A. Introduction

The tobacco plant is native to the Western hemisphere, and the use of tobacco in smokeless forms (placed in the mouth or inhaled as a powder through the nose) predates the arrival and exploration of the West by Europeans. According to the historian Jan Rogozinski, the most common manufactured tobacco product in Europe until the early 1800s was a compressed plug or cake [29]. This product was relatively simple to produce and was amenable to transport and storage. The plug could be cut into large pieces for chewing, grated into smaller pieces for smoking, or ground into a fine powder for nasal inhalation. Smokeless forms were the favored method of use because a day's supply could be carried and conveniently used in industrial and agricultural work settings.

ST was the dominant form of tobacco used in the U.S. until early in the 20th century [29]. Developments in tobacco cultivation, curing and manufacturing, along with the invention of the safety match, resulted in the increased popularity of cigarettes. In addition, at the beginning of the 20th century tobacco spit inaccurately was believed to transmit tuberculosis, so bans on public spitting and spittoons resulted in a decline in ST use. The transmission of tuberculosis now has been understood for decades, and it does not include expectoration [30].

Use of all types of ST traditionally has been most prevalent in Southern states and in rural areas throughout the U.S.

B. Types of ST

As described below, ST is currently used by only a small proportion of American tobacco users. This is one reason that most Americans, including smokers, know almost nothing about ST products, or – even worse – are completely misinformed about even basic product characteristics. Thus, it is important to understand what these products are and how they are used.

ST products are not burned but instead are placed in the cheek or between the lip and gum. ST is used in many countries around the world, including those in the Middle East and on the Indian subcontinent. However, ST products in those regions are considerably different from those used in the West. For example, in India ST products are made by individual farmers and small companies with little control over fermentation and curing, which affects the production of potential carcinogens called tobacco-specific nitrosamines (TSNAs) [31]. In India ST is often combined with betel leaf (Piper betle), sliced areca nut (Areca catechu) and/or powdered agricultural lime [32], additives that enhance the toxicity as well as the psychotropic effect of tobacco [33, 34]. In addition, Indian ST users often smoke concurrently, which complicates efforts to assess the health effects of ST use [35, 36].

This report will focus on ST products used in Western societies, mainly the U.S. and Sweden. But ST is not a homogeneous category, even in these countries. Three traditional types of ST are used in the U.S.: powdered dry snuff, loose leaf chewing tobacco and moist snuff, and it is important to understand the differences among them with respect to their manufacturing and characteristics, the populations that consume them, and the consequential health risks, especially mouth cancer.

Powdered dry snuff (Figure 1)

Figure 1 Powdered dry snuff. Full size image

Dry snuff is made from fermented, fire-cured tobacco that is pulverized into powder. Nasal inhalation of dry snuff was widely practiced in Europe in the 17th and 18th centuries but declined thereafter [37]. Manufacturers in Germany and the U.K. still provide an array of flavored dry snuff products for a small number of contemporary users in those countries. In the U.S. powdered dry snuff, also called dental or Scotch snuff, is sold in small canisters. Since the early 1800s it has been used primarily by women in Southern states [29, 38], who place the powder on the gum or between the gum and cheek. However, use of dry snuff is declining, and sales have fallen 67% in the past 15 years [39].

Loose leaf chewing tobacco (Figure 2)

Figure 2 Loose leaf chewing tobacco. Full size image

Loose-leaf chewing tobacco consists of air-cured leaf tobacco from Pennsylvania and Wisconsin that is shredded, coated with sweet flavoring solutions and packaged in foil-lined pouches. It is consumed primarily by men in the U.S., commonly in conjunction with outdoor activities. Chewing tobacco is typically used in large volumes, resulting in the archetypical golf ball-sized bulge in the user's cheek and large quantities of saliva that users usually expectorate. Consequently, the popularity of this product has waned, with consumption declining gradually over the past century, dropping by about 44% in just the last 15 years [39].

Moist snuff (Figure 3)

Moist snuff consists of fire- and air-cured dark tobaccos that are finely cut or ground. It is packaged in round containers, and the user compresses a "pinch" between the thumb and forefinger and places it inside the lip. Much less bulky than loose leaf chewing tobacco, moist snuff produces less saliva, but expectoration is still common. It is now the most popular form of ST in the U.S.; sales of this product increased by 66% over the past 15 years [39].

