TABLE 1.—Continued Study Sample Methods Observations Comments Greer and Gingival and Poulson, 1983 Periodontal (cont.) * Clinical ¢ 26% of smoke —* Smokeless examination less tobacco tobacco- conducted of users had site associated soft and hard specific gingival periodontal oral tissues. recession. degeneration * Lesions graded = * Users with defined. according to a lesions had * Did not assess scale developed longer use and the interrelation- by Axéll et al. higher daily ship of smoke (1976) and modi- exposure than less tobacco, fied by Greer users without cigarettes, and and Poulson. lesions. alcohol. Teeth . found no evidence of tobacco- associated dental caries." * No evidence of occlusal or incisal abrasion. © One case of cervical erosion. Greer et al., Salivary Glands a ¢ 45 smokeless * Cross-sectional © Of 18 tissue * Authors suggest tobacco users design, samples with that the degree (43 males and 2 . salivary glands, of salivary gland females); 15 sub- ° bes mons graded 4 demonstrated fibrosis, degen- jects in each y sialadenitis and erative change, developed by : f ae group known as Greer and degenerative and sialadenitis juveniles, young changes. may be associ- adults, and Poulson, 1983. ated with geriatric. © Examined only eA reaune tobacco brand ° Ages 13-74 lesions classified Pronie instead of a years. according to sialadenitis was generalized scheme. not shown for response caused ° Dem vad * Histomorpho- any of the three by all tobacco. . logical methods age groups. used on tissue ° Four patients specimens. (ages 21, 25, 50 * No statistical and 66) showed analysis either mild, conducted. moderate, or severe salivary gland fibrosis. 101 TABLE 1.—Continued Study Sample Methods Observations Comments Hirsch et al. Leukoplakia/ 1982 Mucosal Pathology ¢ 50 male habitual Cross-sectional * Interpretation of * Dose considera- snuff dippers. design. histomorphologi- tions were made * 41.3-year mean ° Subjects cal and histo- and confounding age (range 15-84 classified on a chemical results variables con- years}. four-degree scale demonstrated sidered. * Sweden. of lesion severity that the oral Differences in . (developed by muco: ff r eacnon brand of tobacco Axéll et al., i a Jasi uc used were taken 1976}; biopsies Yyperpiasia in into account. were taken. the basal cell Hi 7 layers. © Histomorpho- logical and his- | * Lethal damage tochemical was found in methods con- surface layers. ducted on sub- * Duration of use jects’ tissue and daily expo- specimens, sure to smoke less tobacco were ° Apbaceo and shown to affect histories the severity of ascertained from _ the leukoplakia. a questionnaire. »© Dysplasia could not be predicted by using sug- gested clinical degree of lesion classification. Salivary Glands « Tissue speci- * Statistical The salivary * Degenerative mens from 74% analysis con- glands and ex- changes not spe- of patients ducted: one-way cretory ducts cifically defined included salivary _ analysis of vari- showed degener- by authors. glands. ance and multi- ative changes of ple comparisons 4 More severe * Authors state using the fon ture. re iat generative Scheffe method. ound in the sur- eee ® face epithelium. changes an * 42% of salivary salivary glands glands demon- may be because strated sialaden- of differences in itis and degener- ative changes. Weak oxidative enzyme activi- ties noted in acinic cells in salivary glands with sialadenitis and degenera- tive changes. Some signs of metabolic atypia noted. Markedly degen- erative changes seen in salivary glands associ- ated with the more severely, clinically classi- fied lesions. brands of snuff and snuff- dipping habits. 102 TABLE 1.—Continued Study Sample Methods Observations Comments Jungell and Salivary Glands oriaahi © 441 military ¢ Cross-sectional « Resting salivary ¢ Authors inter- recruits. design. flow of snuff pret difference in . tionnair users was signif- resting salivary ° Ages 17-19 ° Questionnsire icantly higher flow to be a years. ascertain to- than that of reaction to the « Finland. bacco product nonusers. presence of the © 48(11%) were «use and drinking’, stimulated (ocal irritant habits and fre- ‘ snuff. snuff users. salivary flow quency of dental . was higher, but ¢ 18.9-year mean care. ge ( 17-21 not significantly, age lrange ® Clinical examina- among snuff years). tion conducted. users than * Biopsies taken of | among controls. 21 snuff users * There was no with lesions. difference in * Resting and buffering stimulated (par- capacity be- affin served as tween the two the stimulator) groups. salivary excre- tions measured. * Statistical analy- sis conducted: t-test. ¢ 10 nonusers of snuff also mea- sured for sali- vary excretions. Modéer et al., Gingival and 1980 Periodontal * 232 school ¢ Cross-sectional « The use of snuff * Authors state children: 119 design. demonstrated a snuff use may maies, 113 ¢ Interviewed significant influence gingi- females. about tobacco relation to gingi- _—-val tissue product. use his- vitis after con- directly result- ° awe years mean tory and oral trolling for ing in gingivitis. " hygiene prac- plaque. A . * 11% of males tices. « Effects of snuff © Examiners blind were regular « Standardized ects of snuff to responses ndardiz on the gingival from interview. snuff users. dental indices tissue included ¢ Sweden. i to vn oral both location of hygiene’ and. the snuff and as periodontal a predictor of conditions. gingivitis in . general. * Dental caries assessed clini- cally and radio- graphically. * Statistical analyses con- ducted: cross tabulations, mul- tiple regression, and student's t-test. 103 TABLE 1.—Continued Study Sample Methods Observations Comments Offenbacher Leukoplakia/ and Weathers, Mucosal 1985 Pathology * 565 males from ¢ Cross-sectional = * Frequency of * Soft tissue 5 schools. design. ooanence of proonbetd not * 13.8-year mean = * Questionnaire soft tissue escribed. age (range 10-17 _ used to obtain pathology w aS + Method of years). history of tobac- elevated i y selecting schools co product use, efevated In users for subject. ° 75 33 ‘e) dental visits, and (Primarily due to ascertainment smokeless oT be ‘ increa reva- escri tobacco users. social history. . lence of white rote ned. . e t Xami- i e * Georgia. nationconducted Wo cqenme, variables. using some stan- sek f ribu cowal considered. ized indices, "8K for mu _ pathology in * Statistical analy- smokeless ses included: chi tobacco users square, hacia who were free of ratios, kappa co- gingivitis. efficient calcula- tions, and t-tests. ¢ Control group used. Gingival and Periodontal * Norelationship ¢ Smokeless to- between smoke- bacco use is less tobacco use and the preva- lence of gingivitis. Prevalence of gingival reces- sion signifi- cantly elevated in smokeless tobacco users. A significant attributable risk exists for gingi- val recession in smokeless tobacco users. Teeth Smokeless to- bacco users with gingivitis had significantly greater caries prevalence com- pared with non- users without gingivitis. Prevalence of caries was signif- icantly greater in users with gingi- vitis who used both snuff and chewing tobacco compared with nonusers with gingivitis or those who were gingivitis free. viewed as a co- factor with the presence of gin- givitis in pro- moting gingival recession. No clinical defi- nitions provided for the assess- ment of gingivi- tis or gingival recession. 104 TABLE 1.