J Oral Maxillofac
Surg
49’1152-1158.1991
Changing Trends in Oral Cancer in the United States, 1935 to 1985: A Connecticut Study JINKUN CHEN, DMD, MDENTSC,* ELLEN EISENBERG, DMD,t DAVID J. KRUTCHKOFF, DDS, MS,* AND RALPH V. KATZ, DMD, PHD§ An extensive epidemiologic study was undertaken in an attempt to analyze patterns of oral cancer distribution and demography in Connecticut between 1935 and 1985. Sources of data for the investigation included both the Connecticut Tumor Registry (CTR) and the University of Connecticut Oral Pathology Biopsy Service. During the 51-year study period, 9,708 cases of primary oral cancer were reported to the CTR. Male age-adjusted incidence rates for overall oral cancer remained stable between 1935 and 1964 (14.5 to 14.8 per lOO,OOO), with a gradual decline to 10.9 per 100,000 in the early 1980s. In contrast, age-adjusted rates for females advanced approximately threefold, from 1.4 per 100,000 in the 1930s to 4.1 per 100,000 in the early 1980s. There was a decrease in age-specific rates of oral cancer in males aged 70 and older; in contrast, age-specific incidence rates in females increased steadily over the same period. It was also found that female birth cohorts born in 1900 and later exhibited higher oral cancer incidence rates than those of previous cohorts. Between the 1960s and the present, male patients 30 to 39 years of age exhibited a nearly fourfold increase in oral cancer incidence; this was not observed among similarly aged females. Connecticut counties with highest oral cancer incidence rates in both sexes were the more densely populated Hartford and New Haven counties. In general, the picture of oral cancer, as revealed through analysis of cases accessioned by the University biopsy service between 1975 and 1986, exhibited similar trends to those disclosed by analysis of CTR data. The increase in female oral cancer incidence combined with the reduced incidence in males appears to account for the dramatic decline in male-to-female ratio for oral cancer in Connecticut between 1935 and 1985. If this trend continues, the incidence of oral cancer in Connecticut women will equal that of men by the mid-1990s. Excluding the skin, cancers of the oral cavity and oropharynx account for some 3.5% of all reported malignancies within the United States.’ While this figure appears small relative to cancer of all sites. it nonetheless represents a disease that impacts heavily on its victims. their families, and responsible clinicians. Although many aspects of intraoral cancer remain in question, the classic features of the disease are well established. One inescapable fact is that the vast majority of cases are squamous cell carcinomas arising from surface oral epithelium.2,3 Also, it is clear that the pathogenesis of this malignancy is linked strongly to tobacco use, consumption of alcohol, and possibly exposure to other agents, including certain viruses.4”
Received from the University of Connecticut. Farmington. * Formerly, Resident in Oral Pathology. School of Dental Medicine; currently, PhD candidate, Department of Periodontal Physiology, University of Toronto, Canada. t Associate Professor, Department of Oral Diagnosis (Pathology), School of Dental Medicine: Department of Pathology. School of Medicine. $ Professor. Department of Oral Diagnosis (Pathology), School of Dental Medicine: Department of Pathology. School of Medicine. ’ Associate Professor. Department of Behavioral Sciences and Community Health. School of Dental Medicine. Address correspondence and reprint requests to Dr Eisenberg: Department of Oral Diagnosis (Pathology), University of Connecticut Health Center, 263 Farmington Ave. Farmington, CT 06030. 0 1991 American geons
Association
of Oral and Maxillofacial
Sur-
0278-2391/911491 l-0004$3.0010
1152
CHENETAL
1153
The natural history of intraoral squamous ceII carcinoma is for tumors to develop over an extended period of time. During the prodromal phase, it may be possible for the clinician to observe premalignant mucosal alterations, including leukoplakia, erythroplakia, and other subtle changes in surface features.‘.’ Oral sites recognized as cancerprone include the lateral-ventral tongue, floor of mouth, and retromolar trigone-tonsillar pillar-soft palate complex, all of which are readily accessible for examination by the dentist or physician.‘,s Finally, oral cancer is stereotypically considered a malignancy of middle-aged or elderly men who classically smoke. drink alcohol. or both.3.Y Although our experience with oral cancer at the University of Connecticut Oral Diagnostic Service has served to corroborate many of these maxims, it has been our impression that, in recent years, we are seeing an increasing number of oral squamous cell carcinomas both in women and in younger individuals. We felt that if such shifts in age and sex distribution are real, this information in verified form would be of great value to the clinician who deals with oral cancer on a routine basis. Clearly, it could lead to improved detection and early intervention, when the chance of cure with minimal deformity is best. Moreover, changing trends in oral cancer could also impact significantly on preventive aspects of the disease, with improved educational efforts for health professionals as well as the public. Thus, in accordance with our clinical suspicions, we undertook an extensive epidemiologic study of oral cancer in Connecticut in an attempt to test the hypothesis of whether or not well-established patterns of oral cancer demography and distribution remain valid.‘O.” This article reports our findings and discusses their potential significance. Methods The primary data source for this study was the Connecticut Tumor Registry (CTR), the oldest and most comprehensive statewide registry of its kind.” The CTR was established in 1935 for purposes of keeping demographic data on all cases of cancer arising in Connecticut residents. The CTR is thus a rich data source for epidemiologic research and as such was an invaluable resource for this study. Data for this investigation came from all oral cancer cases accessioned by the CTR during the 51year study period. 1935 to 1985 inclusive. Crude, age-specific, and age-adjusted incidence rates for both overall oral cancer” and its predominant form, squamous cell carcinoma,” were analyzed in an effort to demonstrate trends of oral cancer incidence in Connecticut. Age-adjusted rates were derived by
the direct method employing the 1970 US 1 million population distribution as the standard. A secondary, yet important, part of this study involved a survey of oral cancer cases submitted to the University of Connecticut Oral Pathology Biopsy Service over the shorter time span, 1975 to 1986 inclusive.‘0.‘4 With this survey, we sought to compare cases from the biopsy service with those reported to the statewide tumor registry in an effort to determine if biopsies diagnosed by dentists who patronize the service were representative of oral cancer as seen on the statewide level. Results CTR DATA During the 5I-year study period, a total of 9,708 cases of verified primary oral cancer were reported to the Connecticut Tumor Registry. This was 2.4% of the total of 397.430 malignant neoplasms accessioned within the same period. There were 6,181 cases of intraoral squamous cell carcinoma, constituting 63.7% of all oral cancer cases reported to the CTR during this 51-year span. It was found that the oral cavity was the eighth most common site for cancer in Connecticut, following, in decreasing order of frequency, cancer of the breast, colon, bronchus and lung, prostate, rectum, stomach, and urinary bladder (Flannery, personal communication, March 1988). Incidence rates. Over the study period, male age-adjusted incidence rates for overall oral cancer remained relatively stable. from a rate of 14.5 per 100,000 in the late 1930s to a rate of 14.8 per 100,000 in 1960 to 1964. Rates then began to drop gradually to a level of 10.9 per 100,000 in the early 1980s. In contrast, the age-adjusted rate for females advanced steadily from 1.4 per 100,000 in the early 1930s to 4.1 per 100,000 in the early 198Os, an approximate threefold increase” (Fig 1). Age-specific rates of oral cancer for males 70 years and older decreased notably over the years of the study. However, the female age-specific rates increased dramatically, especially among the age groups of 40 to 79 years. In the years between the two time periods 1935 to 1939 and 1980 to 198.5, the incidence rate of females aged 40 to 49 increased from 0.5 to 4.7 per 100,000, a 9.4-fold increase; the 50- to 59-year age group increased from 2.3 to 9.2 per 100,000, a fourfold increase; and the 60- to 69year age group increased from 4.0 to 16.0 per 100,000, also a fourfold increase (Table 1). Anaiyses of trends in incidence rates by birth cohort showed that female cohorts born in 1900 and after exhibited higher oral cancer incidence rates than those of previous cohorts. Patterns for males
1154
CHANGINGTRENDSIN
Male Female
-
1935TO 1985
veolar ridge (8.3% and 12.2%, respectively). The gingiva and ridge area was the only intraoral location where, in recent years, cases of squamous cell carcinoma were more prevalent in females than in malesI (Table 3). Histologic grading. There were 2,743 cases of intraoral squamous cell carcinoma in which the data for histologic grading were available. According to the World Health Organization (WHO) three-grade system,’ the majority of cases (54.3%) were classified as moderately differentiated, 29.1% as welldifferentiated, and 16.6% as poorly differentiated. Squamous cell carcinomas of different anatomic subsites exhibited a similar pattern for both sexes, with only one exception, ie, that carcinoma of the retromolar area in females exhibited predominance of the well-differentiated type. l3 Geographic location. The state average crude incidence rate of overall oral cancer for the past 51 years was 12.2/100,000 for males and 3.2/100,000 for females. There were two counties for which average incidence rates for both sexes were higher than the rate of the state as a whole: these were the more densely populated counties of Hartford (12.8 for males and 3.4 for females per 100,000) and New Haven 112.7 and 3.3 per 100,000, respectively). Sparsely populated Tolland county had the lowest incidence rate for males, which was 42% lower than the state average. For females, the crude incidence rate was 68% lower than the state average. The second-lowest rates were found in Windham county. also relatively sparsely populated.”
