1 INTRODUCTION

Tobacco use is responsible for nearly 9 million annual global deaths (approximately 15% of all deaths worldwide). This is more than any other behavioral risk factor and trailing only high systolic blood pressure among all risk factors in its contribution to human mortality.1 Tobacco smoke disrupts the functioning of nearly every human organ system, causing most deaths through cancer, heart disease, and noncancer respiratory diseases.2 Health risks extend not only to the person using tobacco but to people involuntarily exposed to smoke (second-hand smoking).3 Tobacco experimentation typically begins in adolescence, often due to both social influences and tobacco marketing.4 Later in life, most adult tobacco users find themselves chemically and/or behaviorally dependent on nicotine and unable to quit tobacco use.2 Yet, despite this well-chronicled destruction, industrially produced tobacco products remain legally sold and marketed in nearly every country, well surpassing US$1 trillion in annual sales.

Owing to combined efforts of public messaging, excise taxes, social norm shifting, and numerous other tobacco control strategies, cigarette smoking prevalence in most high-income countries has declined dramatically in recent decades.2, 5-8 However, as the current number of global deaths would indicate, substantial challenges remain. China, by far, is the single largest consumer of cigarettes and where smoking prevalence, especially among men, remains persistently high.9 Though smoking prevalence in Africa has historically been low, aggressive tobacco industry efforts on the continent have health experts projecting increased tobacco use over the coming decades.10 In countries where smoking prevalence has declined, inequalities in tobacco use and cessation have often risen, marked by widened gaps according to socioeconomic disadvantage,11, 12 race/ethnicity,12 and mental illness,13 among other factors, exacerbating health inequity.

The most recent decade has also seen an expanding variety of new or emerging tobacco and/or nicotine products brought to market, most prominently electronic cigarettes (commonly called e-cigarettes). Heated tobacco products14 and nicotine-containing pouches15 are other examples of an increasingly diverse product landscape. Meanwhile, more permissive laws and regulations have broadened access to cannabis (marijuana) products. Cannabis, though not a tobacco product, is frequently consumed in combination with tobacco and by individuals who also use tobacco.16, 17 Smoke from cannabis products shares many chemical properties with tobacco smoke and has been linked to health problems, including potential cardiovascular18 and respiratory19, 20 impairment.

For the practicing clinician, providing sound patient recommendations requires knowledge of the general and oral health implications not only associated with smoking cigarettes but also with cannabis and the wide range of currently available tobacco and nicotine products. Personalized, empathetic patient communication in the dental setting can enhance a patient’s motivation to quit tobacco use, and patients willing to make a quit attempt must be connected with evidence-based resources and support to achieve this tobacco-free goal. This review will provide an overview of selected tobacco and nicotine products with an emphasis on implications for periodontal disease risk and clinical management. Also presented will be strategies for tobacco use counselling and cessation support that dental professionals can readily implement in practice.

2 CIGARETTES

Cigarette smoking elevates the risk of nearly every oral condition that dental professionals are tasked with treating and diminishes the chances of many dental treatments being successful.21-23 Cigarette smoking is strongly associated with heightened risk of cancer of the oral cavity or pharynx,21, 24-26 with evidence supporting a dose-response relationship27 and synergistic risk with alcohol consumption.24, 28 In countries where use of chewing tobacco is uncommon, most oral cancer cases are attributable to tobacco smoking,29, 30 with human papilloma virus infection a growing contributor.31 Apart from gingival and periodontal conditions, associations have also been reported between cigarette smoking and dental caries32 and oral pain,33 with an altered oral microbiome and diminished salivary flow proposed as potential mechanisms, but with less causal certainty for these outcomes.23, 34

The destructive impact of tobacco smoke on gingival tissues was formally reported as early as the mid–19th century.35 Over the following 125 years, multiple clinical and population studies demonstrated strong associations between cigarette smoking and gingival disease,36-38 diminished epithelial attachment and alveolar bone height,39, 40 and tooth loss.41 These studies generally also noted greater levels of plaque and calculus accumulation among smokers,36, 38-40, 42 leading to some academic debate at the time over whether smoking and periodontal disease associations reflected merely poor oral hygiene practices among smokers or a causal contribution of the tobacco exposure itself.40, 43 More recent investigations support a causal role, with large representative patient-based and population-based studies confirming a strong, consistent association of smoking with worse periodontal status,44-48 including independently of dental plaque levels and other plausible confounders, such as age, sex, and socioeconomic position.44, 49-52 These associations persist in prospective longitudinal analyses, demonstrating that cigarette smoking is a major risk factor for losing periodontal support over time53-56 and eventual loss of teeth.57-59

