Mouth cancer for clinicians part 3: risk factors (traditional: tobacco)

Tobacco

Tobacco is derived from plants Nicotinia tabacum and Nicotinia rustica of the genus Nicotiniana. It releases nicotine, (S)-3-(1-methyl-2-pyrrolidinyl) pyridine (Figure 3), the most abundant of the volatile alkaloids in the leaf. Nicotine is one of the most heavily used and highly addictive stimulant drugs. It acts on nicotinic cholinergic receptors, affects most organ systems and binds to a CNS receptor and, like cocaine, heroin and marijuana, raises the level of brain dopamine, as well as opioids and glucose, and activates the nucleus accumbens. The type of nicotine cholinergic receptor and the enzyme CYP2A6 (cytochrome P – a terminal oxidase enzyme) influence the chances of addiction. Nicotine also causes a discharge of adrenaline from the adrenals, which stimulates the CNS, and other endocrine glands, and a sudden release of glucose.

Nicotine is absorbed readily from tobacco smoke in the lungs, acting in seconds on the brain, but affects the body for up to 30 min. Stimulation is followed by depression and fatigue, leading the abuser to seek more nicotine. If a person tries to stop smoking, withdrawal symptoms may appear with excessive anger, hostility and aggression.

Tobacco use also generates several carcinogens (cancer-causing chemicals) from the leaf, and most relevant for mouth cancer are the tobacco-specific nitrosamines (TSNAs) from manufactured tobacco, as well as:

Tobacco contains over 60 carcinogens! Also, the production of free radicals results in alterations in various antioxidant enzymes (glutathione-S-transferase (GST), glutathione reductase, superoxide dismutase, catalase and glutathione peroxidase).

Cigarettes

Smoking tobacco products like cigarettes increases the risk of oral cancer. All forms of tobacco, both smoked and smokeless, are carcinogenic. There is for mouth cancer:

Tobacco also predisposes to:

Use of tobacco puts the user at a higher than average risk of developing these cancers.

IARC classifies tobacco smoking as a cause of mouth, tonsil, pharynx and nasopharynx cancers. Smoking tobacco may cause 70% of mouth and pharyngeal cancers in men, and around 55% in women, in the UK. A meta-analysis showed that current smokers have a three-fold increased risk of mouth cancer, compared with people who have never smoked and nearly seven times the risk of pharyngeal cancer. The more cigarettes someone smokes, and the more years they smoke for, the higher the risk of mouth cancer. Compared with people who do not smoke, the risk of mouth cancer in those who smoke low/medium-tar cigarettes and high-tar cigarettes was 8.5- and 16.4-fold greater, respectively. (Note that cigarettes are classified as low/medium if the tar yield is less than 22 mg and high tar if the tar yield is greater than 22 mg).

Smoking cessation, however, leads to a fall in mouth cancer risk; by 1–4 years after smoking cessation the risk of mouth cancer is 35% lower than that of a current smoker, and by 20 years or more after cessation the risk is reduced to that of a never-smoker. The risk of oropharynx/hypopharynx cancer risk reduces by around half by 5–9 years of smoking cessation, and is almost that of a never-smoker by 20 years.

Tobacco consumption has dropped in the UK probably owing to the increased cost of a packet of cigarettes, as well as the ban on smoking in public buildings and vehicles (buses/trains/planes). On the other hand, self-rolled cigarettes, which have a higher carcinogen content, are also now more popular.

Bidis and kreteks

Bidis are small, thin, hand-rolled cigarettes from south Asia, which comprise tobacco wrapped in a tendu or temburni leaf. Kreteks – sometimes called clove cigarettes – are from Indonesia and typically contain a mixture of tobacco, cloves and other additives. Both bidis and kreteks have higher concentrations of nicotine, tar and carbon monoxide than conventional cigarettes and have at least comparable adverse health effects. People who smoke bidi have around three times the risk of mouth cancer compared with bidi never-smokers.

Cigars and pipes

People who have only smoked pipes or cigars, rather than cigarettes, also have an increased risk of mouth, pharynx and larynx cancers. People who smoke only cigars increase their risk by three-and-a-half times, and those who smoke only a pipe increase their risk by nearly four times. Pipe smokers or people who hold the cigarette for a long time on the lip have an increased risk of lip cancer.

Tobacco is also a major hazard to health and promotes many diseases, particularly heart disease, lung disease and cancers of the lung, oesophagus, mouth and bladder (Tables 2, 3 and Figure 4).