20 1 -
ORALCANCER,
FIGURE 1. Age-adjusted oral cancer incidence rates per 100,000 by time period for males and females. Connecticut. 1935 to 1985. (Reprinted with permission.“)
showed a decreasing trend for birth cohorts after 1900 (Fig 2). During the last 20 years (from the 1960s to the present), the male age-specific incidence rate of intraoral squamous cell carcinoma in patients aged 30 to 39 years showed a nearly fourfold increase from 0.4 per 100,000 in 1965 to 1969 to 1.5 in 1980 to 1985; however, a similar trend was not seen among females of the same age group. Sex. The male-to-female ratio for overall oral cancer (age-adjusted rates) decreased from 10.4 during the period 1935 to 1939 to 2.7 in the span from 1980 to 1985, representing a 74% decrease (Table 2). Site. The most common site for intraoral squamous cell carcinoma in both males and females was the tongue, comprising 41.8% of cases in males and 39.5% in females. The second most common location was floor of the mouth (25.8% in males and 19.3% in females) followed by the palate (10.2% and 13.5%, respectively) and the gingiva, including al-
BIOPSY SERVICE
DATA
A survey I4 of 566 cases of oral cancer accessioned through the University of Connecticut Oral
Table 1. Oral Cancer Age=Specific Incidence Rates by Age Group per 100,000 for Connecticut 1935 to 1985 O-29 yrs M
50-59 yrs
60-69 yrs
30-39 yrs
40-49 yrs
70-79 yrs
80 yrs & over
F
M
F
M
F
M
F
M
F
M
F
M
b
1935-1939 1940-1944 1945-1949 1950-1954 1955-1959 1960-1964 1965-1969 1970-1974 1975-1979 1980-1985
0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
0.0 0.1 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.1
1.4 2.0 1.6 1.8 2.3 2.1 0.9 0.9 1.3 2.2
0.5 0.4 0.5 1.0 0.8 I.0 0.3 0.9 0.5 0.9
6.8 7.7 7.4 10.3 10.8 Il.6 9.6 9.1 10.7 9.4
0.5 1.4 1.5 1.8 1.5 3.1 4.0 3.8 3.6 4.7
26.1 24.1 25.9 26.9 28.5 25.4 28.5 31.3 29.1 27.2
2.3 2.8 2.5 4.3 5.9 6.9 6.1 9.4 10.3 9.2
46.5 46.2 55.9 57.5 57.3 58.9 47.0 47.0 49.1 45.7
4.0 6.9 6.4 7.1 6.4 9.7 10.8 13.7 15.1 16.0
87.2 98.7 82.2 70.0 78.9 84.4 61.8 60.6 59.6 51.3
9.1 12.5 13.5 12.5 10.4 11.5 13.8 16.3 14.7 19.1
139.4 106.6 126.4 131.8 83.3 113.1 67.1 50.8 79.2 44.5
16.4 17.2 12.9 19.4 20.4 13.5 17.5 14.2 16.7 20. I
Allyears
0.0
0.0
1.8
0.7
9.6
2.8
27.6
6.7
51.2
10.9
70.0
14.3
84.2
17.3
Reprinted with permission.”
CHEN
ET AL
FIGURE 2. Birth cohort analysis 1985. (Reprinted with permission.“)
of oral cancer
incidence
rates
Pathology Biopsy Service during the years 1975 through 1986, in general, showed a characterization of Connecticut oral cancer very similar to that of the CTR study.“.‘3.‘6 Invasive squamous cell carcinoma constituted 72.5% of all Biopsy Service malignancies. With cases of lip cancer excluded (2.8% of total), there remained 379 cases of invasive intraoral carcinoma (69.7% of total). Thorough analysis of intraoral carcinoma cases revealed that age, sex, and subsite specificity were essentially similar to that seen in the CTR cases. In contrast, there was a significant difference in patterns of histologic grading in the two data sources in that well-differentiated tumors were more prevalent in cases from the University of Connecticut Biopsy Service, whereas moderately differentiated tumors predominated in the larger statewide study. Other Table 2. Male:Female Ratios of Oral Cancer for Case Numbers, Crude, and AgemAdjusted Incidence Rates by Time Period for Connecticut 1935 to 1985 No. of
Age-Adjusted Rates
Cases
Crude Rates
1935-1939 1940-1944 I945- I949 1950-1954 19551959 I960- I964 1965-1969 I970- 1974 I975 I979 I980- 1985
9.3 6.5 6.7 5.5 5.4 4.5 3.3 2.8 2.6 2.0
9.4 6.6 6.7 5.8 5.5 4.7 3.4 3.0 2.7 2.2
10.4
All years
3.6
3.8
4.4
Year
Age-adjusted by US 1970 Standard Reprinted with permission.”
Million
7.2 7.4 6.2 6.4 5.5 4.0 3.3 3.4 2.7
Population.
per 100.000 for males
(A! and for females
(B), Connecticut,
1935 to
than this notable exception, data from both sets of cases revealed that the general pictures of both overall oral cancer and invasive squamous cell carcinoma were quite similar. I4 Discussion
Clearly, the most dramatic finding of this study was the nearly threefold increase in the age-adjusted incidence rate of intraoral squamous cell carcinoma among Connecticut females over the 51-year period. This increase in female oral cancer incidence combined with a slightly reduced incidence in males in the past 20 years is clearly the major factor responsible for the observed steadily diminishing male-tofemale ratio for oral cancer during the period 1935 to 1985. We project that if this trend continues, the incidence of Connecticut oral cancer in women will equal that in men by the mid-1990s (Fig 3). Although the determination of cause-and-effect relationship is beyond the scope of this descriptive epidemiologic project, the increase in oral cancer incidence rate among Connecticut women over this ZI-year period has paralleled the increased exposure of women to tobacco and alcohol, which began in the 1920s and continues to the present time. The female birth cohort analysis supports this hypothesis in that cohorts with highest oral cancer incidence rates would have been either adolescents or young adults at the time when smoking in females became socially acceptable. The hypothesis is further supported by the findings of Harris, who studied patterns of cigarette smoking among successive birth cohorts of US men and women from 1900 to 1980.” It was found that maximum exposure of women to smoking probably occurred in those who were then in their fifth and sixth decade of life.
