50 principal studies were identified, 20 of snuff, conducted in Scandinavia (two in Denmark, one in Finland and 17 in Sweden), 29 of CT, snuff or overall ST, conducted in the USA, and one of CT, conducted in England. No relevant studies were identified from other parts of North America or Europe. Table (Europe) and Table (USA) give some details of the 50 studies considered. Both tables are sorted by type of study and then by year of publication within type. Six are experimental studies investigating the short-term effect on oral mucosal lesions of quitting ST use, switching to a different brand of snuff, or changing the site of placement of the snuff. Of the 44 epidemiological studies, three are prospective studies and two are case-control studies, though one [5
] is a case-control study of oral and oropharyngeal cancer, with only the control group providing data relevant to this report. There are 39 cross-sectional studies, 26 of populations unselected by ST use and 13 of populations selected by ST use and/or presence of oral lesions. Some of the 50 studies are not independent. Thus, two studies [1
] involve a subset of subjects selected from those in a third [18
], while one study [38
] gives combined results from a number of groups of baseball players, the results for two of these being previously reported [31
]. Also, three studies [40
] give results for different endpoints using differently selected samples from the third National Health and Nutrition Examination Survey (NHANES III).
The earliest publication [13
] was in 1963, with five studies published in the 1970s, 13 in the 1980s, 18 in the 1990s and 13 since 2000. Many of the studies did not give details on when they were conducted. Of the 50 studies, 24 were of males and females, and 24 of males. Two studies [2
] did not give details on the sex of their subjects. Most of the studies were mainly or wholly of adults, but there were 10 cross-sectional studies of children, mainly of school students, but including one of adolescent football players aged 11 to 18 [32
] and one of teenagers attending dental health check-up [9
]. Some of the studies of adults involved quite young populations, including air force trainees [23
], military recruits [7
], college athletes [46
], 19 year olds [12
] and baseball players [31
]. Oral mucosal lesions were considered in 40 of the studies, with 19 considering indices of periodontal or gingival diseases, 10 dental caries, and three oral pain.
Oral mucosal lesions
Fifteen of the studies in Scandinavia provided information relating ST use to oral mucosal lesions. As shown in Table , 11 of these used the endpoint "snuff-dipper's lesion" as defined by Axéll et al
] and a further three used an endpoint which appeared to be similar. For convenience we will refer to these 14 studies as being of snuff-induced lesions (SIL). Only in one study [14
] was a clearly different endpoint used, of "oral leukoplakia", which could occur both in users and non-users of snuff.
Definitions of oral mucosal lesions used in studies in Scandinavia
Table summarizes the main results from the Scandinavian studies relating oral mucosal lesions to the use of moist snuff (snus). The single study of oral leukoplakia [14
], in Denmark, had no control group so could not compare lesion prevalence in snuff users and non-users, though it reported that only 32 of the 450 oral leukoplakia cases studied used snuff and that the presence of symptoms (such as pain or rough feel to the tongue) was much less prevalent in those who used snuff (3.1%) than in those who did not (23.1%, p < 0.01).
Prevalence of oral mucosal lesions in relation to snuff use evidence from Scandinavia
The remaining 14 studies generally reported a 100% prevalence of SIL in snuff users. Partly this was because in seven studies [1
] subjects had been, or appeared to have been, selected on the basis of SIL being present, but this was not always the case [2
]. The only exceptions were a study in Finland [7
] in which all the users with no lesion had either quit or started snuff in the previous three weeks, and a recent study of ice-hockey players in Sweden [20
] which reported no lesions in five users of portion-bag snuff. One study in Sweden [8
] reported total numbers of lesions, but prevalence seems likely to have been very high in snuff users.
