Epidemiology is the branch of science that studiesdisease as it appears in its natural surroundings andas it affects a community of people. Epidemiologicstudies yield important information such as the ori-gin, relative prevalence, and trends of certain dis-eases; they can also furnish etiologic clues. By ana-lyzing blood samples, molecular epidemiologistsare able to assess cancer risks arising from interac-tions of genes and lifestyles. It may be that inheri-tance of certain gene variants (polymorphisms)might increase the likelihood of developing cancer,depending on environmental exposures. The data, inturn, aid in determining appropriate and optimaldirections of health care services, prevention strate-gies, research, and resources.

INCIDENCE

Globally, oral and pharyngeal cancer is the sixthleading cancer site.1 More than 1.2 million new can-cers of all sites (excluding skin) will be diagnosedin the United States each year. Cancers of the lips,tongue, floor of the mouth, palate, gingiva, alveolarmucosa, buccal mucosa, and oropharynx willaccount for approximately 30,000 of these cases (anincidence of about 10 per 100,000). If other headand neck sites (nasopharynx, hypopharynx, larynx,sinuses, and major salivary glands) are includedwith the oral sites, then cancers of all of these sitescombined will account for about 4% of all cancersdiagnosed yearly in the United States. Cancer nowstrikes approximately 1 of every 3 Americans and 3 of every 4 families. It is estimated that more than85 million Americans now living will some daydevelop cancer.

HISTOLOGIC TYPES

Carcinomas account for about 96% of all oral can-cers and sarcomas for about 4%. The most commontype of oral cancer is squamous cell carcinoma,which develops from the stratified squamous epithe-lium that lines the mouth and pharynx. This form ofcancer accounts for approximately 9 of every 10 oralmalignancies. Thus, the oral cancer problem primar-ily concerns the diagnosis, biology, and manage-ment of squamous cell carcinoma.

AGE AND SEX

Of all of the factors that may contribute to the devel-opment of cancer, age is the factor that confers thehighest risk. Oral cancer, like most cancers, is a dis-ease of older age. About 95% of all oral cancersoccur in persons over 40 years old, and the averageage at the time of diagnosis occurs as individualsapproach the age of 65. The importance of this fac-tor in cancer prevalence is augmented because theover 65 population in the United States nowexceeds 36 million, or about 13% of the population.

The over 65 population is expected to continu-ally increase, possibly reaching 20% of the total USpopulation by 2030. Furthermore, the increase in thepopulation over age 65 has far exceeded that of therest of the population in the last decade, and, at pre-sent, more than one-third of the American people areover the age of 45. The average life expectancy ofAmericans is at an all-time high, exceeding74 years, and the age-adjusted death rate is at an all-time low. White women have the longest lifeexpectancy (79 years), followed by black women

1

1EpidemiologySOL SILVERMAN JR., MA, DDS

2 ORAL CANCER

(73 years), white men (72 years), and black men(64 years). A past study of 3,535 consecutive autop-sied patients over 65 years of age showed that 1,149(32.5%) had one or more cancers.

Having said all of this, evidence is emerging thatoral cancers are occurring more frequently inyounger persons (under 40 years).2 Reports indicatethat the tongue is the most common site, and envi-ronmental/lifestyle risk factors, for example,tobacco use, disease, and immunosuppression, donot seem to account for these cancers.3,4 Studies arebeing designed in an attempt to epidemiologicallyconfirm the incidence and possibly explain a proba-ble genetic-environmental influence.

In the United States, more than 50% of all cancersoccur in persons over the age of 65.5 The older age ofcancer patients suggests that a time factor may operate,involving predetermined changes in the biochemical-biophysical processes (nuclear, enzymatic, metabolic,immunologic) of aging cellschanges that may beinfluenced by chemicals, viruses, hormones, nutrients,or physical irritants. Therefore, programmed cell death(apoptosis) can be modified by factors that mayalter cellular production of growth and suppressorproteins. Obviously, over- or underexpression of cellcycleregulating proteins can cause neoplasia.