—Continued Study Sample Methods Observations Comments Peacock et al., Leukoplakia/ 1960 Mucosal Pathology * 1,838 employees © Cross-sectional * Highly signifi- ¢ Examiners blind of local textile design. cant relation- to interview mill. * Interviewed ships between responses. * North Carolina. about tobacco ¢ 4 tobacer * 90% of product use and an d oral cco use employees had given an oral feu oral either poorly eos leukoplakia a examination. fitting complete development dentures or only found for all age few and carious groups and for teeth. both sexes. * Many employees have had the habit since they were 3 years old. Poulson et al., Leukoplakia/ 1984 Mucosal Pathology © 445 subjects: © Cross-sectional © Of 56 smokeless © Examiners blind 52% females, design. tobacco users, 35 _—‘ to responses on 47% males. * Questionnaire a pad jesions questionnaire. © 56 (12.6%) administered ft ti © Definitions of smokeless to- (same as one Sot tissues. clinical states bacco users (all used in Greer * 33 (58.9%) provided. males). and Poulson, smokeless tobac- Comparisons to © 16.7. 1983). co users had mu- nonusers not year mean ws . cosal alterations. age (range 14-19 * Clinical exami- reported. years). nation conducted * Mucosal lesions . . Col of oral hard and —_—were found in * A history of con- Rural Colorado. . : founding vari- soft tissues. area of quid ables obtained. ° Lesions graded placement. Effects of by classification ¢ Duration of use variables not developed by and length of addressed Greer and daily exposure statistically. Poulson, 1983. were factors in the development of lesions. * Multiple lesions in the same subject reported. Gingival and Periodontal * Of 56 smokeless « Periodontal tobacco users,15 degeneration (27%) had site- defined. specific gingival recession: 2 users ° paneer had periodontal lesions only; ates not 13 had both oat all mucosal lesions stalustically. and periodontal destruction. 105 TABLE 2.—Summary of Selected Case Reports Number Product Duration Study Country of Users Age Used of Use Findings Archard USA 3 31 Snuff 1l years A homogeneous eosin- and 42 Snuff 20 years ophilic submucosal Tarpley, 60 Snuff 50 years deposit above the 1972 minor salivary glands did not initiate an in- flammatory response nor support the possi- bility that the deposits were amyloid. Christen, USA 1 36 Snuff 13 years Gingival recession, Armstrong, clinical leukoplakia, and periodontal bone loss, McDaniel, and tooth abrasion 1979 found where tobacco was habitually placed. Christen, USA 14 18-22 Snuff, 6 months 8/14 with clinically McDaniel, chewing to detectable gingival and Doran, tobacco 9 years _ recession; 9/14 with 1979 clinical leukoplakia; 11/14 with erythema- tous soft tissue changes where to- bacco or snuff was habitually held. Frithiof Sweden 21 31-79 Snuff 10-60 years 21/21 with snuff- et al, 1983 induced lesions local- ized to area where snuff was held; 2/21 with observable gingival retraction. Hoge and USA 1 20 Snuff 1 year Gingival recession and Kirkham, hyperkeratosis found 1983 where tobacco was habitually placed. Pindborg Denmark 7 Not Snuff 20-30 years 4/7 had whitish and reported mucous membrane Poulson, with a delicately folded 1962 appearance at site of snuff placement. Pindborg Denmark 12 39-83 Snuff 20-50 years 12/12 with mucous and membrane that was Renstrup, “whitish, sometimes 1963 yellowish-brown, dry appearance with a very delicately folded or finely grooved surface.”’ Zitterbart, USA 1 36 Chewing 24 years Gingival recession, Marlin, and tobacco “smokeless tobacco- Christen, users lesion,” and 1983 abraded occlusal sur- faces of posterior teeth found where tobacco was habitually placed. 106 THE EFFECTS OF SMOKELESS TOBACCO USE ON ORAL LEUKOPLAKIA/MUCOSAL PATHOLOGY AND THE TRANSFORMATION OF ORAL SOFT TISSUES Oral Leukoplakia/Mucosal Pathology Background and Definitions Various oral soft tissue effects of smokeless tobacco use have been reported in the literature. These effects include oral leukoplakia/mucosal pathology. The actual terms used and the definitions employed to describe these conditions vary widely from study to study (table 3). The World Health Organization (WHO) defines oral leukoplakia as a white patch or plaque that cannot be characterized clinically or pathologically as any other disease (1). The mucosal pathology that is found in smoke- less tobacco users also has been referred to as hyperkeratosis, an oral mucosal lesion that exhibits an abnormal whitish (keratinized) appear- ance clinically. The authors’ terms are employed when a specific study’s findings are described. However, in the discussion portion of the report, the general terms of oral leukoplakia/mucosal pathology are used. The association between smokeless tobacco use and oral leukoplakia/ mucosal pathology has been moderately studied. The WHO has stated that tobacco is an etiologic agent for the formation of oral leukoplakia (1). This association was reaffirmed at an International Seminar on Oral Leu- koplakia and Associated Lesions Related to Tobacco Habits (2). In a re view of the effects of tobacco habits other than smoking, the use of smoke- less tobacco/snuff was associated with the presence of leukoplakia (3). Studies in the United States Six studies have addressed the prevalence of oral leukoplakia/muco- sal pathology in smokeless tobacco/snuff users (4-9). In two of these studies, blindness of the examiners toward the tobacco habits of the subjects was maintained, and oral tissue findings in smokeless tobacco users and nonusers were compared (7,9). Three of these studies investi- gated adults (4-6) and three investigated adolescents (7,9). In addition, several case reports have described oral leukoplakia/mucosal pathology findings in smokeless tobacco users (10-13). Highlights of these studies and reports are summarized below. Offenbacher and Weathers investigated the oral tissue effects of smokeless tobacco use in adolescent males from the greater metropoli- tan area of Atlanta, Georgia (9). They used oral examinations and self- administered questionnaires on tobacco use. Of the 565 males who were examined, 75 (13.3 percent) used smokeless tobacco. The difference in the prevalence of mucosal pathology in smokeless tobacco users (22.7 percent) was statistically significant compared with that of nonusers (4.7 percent); however, the authors did not provide specific diagnostic 107 TABLE 3.—Variations in Terms Used and Definitions Provided for Leukoplakia/Mucosal Pathology Associated With Smokeless Tobacco Use by Studies Cited Study Term(s) Used Definition(s) Provided Comments Axéll,1976 = Snuff- A four-category classifi- The authors believe that dipper's cation scheme based on this is a well-defined lesion. tissue color, wrinkling, irritation that excludes it and thickening was used. from the diagnosis of leukoplakia. Christen, Clinical “Implies only the clinical The authors cite the Armstrong, leukoplakia. feature of a white patch WHO 1978 and Waldron and or plaque on the oral and Shafer 1975 McDaniel, mucosa which will not references (1,47). 1979 rub off and which cannot be characterized clinically or histologically as any other specific disease.” Christen, Leukoplakia. ‘‘Implies only the clinical § The authors cite the McDaniel, feature of a white plaque Waldron and Shafer 1960 and Doran, on the mucosa...” reference (48). 