As is evident from the results of the cross-sectional and case-control studies summarized in Table , severity of SIL was clearly associated with the length of time per day snuff was used for and with the amount of snuff consumed per day [5
], though the statistical significance of these relationships could not always be determined. The relationship of severity with duration of use was less marked [5
]. Severity was also lower in users of portion-bag snuff than in users of loose snuff [19
A number of the experimental and epidemiological studies investigated the effect of changing snuff habits on the presence and severity of SIL. The data in Table are all consistent with quitting in the short-term reducing the severity of the lesion [17
] and in the longer term eliminating the lesion [1
], and switching to lower nicotine, lower pH or portion-bag snuff also reducing severity [1
While it is clear from the above that SIL occurs in virtually all current users of moist snuff, with severity related to extent of use, the data in Table tell us little about the long-term health implications of the lesion. The study by Roosaar et al
] provides some additional information. Here 1,115 individuals with SIL were followed-up for 27–29 years, with a total of three incident cases of oral cancer seen, two in concomitant daily smokers. Though this was somewhat higher than expected (standardized incidence rate 2.3, 95% CI 0.5–6.7), none of the three occurred at the site of the original SIL.
Of the 15 Scandinavian studies considered, 14 consider use of moist snuff only and not other types of ST. The study of Andersson et al
], however, considered nine users of CT as well as 45 snuff users. They noted that seven of the CT users showed leukoedema in the buccal mucosa, and that six who placed the tobacco on a permanent site had degree 1 or 2 (Axéll) lesions at the site of placement.
The single study in England [50
], of coal miners, reported that 10 out of 280 CT users, 3.6%, had leukoplakia, as compared to none out of 122 non-chewers (p = 0.05). Here leukoplakia was defined as "a white patch that could not be rubbed off and which could not be diagnosed as being due to any other disease".
Twenty-four US studies provided evidence relating ST use to oral mucosal lesions. As shown in Table , the definitions of the endpoint used varied widely. Eight studies [22
] used a definition modified by Greer and Poulson [27
] from that used by Axéll [15
], and at least three studies [34
] used a similar definition. However, in some studies the endpoints were clearly not comparable, including one [42
] where the endpoint was any type of oral lesion and one [47
] where the definition specifically excluded alterations that resolved rapidly on discontinuation of ST use. Unlike the studies in Scandinavia, the conditions were usually referred to as oral leukoplakia or as oral lesions, with no specific reference to ST or snuff in the name of the condition, as in SIL. An exception was the Tomar et al
] which referred to the endpoint as "smokeless tobacco lesions". Indeed it is clear from Table , which presents the prevalence of these lesions in relation to ST use, that the endpoint definitions did not exclude the possibility of the lesion being present in non-users of ST. In fact, in all but one of the 15 studies which presented findings separately for users and non-users, including the Tomar et al
study, prevalence is greater than zero in the non-users.
Definitions of oral mucosal lesions used in studies in the USA
Prevalence of oral mucosal lesions in relation to ST use – evidence from the USA
Exposure is classified in Table by type (ST, snuff or CT) and by time (current, former, ever or unspecified use which may be equivalent to current). Fourteen of the US studies provided evidence on snuff use. Ignoring one study where the subjects were selected as having a lesion [22
], lesion prevalence in current snuff users was typically in the range 30–70%, though lower in two studies [45
] where the definition implied a more severe lesion, and in one study [31
] where the endpoint of "soft tissue lesion" was not further defined. Though lower than the near 100% prevalence reported in Scandinavia, it was clearly much higher than in non-users, with ORs ranging from 8.2 to 97.1 in six studies [23
]. In contrast the evidence of any increased prevalence in former snuff users is much weaker, with one case-control study [26
] reporting no increase, one cross-sectional study [39
] an increase of borderline significance, another cross-sectional study [31
] an increase, but based on very few subjects, and one experimental study [23
] reporting resolution of the great majority of lesions in US Air Force trainees after 6 weeks of a mandatory tobacco-free period.
