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The Early Detection and Prevention of Oral Cancer Welcome to this online interactive guide to the early detection and prevention of oral cancer in primary care. The information is intended primarily for dental practitioners in Europe, though care pathways and referral guidelines are provided for general medical practitioners and pharmacists. Dental therapists, hygienists, oral health educators and other members of primary care teams will also find topics valuable, in particular the section on smoking cessation. Printable resources (a guide to smoking cessation, some referral guidelines and a referral proforma) are available for you to download. Links to online resources are provided in the text and in the Resources topic. This programme was first produced as a CD-ROM by The Dental Channel Ltd (UK) in consultation with the Department of Health (UK) and the Department of Oral Medicine, King’s College Hospital. An extended version is available at http://www.globaloralcancerforum.org/ and at http://www.dental-channel.co.uk. Course design by The Dental Channel ©MMVII Executive Summary 1. Purpose This “Life long” distance learning (E learning) programme summarises the current state of knowledge, explains how to recognise the early signs and symptoms of incipient and overt oral malignancy, gives advice regarding best practice procedures, and provides additional resources. The objective is to achieve earlier detection of oral cancers and potentially malignant disorders in primary care. 2. Epidemiology Malignant neoplasms in and around the mouth represent one of the ten most common cancers. Almost half a million new cancers of the mouth and pharynx were reported globally in 2005. There is a 15 fold difference in the incidence of oral cancers in different countries of the world. In the European Union (EU) countries there were 67,000 new oral cancers reported in 2004. The incidence of oral cancer increases with age, most commonly occurs in middle-aged and older individuals, although in the past two decades a disturbing number of these malignancies is also being documented in younger adults. The disease is more common in males, with a male:female ratio of over 2:1 However, the disparity in the male:female ratio has become less pronounced because women have taken up risk factors such as tobacco and alcohol, since 1960s. 3. Survival Intra-oral cancer is particularly lethal, whereas that of the lip much less so; the crude five-year survival rates for oral cancer being around 50-60%. There is little evidence that survival itself has improved in recent decades except in specialised head and neck cancer centres. 4. Risk Factors Most cases of oral carcinomas can be attributed to certain lifestyle risk factors and are thus preventable. The most important are in the use of tobacco and drinking alcohol to excess. Smoking cigarettes in the most commonly encountered risk factor in Europe Course design by The Dental Channel ©MMVII although any form of tobacco use carries an increased risk. The rising trend in tongue cancer in young men in western countries noted previously is thought to be due to marked increases in alcohol consumption. The role of binge drinking has not been adequately investigated. For some populations in Asia (and migrants arising therefrom) regular areca nut (betel quid) use is relevant. For those with no tobacco or alcohol habits (up to 25% of younger cases) Human papilloma virus (HPV) infection may be an important risk factor. Healthy diet can help guard against oral cancer. Fresh yellowgreen vegetables and fruits have been identified as beneficial dietary components. These act as antioxidants. 5. Clinical presentation a. cancer Signs and symptoms of oral cancer should be understood by the GPs and the wider dental team and all members should receive updating on recognition of key complaints and early stages. Oral ulcers that fail to resolve within two weeks after appropriate therapy and any new growths for which no other diagnosis can be established should be suspected of cancer. Cancer could also present as a red patch or a red and white mixed lesion, particulary when associated with symptoms. Presence of induration (hardness at the marginss or base) is a key clinical sign of malignancy. b. precancer Disorders of the oral mucosa which on biopsy may be dysplastic but not frankly malignant, may clinically present in a number of ways: ' Leukoplakia The term leukoplakia should be used to recognize predominantly white plaques of questionable risk having excluded (other) known diseases or disorders (that present Course design by The Dental Channel ©MMVII as white patches) that carry no increased risk f or cancer ’. It is recommended that the term be used as a clinical diagnosis. Erythroplakia – a red lesion (defined in a similar way to Leukoplakia, except its red ) for which there is no other attributable cause – is a dangerous sign that needs urgent investigation An erythroleukoplakia (also