Of the more than 1.2 million new cancers occur-ring in Americans each year, the number in men andwomen will be about equal. Oral cancer occursmore frequently in males, but the male-to-femaleratio, which in 1950 exceeded 6 to 1, is now slightlyless than 2 to 1. One possible explanation for thisreduced ratio is the great increase in smoking andalcohol consumption among women. In addition,because cancer is an age-related disease, it should benoted that, in the over 65 age group in the generalpopulation, the number of women exceeds the num-ber of men by almost 20%.

Data obtained by the National Cancer Institute inits SEER (Surveillance, Epidemiology, and EndResults) Program, covering the years 1985 to 1996,demonstrate the age-related distribution of oral andpharyngeal cancers (Table 11). During this period,no significant differences have occurred from theprevious decade.6,7 The impact of age is reflectedfurther by the fact that half of all oral cancersoccurred in persons over 65 years of age. This is a

significant rate of 50 cases per 100,000 populationcompared with a rate of 14 cases per 100,000 inthose aged 40 to 65.

SITES

The tongue is the most common site for oral cancerin both American men and women. This is also trueof developed countries. However, in some devel-oping countries, site prevalences differ, owing to dif-ferent habits. For example, nasopharyngeal cancer inSoutheast Asia and buccal cancer in India are themost common oral and pharyngeal sites. As a matterof fact, oral and pharyngeal cancer is one of the threeleading sites of all cancers in that area of the world.

Data from the SEER Program also showed that30% of all oral cancers diagnosed in the United Statesbetween 1985 and 1996 occurred in the tongue, fol-lowed by the lip and floor of the mouth (Table 12).Oral cancer incidence has remained stable, relative tothe occurrence of newly diagnosed cancers of allsites, with absolute numbers only slightly increasingeach year. The only oral site contrary to this trend wasthe lip, in which a reduction occurred over the past10 years. Decades ago, the lip used to be the leadingoral site. This trend may reflect public educationregarding the dangers of ultraviolet light exposure andthe use of sunscreens and hats outdoors. Comparingthe past two decades, the greatest increase in oral can-cer sites occurred in the tongue (26 to 30%). Oraltongue malignancies (located in the anterior two-thirds) accounted for 53% of tongue cancers. Because47% occurred in the base of the tongue, the problems

Table 11. AGE AND GENDER DISTRIBUTION OF ORAL CANCER

(based on 22,449 cases)Age (yr) n % M:F*< 20 130 < 1 1.02039 1,604 7 2.04049 2,432 11 2.55064 7,163 32 2.465+ 11,170 50 1.6

Adapted from the National Cancer Institutes SEER (Surveillance, Epidemiol-ogy, and End Results) Program. Cancers diagnosed and/or treated during1985 to 1996 according to biostatistical information from nine population-based registries in Connecticut, Hawaii, Iowa, New Mexico, Utah, Atlanta,Detroit, San Francisco-Oakland, and Seattle-Puget Sound.*Male-to-female ratio.

Epidemiology 3

regarding recognition of the signs and symptoms andearly diagnosis are apparent.

Patient profiles are further illustrated by findingsin 595 oral cancer patients seen in our oral medicineclinic (Table 13). At the time of diagnosis, just overhalf of the tumors found in the tongue were localized,whereas the greatest number of localized lesionsoccurred in the lip. However, when the tongue wassubdivided into oral and base, a significant differenceemerged: 73% of oral-tongue carcinomas were local-ized, whereas 78% of the malignancies found in thebase of the tongue already had regional metastases atthe time of diagnosis. These facts again emphasize theimportance of accessibility and early diagnosis. Whenthe localized lesions were compared with those asso-ciated with lymph node involvement, it was foundthat the more advanced lesions were associated with alonger delay time before diagnosis. Pain was by farthe most frequent first complaint, with the secondmost common complaint being a lump.