Laboratory-based and clinical studies offer insight to potential mechanisms of action, providing evidence that tobacco smoke exposure impairs the protective host response to the dental plaque biofilm while additionally heightening the production of potentially destructive inflammatory cytokines and enzymes.60, 61 Furthermore, distinct microbial patterns between the plaque biofilm of tobacco smokers and nonsmokers have been characterized, suggesting a more pathogenic profile.62, 63 The gingival vascular response to plaque bacteria is impeded in tobacco smokers via mechanisms still under study but which may include suppressed angiogenesis or vasoactive smoke constituents.64 Finally, tobacco smoking appears to diminish the reparative capacity of periodontal cells, including fibroblasts, osteoblasts and cementoblasts, reducing the ability to form new tissue and potentially impeding responsiveness to periodontal therapy.65, 66 Whereas whole tobacco smoke is clearly damaging to oral cells and tissues, deciphering which of the many components of tobacco smoke are most responsible for these effects is challenging. A recent review of the in vitro evidence concluded that nicotine, the highly addictive chemical, was alone unlikely to be cytotoxic to oral tissues at physiologic levels.67

Implications for the practicing clinician go beyond the need to expect a higher occurrence of adverse periodontal conditions among cigarette-smoking patients. The predictability and overall success of periodontal treatments will be lessened among tobacco-smoking patients.68, 69 Smoking is associated with worse outcomes following nonsurgical debridement,70-72 open surgical debridement,73, 74 bone grafts,75 guided tissue regeneration,76 and periodontal plastic surgery.77 Smoking is similarly a risk factor for dental implant failure.78, 79 The clinician must identify and document the tobacco use status of all patients. Though tobacco use is not a contraindication for providing surgical or nonsurgical periodontal therapy, patients must be informed of the elevated risk of less favorable treatment outcomes. This conversation should be embraced as an opportunity to assess (and enhance) the patient's motivation to quit smoking and for the clinician to fulfill a professional responsibility to provide supportive, empathetic advice to quit and connect the patient with evidence-based tobacco cessation support, as discussed in Section 8 of this review.

3 SMOKELESS (SPIT) TOBACCO

The term smokeless tobacco has been used to cover a wide variety of noncombustible tobacco products that are held in the mouth or chewed.80 This includes areca nut products, such as betel quid (paan), gutka, and mainpuri in South and Southeast Asia, where the consumption of these and similar products has been strongly associated with oral cancer.80, 81 These smokeless products contain high levels of tobacco-specific nitrosamines, believed to be highly carcinogenic,82 in contrast to low-nitrosamine snus products consumed in Sweden, which most existing epidemiologic studies have not associated with oral cancer.80, 82 In the United States, oral moist snuff is the predominant form of smokeless tobacco used,83 more often among younger men in rural communities.84 In 2017, the United States Food and Drug Administration estimated that a product standard to mandate low nitrosamine content in US smokeless tobacco products would prevent 12 700 cases of oral cancer over 20 years85; however, the proposed standard was not implemented. Other health effects linked to smokeless tobacco use include cancers of the esophagus and pancreas, and plausibly, but less conclusively, adverse cardiovascular outcomes and cancers of the lung and cervix.80

Among noncancer oral health conditions associated with use of moist snuff or chewing tobacco, oral mucosal lesions, including hyperkeratotic or erythroplakic lesions, are commonly found even among young users.86-89 Gingival recession and periodontal attachment loss have been reported near the areas where smokeless tobacco is held in the mouth,86, 87 as well as dental erosion and gingival recession.88, 89 A positive association with severe active periodontal disease was found in the large, representative National Health and Nutrition Examination Survey in the United States.90 For the dental professional, assessing smokeless tobacco use status and offering cessation support tailored to quitting smokeless products is a critical component of care and may help patients successfully quit.91