1156
CHANGING TRENDS IN ORAL CANCER,
Table 3. Site Distribution of Intraoral Squamous Cell Carcinoma by Sex for Connecticut 1935 to 1985 No. of Males (%‘o)
Site
No. of Females (g)
No. of Both Sexes (%c)
Tongue Gingiva Floor of mouth Buccal mucosa Palate Retromolar area Miscellaneous sites
1942 (41.8) 386 (8.3) I I98 (25.8) 253 (5.4) 476 (IO.21
604 (39.5) 186 (12.2) 295 (19.3) 122 (8.0) 206 (13.5)
2546 (41.2) 572 (9.3) 1493 (24.2) 375 16.1) 682 (I I .O)
134 (2.9)
32 (2.1)
166 (2.7)
Total cases
465 I
262 (5.6)
85 (5.6)
347 (5.6)
IS30
6181
Reprinted with permission.”
Additionally, it can be noted that recent smoking cessation rates for men have exceeded those for women. Hence, the above observations are all supportive of the hypothesis that tobacco-related factors have contributed significantly to the trend of increasing oral cancer incidence in the Connecticut female population. The contribution of two known dietary factors among women (poor nutrition during the Great Depression and war years’* and increased alcohol consumption’) also may be significant, but the relationship is less clear. Because, in general, heavy drinkers are also heavy smokers, it is difficult to separate the effects of these two variables.” Carefully controlled future studies will be necessary to determine relative contributions of alcohol and tobacco to the observed increase in female oral cancer incidence. Another factor that supports the argument for the influence of tobacco is the expanding presence of women in the workforce. In recent decades, women have assumed more positions in business and indus11 1
1’
I
I
1
I
I
1
1935.39194044 1945.491950.5419S5.59l%W
I
I
I
I
1965.691970-741975.791980.8S
Year
FIGURE 3. Male:female ratios of age-adjusted incidence rates of oral cancer by time period. Connecticut, 1935 to 1985. (Reprinted with permission. ’ ‘)
1935 TO 1985
try that were previously associated almost exclusively with males. It is therefore plausible that along with their emergence from the relatively protective environment of the home, women have concurrently become exposed to higher concentrations and a greater variety of carcinogenic materials, including tobacco. Whether acting alone or in concert with other cancer-producing factors, such environmental influences may contribute to the observed increased incidence of oral cancer in Connecticut women. Further study is needed to identify risk factors linked to new trends in women’s life-styles and the degree to which they serve to initiate or promote oral carcinogenesis. The fourfold increase in the incidence of intraoral squamous cell carcinoma observed in our data in young males aged 30 to 39 also is worthy of discussion. In that a similar trend was not seen among females of comparable age, this observation could reflect the introduction of possible new risk factors in young men, including, among others, increased exposure to smokeless tobacco or possibly to viral agents. While the use of smokeless tobacco products among Connecticut youngsters is admittedly lower than that of individuals of similar age elsewhere,‘O the practice still enjoys unprecedented popularity.“-” Although the duration and extent of use of these agents varies widely on an individual basis, it is likely that local application and prolonged direct contact of known carcinogens with immature oral mucous membranes may be especially deleterious.‘4 For one thing, the earlier a carcinogen is applied to any susceptible tissue, the sooner the onset of neoplastic transition. It is also possible that early exposure of vulnerable, highly labile, oral epithelium may significantly reduce the period of latency of oral carcinogenesis, resulting in precocity of onset of squamous cell carcinoma. With respect to the possible viral contribution to the etiopathogenesis of oral carcinoma now and in the future, the following merits consideration. The oncogenic properties of several strains of human papillomavirus and some herpes viruses are well established.25-28 These viruses are ubiquitous and are frequently transmitted to the mouth through oral-cutaneous, oral-genital, or oral-anal contact, and may produce recognizable mucosal lesions like verrucae, condylomas, and papillomas.4.‘y.30 Alternatively, they may colonize existing hyperkeratoses to produce changes in epithelium ranging from mild histologic viral modification to frank dysplasia and even carcinoma.3’.32 Given the reputed increasing degree of sexual activity in younger males,33 often with multiple partners, the concomitant likelihood of venereal infection with oncogenic viruses could play a significant role in pathogenesis of oral epi-
1157
CHEN ET AL
thelial cancer. It is conceivable that such viruses, acting as primary oncogenic agents. or in Collusion with various indigenous or acquired factors (including tobacco products, alcohol, and others). could serve to partially account for the observed rise in oral cancer incidence in this population group.
79.30.31
Perhaps the most intriguing conjecture on viral pathogenesis of oral squamous cell carcinoma in younger men is that focused on the uncommon but possible contribution of the human immunodeficiency virus CHIV).“4-37 Recently, squamous cell carcinoma has been found to occur more frequently in HIV-infected homosexual men than is typical of non-HIV-infected individuals in this age group.‘” While it is doubtful that HIV itself exerts a direct carcinogenic influence on oral epithelial tissue. it is conceivable that it may participate in development of oral cancer through its ability to diminish cellmediated immunity, thereby permitting a number of potentially oncogenic opportunistic infections.“.4” In this sense, both impaired immune surveillance and compromised immunity brought on by HIV infection could “fertilize the soil,” thus setting the stage for premature onset of oral cancer. In our analysis dealing with frequencies of occurrence of intraoral squamous cell carcinoma in various anatomic subsites, we found that the tongue was the most common site, followed. in order of decreasing frequency, by floor of mouth, palate. and gingiva (alveolar ridge).‘j This site predilection is in general agreement with previous studies that define the gravity-dependent oral mucosal reservoir regions as “cancer-prone.“7.4’3”’ These areas (floor of mouth. ventrolateral tongue, retromolar-soft palate complex) are exposed to higher concentrations of carcinogens and other harmful products because of their prolonged contact in areas of salivary pooling. The cancer-prone nature of these sites has been corroborated in many studies.“~43.44 As our study demonstrates, the Connecticut oral cancer incidence is evidently somewhat proportional to population density.” This apparent correlation between oral cancer incidence and population density is most likely due to different specific environmental and socioeconomic factors characteristic of the respective regions. In general, more densely populated urban areas expose residents to increased levels of environmental pollutants, such as motor vehicle exhaust and industrial waste. Incorporated into the atmosphere and the water supply, these noxious agents constantly bombard the more confined city dweller with relatively higher levels of carcinogens over extended periods of time. Thus, unlike their rural counterparts, it is likely that individuals living in more densely populated regions are
