Cancer Research UK : Oral Cancer risk factors

Oral Cancer risk factors

The main causes of oral cancer have long been known and many cases of the disease could be prevented. The most important aetiological factors are tobacco usage and excess consumption of alcohol, the two acting separately and synergistically. In developed countries, the risk of oral cancer attributable to these two factors combined is estimated to be more than 80%.1 A deficient diet also predisposes towards the development of oral cancers and it has been estimated that this may be responsible for 10-15% of cases in Europe.2 For lip cancers only, over exposure to UV light is implicated.

This page presents oral cancer risk factors including tobacco, alcohol, diet and nutrition, ultraviolet light and other factors.

Tobacco and oral cancer risk

Tobacco consumption can take many forms and over 90% of patients with oral cancer use tobacco in some form.

In the UK, cigarette, cigar and pipe smoking are the main forms of tobacco use and all are causes of oral cancer.3 In the earlier parts of the last century, pipe smoking was associated with lip cancer (most lip cancers arise on the lower lip) and its decline in popularity may be linked with some of the decrease in lip cancer. A recent case control study in Spain showed an increased risk of lip cancer when smokers were in the habit of leaving the cigarette on the lip.4 Since the 1920s smoking cigarettes has been the main form of tobacco use in the UK. The risk of oral cancer associated with smoking is both dose and duration dependent while smoking cessation leads to a fall in risk.1,5,6 The excess risk of oral cancer from smoking almost disappears within 10 years of giving up.7

In 2003, it was estimated that of the 28% of British men who smoked, 4% smoked cigars and 1% pipes.8 Very few women in the UK smoke pipes or cigars. In one case control study of oral cancer carried out in Cuba, the odds ratio associated with smoking 30 or more cigarettes a day was comparable with that for smoking 4 or more cigars a day. Indian women who practice reverse chutta smoking, with the lighted end of the cigar inside the mouth, have particularly high rates of oral cancer of the palatal mucosa.9 Smoking bidi(s) which are made of hand-rolled tobacco wrapped in tendu leaf also increases the risk of oral cancer.10

A recent evaluation by the International Agency for Research on Cancer (IARC) has confirmed that smokeless tobacco is also carcinogenic.11,12 In the UK and Europe (with the notable exception of Sweden) the use of smokeless tobacco is rare except in minority ethnic groups (see next paragraph).13 In the USA it is a major problem with a reported 6% of the adult male population as regular users14. In some areas, particularly the southern states, the prevalence is much higher with up to a third of young men using smokeless tobacco.15

The primary cause of the very high incidence of oral cancer in South Asia is the widespread habit of chewing betel quid (or paan) and related areca nut use.16 Chewing betel is thought to date back at least 2000 years and worldwide an estimated 200-400 million people practice the habit.17 The components of the betel quid vary between different populations but the main ingredients are the leaf of the vine, Piper betel, areca nuta, slaked lime (calcium hydroxide) and spices.18 Tobacco was introduced to South Asia in the seventeenth century. Areca nut is carcinogenic to humans and the risk of oral cancer is increased with chewing pan without tobacco, although the risk is higher for paan containing tobacco.19-21 As with smoking tobacco, risk is dependent on dose and duration of use.22 Among Asian communities in the UK, Bangladeshis are particularly likely to retain the habit of betel quid chewing as Figure 4.1 shows with one-fifth of men and one-quarter of women using smokeless tobacco.23,24 The prevalence of tobacco chewing increases with age, especially among women. The most commonly used chewing tobacco product is paan with tobacco (used by 14% of Bangladeshi men and 23% of Bangladeshi women).

Figure 4.1: Percentage of South Asians in the UK that use any form of chewing tobacco, 1999

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Oral cancer patients are at risk of developing second primary tumours in the upper aerodigestive tract but their risk of doing so is reduced if they cease to use tobacco after the initial primary is diagnosed.25,26

Although oral cancers are strongly associated with smoking, the oral cancer mortality trends in England and Wales do not match the decreasing trends in smoking (see section on Lung cancer and smoking) in the same way that lung cancer trends do. This suggests that smoking acts in a complex way, possibly with other risk factors, to promote the disease.27

Alcohol and oral cancer risk

Alcohol is the second major risk factor for oral cancer with 75-80% of patients frequently consuming alcohol. For non-smokers it is the most important risk factor. Above 30 grams of alcohol per day, risk increases linearly with amount of alcohol consumed.1 People who both drink and smoke have a much higher risk of oral cancer than those using only alcohol or tobacco as Figure 4.2 demonstrates using US data.28

Figure 4.2: Relative risk of oral/pharyngeal cancer in males by alcohol/tobacco consumption using US measures

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Heavy drinkers and smokers have 38 times the risk of abstainers from both products. It has been suggested that it is the total amount of ethanol ingested rather than the type of product (beer, wine, spirits) which is important.29 However, in a recent case control study in Spain, although risk did increase linearly with increasing ethanol content, there was an independent effect of type of alcohol with spirit drinkers 2 or 3 times more at risk of developing oral cancer than drinkers of only wine or beer.5 The rising trends in oral cancer mortality in Europe have been related to increasing levels of alcohol consumption. For example, in Denmark the alarming increase in oral cancers has been attributed predominantly to greater alcohol consumption.30 An exception to this rise in alcohol consumption is seen in France, where a decrease in alcohol consumption has been linked to the fall in oral cancer mortality rates in the 1980s.31