called speckled leukoplakia) has combined red and white elements in the plaque together with an irregular surface texture. Oral submucous fibrosis presents as a loss of elasticity of the mucosa, with fibrous bands causing limitation of opening of the mouth. Early signs may include blanching of the mucosa, a leathery feeling and presents with burning symptoms at meal times. Other rare forms of potentially malignant disorders are lupus erythematoses, tongue lesions in tertiary syphilis and actinic keratosis of lip. 6. Diagnostic Aids Biopsy is essential to establish diagnosis of lesions suspected of cancer. In those thought to be precursor lesions it is important to exclude malignancy and to estimate the degree of epithelial dysplasia by microscopy which has some value for predicting malignant potential. Ploidy analysis and detecting aneuploidy has been shown to be particularly helpful in distinguishing high-risk lesions. A brush biopsy (i.e transepithelial sample) is adequate to harvest epithelial cells for ploidy analysis. Adjuncts to conventional methods of detection include: Toluidine blue test Chemiluminescence Autofluorescence The utility of these tests in primary care is yet to be Course design by The Dental Channel ©MMVII established. 7. Primary prevention (including tobacco control) The major risk factors for oral cancer are well understood. The preventive approach is therefore clear. GPs have practice protocols to deal with smoking cessation and may have a trained nurse to help their patients. The dental practitioners should provide brief advice to their patients on tobacco cessation and also refer cases to a smoker’s clinic for additional assistance. There are five crucial steps in motivating people to stop smoking, known as the “5 A’s”: Ask Advise Assess Assist Arrange Two videos included in the programme provide tips for practitioners in a clinical setting and links are provided to other useful resources (http://www.tobacco-oralhealth.net) Other cancer prevention approaches related to alcohol moderation (to drink within recommended guidelines), quitting betel quid use and improving diet (rich in antioxidants) are also important. Providing such advice should be undertaken in the primary care setting. The dentists should give advice to patients about their awareness of oral cancer so that they can recognise the signs and symptoms at an early stage and seek early treatment. 8. Secondary prevention (screening) Screening and oral mucosal examination are both elements of routine dental practice (oral health examination). A thorough systemic examination (opportunistic screening ) of the oral mucosa is mandatory every time a dentist starts on a course of treatment or at regular reviews. A routine which is comprehensive, effective and should not take more than three minutes to perform is illustrated in this programme. 9. Tertiary Preventions Course design by The Dental Channel ©MMVII Tertiary prevention is concerned with preventing recurrence or further primary cancers and minimising morbidity. Treated patients should be monitored regularly to screen for the possibility of new lesions (diagnostic adjuncts are recommended for surveillance) and advised on risk factors if these are continuing. 10. Public awareness Oral cancer is often poorly understood by society in general. The symptoms are not widely understood and are frequently ignored in the early stages when it is most amenable to treat. Population surveys amongst adults suggest only about half have heard about oral cancer. 11. Role of primary health care dentists, doctors, pharmacists & hygienists Primary care practitioners can play a key role in both advising their patients about risk factors and case detection. Dentists are important in early detection through opportunistic screening and planned screening of populations at high risk Physicians can attempt a targeted approach on smokers and heavy alcohol drinkers Dental hygienists should bring to the attention of the supervising dentists any suspicious lesions they might notice during hygiene visits Pharmacists have role in smoking cessation and also in directing patients with non healing ulcers who ask for OTC medications to a report to a dentist/GP Dentists should take a leadership role in professional educational activities in their local regions. 12. Medico legal aspects Concern should be aroused by any persistent oral mucosal condition that does not respond to conventional treatment. Any delay can have life threatening consequences for the patient that might lead to allegations of negligence. Effective management should follow best clinical practice such as that provided by this resource, keeping abreast with any published updates, and be backed up by accurate and appropriate record Course design by The Dental Channel ©MMVII keeping. The ‘two week response’ is a useful indicator for patients who have suspicious lesions that have not resolved with attention to possible causes and require referral. 