1979 Frithiof Snuff- “Tissue changes in the The authors cite the etal, 1983 induced oral mucosa” that aredue WHO 1978 reference for lesion. to snuff use. the definition of leuko- plakia and state that “since the snuff-induced lesion, with its typical clinical pattern and its specific etiology, obvi- ously constitutes a definite diagnostic entity, the term ‘leukoplakia’ is avoided...” Greer and Oral These lesions were In addition, lesions were Poulson, mucosal defined by a modification _ classified by their 1983 lesions of a clinical grading texture, contour, and (alterations) method developed by color. associated Axéll et al, 1976. with the use of smokeless tobacco. Hirsch, Snuff- These lesions were _ Heyden, and induced defined by the grading Thilander, lesions. method developed by 1982 Axéll et al, 1976. 108 TABLE 3.—Continued Study Term(s) Used Definition(s) Provided Comments Hoge and Hyper- No definition is provided, | The authors cite the Kirkham, keratotic- although the authors dis- Shafer, Hine, and Levy 1983 appearing cuss the ‘formation of a 1969 reference (49). tissue. hyperkeratotic zone in the region of the ‘snuff pouch’ where the tobacco is habitually held.” Moore, Oral No definition provided. _ Bissinger, leukoplakia. and Proehl, 1952 Offenbacher Mucosal No definitions provided. The pathological findings and pathology, identified by the investi- Weathers, soft tissue gators included morsica- 1985 pathology. tio, ulcer, keratosis/leuko- plakia, vesiculobulious, petechiae, abscess, erythema, mucocele, and pericoronitis. Peacock, Leukoplakia. ‘‘A pearly white plaqueon — Greenberg, the mucous membrane and Brawley, which could not be scraped 1960 off with a tongue blade.” Pindborg Leukoplakia. No definition provided. The investigators and Poulson, described the mucous 1962 membrane as having a slightly whitish, deli- cately folded appearance. Pindborg Snuff- No definition provided. The investigators de- and induced scribed the leukoplakias as Renstrup, leukoplakia. “slightly whitish, some- 1963 times yellowish-brown, dry appearance with a very delicately folded or finely grooved surface.” Poulson, Oral mucosal The clinical appearance of Alterations in texture, Lindenmuth, lesions these lesions was defined color, and contour of the and Greer, (alterations) by a grading method mucosal lesions also were 1984 associated developed by Greer and identified. with the use Poulson, 1983. of smokeless tobacco. Zitterbart, | Generalized No definition provided. The lesion was described Marlin, and smokeless clinically as ‘peculiarly Christen, tobacco- wrinkled and thickened.” 1983 users lesion. 109 criteria in this assessment. The range of mucosal pathologic findings in- cluded such conditions as morsicatio (cheek biter’s lesion), ulcer, kera- tosis/leukoplakia, vesiculobullous, petechiae, abscess, erythema, mucocele, and pericoronitis. Although 50 percent of the smokeless tobacco users with mucosal pathology had keratosis/leukoplakia com- pared with 3.8 percent of the nonusers with mucosal pathology, the authors did not identify the locations of the mucosal pathologies. Peacock, Greenberg, and Brawley reported a significant relationship between chronic tobacco use and the presence of oral leukoplakia* in a study of 1,388 textile mill workers in North Carolina (5). The 362 employees who reported using smokeless tobacco had a significantly higher prevalence of leukoplakia (34 percent) than did the 457 nonusers (7.4 percent). In addition, the authors noted a direct leukoplakia and age effect. In a study conducted in Denver, Colorado, Greer and Poulson exam- ined 1,119 teenagers in grades 9 to 12 to assess the relationship between oral tissue alterations and the use of smokeless tobacco (7). Smokeless tobacco was used by 117 (10.5 percent) of these teenagers. Of these, 42.7 percent had oral mucosal lesionst in the area of tobacco placement. Forty-six percent of the teenagers with mucosal lesions also had con- comitant periodontal tissue degeneration.t Poulson, Lindenmuth, and Greer examined a sample of 445 teenagers in five rural Colorado towns to assess the relationship betwen oral tissue alterations and smokeless tobacco use (8). Smokeless tobacco was used by 56 (12.6 percent) of the teenagers. Of these, 58.9 percent had oral mucosal lesions in the area of habitual tobacco placement. Concom- itant periodontal degeneration was noted in 39.4 percent of those with oral mucosal lesions. Contrasting the results of rural versus urban adolescent smokeless tobacco users, Poulson, Lindenmuth, and Greer suggested that the duration of use may be critical in the development of “oral lesions” (8).§ Those adolescents with oral lesions used smokeless tobacco longer (an average of 3.3 years in the rural and urban groups) than those without lesions in both the rural and urban groups (2.3 years and 2.2 years, respectively). In addition, the authors noted similar effects of different levels of smokeless tobacco use in daily exposure. Users with oral le- sions were exposed 205 minutes per day in the rural group and 177 minutes per day in the urban group compared with users with no oral le- sions (110 minutes and 53 minutes, respectively). Also, more than twice * Leukoplakia was defined as a ‘pearly white plaque on the mucous membrane which could not be scraped off with a tongue blade." + The authors used a modification of the classification method that was developed by Axéllet al. that identifies the oral mucosal lesions according to color, wrinkling, and thickening (14). } The authors define this degeneration as “site-specific gingival recession with apical migration of the gingiva to or beyond the cementoenamel junction, with or without clinical evidence of inflammation.” § The term “oral lesions’ used here includes periodontal tissue degeneration and oral mucosal lesions. 110 as many marked oral mucosal lesions were identified in the rural population as in the urban population. Smith et al. examined a population of 15,500 snuff users by cytologi- cal, histological, and visual means (6). Of these users, 1,751 (11.3 per- cent) demonstrated oral mucous membrane changes. Although no defi- nitions were provided, these changes were described as ‘‘cloudy or gray glistening” areas having ‘wrinkled appearance(s)’’ and presenting ‘white or red granular appearance(s)."’ The authors reported that when snuff was withdrawn, the tissue returned to normal appearance. Moore, Bissinger, and Proehl investigated the relationship between tobacco use and oral cancer in male patients age 50 years and older who attended the General Tumor Clinic in Minneapolis, Minnesota (4). The authors noted that a significant number of the patients who manifested oral leukoplakia (18 of 23—78.3 percent) used smokeless tobacco. A to- bacco user in this study was defined as a person who used the tobacco product for 20 or more years. Apparently, some of these 23 patients were also pipe, cigar, or cigarette smokers, although the exact number was not specified. The authors indicated that the most severe patches of leukoplakia were seen in patients who chewed ‘‘strong’’ tobacco and over a longer duration (no quantification reported). In most instances in which patients had stopped using smokeless tobacco, leukoplakia disappeared. Several case reports (table 2) have described oral leukoplakia/mucosal pathology at the site of smokeless tobacco/snuff placement (10-13). These cases represent males of various ages with differing years of smokeless tobacco/snuff use. Hoge and Kirkham reported that in one patient, withdrawal of snuff resulted in a reversal of the hyperkeratotic lesions (12). Studies in Scandinavia Studies of smokeless tobacco from Scandinavia have investigated the prevalence