REVIEWTobacco, oral cancer, and treatment of dependence
Introduction
Tobacco use is the leading preventable cause of premature death worldwide.1 It was estimated that 4.9 million people died of tobacco-related illness in the year 2000, and by 2020s that figure will rise to 10 million deaths per year, 70% of which will be in developing countries.2 Tobacco is a major independent risk factor for the development of oral and pharyngeal cancer and other malignancies of the upper aerodigestive tract.
Tobacco is consumed in a variety of different ways though smoking of manufactured cigarettes is the most prevalent form of its use. Smokers know that tobacco is harmful to health, though they under estimate their personal risk, but the public in general are unaware of the full spectrum of health risks. Indeed, in the UK only 2/3rd of the general public are aware that smoking may cause oral cancer3 and therefore it is likely that smokers underestimate the magnitude of their personal risk. For many tobacco users the situation is complicated by strong nicotine dependence and multiple barriers to cessation. Tobacco (nicotine) dependence treatment has the potential therefore to save many million of lives.2
This review summarizes the scientific rationale and available nicotine medications, to help clinicians in primary care and hospital settings to optimise their use.
Section snippets
Epidemiology of tobacco use and oral cancer
In the US some 25% of the population smoke, while in the UK the adult smoking rates are currently around 27% and 38% Australians are smokers. Many other countries have high rates of smoking, but the highest reported rates are from China; a national study in 1996 reporting that 63% of males were current smokers.4 About half of all regular cigarette smokers will eventually be killed prematurely by their habit.5
Oral and pharyngeal cancers have striking geographic and ethnic variations around the
Cigarette and cigar smoking
Tobacco consumption and excess alcohol use are the major risk factors for cancers of the oral cavity and pharynx.7 The risk from these two agents are synergistic and heavy smokers (+40 cigarettes/day) and heavy drinkers (30+ drinks per week) have 38 times the risk of developing oral cancer than abstainers from both products.8 From published studies, the relative risks of tobacco use, corrected for other confounding factors, are shown in Table 1. Among young people with oral cancer in southern
Reverse smoking
The habit of reverse smoking is strongly associated with palatal lesions that carry a high risk of developing to an oral cancer. This habit of smoking by holding the burning end of cigarettes or cigars within the oral cavity is reported mainly in parts of India and south America and in the Philippines. In a six-year longitudinal study in Andhra Pradesh in India among tobacco users with palatal lesions (n = 3196) all new cancers that were detected were found among reverse smokers.21 A synergistic
Bidi smoking
Smoking of bidi(s) made of hand-rolled tobacco wrapped in tendu leaf is a known risk factor for oral and pharyngeal cancer. In one Indian study involving 10,287 subjects, excess mortality among bidi smokers was significant and of the same order of magnitude as reported for cigarette smokers among others parts of the world.30 A meta-analysis of 12 case-control studies reported an increased risk of bidi smoking for oral cancer (OR = 3.1 95%CI 2.0–5.0).31 Reported higher odds ratios derived from
Smokeless tobacco
Worldwide oral use of smokeless tobacco (ST) takes many forms and the risks appear different depending on the processing of the product which can markedly affect nitrosamine content.33 In the west ST is available as oral snuff or in moist pouches. ST is a well recognized risk factor for oral cancers in the US (with a RR approaching 50) and “snuff dipper’s cancer” is particularly prevalent in the Southern states.34 But there is a controversy as to the carcinogenicity of Swedish snuff (“snus”) as
Carcinogenicity of tobacco to oral tissues
Tobacco smoke contains many carcinogenic combustion products of which polynuclear aromatic hydrocarbons (PAH) predominate which are primarily contact carcinogens (Table 3). In most target tissues, the principal PAH carcinogen is benzo(a)pyrene, which is activated by P450 isoenzymes to the carcinogen metabolite benzo(a)pyrene-dihydrodihydroxy epoxide.46 Such metabolites react with DNA to form predominantly guanosine adducts. If not detoxified by glutathione S-transferases (GSTs), the resulting
Tobacco dependence
Over the last 15–20 years there has been a great deal of research on the pharmacological effects of nicotine and the pathophysiological basis of nicotine addiction. Nicotine affects mood and performance and shows all the classic hallmarks of a drug of addiction.55, 56 The primary criteria used to classify addictive drugs are; compulsive use, psychoactive effects, and drug-reinforced behaviour. Other additional criteria include, stereotypic patterns of use, use despite harmful effects, relapse
Tobacco dependence treatment