13. Referral If oral cancer is suspected the referral must be marked “Urgent”. Urgent referrals should be faxed to the local hospital. In the UK suspected cancers are referred under the 2 week referral guidelines. Other referrals should be categorised as non-urgent or prompt. Potentially malignant disordes should be referred to a specialist following a mucosal examination for assessment (inc biopsy) and advice on management. Urgent referral of suspected cancers should save lives. Each European country should develop guidelines for urgent referral of Head & Neck cancers. As an example UK guidelines are included in the programme. 14. Recent Advances Cancer is a genetic disease, particularly due to DNA aberrations caused by carcinogens. It is possible to analyse tissue, body fluids (increasingly including saliva) for markers of aberrations in chromosomes, genes or their protein product in patients with cancer or precancer. Loss of sections of specific chromosomes (eg. 3p, 9p and 11q) that harbour tumour suppressor genes or mutations that increase the risk of cancer are now known. Any change of ploidy status can also be assessed from a standard biopsy or a brush biopsy. It is not known precisely how many hits or aberrations are necessary to render a clone of cells malignant. Recent research of the above kind has led to genetic models for development of head and neck cancer. 15. Key messages Course design by The Dental Channel ©MMVII Oral cancer can be lethal It is becoming more common worldwide, no age group is immune. Knowledge regarding major risk factors is well established: oral cancer can be prevented Small lesions are easier to treat: lesions suspected to be malignant should be referred to a specialist without delay. Opportunistic screening may allow identification of asymptomatic early disease that may reduce mobidity. Course design by The Dental Channel ©MMVII Core Knowledge 1. Introduction 2. The Problem 3. What Causes Oral Cancer? 4. How Do We Recognise and Treat Oral Cancer? 5. Diagnosing Oral Cancer 6. Practical Prevention 7. Dentists and Smoking Cessation 8. Screening for Oral Cancer and Potentially Malignant Lesions Course design by The Dental Channel ©MMVII 1. Introduction The key messages of this program are: Oral cancer can be lethal The incidence is increasing in some European countries and particularly in young people.It is becoming more common worldwide Knowledge regarding major risk factors is well established: oral cancer can be prevented Small lesions are easier to treat; lesions suspected to be malignant should be referred to a specialist without delay Opportunistic screening of the oral cavity for malignant and potentially malignant disease at regular dental examinations makes sense Primary care practitioners can play a key role in both advising their patients about risk factors and case detection. Course design by The Dental Channel ©MMVII Oral Malignant Neoplasms Malignant neoplasms in and around the mouth represent one of the ten most common cancers with which primary care givers have to deal. Our involvement includes Advice on preventive practices by avoidance of high risk factors Knowledge of key presentations to advise people on obtaining professional help for early detection of a suspicious lesion. Dentists and doctors screening for early lesions by careful oral examination, Major involvement in the treatment and rehabilitation of those afflicted, and research into the causes and mechanisms of the disease process itself Course design by The Dental Channel ©MMVII The Role of the Primary Care Practitioner Dental practitioners have a particularly important role to play in prevention and early detection. Members of the public attend dental practitioners on a routine basis more frequently than most other branches of the health professions. Dentists are expert in examination of the mouth and related structures, and are best qualified to recognise abnormal changes. They are well educated in the importance of diet and nutrition to the maintenance of health, can recognise the effects of nutritional deficiencies on the oral soft tissues, and can readily recognise in the mouth the consequences of alcohol and tobacco abuse. Similarly general medical practitioners, pharmacists and other members of primary care teams have important roles in early detection and prevention. This program summarises the current state of knowledge, gives advice regarding best practice procedures, and provides additional resources. It is divided into the following sections: An overview of the problem, summarising interesting data on the global variability of disease patterns. Guidelines for a standardised examination of the oral soft tissues Assessment of risk factors in individual patients and advise on their reduction Management of potentially malignant oral lesions in practice How to recognise the tell tale signs and symptoms of overt incipient oral malignancy The roles of the dental profession in community prevention and screening Future prospects for research and improved