of oral leukoplakia/mucosal pathology in users (15-19). Axéll found 1,444 smokeless tobacco users (predominantly men) in the 20,333 Swedes who were examined for soft tissue lesions (17). Of these users, 116 (8 percent) had ‘‘snuff-dipper’s lesion”’ (see table 3 for definitions). The prevalence of oral leukoplakia among the total study population was 3.6 percent. Hirsch, Heyden, and Thilander (18) graded oral mucosal lesions on an established four-point scale (14) and correlated these findings with the snuff habits in 50 Swedes ages 15 to 84 years who used snuff routinely. Younger patients were found to have lower degrees of pathologic changes, while a significant predominance of older patients was noted with higher degrees. The authors reported that patients with oral mucosal lesions of the highest degree had used snuff an average of 34.7 years compared with the 9.2- to 13.6-year average for patients with lower degrees of pathologic changes. They also noted that patients with high degrees of pathologic changes dipped twice as long per day (an 111 average of 10.1 and 10.6 hours per day) as patients with lower degrees of pathologic changes (5.2 and 6.5 hours per day, respectively). Although these patients reported multiple tobacco habits, the authors stated that no differences in clinical grading were found between patients who used snuff only and those who used snuff and other tobacco products. In addition, several case reports have described oral leukoplakia/ mucosal pathology (table 2). In Sweden, Frithiof et al. examined 21 male snuff users ages 31 to 79 years (19). All had snuff-induced lesions that were localized to the area in the oral cavity where the tobacco was held. Similarly, leukoplakia lesions were found at the site of snuff place- ment in all 12 male users of snuff ages 39 to 83 years in a study in Den- mark (15). In this latter study, 3 weeks after one of the patients discon- tinued snuff use, the clinical appearance of the mucous membrane had returned to normal. In another report, four of seven Danish male users of snuff exhibited leukoplakia at the site of snuff placement (16). Discussion The studies from the United States and Scandinavia demonstrate that oral leukoplakia/mucosal pathology is associated with smokeless tobacco/snuff use. In two studies, a higher prevalence of oral leuko- plakia/mucosal pathology was found in users compared with nonusers of smokeless tobacco—22.7 percent compared with 4.7 percent (9) and 34.0 percent compared with 7.4 percent (5). In all of these studies, be- tween 8 and 59 percent of smokeless tobacco/snuff users were found to have oral leukoplakia/mucosal pathology. It appears that the oral leukoplakia/mucosal pathology noted in smokeless tobacco/snuff users is found commonly at the habitual site of tobacco/snuff placement. Using a similar grading classification for snuff-induced lesions (7, 14), all of the mucosal pathology that was noted in four studies was at the site of habitual tobacco placement (7,8, 17,18). Similarly, the majority of the oral leukoplakia/mucosal pathology that was described in the case reports was found where the tobacco/snuff was usually placed. The duration of use (in years) and daily exposure (in hours or minutes) to smokeless tobacco appear to be critical in the development and sever- ity of oral leukoplakia/mucosal pathology. Three studies using similar approaches to the definition of oral leukoplakia/mucosal pathology and to the measurement of exposure noted this effect (7,818). Only two studies were designed to study the concomitant findings of oral leukoplakia/mucosal pathology and other tissue changes. The authors reported that 39.4 (8) and 46.0 (7) percent, respectively, of smokeless tobacco users with oral leukoplakia/mucosal pathology also had periodontal tissue degeneration (gingival recession). These oral soft tissue changes also were found at the site of habitual tobacco placement. In several studies where individuals had stopped smokeless tobacco use, the oral leukoplakia/mucosal pathology disappeared (4,6,12,15). 112 Transformation of Oral Soft Tissues Background and Definitions The previous section that discussed smokeless tobacco-induced leu- koplakia noted that clinically observable changes in soft tissue mor- phology do occur as a result of smokeless tobacco use. Smokeless tobacco-associated lesions that have been traditionally classified as leu- koplakias (white lesions) offer varying clinical degrees of differentiation and may persist or progress with continued smokeless tobacco use. Additionally, some leukoplakias have been observed to resolve clinically upon the cessation of smokeless tobacco use. This section of the report addresses the transformation of oral soft tissues. It discusses the poten- tial for smokeless tobacco-induced lesions to regress, persist, or continue to progress to lesions with higher malignant potential or to malignancy. There are varying clinical and histologic definitions in the scientific literature related to tobacco-induced changes (transformation) of oral soft tissues. The following definitions represent those most frequently encountered. It will be noted when significant variation of these defini- tions occurs in studies cited: * Oral leukoplakia—a white patch or plaque that cannot be charac- terized clinically or pathologically as any other disease (1). * Snuff dipper’s leukoplakia—a leukoplakia associated with the use of smokeless tobacco. These are further characterized as to differ- ing morphologic forms. ¢ Erythroplakia—a lesion present as a bright red patch or plaque that cannot be characterized clinically or pathologically as any other condition, such as carcinoma or infection. ¢ Precancerous condition—a generalized state that is associated with an increased risk of cancer based on epidemiologic or histo- logic evidence. e Precancerous lesion—a morphologically altered tissue in which cancer is more likely to occur than in its apparently normal counterpart. e Acanthosis—an increased thickness of the spinous cell layer of the epithelium. ¢ Hyperkeratosis—an increased thickness of the keratinized layer of the epithelium. ¢ Hyperparakeratosis—an increased thickness of a normally para- keratotic layer of the epithelium, ie., surface cells with retained nuclei. ¢ Hyperorthokeratosis—an incrased thickness of a normally kera- totic layer of the epithelium, i.e., surface cells without retained nuclei. 113 * Chevron keratinization—a keratinization pattern typified by verti- cal streaks of parakeratinization that extend to the epithelial sur- face and create surface irregularities by extensions of the outer sur- face layer. ¢ Dysplasia—abnormal tissue development characterized by vary- ing numbers and degrees of morphologic cell changes that reflect grades of severity. ¢ Dysplastic changes include the following: — Pleomorphism in the size and shape of cells and their nuclei. — Abnormal numbers of cells undergoing mitotic activity (discrep- ancy in maturation). — Atypical mitotic cells. — Cytoplasmic atypicalities (altered nuclear to cytoplasmic ratio). — Hyperchromasia. ~— Irregular nuclear borders. — Basal cell hyperplasia. — Loss of polarity. * Carcinoma in situ—a significant number of dysplastic epithelial cell changes that extend from the basal layer to the surface layer without violation of the basement membrane. * Verrucous carcinoma—a clinically verruciform cancer of epithelial tissue that tends to be slowly and locally invasive with a metasta- sis and mortality potential that is lower than classic squamous cell carcinomas. The cells are well differentiated. ¢ Squamous cell carcinoma—a cancer of the stratified squamous epi- thelium that has varying clinical appearances, is invasive, extends beyond the basement membrane, and has a great potential for metastasis. Evidence of the relationship between smokeless tobacco use and the transformation of oral soft tissues is represented by the following: 1. Clinical reports describing tobacco habits of persons with graded oral lesions. 