In addition to the U.S., there is a long tradition of moist snuff use in Scandinavia, especially in Sweden, where "snus" (the generic term for moist snuff in Swedish, pronounced "snoose") is essentially the only type of ST product in use [40]. There are differences in how American and Swedish moist snuff products are manufactured. Traditional American products undergo fermentation, which imparts characteristic flavors but in the past resulted in higher concentrations of unwanted bacterially mediated by-products, especially TSNAs and nitrite. In Sweden, moist snuff is subjected during manufacturing to a heat treatment akin to pasteurization, yielding virtually sterile products containing very low levels of TSNAs. However, manufacturing refinements over the past 25 years have resulted in lower TSNAs in both Swedish and American products. A 1997 report by the Swedish National Board of Health and Welfare reported that TSNA concentrations in both Swedish and American ST brands had declined substantially [41]. The report concluded: "Recent data suggest that the differences [in TSNA levels reported in American and Swedish ST] have grown smaller, and that it is now questionable to make a sharp distinction between use of American and Swedish moist snuff when assessing risks – at least where TSNA content is concerned."

A separate section of this report will discuss how the high prevalence of snus use in Sweden has played an important role in the low prevalence of smoking, especially among men.

Modern ST products (Figure 4)

Figure 4 Modern smokeless tobacco products. Full size image

Over the past few years several ST products have emerged that are not easily classified into one of the previous groups. In fact, one reason for the popularity of moist snuff is that manufacturers have gradually refined the products in this category to be more user-friendly. The traditional pinch of moist snuff is difficult to keep in place, and the resultant migration is esthetically displeasing. Modern moist snuff products are sold in pre-portioned pouches similar to teabags, but much smaller. Because these products remain stationary in the mouth and generate very little juice, they can be used discreetly with no expectoration. There is a recent trend among manufacturers to offer even smaller pouches that are dry, with a wide range of non-tobacco flavors. Other products in this category consist of small pieces of leaf tobacco and pellets of compressed tobacco that dissolve completely. These products all share one important characteristic: they are of sufficiently small size that they can be used invisibly, and without expectoration.

C. Prevalence

The prevalence of ST use has not received nearly as much attention as that of smoking, but adult prevalence has been documented by the National Health Interview Survey (NHIS). For adults, NHIS defines current ST users as those individuals who have used ST at least 20 times in their lives and are using ST every day or some days. In 1991 the prevalence of current ST use among adult men in the U.S. was about 5.6% (4.8 million), which declined to 4.4% (4.4 million) in 2000. In 1991 about 0.6% (533,000) of adult women in the U.S. were current users, and prevalence declined to 0.3% (324,000) by 2000 [42, 43].

In 2000 the prevalence of ST use was higher among men age 18–44 years (6%) than among those age 45+ years (3%). Men in the Southern U.S. had the highest prevalence (7%) and those in the Northeast had the lowest (2%). As with smoking, prevalence of ST use was higher among men with a high school education or less. Finally, higher male prevalence was seen in rural areas (9%), compared with urban areas (3%) [43].

In the U.S. the number of male smokers is ten-fold higher than the number of ST users, so it follows that concurrent use of both products is common among ST users, but rare among smokers. About 25% of men who use ST report concurrent smoking, whereas concurrent use occurs in fewer than 5% of men who smoke [44]. Cigarette consumption is considerably lower in combined users compared with exclusive smokers [45–47].

D. Health effects

1. Oral leukoplakia

Oral leukoplakia is an ominous sounding term used frequently in discussions about ST use. The term literally means "white plaque," and it is used to describe areas of the mouth lining that become thickened by ST use or smoking. The World Health Organization has determined that leukoplakias resulting from ST use are considerably different from those resulting from smoking. The distinctions are based on the frequency of occurrence, the location in the mouth, and how often these leukoplakias result in mouth cancer [48, 49].

The condition is rare, occurring in less than 1% of the general population, primarily in long-time smokers 40 to 60 years old [50, 51]. Smoking-related leukoplakias most commonly involve the undersurface of the tongue and throat area, locations that account for 75% of oral cancer in the U.S. [51, 52].

Oral leukoplakias occur in up to 60% of ST users [53, 54], within 6 months to 3 years of starting ST use [55, 56]. They primarily occur at the site of ST use and are largely a result of local irritation [55, 57]. The frequency of appearance depends on the type of ST that is used. Moist snuff, which is more alkaline than chewing tobacco, more often leads to leukoplakia [56]. However, moist snuff in pre-portioned pouches causes fewer cases of leukoplakia than does the loose form [58].