Nine of the US studies provided evidence on use of CT, and in all of these lesion prevalence was lower in current users of CT than in current users of snuff. Indeed in the five studies where RRs and CIs could be estimated, risk was not elevated (OR 0.97) in one study [26
], was elevated but not significantly (ORs 3.39 and 3.16) in two studies [23
] and was only significantly elevated (ORs 15.0 and 2.5) in two [34
]. Oral mucosal lesion prevalence was not significantly associated with former CT use [26
Nineteen of the studies provided evidence on overall ST use; in ten of these data by specific type of ST were not available. Given the variation that could have existed in the type of ST used in the different studies (and in the endpoints considered), it is not surprising that there is also marked variation in the prevalence of oral mucosal lesions reported in the different studies. However, it is abundantly clear that there was a marked effect of use on lesion prevalence. Thus, all of the studies for which ORs (with CIs) could be estimated for current or ever ST use showed a significant increase, with ORs over 25 in three studies [21
] and the lowest OR, 3.90, being in a study [42
] where the endpoint was wide ranging and prevalence relatively high in non-users. Again, the evidence of an association was much weaker for former than for current users. Of the six studies reporting relevant data, five [26
] found no relationship, with a significant increase in former ST users reported only in one [44
Aspects of the dose-response relationship have been examined in many of the US studies. In one detailed analysis [34
], odds ratios compared to non-users of ST increased significantly with increasing amount of ST used, hours in the month, and recency of last use, with estimates of 354 (129–970) for users of four or more cans of snuff a week, 34.7 (9.4–128) for users of four or more pouches of CT a week, 361 (107–1215) for more than four hours ST use in the day and 201 (84-9-475) for used ST in the last hour. These associations were all found to be independently significant in a multifactorial analysis, but weaker associations with age of initiation and duration of ST use were not independent risk factors. The findings were unaffected by adjustment for age, race, education, cigarette smoking, alcohol consumption, and dental hygiene.
Though not usually analyzed in such detail, similar findings have been reported by other authors. In users of ST or of snuff, prevalence of oral lesions has consistently been found to increase with increasing amount used and/or frequency of use [23
] and with recency of use [23
]. These studies also found that prevalence increased with duration of use, though they generally did not test whether the effect of duration remained after adjustment for extent of current usage. Relationships of severity of oral lesions to extent and duration of usage have also been found [23
], though not always [30
The epidemiological data from Europe and the USA are consistent with demonstrating a striking and dose-related effect of current snuff use on the prevalence of oral mucosal lesions. In Scandinavia, snuff users have a near 100% prevalence of SIL, but the prevalence of the more varied lesions studied in the USA is typically lower. The association between current CT use and lesion prevalence, mainly studied in the USA, is clearly very much weaker. The lack of any very clear association with former use is consistent with reversibility of the lesion following cessation, and fits in with findings from the experimental studies, which typically show regression of the lesion on quitting after a relatively short period.
Periodontal and gingival diseases
A variety of indices relevant to periodontal and gingival diseases are considered here, as illustrated in the endpoint column for Tables and , where the results relating to ST use are given. Table summarizes findings from seven studies in Sweden, no other Scandinavian studies reporting results, while Table gives results from 13 studies in the USA. Changing and inconsistent diagnostic criteria, as well as a lack of standardized use of methods and terminology [76
] complicate the summarizing of evidence in this area. The endpoints in Tables and are as named by the authors of the original publications cited, and are defined more precisely there. The results are sorted so that similar endpoints are classified together, in order to facilitate the interpretation of the data. Some of the endpoints considered, such as plaque and calculus, do not of themselves indicate disease, but are indirectly related and the results are shown for additional information.
Snuff use and endpoints relevant to periodontal and gingival disease – evidence from Sweden
ST use and endpoints relevant to periodontal and gingival disease – evidence from the USA
The results from Sweden show no significant relationship, in any study, between snuff use and the presence of plaque or calculus, pocket depth, attachment loss, alveolar bone level, bone height or periodontal disease (defined as three or more teeth with pocket depth ≥ 5 mm). One study [6
] reported that snuff users had a significantly (p < 0.001) increased gingival index, but other studies [10
] showed no relationship with gingivitis, gingival index or gingival bleeding. Gingival recession was considered by five Swedish studies. Two of these [17
] provided no data for non-users of snuff, but of the others, one [10
] reported the highest rates of recession, but no significant increase in relation to ever snuff use, one [12
] reported a significant increase (OR 3.72, 95% CI 1.40–9.99), and one [18
] reported a significantly (p < 0.05) higher prevalence in users of loose snuff than portion-bag snuff.
