Mouth cancer for clinicians part 14: cancer prevention

Primary prevention

The goal of primary prevention is to protect healthy people from developing cancer. Primary prevention is by far the most ideal approach; strategies include education of the public, high-risk individuals and healthcare practitioners and, for example:

Secondary prevention

The goal of secondary prevention is to slow or halt disease progression (if possible) in its earliest stages. For example:

Tertiary prevention

The goal of tertiary prevention is to help people manage the long-term health problems faced in cancer, to prevent further issues and to optimize the quality of life (QoL; Article 13) for example, via:

What is primary prevention?

DNA mutations can occur spontaneously, but the rate of mutations is increased by the various ‘cancer risk factors’ (Articles 3, 4, 5). The mainly modifiable lifestyle risk factors, most of which are used because they are addictive, are tobacco and alcohol. In some cases, betel use and similar habits, infections (eg human papillomaviruses [HPV], other microbes), radiation (eg sunlight, ionizing), or other risk factors may be responsible. There is protective benefit from a healthy immune system and from diets rich in fruit and vegetables.

There are a number of strategies which, in theory, may reduce exposure to the risk factors, which include:

Such a healthy lifestyle should not only reduce the risk of mouth cancer, but also has a wide range of other health benefits. Further detail follows below.

What measures are available for primary prevention?

It has been estimated that perhaps 75% of mouth cancers could be prevented by eliminating tobacco use and reducing alcohol consumption (Figure 1).

Tobacco

Tobacco is frequently smoked in cigarettes but there are several other forms used in different cultures (Tables 1 and 2: Article 3). Tobacco in any form, smoked, chewed, or smokeless, should be avoided.

Unfortunately, tobacco use is widespread worldwide and increasing in the young and in resource-poor communities. Tobacco use may be recognized from the history, or odour, or staining of fingers, teeth and even lips, but a fuller smoking history should be taken (Table 3).

Smoking cessation reduces the increased cancer risk by 35% within 1–4 years and by 80% after 20 years of quitting.

Treatment of tobacco dependence can be addressed in primary care (including dentists), and smoking cessation clinics. Smoking cessation should be gradual, because withdrawal symptoms are then less severe.

Evidence from NICE suggests that the following brief interventions for smoking cessation work and should be used:

The five steps in advising people to stop smoking are the ‘five As’:

Advise

Give plain, precise and personalized advice of the benefits of cessation and hazards of not stopping smoking (Figure 2). Other reasons for quitting tobacco (eg benefits in preventing heart disease; Table 4) should be included.

Table 4. Diseases associated with tobacco smoking. (Adapted from Scully C. Scully's Medical Problems in Dentistry 4th edn. Oxford: Elsevier, 2014.)

System	Diseases
Cardiovascular	Ischaemic heart disease
	Peripheral vascular disease
	Buerger disease
Respiratory	Sinusitis
	Chronic obstructive pulmonary disease
Carcinomas	Oropharyngeal and oral
	Bronchial
	Bladder
	Breast
	Colorectal
	Laryngeal
	Pancreatic
Foetus	Higher prevalence of abortion
	Low birthweight
	Higher risk of perinatal and sudden infant deaths
Gastrointestinal	Periodontal disease
	Peptic ulcer
Central nervous system	Alcoholism
	Cerebrovascular disease
	Dementia

Nicotine replacement therapy (NRT)

Nicotine replacement therapy is well-established and includes skin patches, nasal and mouth sprays, chewing gum, inhalators and tablets. NICE guidance from June 2013 recommends the use of licensed nicotine-containing products (NCPs) but does not currently include E-cigarettes. There is little difference in effect of the different types of NRT (Table 5).

Drugs

Two main agents are available.