at greater risk for development of malignancies involving the aerodigestive tract. Aside from industrial pollutants, it is likely that other carcinogens, such as microbial agents, also operate more effectively in crowded population settings.4”-48 Socioeconomic factors often associated with urban life, including poverty, crowding, run-down housing, poor nutrition, and inadequate medical attention, may render the city dweller a more likely candidate for oral cancer than his or her “country cousin.” The findings of this study serve to raise interesting questions regarding possible factors influencing the etiopathogenesis of intraoral squamous cell carcinoma. It would seem that factors other than tobacco and alcohol may be either directly or indirectly involved in the initiation of this malignancy. Specific factors. plus the extent to which they play a role in carcinogenesis, remain to be determined by future scientific investigations. Findings of such studies should provide invaluable information to the clinician with regard to patient and professional education necessary for early detection, prevention, and effective management of oral cancer in years to come. References I. Silverberg E. Lubera .I: Cancer statistics. CA 37:2, 1987 1. Lucas RB: Pathology of Tumors of the Oral Tissues (ed 2). London. Churchill Livingstone, 1972. pp 121-146 3. Rowe NH: Oral cancer: General considerations. J Mich Dent Assoc 56:242, 1974 4. Silverman S Jr: Epidemiology, it, Silverman S Jr ted): Oral Cancer (ed 2). New York. NY, American Cancer Society, 1985. pp 7-34 5. Douglass CW, Gammon MD, Horgan WJ: Epidemiology of oral cancer. in Shklar G (ed): Oral Cancer: The Diagnosis. Therapy, Management and Rehabilitation of the Oral Cancer Patient. Philadelphia. PA. Saunders, 1984. pp 84-89 6. Mahboubi E. Sayed GM: Oral cavity and pharynx, in Schottenfeld D, Fraumeni J Jr teds): Cancer Epidemiology and Prevention. Philadelphia. PA, Saunders. 1982. pp 588-592 7. Shafer WG. Hine MK, Levy BM: A Text Book of Oral Pathology (ed 4). Philadelphia. PA. Saunders, 1983, pp 92119 8. Mashberg A. Barsa P: Screening for oral and oropharyngeal squamous carcinomas. CA 34:262. 1984 9. Wynder E, Bross IJ. Feldman RM: A study of the etiological factors in cancer of the mouth. Cancer 10:1300. 1957 IO. Chen J: Descriptive epidemiology of oral cancer in Connecticut. 1935-1985. Masters thesis. University of Connecticut, Farmington. 1988 I I. Chen J, Katz RV. Krutchkoff DJ: Epidemiology of oral cancer in Connecticut, 1935-1985. Cancer 65:2796. 1990 12. Flannery J, Boice JD, Devesa SS. et al: Cancer registration in Connecticut and the study of multiple primary cancer, 1935-82. NC1 Monogr 68:13. 1985 13. Chen J, Katz RV, Krutchkoff DJ: Intraoral squamous cell carcinoma: Epidemiologic patterns in Connecticut from 1935 to 1985. Cancer 66: 1288, 1990 14. Krutchkoff DJ. Chen J. Eisenberg E. et al: Oral cancer: A survey of 566 cases from the University of Connecticut Oral Pathology Biopsy Service, 1975-1986. Oral Surg Oral Med Oral Pathol 70:192, 1990 15. World Health Organization: Histological typing of oral and
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oropharyngeal tumors, in International Histological Classification of Tumors. Geneva, World Health Organization. 1971, pp 17-18 16. Chen J. Katz RV, Krutchkoff DJ, et al: Lip cancer: An epidemiological analysis of 2291 cases. J Oral Pathol Med (submitted) 17. Harris JE. Cigarette smoking among successive birth cohorts of men and women in the United States during l9001980. JNCI 71:473. 1983 18. Devesa SS, Silverman DT. Young JL, et al: Cancer incidence and mortality trends among whites in the United States, 1947-84. JNCI 79:701, 1987 19. Cann C, Fried MP, Rothman KJ: Epidemiology of squamous cell cancer of the head and neck. Otolaryngol Clin North Am 18:367. 1985 20. Kegeles SS, Burleson JA, Miozza J: Cigarette and smokeless tobacco use among Connecticut adolescents. Am J Public Health 79:1413, 1989 21. United States Department of Health and Human Services: The health consequences of using smokeless tobacco: A report of the Surgeon General. Bethesda, MD, National Institute of Health, DDHS publication no. (NIH) 86-2874 22. Christen AG: The case against smokeless tobacco: Five facts for the health professional to consider. J Am Dent Assoc 101:464. 1980 23. Harper S: In tobacco, where there’s smokeless fire. Advertising Age 5:85, 1980 24. Squier CA. Smokeless tobacco and oral cancer: A cause for concern? CA 34~242. 1984 25. Bishop JM: Cancer genes come of age. Cell 32:1018, 1983 26. Gross G, Plister H, Hagedorn M, et al: Correlation between human papillomavirus (HPV) type and histology of warts. J Invest Dermatol 78:160. 1982 21. Shillitoe EJ, Silverman S Jr: Oral cancer and herpes simplex virus-A review. Oral Surg 48:216, 1979 28. Shillitoe EJ, Greenspan D, Greenspan JS, et al: Antibody to early and late antigens of herpes simplex virus type 1 in patients with oral cancer. Cancer 54:266. 1984 29. Binnie WH. Rankin KV: Etiology, in Wright BA. Wright JM, Binnie WH teds): Oral cancer: Clinical and Pathological Considerations. Boca Raton. FL, CRC Press, 1988, pp 13-32 30. Lack E, Vawter GF. Smith HG, et al: Immunohistochemical localization of human papilloma virus in squamous papillomas of the larynx. Lancet 2592, 1980 31. Lehner T. Shillitoe EJ, Wilton JM, et al: Cell-mediated immunity to herpes virus type 1 in carcinoma and precancerous lesions. Br J Cancer 28:128, 1973 (suppl I) 32. Loning T, Reichart P. Staquet MJ, et al: Occurrence of pap-
CHANGING TRENDS IN ORAL CANCER,
1935 TO 1985
illomavirus structural antigens in oral papillomas and leukoplakias. J Oral Pathol 13:155, 1984 33. Cates Jr W, Toomey KE: Sexually transmitted diseases: Overview of the situation. Primary Care 17: I 1 1990 34. Shillitoe EJ, Greenspan JS, Silverman S Jr: Neutralizing antibody to herpes simplex virus type I in patients with oral cancer. Cancer 49:2315, 1982 35. Silverman Jr S: HIV-associated malignancies. in Silverman Jr S (ed): Color Atlas of Oral Manifestations of AIDS. Toronto, B.C. Decker, 1989, pp 65-80 36. Pindborg JJ: Classification of oral lesions associated with HIV infection. Oral Surg Oral Med Oral Pathol 67:292, 1989 37. Greenspan D, Greenspan J. Pindborg JJ. et al: AIDS and the dental team. Copenhagen, Munksgaard, 1986 38. Silverman S Jr. Migliorati CA. Lozada-Nur F. et al: Oral findings in people with or at high risk for AIDS: A study of 375 homosexual males. J Am Dent Assoc I I‘?:187, 1986 39. Lozada F, Silverman S Jr, Migliorati CA, et al: Oral manifestations of tumor and opportunistic infections in the acquired immunodeficiency syndrome (AIDS): Findings in 53 homosexual men with Kaposi’s sarcoma. Oral Surg Oral Med Oral Path01 56:491. 1983 40. Reichart P. Gelderblom HR, Becker J. et al: AIDS and the oral cavity. The HIV-Infection: Virology. etiology. origin. immunology, precautions and clinical observations in 1IO patients. Int J Oral Maxillofac Surg 16: 129, 1987 41. Lederman M: Bucco-pharyngeal cancer. Br J Radio1 29536, 1956 42. Lederman M: The anatomy of cancer. J Laryngol Otol 78:181. 1964 43. Mashberg A, Meyers H: Anatomical site and size of 222 early asymptomatic oral squamous cell carcinomas: A continuing prospective study of oral cancer II. Cancer 37:2149. 1976 44. Rich AM, Radden BG: Squamous cell carcinoma of the oral mucosas: A review of 244 cases in Australia. J Oral Pathol 13:459. 1984 45. Dorn HF. Cutler SJ: Morbidity from cancer. Public Health Monogr 56: I. 1958 46. Hirayama T: An epidemiological study of oral and pharyngeal cancer in Central and Southeast Asia. Bull WHO 34:41, 1969 47. Wynder DL. Stellman SD. Comparative epidemiology of tobacco-related cancers. Cancer Res 37:4608. 1977 48. Smith EM: Epidemiology of oral and pharyngeal cancers in the United States: Review of recent literature. JNCI 63: 1189. 1979
Surg
49’1152-1158.1991
Changing Trends in Oral Cancer in the United States, 1935 to 1985: A Connecticut Study JINKUN CHEN, DMD, MDENTSC,* ELLEN EISENBERG, DMD,t DAVID J. KRUTCHKOFF, DDS, MS,* AND RALPH V. KATZ, DMD, PHD§ An extensive epidemiologic study was undertaken in an attempt to analyze patterns of oral cancer distribution and demography in Connecticut between 1935 and 1985. Sources of data for the investigation included both the Connecticut Tumor Registry (CTR) and the University of Connecticut Oral Pathology Biopsy Service. During the 51-year study period, 9,708 cases of primary oral cancer were reported to the CTR. Male age-adjusted incidence rates for overall oral cancer remained stable between 1935 and 1964 (14.5 to 14.8 per lOO,OOO), with a gradual decline to 10.9 per 100,000 in the early 1980s. In contrast, age-adjusted rates for females advanced approximately threefold, from 1.4 per 100,000 in the 1930s to 4.1 per 100,000 in the early 1980s. There was a decrease in age-specific rates of oral cancer in males aged 70 and older; in contrast, age-specific incidence rates in females increased steadily over the same period. It was also found that female birth cohorts born in 1900 and later exhibited higher oral cancer incidence rates than those of previous cohorts. Between the 1960s and the present, male patients 30 to 39 years of age exhibited a nearly fourfold increase in oral cancer incidence; this was not observed among similarly aged females. Connecticut counties with highest oral cancer incidence rates in both sexes were the more densely populated Hartford and New Haven counties. In general, the picture of oral cancer, as revealed through analysis of cases accessioned by the University biopsy service between 1975 and 1986, exhibited similar trends to those disclosed by analysis of CTR data. The increase in female oral cancer incidence combined with the reduced incidence in males appears to account for the dramatic decline in male-to-female ratio for oral cancer in Connecticut between 1935 and 1985. If this trend continues, the incidence of oral cancer in Connecticut women will equal that of men by the mid-1990s. Excluding the skin, cancers of the oral cavity and oropharynx account for some 3.5% of all reported malignancies within the United States.’ While this figure appears small relative to cancer of all sites. it nonetheless represents a disease that impacts heavily on its victims. their families, and responsible clinicians. Although many aspects of intraoral cancer remain in question, the classic features of the disease are well established. One inescapable fact is that the vast majority of cases are squamous cell carcinomas arising from surface oral epithelium.2,3 Also, it is clear that the pathogenesis of this malignancy is linked strongly to tobacco use, consumption of alcohol, and possibly exposure to other agents, including certain viruses.4”