The two US studies to provide some data relating to use of CT [31
] found no evidence of a relationship with plaque, gingival bleeding or attachment loss, though one of these [31
] reported a non-significant increase for gingival recession. However, some of the studies found a relationship between snuff or unspecified ST with some indices of periodontal or gingival diseases. While no significant increases were seen for plaque, calculus, gingivitis, gingival bleeding or pocket depth, the data, though somewhat inconsistent, suggested a relationship with gingival recession. Here, six studies provide relevant data, three in children or adolescents [29
] and three in baseball players [31
]. The two which reported very low rates of gingival recession [30
] found no association, but four [29
] did, significant except in the case of one small study [31
]. One of the studies [29
] reported high rates of recession and a strong relationship (OR 9.15, 95% CI 5.40–15.5), even stronger in patients with gingivitis. Two studies [24
] also reported a significant association of snuff or ST with attachment loss, though another study [30
] reported no significant relationship. Of two studies of periodontal diseases (see footnotes to Table for definitions), one [36
] found no relationship with ST use, but the other [43
] reported a significant increase in current users.
Based on the overall data from the US and Sweden, the evidence of a relationship with snuff or unspecified ST use is weak for gingivitis (or gingival bleeding), where a significant association is reported in only one out of eight studies, and for the more general term periodontal disease, where one of the three studies found a relationship. It is, however, rather stronger for attachment loss, where significant associations were reported in two out of four studies, and particularly for gingival recession, where four out of eight studies reported a significant relationship, and an additional study [18
] found that prevalence was almost nine times higher in loose snuff users than in portion-bag snuff users. Very limited evidence for CT did not demonstrate any relationship with periodontal or gingival diseases.
Table (Sweden) and Table (USA) summarize results relating ST use to presence of teeth and indices of dental caries. They are laid out in a style similar to Tables and , with results grouped according to the endpoints considered. Endpoints in Tables and are named as in the original publications cited here, with the reader referred to these publications for further definition.
Snuff use and endpoints relevant to dental caries and tooth loss – evidence from Sweden
ST use and endpoints relevant to dental caries and tooth loss – evidence from the USA
Two studies from Sweden [11
] provided no indication of an effect of snuff use on the number of teeth present. One of these studies [20
] also reported no relationship with having filled teeth. The third study [9
], of 14–19 year olds attending dental check-up, reported significant (p < 0.001) increases in snuff users in the mean number of decayed, missing and filled teeth, of decayed and filled proximal surfaces and of initially decayed proximal surfaces, though not in the mean number of decayed proximal surfaces. It should be noted, however, that these analyses were not adjusted for age, the snuff dippers being markedly older (71% aged 17–19) than the non-tobacco users (52% aged 17–19, p < 0.001). Within specific years of age, significant differences were generally not seen (except for decayed, missing and filled teeth in 17 year olds), but an overall age-adjusted test was unfortunately not reported. The analyses were also not adjusted for education.
Tooth loss in relation to ST use was investigated in three US studies. While one [38
] found no association with ST use, one [40
] found a significant relationship with current snuff but not current CT use, and the third [25
] reported a significant 14% increase in the rate of tooth loss in a large prospective study in which adjustment was made for a range of potential confounding variables, including age and social status.
Dental caries was studied in seven US studies. In six of these [27
] there was no significant evidence of a relationship with unspecified ST use. The seventh and by far the most comprehensive investigation [40
] was based on the NHANES III study. Results for a range of the endpoints studied are shown in Table . No significant difference was seen for snuff use for any index of dental caries (though, as noted above, it was for number of teeth present). In contrast, CT use was significantly associated with decayed or filled permanent teeth, decayed or filled root surfaces, and decayed root surfaces. In an analysis adjusted for age, race/ethnicity, education, and past-year dental visits, the OR for decayed or filled root surfaces was 4.18 (1.96–9.92) for current users of CT only and 0.67 (0.26–1.74) for current users of snuff only, compared to never users of tobacco. In current users of CT, the OR increased with the number of packs per week (trend p = 0.0002) and with years of use (trend p = 0.002). None of the other studies reported dose-response data for dental caries.
The overall evidence is suggestive of a possible relationship of ST use, particularly CT, with the risk of dental caries.