2. Followup (cohort) studies of tissue changes, including trans- formation to malignancy, among patients with leukoplakia. 3. Case-control studies or case series of oral cancer describing con- comitant leukoplakia. A review of the evidence in each of these study areas follows: Clinical Reports of Oral Lesions in Association With Smokeless Tobacco Use Hirsch, Heyden, and Thilander (18) graded oral snuff-induced mucosal lesions in 50 patients on a four-point scale according to criteria developed by Axéll (14): 114 Degree 1: A superficial lesion with a color similar to the surround- ing mucosa, slight wrinkling, and no obvious thickening. Degree 2: A superficial whitish or yellowish lesion with wrinkling and no obvious thickening. Degree 3: A whitish-yellowish to brown lesion with wrinkling, intervening furrows of normal mucosal color, and obvi- ous thickening. Degree 4: A marked white-yellowish to brown lesion with heavy wrinkling, intervening deep and reddened furrows, and heavy thickening. Snuff habits and drinking habits of the patients were obtained from questionnaires. Patients in the degree 4 category had been snuff dippers significantly longer than the rest of the patients. Also, patients in de- grees 3 and 4 dipped approximately twice as long per day as did pa- tients in degrees 1 and 2. The daily exposure to snuff was significantly longer in degree 4 (10.6 hours) than in degrees 1 (5.2 hours) and 2 (6.5 hours). When total exposure was compared between the four clinical groups taking into account hours of use per day as well as years of use, significant differences were found. In this study, no significant differences could be found with regard to clinical grading and histological appearances between patients with multiple habits (snuff, smoking, and drinking) and those who only used snuff. The four clinical degrees of lesions exhibited an age-dependent ef- fect with younger patients usually found in clinical degrees 1, 2, and 3 and a significant predominance of older patients noted in degree 4. Degree 4 lesions included an increased number of mitotic figures, edema, and slight to moderate inflammation compared with the other three degrees. Kighteen percent of the patients exhibited slight epithe- lial dysplasia, and lesions with slight epithelial dysplasia were found in all categories. Patients in the dysplastic group had been snuff dippers longer on average (23.9 years) as compared with those without dyspla- sia (19.5 years). No case of moderate or severe dysplasia was noted. (The authors referenced the WHO Collaborating Center for Oral Precancer- ous Lesions as the definition for dysplasia (1).) Axéll, Mérnstad, and Sundstrém obtained biopsies of the oral mucosal lesions of 114 male dippers ages 20 to 88 years from a sample of 1,200 Swedish snuff dippers (14). Clinically, lesions were graded (degrees 1 through 4) based on color and morphology. Lesions of higher clinical degrees were associated with greater daily exposure to snuff in terms of hours and grams of exposure. All but one of the biopsies showed increased epithelial thickness. The outer layers appeared vacuo- lated with occasional remnants of cell nuclei. Lesions in degrees 3 and 4 had more pronounced surface layers. Acanthosis was evident in all of the clinical groups. None of the biopsies showed changes that were interpreted as cellular atypia or epithelial dysplasia. The cessation of 115 snuff dipping for a few days was reported to result in clinical regression of the lesions with loss of the vacuolated layer. Greer et al. reviewed clinically and histologically examined smokeless tobacco-induced leukoplakias from 45 patients ages 13 to 74 years (20), following criteria that were previously established by Greer and Poulson (7) as adapted from Axéll. The vast majority of the mucosal lesions were corrugated, white, and raised. No evaluations for an inter- relationship between smokeless tobacco use, smoking, and alcohol use and clinical or histologic tissue changes were attempted. Histologic examinations for specific changes were reported. Dark cell keratino- cytes characterized by a strong affinity for basic dyes and by electron density of their cytoplasm and nucleus and suggested as dedifferenti- ated precursors of a neoplastic keratinocyte were found in 17 of 45 cases. However, their presence was unrelated to the clinical degree of the lesion. While they have also been observed in leukoplakias that are associated with smoking (or other causes), the control group of nontobacco-induced hyperkeratoses demonstrated dark cell keratinocytes in only 3 of 45 cases. Chevron keratinization of the epithelial layer representing altered cellular maturation was present in 42 of 45 smokeless tobacco-induced leukoplakias but in only 4 of 45 control leukoplakia cases. Koilocytotic changes appearing as vacuolated epithelial cells that may obscure the cytoplasm or appear with pyknotic nuclei, which are often associated with inclusion of viral particles in epithelial cells, were present in 27 of 45 smokeless tobacco-induced leukoplakias, In the entire sample of 45 cases, only 1 case of dysplasia (described as ocewring in a long-term smokeless tobacco user) was identified. Three of the following characteristics had to be present for a lesion to be characterized as dysplastic: * Loss of cellular polarity. ¢ Basal cell hyperplasia. ¢ Altered nuclear/cytoplasmic ratios. ¢ Anaplasia. ¢ Dyskeratosis. Atypical mitoses. Because the dysplasia case also involved the use of alcohol and smok- ing, it is not possible to attribute its appearance solely to smokeless tobacco use. Ina study of 21 Finnish military recruits ages 17 to 21 years, mucosal lesions corresponded to the site of snuff placement and included the alveolar and labial mucosa to varying degrees (21). The duration and in- tensity of snuff use for this specific group could not be determined from the study. Epithelial hyperplasia and acanthosis were universally found under the light microscope. Hyperorthokeratinization was noted in 12 cases, hyperparakeratinization in 9 cases, and Chevron-type keratiniza- 116 tion in 1 case. One case of mild epithelial dysplasia was noted that in- cluded atypical and increased mitoses and loss of basal cell polarity. The authors concluded that this suggests a positive relation between snuff dipping and malignant changes. Van Wyk biopsied 25 snuff-induced lesions from Bantu smokeless tobacco users whose lesions had existed from a few weeks to 40 years (22). Comparison biopsies were also taken from healthy parts of the mucosa in the users, from healthy mucosa in nonusers, and from other white lesions and squamous carcinomas. From the biopsies obtained from snuff users, 18 cases of acanthosis, 23 cases of parakeratosis, 5 cases of keratosis, and 4 cases with numerous mitotic figures, pleo- morphism, hyperchromatism, and an irregular basal cell layer were noted. Additionally, 11 showed a disrupted appearance of the