Received from the University of Connecticut. Farmington. * Formerly, Resident in Oral Pathology. School of Dental Medicine; currently, PhD candidate, Department of Periodontal Physiology, University of Toronto, Canada. t Associate Professor, Department of Oral Diagnosis (Pathology), School of Dental Medicine: Department of Pathology. School of Medicine. $ Professor. Department of Oral Diagnosis (Pathology), School of Dental Medicine: Department of Pathology. School of Medicine. ’ Associate Professor. Department of Behavioral Sciences and Community Health. School of Dental Medicine. Address correspondence and reprint requests to Dr Eisenberg: Department of Oral Diagnosis (Pathology), University of Connecticut Health Center, 263 Farmington Ave. Farmington, CT 06030. 0 1991 American geons
Association
of Oral and Maxillofacial
Sur-
0278-2391/911491 l-0004$3.0010
1152
CHENETAL
1153
The natural history of intraoral squamous ceII carcinoma is for tumors to develop over an extended period of time. During the prodromal phase, it may be possible for the clinician to observe premalignant mucosal alterations, including leukoplakia, erythroplakia, and other subtle changes in surface features.‘.’ Oral sites recognized as cancerprone include the lateral-ventral tongue, floor of mouth, and retromolar trigone-tonsillar pillar-soft palate complex, all of which are readily accessible for examination by the dentist or physician.‘,s Finally, oral cancer is stereotypically considered a malignancy of middle-aged or elderly men who classically smoke. drink alcohol. or both.3.Y Although our experience with oral cancer at the University of Connecticut Oral Diagnostic Service has served to corroborate many of these maxims, it has been our impression that, in recent years, we are seeing an increasing number of oral squamous cell carcinomas both in women and in younger individuals. We felt that if such shifts in age and sex distribution are real, this information in verified form would be of great value to the clinician who deals with oral cancer on a routine basis. Clearly, it could lead to improved detection and early intervention, when the chance of cure with minimal deformity is best. Moreover, changing trends in oral cancer could also impact significantly on preventive aspects of the disease, with improved educational efforts for health professionals as well as the public. Thus, in accordance with our clinical suspicions, we undertook an extensive epidemiologic study of oral cancer in Connecticut in an attempt to test the hypothesis of whether or not well-established patterns of oral cancer demography and distribution remain valid.‘O.” This article reports our findings and discusses their potential significance. Methods The primary data source for this study was the Connecticut Tumor Registry (CTR), the oldest and most comprehensive statewide registry of its kind.” The CTR was established in 1935 for purposes of keeping demographic data on all cases of cancer arising in Connecticut residents. The CTR is thus a rich data source for epidemiologic research and as such was an invaluable resource for this study. Data for this investigation came from all oral cancer cases accessioned by the CTR during the 51year study period. 1935 to 1985 inclusive. Crude, age-specific, and age-adjusted incidence rates for both overall oral cancer” and its predominant form, squamous cell carcinoma,” were analyzed in an effort to demonstrate trends of oral cancer incidence in Connecticut. Age-adjusted rates were derived by
the direct method employing the 1970 US 1 million population distribution as the standard. A secondary, yet important, part of this study involved a survey of oral cancer cases submitted to the University of Connecticut Oral Pathology Biopsy Service over the shorter time span, 1975 to 1986 inclusive.‘0.‘4 With this survey, we sought to compare cases from the biopsy service with those reported to the statewide tumor registry in an effort to determine if biopsies diagnosed by dentists who patronize the service were representative of oral cancer as seen on the statewide level. Results CTR DATA During the 5I-year study period, a total of 9,708 cases of verified primary oral cancer were reported to the Connecticut Tumor Registry. This was 2.4% of the total of 397.430 malignant neoplasms accessioned within the same period. There were 6,181 cases of intraoral squamous cell carcinoma, constituting 63.7% of all oral cancer cases reported to the CTR during this 51-year span. It was found that the oral cavity was the eighth most common site for cancer in Connecticut, following, in decreasing order of frequency, cancer of the breast, colon, bronchus and lung, prostate, rectum, stomach, and urinary bladder (Flannery, personal communication, March 1988). Incidence rates. Over the study period, male age-adjusted incidence rates for overall oral cancer remained relatively stable. from a rate of 14.5 per 100,000 in the late 1930s to a rate of 14.8 per 100,000 in 1960 to 1964. Rates then began to drop gradually to a level of 10.9 per 100,000 in the early 1980s. In contrast, the age-adjusted rate for females advanced steadily from 1.4 per 100,000 in the early 1930s to 4.1 per 100,000 in the early 198Os, an approximate threefold increase” (Fig 1). Age-specific rates of oral cancer for males 70 years and older decreased notably over the years of the study. However, the female age-specific rates increased dramatically, especially among the age groups of 40 to 79 years. In the years between the two time periods 1935 to 1939 and 1980 to 198.5, the incidence rate of females aged 40 to 49 increased from 0.5 to 4.7 per 100,000, a 9.4-fold increase; the 50- to 59-year age group increased from 2.3 to 9.2 per 100,000, a fourfold increase; and the 60- to 69year age group increased from 4.0 to 16.0 per 100,000, also a fourfold increase (Table 1). Anaiyses of trends in incidence rates by birth cohort showed that female cohorts born in 1900 and after exhibited higher oral cancer incidence rates than those of previous cohorts. Patterns for males
1154
CHANGINGTRENDSIN
Male Female
-
1935TO 1985
veolar ridge (8.3% and 12.2%, respectively). The gingiva and ridge area was the only intraoral location where, in recent years, cases of squamous cell carcinoma were more prevalent in females than in malesI (Table 3). Histologic grading. There were 2,743 cases of intraoral squamous cell carcinoma in which the data for histologic grading were available. According to the World Health Organization (WHO) three-grade system,’ the majority of cases (54.3%) were classified as moderately differentiated, 29.1% as welldifferentiated, and 16.6% as poorly differentiated. Squamous cell carcinomas of different anatomic subsites exhibited a similar pattern for both sexes, with only one exception, ie, that carcinoma of the retromolar area in females exhibited predominance of the well-differentiated type. l3 Geographic location. The state average crude incidence rate of overall oral cancer for the past 51 years was 12.2/100,000 for males and 3.2/100,000 for females. There were two counties for which average incidence rates for both sexes were higher than the rate of the state as a whole: these were the more densely populated counties of Hartford (12.8 for males and 3.4 for females per 100,000) and New Haven 112.7 and 3.3 per 100,000, respectively). Sparsely populated Tolland county had the lowest incidence rate for males, which was 42% lower than the state average. For females, the crude incidence rate was 68% lower than the state average. The second-lowest rates were found in Windham county. also relatively sparsely populated.”
