors
Oral Lichen Planus
Wickham striae, or interconnecting white lines,
are common in reticular lichen planus.
Lesions are usually on the buccal mucosa, but
the tongue and gingiva may also be affected.
 Lesions may be erosive with
pseudomembrane-covered ulcerations and
erythema.
Oral Lichen Planus
 Findings from various studies indicate a risk
of malignancy, particularly in the
erythematous areas of the erosive form.
 Lichen planus is not presently classified as
precancerous, but further definitive studies
may prove otherwise.
 A close examination of Lichen planus lesions
in patients with the disease is prudent.
Immunosupression

Persons with AIDS and those undergoing
immuno-supression for organ or bone marrow
transplantation may be at increased risk for
various oral, head, and neck malignancies
(Neville, et al. 1995)
 AIDS patients usually develop Kaposi sarcoma
and lymphoma, rather than squamous cell
carcinoma (Sapp, Eversole, and Wysocki, 1997)
Chronic Irritation
 Irritation
may be caused by ill-fitting
dentures and broken teeth or fillings
 Chronic
irritation does not initiate oral
cancer, but it is possible it may hastens
its progress
 The
debate as to chronic irritation as a
risk factor is ongoing
Candidiasis
Chronic candidiasis has been implicated as a risk
factor in oral cancer.

 Certain strains of Candida Albicans produce
nitrosomines, which are carcinogenic.
 Definitive studies have not proven candidiasis
infection to be a causative agent, but it may have the
potential to promote the development of oral cancer.
Candidiasis may be superimposed upon a preexisting
leukoplakia.
Relationship Between Cell Events and
Lesion Appearance
DNA
Adducts
Smoking
DNA Damage
DNA Repair
Cell Growth
DNA Content
Apoptosis
Environmental
Factors
Virus
Diet
Premalignant
Oral Leukoplakia [White Lesions]
Erythroplakia [Red Lesions]
Oral Carcinoma
Malignant
State of Prevention Science
• Discontinue smoking and alcohol consumption
(health professional/patient)
• Head and neck examination (health professional)
• Medical history (health professional)
• Improve diet: fruits and vegetables (health
professional/patient)
Other Factors that Play a Role in
Prevention:
•
Genetics
•
Oral health
•
Sexually transmitted infections
Discontinuing Smoking and
Alcohol Consumption
•Tobacco Control•counseling
•behavior modification
(dentist/patient/specialist)
•Referral to other health practitioners•Oral Medicine
•Oral Maxillofacial Pathology
•Diet•Nutritional counseling
Oral Cancer Examinations
 Obtain annual oral cancer examinations
after age 40
 Ask medical and dental providers for an
annual examination
Tobacco
 Tobacco cessation should be
recommended to all patients who use
tobacco products.
 The accompanying Tobacco Control
Program will provide you with tobacco
cessation techniques to use with your
patients.
Alcohol
 People who drink alcohol and don’t use tobacco
are at a greater risk for oral cancer, but the
combination of the two is most deadly.
 Most oral cancers could be prevented if people
quit using tobacco in any form and quit heavy
drinking.
 Quitting tobacco and limiting alcohol use sharply
reduces any risk of oral cancer, even after many
years of use.
Nutrition
 Consume a diet high in fiber
 Consume enough folic acid, vitamins and
minerals
 Eat at least five servings of fruits and
vegetables daily
 Provide nutritional supplements for
individuals unable to intake adequate
quantities of food
Alternative Cancer Treatments for Oral
Cancer Prevention and Treatment
Retinoids have been used
to:
•Prevent premalignant
oral lesions
•Reduce the growth of
established oral
carcinoma
•Reduce formation of
second primary oral
cancer
•Vitamin E has been shown to:
-prevent oral premalignant lesions
-enhance the anti-oral tumor capacity of
chemotherapy and other agents
-block the cancer formation activity of
tobacco carcinogens
•Vitamin E and PAH both form complexes
which modify Phase I and II enzyme genes
expression and expression of endocrine
factors
DNA Damage
Decreased
DNA Repair Increased
then Decreased
DNA Content
Decreased
Apoptosis
Increased
Fewer Smaller
Oral Tumors
Green Tea Effect on Smokers
Compared to Non-Smokers
Molecular and cellular effects of green
tea on oral cells from smokers: A pilot
study.