In the United States, the increased male preva-lence of oral cancer appears to be attributable in

great part to the proportionately higher number oflip cancers that occur in men. The preponderance ofcases in men may also be partly accounted for byoutdoor occupations and recreational activities, aswell as histories of heavier daily tobacco and alcoholconsumption by male patients. Varying frequenciesof lip cancer do occur in metropolitan centers, butexplanations usually are not evident. Again, thedecreasing frequency of lip cancer may reflect pub-lic education about the dangers of sunlight exposureand preventive measures.

STAGE AT DIAGNOSIS AND SURVIVAL

Approximately half of all patients with oral and pha-ryngeal cancers will survive their disease 5 yearsfollowing treatment (see Chapter 5, Spread ofTumor, Staging, and Survival). The outcomes aremore favorable for whites than for blacks (58% ver-sus 34% 5-year survival rates). Although geneticsmust play some critical role, socioeconomic status,education, and access to the health care system alsohave an influence. However, the primary explanationis based on the poor survival rates for advancedtumors compared with early, localized cancers(Table 14). If all diagnosed and treated oral cancercases were early, localized tumors, almost 4 of5 patients would survive 5 years. Unfortunately,unsatisfactory progress has been made during thelast three decades in regard to early diagnosis (Table15). Additionally, based on more than 25,000SEER Program oral/pharyngeal cases for whichthere was adequate information, localized/early oralcancers were outnumbered by advanced tumors 59to 41%. The lip was the only major site where local-

Table 12. ORAL CANCER: 3 LEADING SITESSite Cases (%) M:F* Mean AgeTongue 30 2.0 61Lip 17 5.0 66Mouth floor 14 2.2 62

Adapted from the National Cancer Institutes SEER (Surveillance, Epidemiol-ogy, and End Results) Program, 19851996.*Male-to-female ratio; 94% lower lip.

Table 13. CHARACTERISTICS OF ORAL CARCINOMAS IN 595 PATIENTS:ASSOCIATION OF SITE, STAGE,AND DIAGNOSTIC PATTERNS

Localized Mean Pain as First Stage at Delay First Consultation

Diagnosis Time Complaint with a Site (%) (mo)* (%) Dentist (%)Tongue 51 4.2 66 36Oropharynx 43 3.0 56 16Mouth floor 64 3.4 59 44Gingiva 56 3.5 64 52Buccal 79 3.4 52 50Lip 88 5.0 27 46Hard palate 75 4.5 50 57

Adapted from the Oral Medicine Clinic, University of California at San Francisco.*Time from patients recognition of first sign/symptom to diagnosis.

Table 14. ORAL CANCER: RELATIVE 5-YEAR SURVIVAL RATES BY

STAGE AT DIAGNOSIS, 19921997Stage Distribution (%) Alive at 5 Yr (%)Localized 41 82Regional 48 46Distant 11 21All stages 100 56

Adapted from the National Cancer Institutes SEER (Surveillance, Epidemiol-ogy, and End Results) Program, 19731998.Localized = tumor confined to the oral cavity; Regional = tumor spread tocervical lymph node(s); Distant = tumor spread to other organ(s).

4 ORAL CANCER

ized cancers were more frequently found than can-cers that were advanced. Because advances in treat-ment approaches have not led to significantlyimproved survival, earlier diagnosis is obviously akey factor in improving oral cancer control andreducing morbidity and mortality.

RACE AND GENETICS

Ethnic background is known to influence many typesof cancer. For example, cancer in blacks is increasingat a faster rate than in whites. Oral and pharyngealcancer is the fourth leading cancer site in black menand the seventh leading site of cancer in non-Hispanicwhite men. Oral cancers in men and women occurless frequently in Asians and Hispanics compared towhites and blacks. Although this finding suggestsgenetic factors, differences in habits and lifestyle arestrongly implicated (see Chapter 2, Etiology andPredisposing Factors). As another example, cancerof the nasopharynx is 20 to 30 times more prevalentin Chinese than in whites. The rate of nasopharyngealcarcinoma is highest in Chinese who have remainedin Asia, for example, those in Southeast Asia, whereit is one of the most common cancers (see Chapter 11,Other Malignancies and Oral Oncology).