basement membrane. Those not associated with inflammation were considered possibly to be premalignant. Epithelium featuring these characteristics has been referred to by some as “disquiet epithelium.” Contrarily, the author stated that “the impression is gained that no relationship exists between oral malignancy and the use of snuff.’” This was based on the widespread use of snuff but the occurrence of only one case of alveolar or sulcular cancer (not in a snuff user) in the hospital during this study. Several investigators have described connective tissue changes in snuff-induced lesions. A hyalinized, eosinophilic material that occurs well below the epithelium and around the minor salivary glands or in a plane that is generally parallel to the epithelial surface has been reported by Pindborg et al. (16), Archard et al. (23), Axéll et al. (14), and Greer et al. (20). The exact nature of and underlying explanation for the finding are not clear. Additionally, the role of such a histologic finding in the development or progression of premalignant or malignant lesions has not been identified. Cohort Studies Several investigations have followed persons with oral lesions for subsequent health outcomes. Smith reported the 10-year followup results on a group of patients with smokeless tobacco-induced leuko- plakias (24). In the original study, oral cytologies were performed on 1,751 patients presenting with leukoplakias out of 15,500 snuff users (6). Results of the oral cytology examination consistently indicated only benign hyperkeratoses.* Biopsies were made of 157 leukoplakic lesions. However, no objective criteria for lesions selected for biopsy were of- fered. None of the biopsies showed changes consistent with dyskera- tosis or malignancy. These patients were followed with repeat cytology smears for 5.5 years. No additional significant mucosal changes were * The use of oral cytology for detecting dysplastic changes in leukoplakic lesions is less than satisfactory because of a high rate of false negative findings. The hyperkeratinized nature of leukoplakic lesions renders them resistant wo eae cytology scraping technique. Cellular changes in deeper layers of the epithelium would thus likely be missed (25). 117 reported. In a subsequent 4.5-year followup (10 years total followup), periodic biopsies were done on 128 of the 157 patients who had originally received biopsies (24). The authors reported no dyskeratosis or carci- nomas in the followup study. The method of followup was not specified. Significant numbers of patients were lost, and the clinical and histologic diagnostic criteria were not fully described. A prospective study of oral cancer among persons with oral leuko- plakia or other possible precancerous lesions was conducted in the Ernakulum district, Kerala State, India, as part of a 10-year followup to a much larger study of 50,915 adults in 5 rural districts of India (26). Among those individuals who had been diagnosed as having a leuko- plakia during the original survey, there was a malignant transforma- tion rate of 9.7/1,000 per year for those who only chewed tobacco. For those who both smoked and chewed, the rate was 5/1,000 per year, while no malignancies were reported for individuals with or without tobacco habits who had not had a previous oral lesion. The transformation rates among those with lesions were much higher than rates reported in the United States or European studies. While these results are not directly comparable to United States or European studies since the tobacco chewed in India is a variable mixture of betel leaf, areca nut, slake lime, and coarse tobacco, they suggest that the persons with leukoplakia are at increased risk of oral cancer. Specific clinical morphotypes of leukoplakia demonstrated varying potentials for malignant transfor- mation: homogeneous, 2.27 percent; speckled, 21.4 percent; and ulcer- ated, zero percent. In a small study of English coal miners, 8 of 22 patients with leuko- plakia who chewed tobacco were followed for 5 years (27). Five of the eight cases showed no advance in the lesions, and two showed regres- sion. The author does not specify whether these were clinical or histo- logic determinations or whether the smokeless tobacco habit persisted in all cases. One lesion that had been regarded as benign showed some hyperorthokeratosis and acanthosis of the epithelium but with no more than “minor epithelial atypia.’’ The clinical appearance of this lesion was reported to have regressed initially over an intermediate 2-year period despite continuance of the habit of tobacco chewing and smok- ing. Subsequent followup over a 2-year period indicated that the lesion had progressed to an exophytic squamous cell carcinoma. The site of the lesion was where the patient had held tobacco for 30 years. While the malignant transformation rate in the group of chewing tobacco- associated leukoplakias was 12.5 percent, the small numbers and high dropout rate limit the significance of the finding. Of significance was the unpredictable course of the malignant lesion, initially regressing and then transforming into a squamous cell carcinoma. In a Danish study, 32 patients with snuff-induced leukoplakias from a group of 450 patients with leukoplakia were observed for a median time of 4.1 years (28). Each patient had also used alcohol, with 17 per- 118 cent claiming daily use. Thirty-three biopsies demonstrated hyperplas- tic epithelium with hyperparakeratosis in 87 percent of the cases; half showed vacuolated cells. One initial case of epithelial dysplasia was found, and one carcinoma was found to develop from a nondyskeratotic leukoplakia over the followup period. This represents a rate of premalig- nant or malignant transformation of 6.2 percent for either dysplasia or carcinoma. In comparing the rate of development of dysplasia and car- cinoma from snuff-induced leukoplakias to nonsnuff-induced leuko- plakias, the authors found no statistically significant differences. How- ever, the rate of transformation in both groups was higher than would be expected in individuals without leukoplakic mucosa. In an earlier report on a small sample of 12 white male snuff-using leukoplakia patients (use from 20 to 50 years), Pindborg and Renstrup did not find any malignant transformation (15). Biopsies were taken from sites where the snuff was held. All 12 showed unkeratinized hyper- plasia of the epithelium with a few deep streaks of parakeratosis and downgrowth and broadening of the rete pegs with the outer layers of cells being vacuolated and large. The authors state that snuff-induced leukoplakias are easily reversible. Based on the limited size of this sam- ple, definitive conclusions could not be made. Oral Lesions Concomitant With Oral Cancer Three hundred and thirty-three patients with cancers of the buccal cav- ity and pharynx from the Robert Winship Memorial Clinic in Atlanta, Georgia, were compared with three control groups: a group with dis- eases of the mouth other than cancer or with no diseases; a group with cancer of sites other than the mouth, pharynx, or larynx; and a group without cancer and whose mouths were not examined—see chapter 2 (29). The authors, citing leukoplakia as a precancerous condition, found leukoplakias ‘‘more commonly in women with low grade squamous car- cinomas arising in the mouth and with multiple cancers. Snuff dipping was frequently associated with leukoplakia and low grade cancer aris- ing in the mouth.” In