Schwartz JL, Vikki B, Larios E, and
Chung FL.
Molecular Nutrition and Food Research.
In Press, 2004.
Background For Green Tea Study
• 80 articles published showing green tea offers
protection against tumorigenesis including initiation,
promotion and progression (skin, lung, liver, mammary,
colon).
• Green tea contains-antioxidant, ”polyphenolics” (e.g.,
epigallocatechin gallate (EGCG)).
• Studies in animals and cells point to a mechanism that
involves p53 induction of apoptosis.
• Delivery of tea polyphenols through a drink, leaves or
extract has suggested possible delivery systems to
reduce risk for oral cancer formation
35
30
25
% of Cells
B[a]P-N2dG
Adducts
smoker 3
20
smoker 2
15
smoker 1
10
5
0
w eek 0
w eek 1
w eek 2
w eek 3
w eek 4
Weeks of Treatm ent
100
Adducts
80
% of cells
8-OH-dG
smoker 1
60
smoker 2
40
smoker 3
20
0
week week week week week
0
1
2
3
4
Weeks of Treatment
Cyclin D1
30
Caspase-3
smoker1
smoker2
smokers3
20
10
0
w
ee
k
w 0
ee
k
w 1
ee
k
w 2
ee
k
w 3
ee
k
w 4
ee
k
w 0
ee
k
w 1
ee
k
w 2
ee
k
w 3
ee
k
4
Cell Cycle
and
Apoptosis
Markers
% of Cells
40
DNA
(aneuploid)
Content
p53
smoker1
smoker2
Weeks of Treatment
4
3
w
ee
k
2
w
ee
k
1
w
ee
k
0
w
ee
k
4
w
ee
k
3
w
ee
k
2
w
ee
k
1
ee
k
w
w
ee
k
0
smokers3
ee
k
DNA Content
45
40
35
30
25
20
15
10
5
0
w
Tumor
Suppressor
% of Cells
Weeks of Treatment
Green Tea Study Summary
•Oral cytology in conjunction with
“chemoprevention” agents can be used to
monitor specific molecular events on a
continuous basis.
•Green tea polyphenols in some smokers can
reverse the effects of exposure to tobacco
smoke
(e.g., cell proliferation is slowed and
increased apoptosis is noted).
Limit Sun Exposure
 To help prevent lip cancer:
- Use lip balm containing sun screen
- Use wide-brimmed hats
- Avoid outdoor activities in midday when
ultraviolet exposure is at its peak
Report These Signs or
Symptoms to Doctor or Dentist:
 A sore or area in the mouth that does not heal
after 2 weeks
 Persistent pain in the mouth
 Persistent lump or thickening in the cheek
 Sore throat or feeling that something is caught
in the throat
 Difficulty chewing or swallowing
 Difficulty moving the jaw or tongue
 Voice changes
Additional Signs and Symptoms:
 Numbness in the tongue or other mouth area
 Swelling in the jaw that causes dentures to fit
poorly or become uncomfortable
 Loosening of the teeth or pain around the teeth
or jaw
 Lump or mass in the neck
 Weight loss (unexplained)
 Persistent bad breath
Role for the Health Professional
• Screen patients at risk
• Provide dental care to improve response to
cancer treatment
• Treat oral complications
• Provide referral to other specialists
Prevention A Key Role for the
Health Professional
• Health professionals will use oral cells to
- Screen for an array of genetic and molecular
disorders
- Assess prevention of tobacco related cancers
by various agents
- Evaluate environmental carcinogens
Summary
 Major risk factors are tobacco and alcohol
 Sun is a major risk factor for lip cancer
 Other factors contribute to a lesser extent,
but studies are ongoing
 Prevention includes controlling tobacco
and alcohol use, UV exposure, nutrition,
and annual oral cancer exams
 Awareness of the common signs and
symptoms is important for everyone