In the UK, consumption of alcohol has more than doubled since the middle of the last century, from 3.9 to 8.6 litres of pure alcohol per head per year– see Figure 4.3.32,33

Figure 4.3: Alcohol consumption in the UK, 1900-2000, per capita consumption of 100 per cent alcohol

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The percentage of the population who exceed the recommended weekly guideline of 21 units for men and 14 for women is steadily rising. b In 1988 around 10% of women and 26% of men exceeded the limits compared with 18% and 30% in 2002.34 The heaviest drinkers are aged 16-24 years and this age group is also the most likely to binge drink.33

At present the UK level of drinking (8.6 litres per year) is lower than in most European countries, for example, France (10.7 litres), Portugal (11.0 litres), Spain (9.9 litres) and Germany (10.6 litres). However, whereas consumption is either falling or stabilising in most of these countries, in the UK it is rising quickly. It is estimated that if current trends continue, the UK could rise to near the top of the consumption table within the next ten years.33 Co-ordinated and funded action is needed to tackle the UK’s complex drinking problems.35

Concern has also been expressed about the use of mouthwashes, particularly those with high alcoholic content.36 Further studies need to be carried out to clarify the role of mouthwashes and the development of oral cancer, but the avoidance of high alcoholic mouthwashes seems prudent.

Diet, nutrition and oral cancer risk

Dietary deficiencies, particularly of vitamin A (and related carotenoids), vitamin C, vitamin E, iron, selenium, folate and other trace elements have been linked to increased risk of oral cancer.37-39 Many studies have found that oral cancer patients have a history of low fruit and vegetable intake.40 Intervention studies where diets have been supplemented have shown some beneficial effect on pre-malignant conditions and reducing the risk of a second oral cancer but further work into diet and the role of chemoprevention in oral cancers is needed.2,41,42

Risk of oral cancer appears to fall with increasing body mass index (BMI). A recent case-control study in Spain reported a significant reduction in risk of oral cancer with higher BMI at diagnosis and two years prior to diagnosis, after adjustments for smoking, drinking, fruit and vegetable intake.43

Ultraviolet light and oral cancer risk

Solar irradiation is a major risk factor for cancer of the lip. The vast majority of lip cancers occur on the lower lip and many patients have outdoor occupations where sun exposure is increased. Lip cancer is three times more common in men than women which may be an effect of occupation, smoking and sun-exposure.4 The use of sunscreens and protective clothing would significantly reduce exposure.

Other oral cancer risk factors

The role of viruses remains unclear. Evidence is perhaps strongest for infection with high-risk human papillomaviruses (HPV).44-46 Studies show an increased risk of oral cancer in women with cervical cancer suggesting a common risk factor other than smoking, such as HPV infection: transmission of HPV via oral sex is one possibility. A recent multicentre case control study reported that infection with HPV16 increased the risk of cancer of the oral cavity and particularly oropharynx.47 The role of infection with Epstein-Barr virus and herpes simplex viruses remains uncertain.48,49 Renal transplant patients have been reported to be at increased risk of developing lip cancers50 which may be a result of immunosuppression. Poor oral hygiene and ill-fitting dentures may also play a role in localising a site where tumours may develop, but both this and oral sepsis are very unlikely to cause oral cancer in the absence of other well-established risk factors.

Several oral lesions and conditions precede oral carcinoma and the most common of these are leukoplakia and erythroplakiab. Leukoplakia has many clinical variants but is much less likely to progress to malignancy than erythroplakia. The precise prevalence of these conditions in the UK is unknown. Estimates of leukoplakia prevalence outside the UK range from 0.2 to 11.7% of the population and the prevalence of erythroplakia is considerably less.51 It has recently been estimated that the annual transformation rate of oral leukoplakia to oral squamous cell carcinoma may not exceed 1%.52 Erythroplakia is rare and mainly occurs in people aged over 60.53

Oral cancer risk in young and middle-aged adults

The rising incidence and mortality rates in young and middle-aged adults is incontrovertible, but there has been debate over the causes of this increase and whether their disease is inherently more aggressive than that occurring in older patients.48,54-56 A series of studies in southern England looking at risk factors for patients under 45 years concluded that most young patients are exposed to the traditional risk factors of tobacco smoking and alcohol while consumption of fresh fruit and vegetables is protective. 48,57,58 However, the relatively short duration of exposure to these known risk factors suggests that other factors may also be involved and there was a small sub-group of patients who had little, if any, exposure to the major risk factors.

In 1992 the Government recommended weekly limits. In 1995 this was amended to daily recommendations of 3-4 units for men and 2-3 units for women, with two non-drinking days after an episode of heavy drinking. One unit is 8g of alcohol, equivalent to half a pint of beer, one small (125ml) glass of wine and one measure of spirits. New recommendations are expected this year. The European Code against Cancer recommends lower limits of 2 drinks a day for men and 1 for women.

aareca nut is the seed of the fruit of the oriental palm, Areca catechu

bOther rare precancerous conditions include lichen planus, oral submucous fibrosis, syphilitic glossitis and sideropenic dysphagia.

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