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 QUIT-YES or

Statistics Of The Adult Population Who Smoke The percentage of women who smoke has increased 300% in the last 50 years.  The percentage of women who smoke has increased 300% in the last 50 years.  Male to female ratio in 1950 was 6 to 1; today the ratio is 2 to 1.

Current* Cigarette Smoking Prevalence (%), by Gender and Race/Ethnicity, High School Students, US, *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.

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 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 by- product, which is an animal carcinogen (NIDCR, 2004) A combination of both alcohol and tobacco provides the greatest risk of oral cancer.  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 Plummer- Vinson 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  2/3 rds 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 Environmental Factors Virus Diet DNA Damage Oral Leukoplakia [White Lesions] Erythroplakia [Red Lesions] Premalignant Oral Carcinoma Malignant DNA Repair DNA Content Cell Growth Apoptosis

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

B[a]P-N 2 - dG Adducts 8-OH-dG Adducts

Cyclin D1Caspase-3 p53 DNA (aneuploid) Content Cell Cycle and Apoptosis Markers Tumor Suppressor DNA Content

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 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