4 CIGARS AND PIPES

Relative to cigarettes, fewer studies evaluate periodontal health outcomes associated with use of other combustible tobacco products. However, given similarities in the toxicologic profiles of cigarette and cigar smoke,92 it is reasonable to expect adverse oral health effects. In the United States, cigars are the non–cigarette product among adults used most (4% prevalence), and use prevalence among young adults aged 18-24 years is more than threefold higher (14%).93, 94 Dental professionals must ask their patients about all forms of tobacco use and be particularly mindful that the oral health risks of any combustible products are likely to resemble those of cigarette smoking.

A longitudinal evaluation of the Baltimore Longitudinal Study of Aging found that cigar and/or pipe users had more missing teeth and more sites with severe loss of attachment and advanced recession compared with nonsmokers.95 Another longitudinal study evaluated tooth loss risk and alveolar bone loss in cigar and pipe smokers.96 These authors reported that cigar and pipe users were at a higher risk of tooth loss than nonsmokers were and that more calculus and interdental bone loss were observed in cigar and pipe users than in nonsmokers.96 An earlier cross-sectional analysis of this same male veteran population in the United States had reported greater accumulation of plaque and calculus in cigar/pipe smokers than in nonsmokers after adjusting for age.97 However, when compared with cigarette smokers, cigar/pipe users had lower accumulations of plaque and calculus and less alveolar bone loss.97 These studies were limited to older, male, predominantly white populations and often grouped cigar and pipe users together. Two nationally representative (United States) cross-sectional studies have considered exclusive groups of cigar and pipe users. In the first, more severe periodontal disease was observed among cigar smokers compared with nonsmokers, but small sample sizes precluded a detectable difference between cigar and cigarette users.98 More recently, cigar-product users and pipe users were both at higher odds of self-reporting gum disease diagnosis and treatment than non–tobacco users were.99 To our knowledge, no studies have examined possible differences in oral health effects by type of cigar, such as premium cigars versus cigarillos or cigarette-like small cigars.

5 HOOKAH

Use of a hookah, also referred to as a tobacco waterpipe or narghile, dates back several centuries and is a cultural norm in many countries of North Africa and the Middle East. In other parts of the world, the popularity of hookahs has recently increased, particularly among youth and young adults.100-102 Often perceived as less harmful than cigarette smoking,100 hookah smoke contains levels of volatile organic compounds, ultrafine particles, nicotine, and carbon monoxide matching or exceeding cigarette smoke.103, 104 Epidemiologic studies have associated hookah use with respiratory and cardiovascular diseases.105

Several cross-sectional studies compare periodontal and peri-implant health of hookah smokers with both cigarette smokers and nonsmokers. One study found higher plaque index, increased bleeding on probing, and more sites with attachment loss and probing depth greater than 3 mm in hookah users compared with nonsmokers, with no difference in these parameters between hookah users and cigarette smokers.106 Another evaluation similarly identified greater marginal bone loss and more missing teeth among hookah users than among nonsmokers and reported comparable periodontal status between hookah and cigarette smokers.107 In a third study, increased periodontal bone loss and greater prevalence of vertical bone defects were found in hookah users than in nonsmokers.108, 109 Few studies have evaluated peri-implant health in hookah users. A recent review of case-control studies reported worse peri-implant inflammatory parameters and more implant sites with deep probing depths, bleeding on probing, and peri-implant bone loss among hookah users than among nonsmokers.110

Nearly all of the aforementioned research was conducted in Saudi Arabia, where use patterns and the hookah product itself might differ from the rest of the world, limiting generalizability. In countries where hookah use is often infrequent and primarily a behavior of young adults, there is a dearth of research evaluating periodontal health outcomes. In one cross-sectional evaluation in the United States, hookah use was observed almost exclusively among younger people, who self-reported gum disease at a similar prevalence as tobacco never-users.99

6 CANNABIS

A decades-long trend in several countries has seen increasingly liberalizing laws and attitudes around the use of cannabis (marijuana) products for medicinal and recreation use. With policies favoring decriminalization and creation of legal commercial marketplaces, use of cannabis products has risen. Cannabis is the most commonly used recreational drug worldwide after tobacco and alcohol.111 In the United States, 46% of residents aged 12 years and older reported lifetime cannabis use in 2019,112 with the largest increases in current use observed among older adults.113 Given the high use prevalence, the frequent consumption in combination with tobacco and/or by individuals who also use tobacco,17 and the potential for periodontal harm from cannabis smoke itself,114 the practicing clinician should anticipate encountering cannabis-using patients on a regular basis and be prepared to manage potential oral and periodontal complications.