Studies of human cancer of specific types haveshown aggregation in some families, implying agenetic influence.8 Examples of these types includerare cancers with mendelian inheritance, such asretinoblastoma in childhood; more common cancers,such as breast, prostate, or colon; and familial can-cer syndromes, which can include leukemias, sarco-mas, and brain tumors. No such evidence of familial

grouping has been presented for oral cancer. As thegenetic code becomes further unraveled, inheritedrisks undoubtedly will be clarified.

Most human tumors show chromosome aberra-tions that are usually proportional to the degree ofmalignancy and vary with each tumor and patient(Figure 11). It is not known whether the chromoso-mal abnormalities are the cause or the result ofmalignancy. However, identification of chromoso-mal deletions and gene mutations will surely helpour understanding of causes, prevention, treatments,and prognosis of malignancies.

MULTIPLE CANCERS

The data unequivocally show that persons with oraland pharyngeal cancers are at an increased risk fordeveloping subsequent additional malignancies.913 Inone study of 153 patients with carcinoma of themouth floor who were treated and observed between1957 and 1973 at the University of California at SanFrancisco (UCSF), 36% of the patients had at leastone second primary cancer. Twenty-three patients(15%) had a second primary oral cancer. In a similarfollow-up study at UCSF involving 204 patients withcarcinoma of the oral tongue who were observedbetween 1940 and 1971, 19% had second primarycancers, and 61% of these were second oral primarymalignancies (12% of the total group). A 1981 reportof 377 patients treated for cancer in the floor of the

Table 15. ORAL CANCER:COMPARING SITES AND STAGE

AT DIAGNOSIS, UNITED STATES, 1973199619731984 19851996

Site n L (%) n L (%)Tongue 4,794 44 5,993 45Lip 4,014 86 3,402 94Mouth floor 3,042 43 2,804 44Other sites 4,135 41 4,701 43

Adapted from the National Cancer Institutes SEER (Surveillance, Epidemiol-ogy, and End Results) Program.L = localized tumor (cancer stages 1 and 2); n = number of cases.

Figure 11. Chromosome preparation from a malignant cell; noteaneuploidy. Karyotyping is used to characterize aberrations of can-cer cells.

Epidemiology 5

mouth found that 18% developed new cancers of therespiratory and upper digestive tracts and 9% had sec-ond primary cancers occurring in the mouth. Studiesreported in 1992, 1994, and 1995 from three differentcenters further support the previous findings. Secondprimary tumors were common in those patients whoalready had oral and pharyngeal carcinomas, withoccurrences ranging as follows: 9.1% in a mediantime of 36 months in 3,436 patients; a yearly rate of3.7% among 21,371 patients from data collectedbetween 1973 and 1987; and 19% of 851 patients fol-lowed from 1978 to 1990. In all three reports, tobaccoincreased the risks, and most second primaries werein oral and oropharyngeal sites. Second primarytumors occurred more often than expected.

A report from our clinic in 1994 showed that72% of 403 patients with oral and pharyngeal can-cers smoked.14 Of those who continued to smokeafter diagnosis and treatment, 36% developed sec-ond primary oral/oropharyngeal cancer, comparedwith 14% in those patients who never smoked,stopped smoking, or greatly reduced their smoking.In a recent Japanese study reported in 2002,15

among 1,609 early-stage oral and pharyngeal squa-mous cell carcinoma patients, 333 second primarycancers were documented in 258 patients; 235(71%) of the second primary carcinomas occurred inrespiratory and upper digestive anatomic sites.