Indeed, tobacco smoking is the largest avoidable cause of death and serious disability in the UK and most other developed countries. In the UK, around one in five adults, or about ten million people, are current smokers, five million of whom are expected to die prematurely from the habit. Smoking currently accounts for around 100,000, or about one in six, deaths each year in the UK.

Smoking is strongly associated with socioeconomic disadvantage and, in most high income countries, the prevalence of smoking is considerably higher among more deprived people than in those from affluent backgrounds. In the UK, the unemployed are twice as likely to be smokers compared to employed people and smoking is highly prevalent among the homeless, those in custodial care and other marginalized or disadvantaged groups. Smoking is also more than twice as prevalent among people with mental health issues. Smokers in disadvantaged groups also typically start at a younger age (Figure 5), and they smoke more cigarettes per day (Figures 6, 7, 8 and 9), and take in more nicotine from each cigarette. Smoking thus strongly exacerbates health inequalities.

Environmental (second hand) tobacco smoke (ETS)

Passive smoking can cause lung cancer, increases the risk of respiratory illnesses and may cause sudden infant death. Exposure to second-hand smoke also causes lower respiratory infections, asthma and wheezing illness, meningitis and middle ear disease. Smoking in pregnancy harms the foetus, increasing the risk of premature birth, low birth weight, foetal anomalies, and foetal mortality.

People exposed to secondhand smoke at home or in the workplace have a small increase in their risk of mouth or oropharyngeal cancer. Never-smokers who have ever been exposed to ETS at home or work have an 87% higher risk, and those exposed in this way for 15 years or more have more than double the risk.

Waterpipes

A frequent habit that emanated particularly in the Levant (the geographic and cultural region consisting of the eastern Mediterranean littoral between Anatolia and Egypt) and can now be seen worldwide, is of smoking tobacco in a waterpipe (Figure 10). A waterpipe is known by a variety of names (arghila, argileh, boory, goza, hookah, hubble bubble, narghile, nargile, nargila, narjeela, mada'a orarghile, shisha and qalyān).

Waterpipes contain tobacco flavoured with molasses in a mixture termed either tobamel (from tobacco plus ‘mel’ for ‘honey’ in Latin) or mu'essel (‘honeyed’ in Arabic). The flavoured tobacco is indirectly heated by burning embers or charcoal, and waterpipe users are exposed to similar nicotine levels as are tobacco cigarette smokers, but with higher levels of carbon monoxide, and they have carboxyhaemoglobin levels in their blood.

Waterpipe smoking is as harmful to health as is cigarette smoking. The harm relates to inhalation of tobacco smoke and also carbon monoxide. Second-hand smoke from waterpipes is a mixture of tobacco smoke in addition to the smoke from the fuel and therefore poses a risk for non-smokers.

Sharing a waterpipe mouthpiece is common and may pose other hazards, such as risk of communicable disease transmission, including tuberculosis and viral hepatitis. Local Government Regulation in England has issued supplementary guidance to regulatory officers on the enforcement of a smoking ban in ‘shisha bars’ (Figure 11).

Smokeless tobacco

There is a range of smokeless tobacco products, including:

Such more ‘sanitized’ forms of smokeless tobacco available in parts of Europe and the USA are carcinogenic despite claims to the contrary.

Smokeless tobacco is of two main types: chewing tobacco and snus (Figure 12). Both these types are addictive and can cause health problems. The ingredients are a variety of tobacco, sugar, salt, slaked lime, spices and flavourings. Chewing tobacco usually comes as leaves or plugs which release nicotine and flavours. Snus comes as a moist powder, or packed in small bags, which are put in the lower labial sulcus, inside the lower lip, where it may cause white lesions (snuff-dippers keratosis).

Smokeless tobacco is used mainly by people from South Asia, South East Asia, the Middle East and East Africa and has many different names, including:

In the UK and Europe (except for Sweden), smokeless tobacco is rarely used except in minority ethnic groups. The cancer risk of smokeless tobacco seems to vary by geographical location, probably due to differences in the composition and format (eg chewing or inhaling nasally). Tobacco chewing in people from parts of Asia appears to predispose to mouth cancer, particularly when it is started early in life and is used frequently and for prolonged periods. The IARC classifies smokeless tobacco as a cause of mouth cancer. Risk of mouth cancer is increased five-fold in India and other Asian countries, and seven-fold in Sudan, doubled among smokeless tobacco users in the United States and Canada, but in the Nordic countries there appears to be no such increase.

One of the most dangerous and popular uses of smokeless tobacco is with areca (or betel) nut used in ‘betel quid’ made up of betel leaf, areca nut and slaked lime (Article 4).