treatment modalities. Course design by The Dental Channel ©MMVII 2. The Problem Oral cancer is increasing in incidence world-wide. In order to comprehend the problem the following demographic data need to be considered: The size of the problem Age distribution Gender distribution Ethnic basis Site distribution Trends Young people Mortality/survival The role of the primary care provider in prevention Course design by The Dental Channel ©MMVII The Problem – Introduction Oral cancer is increasing in incidence world-wide. Throughout the world, malignant neoplasms of the mouth and pharynx rate as the tenth most common cancer in men and the seventh in women, (sixth overall), although there are marked geographical variations. Almost half a million new cancers of the mouth and pharynx were reported in 2005. Oral cancer is often poorly understood by society in general. The symptoms are not widely understood and are frequently ignored in the early stages when it is most amenable to treatment. Indeed many people do not realise that cancer can arise in the mouth. Over 90% of malignant neoplasms in the oral cavity are squamous cell carcinomas of the lining oral mucosa, tongue and lip. Most of the remainder arise from the salivary glands or within the bones of the jaws. There is a 15 fold difference in the incidence of oral cancers in different countries of the world. Examples of high incidence regions are: Countries in South Asia including Sri Lanka, India, Pakistan, Taiwan France, Hungary, Slovakia and Slovenia Brazil, Uruguay and Puerto Rico and Cuba Papua New Guinea, and other pacific islands in Melanesia Wide variations are also reported within Europe Indeed in the European Union as a whole, oral cancer is more common now than cervical cancer (Figure 6). Course design by The Dental Channel ©MMVII Age Distribution The incidence of oral cancer increases with age: in most reports themean age is 62-65 years. During the last three decades there has been an alarming rise in the incidence of oral cancer amongst young men in many western European countries; this rise is particularly noted for tongue and oropharyngeal cancers. Course design by The Dental Channel ©MMVII Gender distribution In industrialised countries men are affected almost twice as often as women, probably due to their higher indulgence in risk factors such as alcohol and tobacco consumption for intra oral cancer, and exposure to sunlight from outdoor occupations that predispose to lip cancer. This sex difference however is beginning to be less prominent due to women adapting lifestyles that are more common amongst males. Men and women are almost equally affected in some of the ethnic groups in Singapore, Denmark and Hawaii. Course design by The Dental Channel ©MMVII Ethnic Basis Ethnicity strongly influences incidence due to social and cultural practices. Where such habits (e.g. areca nut use) represent risk factors for cancer development, oral cancer is higher in that population. Migration by emigrants from high prevalence regions to other parts of the world results in comparatively high cancer incidence in immigrant communities. Other studies show that black US Americans, for example, experience significantly more pharyngeal and laryngeal cancers than their white counterparts. Nasopharyngeal cancers are more common in Chinese. Course design by The Dental Channel ©MMVII Site Distribution Lip cancer is most common in fair-skinned races, particularly in rural areas and in men who work out of doors, e.g. farmers and fishermen. Within Europe highest rates are reported in Southern Spain. Intra-oral cancer in western countries most commonly affects the lateral borders of the tongue and the floor of the mouth. Course design by The Dental Channel ©MMVII Trends The rising trend in tongue cancer in young men in western countries noted previously is thought to be due to marked increases in alcohol consumption, starting to drink at a young age, and probably binge drinking. The contribution of the increased use of oral smokeless tobacco products to these rising trends, especially in the USA, leisure drugs (cannabis/marijuhana) remains controversial) There is emerging evidence that and oro-genital viral infections with HPV may account for the rising ioncidence of oro-pharyngeal cancers in young people. Course design by The Dental Channel ©MMVII Mortality/Survival Intra-oral cancer is particularly lethal, whereas that of the lip much less so; the crude five-year survival rates for oral being 50-60% and 80% for lip cancers. Mortality rates are largely dependant on the size of the primary lesion, with subjects with small cancers performing well compared to those with large tumours. Although technology and surgical techniques have improved the quality of life of those surviving, there is little evidence that survival itself has improved in recent decades except in specialised centres. This is partly because, with improved loco-regional control, patients are dying from second primary cancers, particularly