In developed countries, approximately 30–40% of smokers make an attempt to stop smoking in any year. However, without formal assistance, only about 2–3% of smokers making a quit attempt on their own, succeed in abstaining for at least a year. Recognition of the tenacious nature of nicotine addiction and the great difficulty most tobacco users have in overcoming it despite interest in stopping has finally galvanised the health care system in some countries to fund formal cessation programmes,
Diagnosis, screening, and brief interventions
In the US, at least 70% of smokers consult a physician every year and more than 50% consult a dentist65 and this is probably the case in many other western countries. These are obvious locations for nicotine dependence programmes. Implementing clinic systems designed to increase the assessment and documentation of tobacco use status markedly increases the rate at which clinicians intervene with their patients who smoke.66 Recommendations for a successful intervention for tobacco users were
Brief clinical intervention
Because of the clinically significant benefit afforded by even the simplest forms of counselling, health care staff should be prepared to undertake at least brief counselling on a routine basis with all their tobacco using patients. There is a strong dose-response relation between the intensity of counselling or behavioural support and its effectiveness.66, 77 Even physician advice as brief as 3 min significantly increases long-term smoking abstinence rates. Such advice from a family doctor (GP)
Intensive clinical interventions
There is substantial evidence to suggest that intensive interventions produce higher success rates than do brief interventions. Specialist smokers’ clinics providing intensive behavioural support combined with pharmacotherapy can achieve one years sustained abstinence rate of 15–25%.66, 68, 77 They are aimed at the more nicotine dependent and those with concurrent medical and psycho-social problems, who are unlikely to stay off tobacco with briefer interventions. Though the success rates are
Nicotine replacement therapy (NRT)
The rationale for nicotine replacement therapy (NRT) is to reduce the severity of nicotine withdrawal symptoms by providing weaning doses of nicotine in a “clean” form to smokers for about 8–12 weeks after stopping smoking. The objective of therapy is to increase short and long term quit rates and reduce the risk of a relapse. In many countries some, or all of, the products are available either over the counter (OTC) for pharmacy sales or on general sale (e.g. in supermarkets) in addition to be
NRT in clinical practice
It must be remembered that none of these products are panaceas, but they undoubtedly help when used correctly. One of the main challenges is to ensure that patients use sufficient doses of NRT for therapeutic effect. Under-dosing is a common problem, as are intermittent use leading to widely fluctuating blood nicotine levels, and weaning too quickly. Explaining the rationale for use is essential as these products cannot replace the need for personal effort, sustained motivation and
Safety of NRT
Nicotine administered as a medication is always safer than that obtained by tobacco use.58 While in theory all forms of NRT have some potential to sustain nicotine dependence, only a very small proportion of NRT users become long-term users.91 The active ingredient in NRT is nicotine but in its pure form has no known risk in tobacco-related cancers and is not implicated in chronic obstructive lung disease.92 There is no known increased cardiovascular risk with NRT except with acute disease
Special groups
In the west, tobacco use is becoming more concentrated among the more deprived sections of society as the more affluent are quitting at a greater rate. Treatment approaches need to be tailored so that they appeal to and serve the different needs of this population, as well as reflecting the changing socio-demographic profile of tobacco users in terms of ethnicity, race, sex and age in a population. Patterns of use, dependency levels, and difficulty in quitting vary among these sub groups.101,
Pharmacological and behavioural treatment for smokeless tobacco cessation
Unfortunately there are not yet enough large scale methodologically rigorous randomized placebo controlled trials of NRT for cessation of smokeless tobacco to determine whether this treatment is effective. Evidence that behavioural approaches work with this population, though slim as the trials have tended to be small, is encouraging and justifies their use at the present time. There is an urgent need for research on both approaches, particularly studies conducted outside the US where most of
Cessation of tobacco use—Approaches to reduce risk of oral cancer
Sustained and intensive educational programs on tobacco use resulting in cessation have shown a substantial fall in the incidence of oral leukoplakia in intervention cohorts in India.115, 116 Outreach programmes from hospitals can educate communities about dangers of tobacco use when combined with oral examinations for the detection of oral precancer.117 So far in the industrialised countries there have been no specific interventional programs reported. Dentists are uniquely placed to impact
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