20 1 -
ORALCANCER,
FIGURE 1. Age-adjusted oral cancer incidence rates per 100,000 by time period for males and females. Connecticut. 1935 to 1985. (Reprinted with permission.“)
showed a decreasing trend for birth cohorts after 1900 (Fig 2). During the last 20 years (from the 1960s to the present), the male age-specific incidence rate of intraoral squamous cell carcinoma in patients aged 30 to 39 years showed a nearly fourfold increase from 0.4 per 100,000 in 1965 to 1969 to 1.5 in 1980 to 1985; however, a similar trend was not seen among females of the same age group. Sex. The male-to-female ratio for overall oral cancer (age-adjusted rates) decreased from 10.4 during the period 1935 to 1939 to 2.7 in the span from 1980 to 1985, representing a 74% decrease (Table 2). Site. The most common site for intraoral squamous cell carcinoma in both males and females was the tongue, comprising 41.8% of cases in males and 39.5% in females. The second most common location was floor of the mouth (25.8% in males and 19.3% in females) followed by the palate (10.2% and 13.5%, respectively) and the gingiva, including al-
BIOPSY SERVICE
DATA
A survey I4 of 566 cases of oral cancer accessioned through the University of Connecticut Oral
Table 1. Oral Cancer Age=Specific Incidence Rates by Age Group per 100,000 for Connecticut 1935 to 1985 O-29 yrs M
50-59 yrs
60-69 yrs
30-39 yrs
40-49 yrs
70-79 yrs
80 yrs & over
F
M
F
M
F
M
F
M
F
M
F
M
b
1935-1939 1940-1944 1945-1949 1950-1954 1955-1959 1960-1964 1965-1969 1970-1974 1975-1979 1980-1985
0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
0.0 0.1 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.1
1.4 2.0 1.6 1.8 2.3 2.1 0.9 0.9 1.3 2.2
0.5 0.4 0.5 1.0 0.8 I.0 0.3 0.9 0.5 0.9
6.8 7.7 7.4 10.3 10.8 Il.6 9.6 9.1 10.7 9.4
0.5 1.4 1.5 1.8 1.5 3.1 4.0 3.8 3.6 4.7
26.1 24.1 25.9 26.9 28.5 25.4 28.5 31.3 29.1 27.2
2.3 2.8 2.5 4.3 5.9 6.9 6.1 9.4 10.3 9.2
46.5 46.2 55.9 57.5 57.3 58.9 47.0 47.0 49.1 45.7
4.0 6.9 6.4 7.1 6.4 9.7 10.8 13.7 15.1 16.0
87.2 98.7 82.2 70.0 78.9 84.4 61.8 60.6 59.6 51.3
9.1 12.5 13.5 12.5 10.4 11.5 13.8 16.3 14.7 19.1
139.4 106.6 126.4 131.8 83.3 113.1 67.1 50.8 79.2 44.5
16.4 17.2 12.9 19.4 20.4 13.5 17.5 14.2 16.7 20. I
Allyears
0.0
0.0
1.8
0.7
9.6
2.8
27.6
6.7
51.2
10.9
70.0
14.3
84.2
17.3
Reprinted with permission.”
CHEN
ET AL
FIGURE 2. Birth cohort analysis 1985. (Reprinted with permission.“)
of oral cancer
incidence
rates
Pathology Biopsy Service during the years 1975 through 1986, in general, showed a characterization of Connecticut oral cancer very similar to that of the CTR study.“.‘3.‘6 Invasive squamous cell carcinoma constituted 72.5% of all Biopsy Service malignancies. With cases of lip cancer excluded (2.8% of total), there remained 379 cases of invasive intraoral carcinoma (69.7% of total). Thorough analysis of intraoral carcinoma cases revealed that age, sex, and subsite specificity were essentially similar to that seen in the CTR cases. In contrast, there was a significant difference in patterns of histologic grading in the two data sources in that well-differentiated tumors were more prevalent in cases from the University of Connecticut Biopsy Service, whereas moderately differentiated tumors predominated in the larger statewide study. Other Table 2. Male:Female Ratios of Oral Cancer for Case Numbers, Crude, and AgemAdjusted Incidence Rates by Time Period for Connecticut 1935 to 1985 No. of
Age-Adjusted Rates
Cases
Crude Rates
1935-1939 1940-1944 I945- I949 1950-1954 19551959 I960- I964 1965-1969 I970- 1974 I975 I979 I980- 1985
9.3 6.5 6.7 5.5 5.4 4.5 3.3 2.8 2.6 2.0
9.4 6.6 6.7 5.8 5.5 4.7 3.4 3.0 2.7 2.2
10.4
All years
3.6
3.8
4.4
Year
Age-adjusted by US 1970 Standard Reprinted with permission.”
Million
7.2 7.4 6.2 6.4 5.5 4.0 3.3 3.4 2.7
Population.
per 100.000 for males
(A! and for females
(B), Connecticut,
1935 to
than this notable exception, data from both sets of cases revealed that the general pictures of both overall oral cancer and invasive squamous cell carcinoma were quite similar. I4 Discussion
Clearly, the most dramatic finding of this study was the nearly threefold increase in the age-adjusted incidence rate of intraoral squamous cell carcinoma among Connecticut females over the 51-year period. This increase in female oral cancer incidence combined with a slightly reduced incidence in males in the past 20 years is clearly the major factor responsible for the observed steadily diminishing male-tofemale ratio for oral cancer during the period 1935 to 1985. We project that if this trend continues, the incidence of Connecticut oral cancer in women will equal that in men by the mid-1990s (Fig 3). Although the determination of cause-and-effect relationship is beyond the scope of this descriptive epidemiologic project, the increase in oral cancer incidence rate among Connecticut women over this ZI-year period has paralleled the increased exposure of women to tobacco and alcohol, which began in the 1920s and continues to the present time. The female birth cohort analysis supports this hypothesis in that cohorts with highest oral cancer incidence rates would have been either adolescents or young adults at the time when smoking in females became socially acceptable. The hypothesis is further supported by the findings of Harris, who studied patterns of cigarette smoking among successive birth cohorts of US men and women from 1900 to 1980.” It was found that maximum exposure of women to smoking probably occurred in those who were then in their fifth and sixth decade of life.