in the upper aero-digestive tract. Within the mouth, factors which influence survival are the site (generally the further posteriorly in the mouth the lesion occurs the worse the prognosis), the size of lesion at diagnosis, the pathological status i.e. its degree of differentiation and the features of the infiltrative margin of the malignancy, the ploidy status, and whether the involvement of the regional lymph nodes in the form of metastases or extra capsular spread are present. For some reason there is recent evidence that married status is also a significant factor in survival. This may be explained in the psychological support received from the partner helping to combat the disease or generally poor nutrition among older subjects living alone and making their own meals. The affluence of subjects also influences survival. In the UK any improvement in survival are limited to affluent social classes. Extensive research in the past decade suggests that accumulation of several/multiple genetic/chromosomal aberrations due to mutagenic damage may also influence outcome, along with the immune status of the individual. Smaller lesions can be cured by surgery and radiotherapy but advanced lesions, sadly the most common in all parts of the world, demand a radical combined approach, perhaps also involving chemotherapy. Course design by The Dental Channel ©MMVII The Role of the Health Provider in Prevention Dentists hold a vital role in the prevention and early detection of oral cancer. This is primarily due to their familiarity with the structures and health of the oral cavity and its associated tissues, and the regularity with which the patients attend for routine oral examination. General medical practitioners are aware of the social histories of their registered patients, in particular their smoking habits and any alcohol abuse. This allows GPs to produce brief interventions, provide medications to help quitting and also may employ specialist nurses in practice to provide counselling. Examination of the tongue and anterior pharynx is a common practice amongst GPs. On such occasions when the opportunities arise high risk subjects could receive a full mouth examination by their practitioner. This would enable early detection of asymptomatic disease unknown to the patient. Regular tobacco users could be easily identified by dental hygienists observing tobacco stains on dental structures or dorsal tongue. They may also have progressive periodontal destruction. The hygienist can play an important role in tobacco cessation following additional training. If any white, red or otherwise suspicious lesion is noted during prophylaxis this should be brought to the immediate attention of the dental practitioner. Pharmacists now play a significant role in the delivery of tobacco cessation services, particularly through the supply of nicotine replacement products. During such advice the risk of oral cancer could be mentioned as part of a common risk factor approach. Tobacco use and heavy alcohol consumption are important risk factors in the aetiology of oral pre-cancerous and neoplastic lesions. The dentist’s role, and particularly that of a whole dental team, in helping patients to quit the use of tobacco and moderate alcohol intake is of great importance. Indeed, it is an area of dental practice in which the overlap between oral health and general health can be most keenly emphasised, a feature used in many practice based smoking cessation programmes. The risk of developing oral cancer falls dramatically with the halting of tobacco use so that by 10 years after cessation the patient is at no greater risk than an individual who has never smoked. Healthy diet can also help guard against oral cancer. Fresh yellow-green vegetables and fruits have been identified as beneficial dietary components in this as in other cancers, as has the supplementation of vitamins A C and E. These act as antioxidants, mopping up any cellular or nuclear aberrations allowing repair. Similarly, dietary advice of a general nature can help to improve general personal as well as oral health with regard to cancer and the other common oral diseases. Course design by The Dental Channel ©MMVII Screening and mucosal examination are both elements of routine dental practice. These two activities are unquestionably vital ways in which practitioners can help detect individuals with unhealthy lifestyles, as well as the earliest signs of the disease, permitting the greatest opportunity for a successful resolution and preventing the progress to advanced lesions. Course design by The Dental Channel ©MMVII 3. What Causes Oral Cancer? Most cases of oral carcinomas can be attributed to certain lifestyle risk factors and are thus preventable. The most important are the use of tobacco and drinking alcohol to excess. For some populations regular areca nut in betel quid use is relevant. Alcohol misuse is emerging as an important issue. Smoking cigarettes is the most commonly encountered risk factor, but