Electronic cigarettes (E-cigarettes)

Electronic cigarettes (E-cigarettes) include electronic vaping devices, personal vaporizers or VPs, and electronic nicotine delivery systems (ENDS). E-cigarettes are battery-powered devices that simulate conventional cigarettes that deliver nicotine in many instances, plus diluents like propylene glycol and glycerine and flavourings. They contain a heating element and thereby provide an aerosol of vaporized chemicals to the user (Figure 3). Glycerine helps produce the vapour and can add sweetness. Propylene glycol makes up 90% of the solution and contributes to the ‘smoke’. Other flavours added may include tiramisu, pomegranate or pina colada. Other added substances with claimed benefits may include: rimonabant for weight loss or tadalafil to heighten sexual activity.

There is little firm evidence of health benefits or hazards of E-cigarette use. Rates of relapse are highest in the first few weeks and months, and diminish considerably after 3 months. An advantage over conventional smoking would appear to be a significant reduction in carcinogen exposure, though some studies have detected traces of tobacco specific N-nitrosamines. Very low levels of a carcinogen, diethylene glycol, have been detected in some E-cigarettes, as have lead, nickel and chromium.

The overall effect of E-cigarette use on public health is still unclear and there are some concerns about the effect on the developing brain, an increased risk for addiction, and the potential for E-cigarettes to lead to conventional tobacco use. Minor side-effects may include mouth and throat irritation, headache, vertigo, and/or nausea. More serious effects reported include aspiration pneumonia, cardiac arrhythmias and facial burns following explosion of a device.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has expressed concerns ‘about the quality and inaccurate labelling of electronic cigarettes’. E-cigarettes are regulated by the EU Tobacco Products Directive (TPD) and relations have just changed (www.cigelectric.co.uk/e-ciguk-regulation-2016/) and now stipulate some core requirements concerning, for example, limiting the strength and size of the nicotine-containing ‘e-liquid’, incorporating safety features to packaging and including warnings about the addictive nature of nicotine. In the USA, the Food and Drug Administration (FDA) has expressed concerns with manufacturing practices and the presence of carcinogens in products tested. Public Health England (PHE) summarized a report (2014) as follows; ‘The emergence of electronic cigarettes and the likely arrival of more effective nicotine-containing devices currently in development provides a radical alternative to tobacco, and evidence to date suggests that smokers are willing to use these products in substantial numbers. Electronic cigarettes, and other nicotine devices, therefore offer vast potential health benefits, but maximising those benefits while minimising harms and risks to society requires appropriate regulation, careful monitoring, and risk management. However the opportunity to harness this potential into public health policy, complementing existing comprehensive tobacco control policies, should not be missed.'

E-cigarettes are not regulated under current smoke-free legislation in the UK.

Alcohol

Alcohol use should be minimized: aim to drink no more than 1 standard drink a day (2–3 units) for women, or 2 standard drinks a day (3–4 units) for men. Screen all patients for excessive alcohol consumption with a validated questionnaire such as the Fast Alcohol Screening Test (FAST).

Some UK alcohol support services are shown in Table 6.

Betel and khat

Betel nut (or areca nut) chewing, even without tobacco, should be avoided. In the UK, knowledge about the betel risks and about mouth cancer are lacking in many high-risk south Asian populations where control could be achieved by implementation of policies to reduce betel quid chewing and improve public awareness of the dangers of use (Table 6). Khat use should also be discouraged (Figure 4).

Diet

Fruit and vegetables appear to protect, mediated via folate, antioxidants (carotene, carotenoids, flavanones, flavonoids, phytosterols, vitamins A, C and E, riboflavin), iron and magnesium. Eat at least 5 servings of fruit and vegetables daily; cereals, dairy products and olive oil may also be protective. No single dietary factor alone appears responsible: antioxidants may be anti-carcinogenic, eg in green tea, but a Cochrane review concluded that the evidence is insufficient and conflicting. Similarly, any role of polyphenols, abundant in vegetarian diets, and recent reports of a protective effect of coffee and of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, call for more investigation. One study found a significant protective association of aspirin use.

UV irradiation

UV rays from the sun are damaging. Protection against solar irradiation would reduce the incidence of lip cancers among white-skinned populations. Protect the lips with sunscreen and a wide-brimmed hat, and when the sun is strong, spend time in the shade.