a case-control study in Minnesota of cancers of the alveolar ridge, floor of the mouth, and buccal mucosa, it was noted that leukoplakias and cancers of the mouth were related to the use of snuff or chewing to- bacco (4). The most severe leukoplakias were reported among those who used ‘‘strong snuff’’ (no definition was provided) and held the quid at the same site for many years. Patients who quit using smokeless to- bacco reportedly had leukoplakias disappear in most instances. A number of patients had multiple primary carcinomas that were also specific to the site of quid placement. Cancer lesions were described as having developed slowly over a period of several years, although no evidence of periodic clinical or histologic assessment was provided. McGuirt reported on 76 oral cancer patients, most with carcinomas of the alveolar ridge or buccal mucosa, identified from the tumor registry 119 at the North Carolina Baptist Hospital who had a documented history of heavy smokeless tobacco use (30). Fifty-seven of these patients used snuff and reported no cigarette, pipe smoking, or alcohol habits. The range of use was from 10 to 75 years. Leukoplakias had previously been excised in 13.9 percent of the cases, and 47 percent had associated leukoplakias at the time of surgery. The author cited “panmucosal in- sult” from smokeless tobacco use as the cause of multiple lesions and recurrences—a type of field cancerization. From histologic evaluations of oral tissue among 23 Swedish patients with anterior oral vestibular cancer who were snuff users, leukoplakic lesions were noted outside the snuff-associated tumor in 5 (31). Leuko- plakia and multiple carcinomas occurred together with the snuff- associated lesion in three cases. Eleven of nineteen cases assessed for presence of candida were positive. The temporal relationship between candida and carcinoma was not ascertainable, nor was the potential etiologic role of candida. Rosenfeld and Callaway examined data from records at Vanderbilt University Hospital, Nashville General Hospital, and the office of Rosenfeld for cases of squamous cell carcinoma arising in the mucous membrane of the anterior two-thirds of the tongue, the floor of the mouth, the gingiva, and the buccal area (32). A total of 525 cases were examined in users and nonusers of smokeless tobacco—300 occurred on the gingiva and buccal areas. Among women with cancer of the buccal or gingival area, 90 percent had a history of snuff use. While no periodic quantitative or qualitative assessment of the natural history of the cancers is provided, the authors do offer the following clinical impres- sion of snuff-induced lesions in their study: These carcinomas arising in the inner cheek and gingiva frequently start as leukoplakia. Progressive thickening, cornification, and even- tual cauliflower-like ulcerations ensue. All stages in the progressive disease may be seen in microscopic sections from a mere slight in- crease in the keratin layer, through carcinoma in situ to invasive malignancy. Twenty-five cases of histologically confirmed buccal gingival cancer in female snuff users were identified at the University of Arkansas Medical Center from 1950 to 1959 (33). Eleven cases occurred at buccal sites, 10 gingival, and 4 buccal and gingival. The patients (ages 44 to 84 years—mean 67.5) had a smokeless tobacco habit between 20 and 50 years. The lesions corresponded to the site of habitual tobacco placement. Leukoplakia was a concomitant lesion and had been pres- ent for many years. Repeat biopsies of lesions were made over long periods in some of the patients. Leukoplakic lesions from other parts of the mouth often showed atypia. An evolution from leukoplakia to pseudoepitheliomatous hyperplasia to early squamous cell carcinoma was found. 120 Discussion In characterizing the role of smokeless tobacco use in the clinical and histologic course of oral lesions, there are several problems. First, oral leukoplakia should be considered a dynamic changing lesion of the oral mucosa (34). Lesions retain the potential to resolve, remain static, or progress depending on a variety of factors that may be either exoge- nous (e.g., smokeless tobacco use) or endogenous (e.g., natural tissue defenses and repair potential). To achieve comparability of results among investigators, a standard system for gauging epithelial dysplasia is needed. Patients then could be followed prospectively to quantify the incidence of dysplastic change, incidence of transforma- tion from a dysplastic state to a cancerous state, or in some cases transformation from an apparently benign to a cancerous state. But ethical considerations do not allow lesions to be monitored continuously from benign states to moderate and severe dysplasias and carcinoma in situ. The next best alternative would be to provide estimates of risk for malignant transformation based on empirical and clinical observations or at least to quantify descriptively the association that smokeless tobacco-induced lesions have with other lesions or other potential etiologic factors. The body of literature on smokeless tobacco-induced lesions and their potential for malignant transformation allows for the development of a conceptual model of the natural history of smokeless tobacco-induced lesions (figure 1). This model is a composite of various prospective, retrospective, cross-sectional, and case studies that relate to smokeless tobacco-induced lesions. It depicts progressive changes that may occur in some individuals who are habitual users of smokeless tobacco and potential outcomes that could include death or disfigure- ment for some individuals who use smokeless tobacco for several dec- ades. The data are clear that habitual smokeless tobacco use can pro- duce mucosal lesions (see leukoplakia discussion). It is also clear that where groups of patients with smokeless tobacco-induced leukoplakias have been followed for several years, cases of cancer have been identi- fied. Finally, when considering studies of oral cancers in habitual smokeless tobacco users, there appears to be a consistent finding of leukoplakias either having been previously excised in the area of habit- ual tobacco placement or being found concurrently with and in proxim- ity to oral cancers. In comparing studies on the transformation potential of smokeless tobacco-induced leukoplakias, it is found that different criteria have been used by various investigators in defining dysplastic changes. The number and nature of criteria that are considered and that are consid- ered adequate to classify a case as dysplastic are not consistent. Addi- tionally, the degree of agreement on diagnosis based on histology and clinical history between individuals has been shown to be quite variable. Pindborg, Reibel, and Holmstrup tested the degree to which a group of 121 FIGURE 1.—A Conceptual Natural History of Oral Mucosal Changes Associated With the Use of Smokeless Tobacco Diagnostic Oral Tissue Smokeless Tobacco Level Status Exposure Time HEALTH | Smokeless Months Tobacco to Habit Years Oral Lesions me een Low CLINICAL Leukcplakias Erythroplakias Degree | Probability Low + ¢ Degree || t ' Probability Degree iI! Moderate Probability High _—_—_ Dysplastic Changes Probability High HISTOLOGIC CANCER ee ee eens High Verrucous Carcinoma Squamous Cell Carcinoma 40+ —_—_— ® Locally Invasive *® Highly Invasive Years { * Unlikely Metastasis * Likely Metastasis t ' CLINICAL and Death Possible Death Highly HISTOLOGIC or Loss of Tissue Possible or Potential and Function * for Disfigurement * Potential for Recurrence in Survivors * —_—— L “These factors depend upon stage of diagnosis, form of treatment and continuation of habit(s}. 