1156
CHANGING TRENDS IN ORAL CANCER,
Table 3. Site Distribution of Intraoral Squamous Cell Carcinoma by Sex for Connecticut 1935 to 1985 No. of Males (%‘o)
Site
No. of Females (g)
No. of Both Sexes (%c)
Tongue Gingiva Floor of mouth Buccal mucosa Palate Retromolar area Miscellaneous sites
1942 (41.8) 386 (8.3) I I98 (25.8) 253 (5.4) 476 (IO.21
604 (39.5) 186 (12.2) 295 (19.3) 122 (8.0) 206 (13.5)
2546 (41.2) 572 (9.3) 1493 (24.2) 375 16.1) 682 (I I .O)
134 (2.9)
32 (2.1)
166 (2.7)
Total cases
465 I
262 (5.6)
85 (5.6)
347 (5.6)
IS30
6181
Reprinted with permission.”
Additionally, it can be noted that recent smoking cessation rates for men have exceeded those for women. Hence, the above observations are all supportive of the hypothesis that tobacco-related factors have contributed significantly to the trend of increasing oral cancer incidence in the Connecticut female population. The contribution of two known dietary factors among women (poor nutrition during the Great Depression and war years’* and increased alcohol consumption’) also may be significant, but the relationship is less clear. Because, in general, heavy drinkers are also heavy smokers, it is difficult to separate the effects of these two variables.” Carefully controlled future studies will be necessary to determine relative contributions of alcohol and tobacco to the observed increase in female oral cancer incidence. Another factor that supports the argument for the influence of tobacco is the expanding presence of women in the workforce. In recent decades, women have assumed more positions in business and indus11 1
1’
I
I
1
I
I
1
1935.39194044 1945.491950.5419S5.59l%W
I
I
I
I
1965.691970-741975.791980.8S
Year
FIGURE 3. Male:female ratios of age-adjusted incidence rates of oral cancer by time period. Connecticut, 1935 to 1985. (Reprinted with permission. ’ ‘)
1935 TO 1985
try that were previously associated almost exclusively with males. It is therefore plausible that along with their emergence from the relatively protective environment of the home, women have concurrently become exposed to higher concentrations and a greater variety of carcinogenic materials, including tobacco. Whether acting alone or in concert with other cancer-producing factors, such environmental influences may contribute to the observed increased incidence of oral cancer in Connecticut women. Further study is needed to identify risk factors linked to new trends in women’s life-styles and the degree to which they serve to initiate or promote oral carcinogenesis. The fourfold increase in the incidence of intraoral squamous cell carcinoma observed in our data in young males aged 30 to 39 also is worthy of discussion. In that a similar trend was not seen among females of comparable age, this observation could reflect the introduction of possible new risk factors in young men, including, among others, increased exposure to smokeless tobacco or possibly to viral agents. While the use of smokeless tobacco products among Connecticut youngsters is admittedly lower than that of individuals of similar age elsewhere,‘O the practice still enjoys unprecedented popularity.“-” Although the duration and extent of use of these agents varies widely on an individual basis, it is likely that local application and prolonged direct contact of known carcinogens with immature oral mucous membranes may be especially deleterious.‘4 For one thing, the earlier a carcinogen is applied to any susceptible tissue, the sooner the onset of neoplastic transition. It is also possible that early exposure of vulnerable, highly labile, oral epithelium may significantly reduce the period of latency of oral carcinogenesis, resulting in precocity of onset of squamous cell carcinoma. With respect to the possible viral contribution to the etiopathogenesis of oral carcinoma now and in the future, the following merits consideration. The oncogenic properties of several strains of human papillomavirus and some herpes viruses are well established.25-28 These viruses are ubiquitous and are frequently transmitted to the mouth through oral-cutaneous, oral-genital, or oral-anal contact, and may produce recognizable mucosal lesions like verrucae, condylomas, and papillomas.4.‘y.30 Alternatively, they may colonize existing hyperkeratoses to produce changes in epithelium ranging from mild histologic viral modification to frank dysplasia and even carcinoma.3’.32 Given the reputed increasing degree of sexual activity in younger males,33 often with multiple partners, the concomitant likelihood of venereal infection with oncogenic viruses could play a significant role in pathogenesis of oral epi-
1157
CHEN ET AL
thelial cancer. It is conceivable that such viruses, acting as primary oncogenic agents. or in Collusion with various indigenous or acquired factors (including tobacco products, alcohol, and others). could serve to partially account for the observed rise in oral cancer incidence in this population group.
79.30.31
Perhaps the most intriguing conjecture on viral pathogenesis of oral squamous cell carcinoma in younger men is that focused on the uncommon but possible contribution of the human immunodeficiency virus CHIV).“4-37 Recently, squamous cell carcinoma has been found to occur more frequently in HIV-infected homosexual men than is typical of non-HIV-infected individuals in this age group.‘” While it is doubtful that HIV itself exerts a direct carcinogenic influence on oral epithelial tissue. it is conceivable that it may participate in development of oral cancer through its ability to diminish cellmediated immunity, thereby permitting a number of potentially oncogenic opportunistic infections.“.4” In this sense, both impaired immune surveillance and compromised immunity brought on by HIV infection could “fertilize the soil,” thus setting the stage for premature onset of oral cancer. In our analysis dealing with frequencies of occurrence of intraoral squamous cell carcinoma in various anatomic subsites, we found that the tongue was the most common site, followed. in order of decreasing frequency, by floor of mouth, palate. and gingiva (alveolar ridge).‘j This site predilection is in general agreement with previous studies that define the gravity-dependent oral mucosal reservoir regions as “cancer-prone.“7.4’3”’ These areas (floor of mouth. ventrolateral tongue, retromolar-soft palate complex) are exposed to higher concentrations of carcinogens and other harmful products because of their prolonged contact in areas of salivary pooling. The cancer-prone nature of these sites has been corroborated in many studies.“~43.44 As our study demonstrates, the Connecticut oral cancer incidence is evidently somewhat proportional to population density.” This apparent correlation between oral cancer incidence and population density is most likely due to different specific environmental and socioeconomic factors characteristic of the respective regions. In general, more densely populated urban areas expose residents to increased levels of environmental pollutants, such as motor vehicle exhaust and industrial waste. Incorporated into the atmosphere and the water supply, these noxious agents constantly bombard the more confined city dweller with relatively higher levels of carcinogens over extended periods of time. Thus, unlike their rural counterparts, it is likely that individuals living in more densely populated regions are