There are distinct differences in how often ST and smoking leukoplakias show pre-cancerous changes called dysplasia. Dysplasia is seen infrequently in ST leukoplakias (less than 3%) [49, 59–61]. Furthermore, even when dysplasia is present in ST leukoplakia, it usually is found in earlier stages than in leukoplakias due to smoking [62, 63], where it is seen in about 20% of cases [64].

ST leukoplakias only rarely progress to cancer. For example, one prospective study found no case of cancer in 1,550 ST users with leukoplakia who were followed for 10 years [65], and a second study reported no case of oral cancer among 500 regular ST users followed for six years [66]. A retrospective study of 200,000 male snuff users in Sweden found only one case of oral cancer per year, an extremely low frequency [67]. In comparison, a follow-up study reported that 17% of smoking leukoplakias transformed into cancer within seven years [68].

In conclusion, oral leukoplakia occurs commonly in ST users, but it primarily represents irritation and only very rarely progresses to oral cancer.

2. Oral cancer

ST use has been associated with oral cancer for many decades. It is widely perceived – both by laypersons and medical professionals – that the association is strong and applies to all ST products. However, epidemiologic studies dating back to the 1950s provide convincing evidence that most ST products increase oral cancer risks only minimally.

Rodu and Cole reviewed 21 epidemiologic studies published from 1957 to 1998 [69]. Unlike previous reviewers, these authors derived relative risk (RR) estimates for cancers of the mouth and associated upper respiratory sites related to use of chewing tobacco, moist snuff, dry snuff and a fourth category in which the type of ST was unclear or undetermined (ST unspecified). This study found that use of chewing tobacco and moist snuff were associated with only minimally elevated risks, while use of dry snuff conferred somewhat higher risks.

Chewing tobacco has been studied at least once in each of four decades from the 1960s to the 1990s. The data clearly show that chewing tobacco use is associated with only slightly elevated cancer risks; RRs for all anatomic sites are under 2 with confidence intervals including 1 (i.e. the risk elevation was not statistically significant) (Table 1). The first study evaluating the risk of chewing tobacco appeared in 1962 [70]. There were two studies in 1977 [71, 72], two in 1988 [73, 74], and four studies from 1993 to 1998 [75–78].

Table 1 Chewing Tobacco and Cancer of the Mouth and Upper Respiratory Sites Full size table

As with chewing tobacco, summary RRs are only slightly elevated for moist snuff, with three RRs at or below 1 and the highest RR at 1.2 (Table 2). RRs for moist snuff were reported first in 1977 [71]. Another study appeared in 1988 [74], and five additional studies were published from 1993 to 1998, as this ST type came under intense scrutiny [75–79].

Table 2 Moist Snuff and Cancer of the Mouth and Upper Respiratory Sites Full size table

Two of the seven studies on moist snuff were Swedish, both appearing in 1998 [78, 79]. These studies have received considerable attention among tobacco researchers, particularly in Europe, because they are viewed as showing no oral cancer risk for Swedish products. They formed the basis for the Swedish government's decision in 1999 to recommend that the European Union (EU) oral cancer warning labels be removed from ST products. An EU directive in 2001 accomplished that objective and specified a new warning, "This tobacco product can damage your health and is addictive" [80]. Notably, the other five studies contributing to the summary RRs for moist snuff were American, and they reported RRs very similar to those of the Swedish studies.

Summary RRs for dry snuff use are higher, ranging from 4 to 13, although the confidence intervals for these estimates are wide (Table 3). The first study appeared in 1962 [70], followed by studies in 1981 [81], 1988 [73], and 1994 [76], spanning a period of 32 years.

Table 3 Dry Snuff and Cancer of the Mouth and Upper Respiratory Sites Full size table

RRs for ST-unspecified range from 1.5 to 2.8, and most are statistically significant. For all sites the summary RR is 1.9 (CI = 1.5–2.3), which is intermediate between the low risks reported for chewing tobacco (1.2, 1.0–1.4) or moist snuff (1.0, 0.8–1.2) and the higher risk for dry snuff (5.9, 1.7–20) (Table 4). The intermediate risks for this ST category probably reflect the use of either the lower- or higher-risk products among different groups within the studies. Eight studies provided RRs for ST-unspecified, five of which appeared between 1957 and 1969 [82–86]. Additional studies appeared in 1992 [87], 1993 [75] and 1998 [88].