MORTALITY

Worldwide, cancer of various forms accounts formore than 2 million deaths each year. In the UnitedStates, cancer is a leading killer, second only to car-diovascular disease (Table 16). In women over 50,cancer is the leading cause of death. Cancer isresponsible for about 1 of every 4 American deathsmore than 550,000 deaths each year (more than10,000 deaths every week!). Someone in the UnitedStates dies of cancer almost every minute.

The number of cancer deaths has risen almostwithout interruption in the United States. Oral andpharyngeal cancers cause nearly 10,000 deathsyearly, accounting for about 0.4% of all deaths (seeTable 16). The relative survival rate of blackpatients is lower than that of white patients and, inrecent years, these figures have apparently not

improved (Table 17). This observation may beattributable to socioeconomic disadvantages in thehealth care system, as well as to the known greaterprevalence of smoking and alcohol consumption inthat population. Oral and pharyngeal cancer occur-rence and mortality rates are lower in Asians and His-panics than in whites and blacks. For a comparisonwith some other cancer sites, see Table 18. Deathrates from around the world (Table 19) suggestmarked differences in the occurrence of oral cancer,variations that probably reflect different combina-tions of ethnic, cultural, and environmental factors.

ACQUIRED IMMUNE DEFICIENCY SYNDROME

The current epidemic of the acquired immune defi-ciency syndrome (AIDS) continues unabated, withmore than 36 million persons throughout the worldnow infected with the human immunodeficiency virus(HIV). As the virus multiplies and mutates, producingimmune deficiency, the now immunocompromisedhost is at risk of developing malignancies as well asopportunistic infections. The malignancies associatedwith HIV infection can occur in the head and neck andinvolve the oral cavity and pharynx. These primarily

Table 16. SELECTED CAUSES OF DEATH, UNITED STATES, 2001 (2,337,256)

Rank Disease n Rate % of Deaths

1 Heart disease 724,860 189.0 31.02 Cancer 541,530 162.0 23.23 Stroke 158,450 39.0 6.86 Pneumonia 91,870 21.9 3.97 Diabetes 64,750 18.5 2.8

10 Cirrhosis 25,190 8.1 1.115 AIDS 13,430 4.0 0.6

Adapted from the National Center for Health Statistics, Centers for DiseaseControl and Prevention.n = number of cases.

Table 17. ORAL CANCER: 5-YEAR RELATIVE SURVIVAL RATES (%), UNITED STATES

Race 19741976 19831985 19921997

White 55 55 58Black 36 35 34All races 53 53 56

Adapted from CA Cancer J Clin 2001;51:35.

6 ORAL CANCER

include Kaposis sarcoma, non-Hodgkins lymphoma,and squamous cell carcinoma. Therefore, establish-ing the diagnosis, infection control, and treatment areall-important considerations for health professionals(see Chapter 12, Human Immunodeficiency VirusAssociated Oral Malignancies).

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and esophageal cancer outside of North America andWestern Europe. Cancer 1977;40:187986.

2. Myers JN, Elkins T, Roberts D, Byers RM. Squamous cellcarcinoma of the tongue in young adults: increasing inci-dence and factors that predict treatment outcomes. Oto-laryngol Head Neck Surg 2000;122:4451.

3. Pitman KT, Johnson JT, Wagner RL, Myers EN. Cancer ofthe tongue in patients less than forty. Head Neck 2000;22:297302.

4. Schantz SP, Yu G-P. Head and neck cancer incidence trendsin young Americans, 1973-1997, with a special analysisfor tongue cancer. Arch Otolaryngol Head Neck Surg2002;128:26874.

5. Edwards BK, Howe HL, Ries LA, et al. Annual report to thenation on the status of cancer, 19731999, featuring impli-cations of age and aging on U.S. cancer burden. Cancer2002;94:276692.