A limited number of epidemiologic studies have evaluated the association between cannabis use and periodontitis. Using data from the Dunedin Multidisciplinary Health and Development Study birth cohort in New Zealand, cannabis use measured between ages 18 and 26 years was associated with greater odds of experiencing 3 mm or more clinical attachment loss between ages 26 and 32 years, including after controlling for tobacco use and other sociodemographic and behavioral risk factors.115 Following this same cohort to age 38 years confirmed the positive association between cannabis use and declining periodontal health.116 Using data the from Aboriginal Birth Cohort study in Australia, investigators examined the prevalence of periodontitis among young adults (mean age 18 years).117 Almost all cannabis users also used tobacco, precluding an assessment of cannabis-only use on periodontal outcomes; however, among tobacco users, co-use with cannabis was associated with a higher prevalence of periodontal disease.117 In contrast, a cross-sectional study evaluating the presence of periodontal disease in Chilean adolescents did not identify an association between cannabis use and clinical attachment loss.118 Most of the evidence summarized here draws on observations made about youth and young adults, among whom severe periodontal disease is less prevalent. Among adults aged 40-70 years in Puerto Rico, frequent cannabis use was associated with prevalent severe periodontitis.119 In one nationally representative study (United States) of adults aged 30 years and older, both the mean number of deep pockets and mean clinical attachment loss were higher among frequent cannabis users than among nonusers.120 Even when this analysis was restricted only to tobacco never-users, the odds of severe periodontitis were approximately double among frequent cannabis users.120

The potential connections between cannabis use and other oral health conditions are less well studied. Associations have been reported with gingival hyperplasia, xerostomia, leukoedema, and oral infections.114, 121 Though smoking remains the most common route of cannabis administration, a growing proportion of people consume cannabis as edible products or using vaporizers to produce an inhalable aerosol.122 It is not known how or whether these other routes of cannabis administration relate to periodontal diseases.

For the dental professional, caring for the cannabis-using patient involves more than asking all patients about use and advising nonjudgmentally about potential periodontal disease risks. For instance, postoperative instructions should clearly implicate cannabis smoke in addition to tobacco smoke as potential risk factors for complications following intraoral surgeries. When patients attend appointments currently under the influence of cannabis, there are several issues for the dental professional to consider. Owing to the altered mental state, the provider may judge that the patient does not have capacity to consent for treatment and it may be best to postpone treatment, if possible. Additionally, epinephrine in local anesthetic solutions may trigger a serious tachycardic event in cannabis-intoxicated patients.114, 123 Whereas some patients might self-medicate with cannabis to address dental pain or appointment-related anxiety, the patient under the influence of cannabis may experience heightened anxiety and dysphoria during a dental visit.114 Therefore, a discussion about cannabis with patients prior to scheduling any surgical procedures can help to avoid potential risks and complications related to managing a patient under the influence of a psychoactive drug.

7 E-CIGARETTES AND OTHER NOVEL PRODUCTS

For many decades it has been understood that most of the harms from tobacco use come from the combustion process and the resultant complex cocktail of ingredients, and not from nicotine, the highly addictive chemical. Developing alternative ways of delivering nicotine is not a new pursuit; there are a wide array of nicotine replacement therapies that have been used to aid tobacco cessation in a medicalized context for over 30 years.124 The concept of e-cigarettes was first patented in the 1960s,125 but their use has only become widespread over the last decade. E-cigarettes represent a class of battery-powered products that heat a liquid solution, typically containing nicotine, into an inhalable aerosol.126 E-cigarettes were not developed through the medical pharmaceutical route and are usually considered a consumer product, similar to tobacco products or, in some regulatory contexts, classified as tobacco products.127 Although commercial availability and promotion are potentially part of the appeal of these products, there have been many challenges around regulation, product quality, product perceptions, and limited supporting scientific evidence.