at greater risk for development of malignancies involving the aerodigestive tract. Aside from industrial pollutants, it is likely that other carcinogens, such as microbial agents, also operate more effectively in crowded population settings.4”-48 Socioeconomic factors often associated with urban life, including poverty, crowding, run-down housing, poor nutrition, and inadequate medical attention, may render the city dweller a more likely candidate for oral cancer than his or her “country cousin.” The findings of this study serve to raise interesting questions regarding possible factors influencing the etiopathogenesis of intraoral squamous cell carcinoma. It would seem that factors other than tobacco and alcohol may be either directly or indirectly involved in the initiation of this malignancy. Specific factors. plus the extent to which they play a role in carcinogenesis, remain to be determined by future scientific investigations. Findings of such studies should provide invaluable information to the clinician with regard to patient and professional education necessary for early detection, prevention, and effective management of oral cancer in years to come. References I. Silverberg E. Lubera .I: Cancer statistics. CA 37:2, 1987 1. Lucas RB: Pathology of Tumors of the Oral Tissues (ed 2). London. Churchill Livingstone, 1972. pp 121-146 3. Rowe NH: Oral cancer: General considerations. J Mich Dent Assoc 56:242, 1974 4. Silverman S Jr: Epidemiology, it, Silverman S Jr ted): Oral Cancer (ed 2). New York. NY, American Cancer Society, 1985. pp 7-34 5. Douglass CW, Gammon MD, Horgan WJ: Epidemiology of oral cancer. in Shklar G (ed): Oral Cancer: The Diagnosis. Therapy, Management and Rehabilitation of the Oral Cancer Patient. Philadelphia. PA. Saunders, 1984. pp 84-89 6. Mahboubi E. Sayed GM: Oral cavity and pharynx, in Schottenfeld D, Fraumeni J Jr teds): Cancer Epidemiology and Prevention. Philadelphia. PA, Saunders. 1982. pp 588-592 7. Shafer WG. Hine MK, Levy BM: A Text Book of Oral Pathology (ed 4). Philadelphia. PA. Saunders, 1983, pp 92119 8. Mashberg A. Barsa P: Screening for oral and oropharyngeal squamous carcinomas. CA 34:262. 1984 9. Wynder E, Bross IJ. Feldman RM: A study of the etiological factors in cancer of the mouth. Cancer 10:1300. 1957 IO. Chen J: Descriptive epidemiology of oral cancer in Connecticut. 1935-1985. Masters thesis. University of Connecticut, Farmington. 1988 I I. Chen J, Katz RV. Krutchkoff DJ: Epidemiology of oral cancer in Connecticut, 1935-1985. Cancer 65:2796. 1990 12. Flannery J, Boice JD, Devesa SS. et al: Cancer registration in Connecticut and the study of multiple primary cancer, 1935-82. NC1 Monogr 68:13. 1985 13. Chen J, Katz RV, Krutchkoff DJ: Intraoral squamous cell carcinoma: Epidemiologic patterns in Connecticut from 1935 to 1985. Cancer 66: 1288, 1990 14. Krutchkoff DJ. Chen J. Eisenberg E. et al: Oral cancer: A survey of 566 cases from the University of Connecticut Oral Pathology Biopsy Service, 1975-1986. Oral Surg Oral Med Oral Pathol 70:192, 1990 15. World Health Organization: Histological typing of oral and
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oropharyngeal tumors, in International Histological Classification of Tumors. Geneva, World Health Organization. 1971, pp 17-18 16. Chen J. Katz RV, Krutchkoff DJ, et al: Lip cancer: An epidemiological analysis of 2291 cases. J Oral Pathol Med (submitted) 17. Harris JE. Cigarette smoking among successive birth cohorts of men and women in the United States during l9001980. JNCI 71:473. 1983 18. Devesa SS, Silverman DT. Young JL, et al: Cancer incidence and mortality trends among whites in the United States, 1947-84. JNCI 79:701, 1987 19. Cann C, Fried MP, Rothman KJ: Epidemiology of squamous cell cancer of the head and neck. Otolaryngol Clin North Am 18:367. 1985 20. Kegeles SS, Burleson JA, Miozza J: Cigarette and smokeless tobacco use among Connecticut adolescents. Am J Public Health 79:1413, 1989 21. United States Department of Health and Human Services: The health consequences of using smokeless tobacco: A report of the Surgeon General. Bethesda, MD, National Institute of Health, DDHS publication no. (NIH) 86-2874 22. Christen AG: The case against smokeless tobacco: Five facts for the health professional to consider. J Am Dent Assoc 101:464. 1980 23. Harper S: In tobacco, where there’s smokeless fire. Advertising Age 5:85, 1980 24. Squier CA. Smokeless tobacco and oral cancer: A cause for concern? CA 34~242. 1984 25. Bishop JM: Cancer genes come of age. Cell 32:1018, 1983 26. Gross G, Plister H, Hagedorn M, et al: Correlation between human papillomavirus (HPV) type and histology of warts. J Invest Dermatol 78:160. 1982 21. Shillitoe EJ, Silverman S Jr: Oral cancer and herpes simplex virus-A review. Oral Surg 48:216, 1979 28. Shillitoe EJ, Greenspan D, Greenspan JS, et al: Antibody to early and late antigens of herpes simplex virus type 1 in patients with oral cancer. Cancer 54:266. 1984 29. Binnie WH. Rankin KV: Etiology, in Wright BA. Wright JM, Binnie WH teds): Oral cancer: Clinical and Pathological Considerations. Boca Raton. FL, CRC Press, 1988, pp 13-32 30. Lack E, Vawter GF. Smith HG, et al: Immunohistochemical localization of human papilloma virus in squamous papillomas of the larynx. Lancet 2592, 1980 31. Lehner T. Shillitoe EJ, Wilton JM, et al: Cell-mediated immunity to herpes virus type 1 in carcinoma and precancerous lesions. Br J Cancer 28:128, 1973 (suppl I) 32. Loning T, Reichart P. Staquet MJ, et al: Occurrence of pap-
CHANGING TRENDS IN ORAL CANCER,
1935 TO 1985
illomavirus structural antigens in oral papillomas and leukoplakias. J Oral Pathol 13:155, 1984 33. Cates Jr W, Toomey KE: Sexually transmitted diseases: Overview of the situation. Primary Care 17: I 1 1990 34. Shillitoe EJ, Greenspan JS, Silverman S Jr: Neutralizing antibody to herpes simplex virus type I in patients with oral cancer. Cancer 49:2315, 1982 35. Silverman Jr S: HIV-associated malignancies. in Silverman Jr S (ed): Color Atlas of Oral Manifestations of AIDS. Toronto, B.C. Decker, 1989, pp 65-80 36. Pindborg JJ: Classification of oral lesions associated with HIV infection. Oral Surg Oral Med Oral Pathol 67:292, 1989 37. Greenspan D, Greenspan J. Pindborg JJ. et al: AIDS and the dental team. Copenhagen, Munksgaard, 1986 38. Silverman S Jr. Migliorati CA. Lozada-Nur F. et al: Oral findings in people with or at high risk for AIDS: A study of 375 homosexual males. J Am Dent Assoc I I‘?:187, 1986 39. Lozada F, Silverman S Jr, Migliorati CA, et al: Oral manifestations of tumor and opportunistic infections in the acquired immunodeficiency syndrome (AIDS): Findings in 53 homosexual men with Kaposi’s sarcoma. Oral Surg Oral Med Oral Path01 56:491. 1983 40. Reichart P. Gelderblom HR, Becker J. et al: AIDS and the oral cavity. The HIV-Infection: Virology. etiology. origin. immunology, precautions and clinical observations in 1IO patients. Int J Oral Maxillofac Surg 16: 129, 1987 41. Lederman M: Bucco-pharyngeal cancer. Br J Radio1 29536, 1956 42. Lederman M: The anatomy of cancer. J Laryngol Otol 78:181. 1964 43. Mashberg A, Meyers H: Anatomical site and size of 222 early asymptomatic oral squamous cell carcinomas: A continuing prospective study of oral cancer II. Cancer 37:2149. 1976 44. Rich AM, Radden BG: Squamous cell carcinoma of the oral mucosas: A review of 244 cases in Australia. J Oral Pathol 13:459. 1984 45. Dorn HF. Cutler SJ: Morbidity from cancer. Public Health Monogr 56: I. 1958 46. Hirayama T: An epidemiological study of oral and pharyngeal cancer in Central and Southeast Asia. Bull WHO 34:41, 1969 47. Wynder DL. Stellman SD. Comparative epidemiology of tobacco-related cancers. Cancer Res 37:4608. 1977 48. Smith EM: Epidemiology of oral and pharyngeal cancers in the United States: Review of recent literature. JNCI 63: 1189. 1979