Table 4 ST-Unspecified and Cancer of the Mouth and Upper Respiratory Sites Full size table

Prior to the 2002 analysis by Rodu and Cole, the distinctive risk profiles of moist snuff and chewing tobacco on one hand, and dry snuff on the other, had gone unnoticed. In fact, the low oral cancer risk associated with chewing tobacco had been discussed briefly in only one article [89]. No distinction in risks had been made previously between dry snuff and moist snuff, even though these products are considerably different with regard to tobacco content and processing, as noted earlier.

The majority of epidemiologic studies regarding ST and oral cancer have limitations, many of which are typical for case-control studies, and some important for understanding unique oral cancer risks. Most of them did not control for confounding by two strong determinants of oral cancer, cigarette smoking and alcohol use. Positive confounding by smoking would occur if ST users smoke more than do nonusers of ST. This would result in artificially high risk estimates for oral cancer among ST users. On the other hand, negative confounding is plausible and would occur if smoking rates are lower among ST users than among nonusers of ST. This would result in artificially low risks for oral cancer among ST users.

Only three studies [78, 79, 81] controlled for alcohol use, where only positive confounding is likely. Thus, control for alcohol consumption in all studies probably would have reduced somewhat many of the estimates of mouth cancer risk associated with ST use.

However, even with these limitations, the results of these studies are reasonably consistent with regard to mouth cancer risks from long-term use of moist snuff and chewing tobacco. In their review Rodu and Cole concluded that "the abundance of data now available indicates that commonly used ST products increase the risk of oral and upper respiratory tract cancers only minimally."

Since the 2002 review four epidemiologic studies, one from Sweden and three from the U.S., have been published [90–93]. In all of these studies ST use was not associated with a significant increase in mouth cancer risk. In 2004 a group of epidemiologists concluded that the evidence linking ST use and oral cancer was "not decisive" [94]. These investigators commented that many claims in the media "overemphasize the risk of oral cavity cancer [from ST use], reaching beyond the scientific data."

In 2005 the American Cancer Society (ACS) reported that ST users did not have significantly increased risks for oral and pharyngeal cancer in either the first or the second Cancer Prevention Study [92]. Despite this finding, the ACS website continues to focus on ST as a cause of mouth cancer, erroneously stating that "risk of cancer of the cheek and gums may increase nearly 50-fold among long-term snuff users" [95]. A later section of this report will discuss this type of misinformation.

3. Other cancers

As noted above, cigarette smoking is associated with increased risk for several cancers in locations not in contact with cigarette smoke. In comparison, numerous epidemiologic studies have not demonstrated that ST use is associated with risk of cancer at any site outside the mouth. In 2004 Waterbor et al. assessed the epidemiologic research literature and summarized the evidence regarding ST use and cancers in various locations [94]. Table 5 shows the conclusions of Waterbor et al. with respect to cancer risks associated with ST use, compared with the established risks for smoking.

Table 5 Risk of Cancer in Various Sites Associated with ST Use and Smoking Full size table

4. Cardiovascular diseases

Over the past 15 years, eight epidemiologic studies have examined the risk of cardiovascular diseases among ST users. Six of the studies found that ST users had no increased risk for heart attacks or strokes [47, 90, 97–100]. The other two reported modestly positive associations, with ST users having RRs of 1.2 and 1.4 [92, 101], which are lower than those of smokers. In 2003, Asplund completed a comprehensive review of the cardiovascular effects of ST use [102]. He concluded that, in distinct contrast to smokers, ST users do not exhibit any significant differences from nonusers of tobacco with regard to the following measures of cardiovascular health: heart rate, blood pressure, cardiac output and maximal working capacity, levels of hemoglobin and hematocrit, leukocytes, antioxidant vitamins, fibrinogen, components of the fibrinolytic system, C-reactive protein and thromboxane A2 production. In addition, ST users did not show important smoking-associated vascular changes, including increased thickness of blood vessels and atherosclerotic plaque development. In summary, most of the medical and epidemiologic evidence documents that ST users do not have elevated risks for cardiovascular diseases.

Two studies based in Sweden have examined the impact of ST use as a risk factor for adult-onset diabetes. One of these studies found that current ST users had a slightly elevated risk (Odds ratio = 1.5, CI = 0.8–30) [103], while the other reported that the risk of diabetes in ST users was not significantly increased [104].