E-cigarettes have undergone substantial evolution over the past decade and can vary widely in appearance and attributes. However, some common features are that they are usually rechargeable, often come as refillable "tanks" or pre-filled "pods," and in a range of flavors and nicotine strengths. The e-cigarette is usually filled with a liquid that has three main components: a carrier solution (propylene glycol or vegetable glycerin), nicotine (unless a nicotine-free version), and flavorings.

Recent clinical trials suggest that e-cigarettes may be effective cigarette cessation aids, with them outperforming conventional nicotine replacement therapy in two trials when used in combination with cessation counseling.128, 129 Epidemiologic data from England have shown an increase in overall tobacco quit rates and quit success as the prevalence of e-cigarette use among smokers has increased.130 However, this is not a universal picture, as cohort analyses from the United States have reported no improvement in smoking abstinence with e-cigarette use.131, 132 The proportion of smokers who quit by using e-cigarettes and who then remain long-term users of e-cigarettes remains an open question.133 E-cigarettes are sometimes presented as a less-harmful alternative for nicotine-dependent tobacco smokers unwilling or unable to cease nicotine use, because the products deliver much lower levels of toxicants relative to cigarette smoke.134, 135

However, important concerns surrounding e-cigarettes include rising use prevalence among youth and young adults,136 potential risks for cardiovascular and lung health,137-139 and questions about cessation effectiveness outside clinical trials. The uncertainty and complexity of what impact widespread e-cigarette availability has had, and will have, on public health has spurred much controversy and policy debate.

Given the well-established effect of tobacco smoke on the periodontium and the oral mucosa, it is important to understand the effects of e-cigarette aerosol, which also passes in close proximity to these tissues. Research in this field is still emerging, and there are many challenges with conducting and interpreting these studies; for example, e-cigarette users are often recent or current tobacco smokers, meaning it is hard to attribute effects to e-cigarette use directly. Additionally, product evolution has often outpaced research, and the chronic and long-term pathophysiology of periodontitis means that effects could take several years to manifest. It has proven difficult to translate the results of in vitro experiments, some of which report harm to oral-derived cells from e-cigarette aerosols,140 into clinically relevant exposure doses and outcomes. For clinical and population-based studies, separating any effect of current e-cigarette use from those of past or concurrent combustible tobacco use presents another challenge. Among existing findings, exposure to e-cigarette aerosol appears to induce potentially adverse changes in the oral microbiome distinct from those observed with cigarette smoking.141, 142 Clinical studies have been largely cross-sectional and sometimes measured oral health conditions as ancillary outcomes to studies outside dental settings. They have reported associations with a wide range of conditions, including throat irritation, gingival bleeding, and oral trauma from exploded e-cigarette devices.140 Population-based studies have largely been confined to self-reported outcomes and cross-sectional designs, with some reporting associations between e-cigarette use and prevalent oral conditions,99, 143 but a need exists for additional well-controlled, prospective data.

Doubtlessly, more research is required to understand the extent to which e-cigarettes may independently affect oral health. For the clinician, asking patients specifically about e-cigarettes must be part of recording tobacco use history. The patient deserves a balanced description of the potential risks of e-cigarettes, as well as their potential as a less harmful alternative to combustible tobacco. The tobacco-smoking patient motivated to try e-cigarettes as a cessation aide should not be discouraged from the quit attempt but should also be presented with a menu of evidence-based cessation strategies, as described in an upcoming section. Youth and tobacco non-users should be encouraged not to engage in e-cigarette use. For youth particularly, nicotine exposure may adversely affect adolescent brain development and risk of long-term nicotine dependence.144