Exercise

High recreational physical activity significantly reduces head and neck cancer risks among subjects ≥45 years-old, quite apart from the wider health benefits.

HPV

HPV infection can be minimized by practising safer sex, and by HPV vaccination. HPV vaccines have been available for some years, and are administered to young people in an effort to prevent cervical cancer. The 2007 Australian HPV vaccination for women programme had, by 2011, already shown significant declines in the proportion of young women with genital warts, an absence of genital warts in vaccinated women, and large declines in genital warts in heterosexual men.

The effect of an HPV vaccine tested on 5,840 sexually active women in Costa Rica (ages 18–25 years) showed that, after 4 years, mouthwash samples in 15 women after a placebo vaccine were infected, but only 1 woman who had received the HPV vaccine was infected with HPV.

The vaccines appear to afford protection against other HPV-related lesions, including oral lesions, but there is no hard evidence yet as to a significant protective effect against mouth cancer. Research is active in this area as are efforts to promote male vaccination.

There are always safety concerns about vaccines: one study of the safety and immunologic responses to an immunomodulatory HPV peptide vaccine GL-0810 (against HPV-16) showed it to be well tolerated in patients with recurrent HNSCC, with T cell and antibody responses seen in most patients.

What is secondary prevention of mouth cancer?

The treatment of early stage mouth cancers achieves higher survival rates with reduced attendant morbidity, however, many patients present with late stage disease and there is still the difficulty of reaching high-risk patient groups. Therefore, screening for potentially malignant disorders or early stage oral cancers is worth considering. However, the UK Working Group on Screening for Oral Cancer and Precancer concluded that there was insufficient evidence to support population screening because of the relative rarity of the cancer, a lack of knowledge of the natural history, disagreement over management and the lack of evidence on the efficacy of different screening methods. Others have reached similar conclusions. An alternative strategy would be to encourage opportunistic screening of high-risk groups attending primary care services. Screening thus remains a controversial issue.

Potentially Malignant Disorders (PMD) should be monitored; NICE guidelines clearly state that patients with oral lichen planus should be monitored for oral cancer as part of the routine dental examination (Referral Guidelines for Suspected Cancer. Clinical Guideline 27 NICE June 2005). NICE guidelines are under consideration at present.

What is tertiary prevention of mouth cancer?

Lifestyle changes might improve survival and QoL among treated cancer patients. Smoking during radiotherapy is likely to aggravate adverse effects, and it reduces the effect of radiotherapy. Smoking cessation even after a mouth cancer diagnosis improves prognostic outcomes: cancer patients who continue to smoke during their radiotherapy have a poorer response and survival than those who claim to quit smoking prior to cancer treatment. The risk for multiple primary cancers is higher in those who continue to smoke and drink alcohol after therapy. Among patients treated for head and neck cancer, about 50% continued to smoke after one year of treatment and 30% developed a second primary tumour (compared with 13% who quit). Alcohol, especially spirits, will irritate the areas affected by treatment.

Who is responsible for health promotion for mouth cancer prevention?

Health promotion for mouth cancer prevention is the remit of the whole healthcare team, and there are a number of national (eg Mouth Cancer Week) and international initiatives (eg www.ncbi.nlm.nih.gov/pubmed/18691457), some of which have been brought together under the umbrella of the International Consortium on Head and Neck Cancer Awareness (ICOHANCA; www.oraloncology.com/article/S1368-8375(07)00174-1/abstract) and, more recently, the Global Cancer Forum (www.globaloralcancerforum.org/) whose object is to increase cancer awareness, and lead to prevention and earlier diagnosis.

What is the wider importance of health promotion?

A healthy lifestyle is theoretically possible, involves lifestyle decisions and protects not only against many cancers, but also against several other conditions, many of which are also life-threatening (Table 7). Mouth cancer prevention strategies thus have potential for much wider health benefits.