6. Shiboski CH, Shiboski SC, Silverman S Jr. Trends in oralcancer rates in the United States, 1973-1996. CommunityDent Oral Epidemiol 2000;28:24956.

7. Silverman S Jr. Demographics and occurrence of oral andpharyngeal cancers: the outcomes, the trends, the chal-lenge. J Am Dent Assoc 2001;132:7S11S.

8. Albert S, Child M. Familial cancer in the general population.Cancer 1977;40:16749.

9. Day GL, Blot WJ. Second primary tumors in patients withoral cancer. Cancer 1992;70:149.

10. Jones AS, Morar P, Phillips DE, et al. Second primary tumorsin patients with head and neck squamous cell carcinoma.Cancer 1995;75:134353.

11. Schwartz LH, Ozahin M, Zhang GN, et al. Synchronous andmetachronous head and neck carcinomas. Cancer1994;74:19338.

12. Tepperman BS, Fitzpatrick PJ. Second respiratory and upperdigestive tract cancers after oral cancer. Lancet 1981;2:5479.

13. Wynder EL, Mushinski MH, Spivak JC. Tobacco and alcoholconsumption in relation to the development of multipleprimary cancers. Cancer 1977;40:18728.

14. Gorsky M, Silverman S Jr. Tobacco use in patients with headand neck carcinomas: habit changes and second primaryoral/pharyngeal cancers in patients from San Francisco.Cancer J 1994;7:7880.

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Table 18. CANCER IN THE UNITED STATES,2002: ESTIMATES FOR SELECTED SITES

Site New Cases M:F* Deaths

All sites 1,284,900 1.00 555,500Breast 202,000 39,600Prostate 189,000 30,200Lung 169,400 1.10 154,900Colorectal 148,000 0.96 56,600Urinary bladder 56,500 2.80 12,600Kidney 31,800 1.50 11,600Pancreas 30,300 0.94 29,700

Adapted from the American Cancer Society, Cancer Facts and Figures, 2002.Oral and pharyngeal cancers account for about 30,100 new cases.*Male-to-female ratio.

Table 19. AGE-ADJUSTED DEATH RATES FOR ORAL CANCER PER 100,000 POPULATION*

Country Men (Rank) Women (Rank)Hungary 20.0 (1) 2.4 (1)Slovakia 16.8 (2) 1.2 (15)France 11.3 (5) 1.3 (9)Russian Federation 9.1 (8) 1.1 (26)Spain 7.0 (14) 0.9 (36)Germany 6.5 (15) 1.2 (14)Cuba 5.5 (20) 1.5 (4)Denmark 4.5 (23) 1.6 (3)Canada 3.8 (27) 1.2 (17)United States 3.2 (29) 1.1 (23)Japan 3.1 (31) 0.8 (37)United Kingdom 2.9 (32) 1.1 (22)Netherlands 2.8 (33) 1.0 (32)China 2.6 (36) 1.1 (24)Venezuela 2.5 (37) 1.2 (11)Sweden 2.2 (40) 0.9 (35)Chile 2.1 (42) 0.6 (43)Mexico 1.9 (43) 0.7 (41)Israel 1.5 (45) 0.7 (40)

Adapted from CA Cancer J Clin 2000;50:323.*Selected from 45 nations studied by the World Health Organization,19941997.

Oral CancerCopyrightDedicationContentsAcknowledgmentsPrefaceContributorsCh01: EpidemiologyCh02: Etiology and Predisposing FactorsCh03: Leukoplakia and ErythroplasiaCh04: DiagnosisCh05: Spread of Tumor, Staging, and SurvivalCh06: TreatmentCh07: Complications of TreatmentCh08: Restoration of Palate, Tongue, Mandible, and Facial DefectsCh09: Leukemia and LymphomaCh10: Malignant Salivary Gland TumorsCh11: Other Malignancies and Oral OncologyCh12: Human Immunodeficiency VirusAssociated Oral MalignanciesIndexExit