E-cigarettes are not the only class of recently introduced products that deliver nicotine without combustion. Newly formulated heated tobacco products create an inhalable aerosol by heating tobacco-containing material to a temperature below the combustion threshold and are reported by their manufacturers to deliver lower levels of harmful chemicals than conventional cigarettes.145 At least one clinical trial, sponsored by a heated tobacco product manufacturer, has announced plans to assess potential periodontal effects.146 Nicotine pouches have been introduced by large tobacco manufacturers as a "tobacco-free" portioned, flavored oral nicotine product.15 Novel nicotine lozenges, gums, mints, and even nicotine-infused toothpicks may resemble nicotine replacement therapies but are not marketed for cessation. Limited evidence exists on which to evaluate the overall health implications of these novel products, let alone possible effects on oral health. Though plausibly delivering a less harmful toxicant profile than combustible tobacco, reducing harm to the user is dependent on using these novel products as a substitute for, rather than complement to, cigarette smoking, which may not match the real-world use profile.147

8 TOBACCO CESSATION INTERVENTIONS FOR PERIODONTAL PATIENTS 8.1 The role of dental professionals in tobacco cessation

Dental professionals are well positioned to provide tobacco cessation treatment to their patients. Not only do dental professionals see a large number of tobacco users, but they often have more time with patients and see patients more regularly than other health professionals do.148 In addition, the negative health effects of tobacco use are often first identified in the oral cavity, underscoring the importance of managing tobacco-related risk factors for the dental professional. In a systematic review, it was found that tobacco cessation interventions by dentists and dental hygienists during oral examinations can increase cessation among cigarette smokers and smokeless tobacco users.149 Multiple dental professional organizations not only promote tobacco cessation in dental practice but characterize it as a professional responsibility to provide tobacco cessation treatment and education to patients.150-152

Despite their important role in tobacco cessation, dental professionals often fall behind other health professionals in providing such care. For example, in a study of health professionals, 80% of dentists and dental hygienists reported asking patients about their tobacco use, but less than 40% reported providing assistance to patients or referring them to cessation programs.153 In another national study of US dentists, over 90% of respondents reported asking patients about tobacco use, but only 45% reported routinely offering assistance, including referring patients to cessation counseling and/or prescribing cessation medication.154 Similar patterns were seen in a survey of UK dental professionals, with 79% reporting they "always" enquired about the smoking status of their patients and 77% offering advice.155 Though most dentists and dental hygienists report asking patients about cigarette smoking, inquiries about non–cigarette products, such as cigars, hookahs, e-cigarettes, or cannabis are much less common.156, 157 As the use of alternative tobacco products increases, dental professionals must ask about use of all tobacco, nicotine, and cannabis products when reviewing a patient's health history to address fully the risks of long-term use and potential negative oral and systemic health consequences.

8.2 Interventions for tobacco cessation in practice

The five A’s approach to tobacco cessation (Figure 1) is an evidence-based intervention supported by several countries and organizations, including in the United States,158 Canada,159 Australia,160 and the World Health Organization.148 This intervention involves all members of the dental team and can be incorporated as a standard of practice in dental settings.

Key steps in the five A’s and ask-advise-act (AAA) models for tobacco cessation. This depicts two models for organizing the approach to providing tobacco cessation support in a clinical setting: the five A's model (which involves the action steps ask, advise, assess, assist, and arrange) and the AAA model (which involves the action steps of ask, advise, and act). The five R's approach is used to frame a motivation-enhancing conversation with a patient not yet ready to quit tobacco use. Abbreviation: OARS, open-ended questions, affirmations, reflections, and summaries

The first step of the five A’s approach is systematically asking all patients aged 12 years and older about current and former tobacco use. This involves screening patients at every encounter for use of all tobacco products, including related products like e-cigarettes and cannabis. All adolescent patients (age 12-18 years) should be advised not to use tobacco or nicotine. Information obtained from the patient about tobacco, nicotine, and cannabis use should be documented in the patient's dental chart or health record.

Once tobacco use is identified, the next step is advising patients to quit. This message should be clear, strong, nonjudgmental, and personalized. Advice can be personalized by linking the patient's tobacco use to health concerns or certain social factors. For example, a person with young children or grandchildren may be motivated by concerns over exposing others to smoke, whereas a person with periodontal disease may be concerned with the long-term effects on their oral health. In some cases, in order to identify personal factors that may motivate them to consider quitting, it may be useful to ask a patient what they do not like about their tobacco use.148

After advising a patient to quit, the dental professional must then assess a patient's readiness to quit. For many patients, quitting tobacco use is a recurring process, and readiness to quit will change over time. This process is known as the trans-theoretical model