122 oral pathologists could agree on diagnoses where nine cases of epithelial dysplasia, carcinoma in situ, or initial squamous cell carcinoma were examined (35). Color photomicrographs and information on the topog- raphy of the biopsy were presented. The authors’ diagnoses were based on the criteria that are described in the report from the WHO Interna- tional Collaborating Center for Oral Precancerous Lesions (1). The degree of agreement with the authors’ diagnoses for the nine cases ranged between 10 and 78 percent. This could partially explain the range in prevalence and incidence of malignant transformation that is reported by various investigators. Other contributing factors in comparing studies could include differ- ent population groups in terms of age and gender and other confound- ing variables (e.g., smoking, alcohol use, and type of smokeless tobacco product used). Each of these limitations is suggestive of the type of research that is needed. THE EFFECTS OF SMOKELESS TOBACCO USE ON THE GINGIVA, PERIODONTAL TISSUE, AND SALIVARY GLANDS Background and Definitions Reports of gingivitis, gingival recession, and degenerative salivary gland changes associated with smokeless tobacco use are contained in the literature. As with the previous section on oral leukoplakia, the terms used and the definitions employed to describe gingivitis and gingival recession vary widely from study to study. Table 4 displays the variations found in the literature. As each study is described in the fol- lowing narrative, the authors’ terms are employed. However, in the discussion portion of this report, the general terms of gingivitis and gin- gival recession are used. General definitions for these terms and for sialadenitis follow: * Gingivitis—This condition refers to clinically detectable acute or chronic inflammation, either local or general, of the gingiva. *¢ Gingival recession—In general, this condition describes the apical migration of the gingiva with or without clinical evidence of inflammation. ¢ Sialadenitis—Inflammation of the salivary glands. Gingival and Periodontal Tissue Studies that assess the relationship between smokeless tobacco use and gingival and periodontal tissue effects are limited. The literature consists of several cross-sectional studies in teenagers and a few case reports. 123 TABLE 4.—Variations in Terms Used and Definitions Provided for Gingivitis and Gingival Recession by Studies Cited Study Term(s) Used Definition(s) Provided Comments Christen, Gingival recession, _No definitions The tissue changes Armstrong, periodontal Pocket, provided. were described in and and loss of alveolar general by the McDaniel, bone. authors. 1979 Christen, Clinically detectable No definitions _- McDaniel, gingival recession. provided. and Doran, 1979 Greer and Tobacco-associated ‘‘Defined as site- _ Poulson, periodontal specific gingival 1983 degeneration and recession with apical periodontal lesions. _ migration of the gingiva to or beyond the cementoenamel junction, with or without clinical evidence of inflammation.” Hoge and Gingival recession. _No definition provided. The authors defined Kirkham, the recession as having 1983 “exposed approxi- mately 5 mm of labial root surface” and having destroyed the “entire functioning border of keratinized gingiva.” Modeer, Gingivitis/gingival | Estimated onthe basis — Lavstedt, inflammation. of the gingival index and ABhund, of Lée and Silness, 1980 1963 (50). otinibachsr Gingivitis. No definition provided. — ani . . . eae . . . . Gingival recession. _ No definition provided. The gingival recession baal 5, was “considered slight to moderate, ranging in 1-4 mm apical migra- tion when present.” Poulson, Tobacco-associated ‘Defined as site _ Lindenmuth, periodontal degener- specific gingival and Greer, _ ation (other terms recession with apical 1984 include “periodontal migration of the deterioration,” and _ gingiva to or beyond “localized periodon- _ the cementoenamel tal degeneration junction, with or associated with the —_ without clinical site of tobacco evidence of placement’). inflammation.” Zitterbart, —_ Gingivitis. No definition provided. — Marlin, and Gingival recession. No definition provided. The clinical findings 1983 were described for each tooth site involved. 124 Studies in the United States Three cross-sectional studies have investigated the relationship of gingival and periodontal tissue changes and smokeless tobacco use in teenagers in the United States (7-9). Offenbacher and Weathers exam- ined the effects of smokeless tobacco use on mucosal pathology, on the presence of gingivitis and gingival recession, and on dental caries status (discussed in next section) (9). Of the 75 smokeless tobacco users, the authors noted 72 percent with gingivitis and 60 percent with gingival recession. In those with gingival recession, 6.6 percent presented with recession in direct juxtaposition to the location of the tobacco place- ment. The authors did not describe how many users of smokeless tobac- co had demonstrated combinations of these oral conditions. Also, no specific clinical definitions were given for the assessment of gingivitis or gingival recession, although the latter findings were described as “slight to moderate, ranging from 1 to 4 mm apical migration of gingi- val tissue.” The higher prevalence of gingival recession among smoke- less tobacco users (60 percent) as compared with that found in nonusers (14.1 percent) was found to be statistically significant. There were no statistically significant differences in gingivitis prevalence between smokeless tobacco users (72 percent) and nonusers (77.1 percent). Of 117 adolescent smokeless tobacco users in Denver, Colorado, Greer and Poulson noted that 25.6 percent had tobacco-associated periodontal degeneration (7). As noted earlier, this condition was de- fined as “site-specific gingival recession with apical migration of the gingiva to or beyond the cementoenamel junction, with or without clini- cal evidence of inflammation.”’ Concomitant mucosal lesions were noted in 76.6 percent of those who had periodontal degeneration (gingival recession). In a study of rural Colorado teenagers, Poulson, Lindenmuth, and Greer (8) described 26.8 percent of 56 smokeless tobacco users with peri- odontal degeneration (gingival recession) as defined by Greer and Poulson (7). Eighty-seven percent of these had concomitant mucosal lesions. Several case reports (table 2) describe the occurrence of gingival reces- sion and periodontal tissue destruction in individual smokeless tobacco/ snuff users (10-13). The patients in these case reports were males who ranged in age from 18 to 36 years with varying duration of the smoke- less tobacco/snuff habit ranging from 1 to 24 years. Although not uni- versally found, gingival recession was usually noted, and the majority of patients presented with recession that was specific to the site where the tobacco/snuff was habitually placed. Periodontal bone loss at the site of snuff placement was described in another patient who used snuff for 13 years (10). In one patient, 3 weeks after cessation of snuff use, there was no regeneration of the lost gingi- val tissue, although, as noted earlier, the hyperkeratotic areas had dis- appeared (12). 125