rolled up (non-filter) cigarettes have higher risks as well as smokeless tobacco products (Warnakulasariya 2004). In a minority of cases, particularly amongst younger patients known risk factors are absent, producing a challenge for research into their aetiology (Llewleyn 2001). HPV infection is proposed as a likely cause. Diet plays an important role; regular consumption of fresh fruits and vegetables provides protection against cancer. Course design by The Dental Channel ©MMVII Tobacco Tobacco use – smoked or in smokeless forms - is far and away the most important risk factor for oral cancer. Over 75% of mouth and pharyngeal cancers are directly attributed to smoking (and alcohol) use. The risk of oral cancer increases with the amount of tobacco consumed per day, and the number of years of consumption. All tobacco products are carcinogenic, and there is no evidence to suggest that replacing smoking with another tobacco product Is harmless. Doctors and dentists should always ask their patients about their tobacco habits and counsel them to quit. It is well-established that advice from primary health care professionals (for example, from General Medical Practitioners) is one of the most effective ways of achieving smoking cessation and a comparable quit rate of 11% maintained over a nine-month period has been shown using general dental practitioners in the United Kingdom. There is good evidence that after about 10 years of quitting tobacco use, the cancer risk returns to that of the ‘never smoker’. A recent study in India showed a significant reduction in the incidence of premalignant lesions in chewers and smokers who have quit. However counselling to quit smoking is not applied in a systematic and frequent enough manner amongst UK dentists. Dentists should remember the five A’s: 1. Ask your patients about tobacco use 2. Advise them to quit 3. Assess their determination to quit 4. Assist them 5. Arrange follow up and support. Several methods can be suggested. Nicotine replacement therapy is effective in helping people to stop smoking: it roughly doubles the chance of achieving long-term abstinence. There are other therapies discussed in the section on tobacco cessation. Following brief advice it is recommended to arrange referral to a local smoker’s clinic run by the health authority. The effectiveness of complimentary therapies has not Course design by The Dental Channel ©MMVII been proven. Course design by The Dental Channel ©MMVII Alcohol Excessive consumption of alcohol is the second most important risk factor. It acts synergistically with tobacco so that the combined damage is more than multiplied. Though ethanol per se has not been shown to carcinogenic, acetaldehyde, a metabolite of alcohol, is carcinogenic to man. Course design by The Dental Channel ©MMVII Areca Nut Areca nut alone can be carcinogenic and appears to be responsible for the high incidence of oral cancer in some countries e.g. Melanesia and Taiwan, where it is often consumed without tobacco. There is also recent evidence from several countries that areca nut alone may cause cancer. Those who consume areca nut (without tobacco) have an increased incidence of oral cancer. The International Agency on Research for Cancer (IARC) has recently classified areca nut as a Class I carcinogen. Areca nut is the major cause of the distressing condition Oral Submucous Fibrosis, which has a high rate of malignant transformation (up to 7% over 10 to 15 years). Course design by The Dental Channel ©MMVII Diet Diet is probably the next most powerful factor in cancer control: a healthy diet protects. The antioxidant vitamins A, C and E scavenge potentially mutagenic free radicals from damaged cells. They are best delivered naturally in red, yellow and green fruits and vegetables, and we should encourage people to eat about five helpings of such foods a day. Course design by The Dental Channel ©MMVII Other Factors The presence of potentially malignant disorders such as some white plaques, some red plaques, and submucous fibrosis certainly indicate that a patient is at increased risk of developing an oral cancer. It is estimated that someone with a white or red patch may have an increased risk one hundred times greater than a person with a healthy normal mucosa. This will usually justify removal or other treatment, but most result from the same risk factors discussed above, elimination of which is therefore even more important in such patients. Infections of oral mucosa may also be important. It has long been known that white patches harbouring yeasts or hyphae of the fungus Candida albicans carry an increased risk of progressing to malignancy and where present appropriate anti-fungal therapy (systemic and/or systemic) should be pursued. Of great current interest is the possibility of a role for Human Papilloma virus (HPV). The so-called high oncogenic potential HPVs types 16 and 18 are known to be important in cancer of the uterine cervix, and are increasingly being found in oral lesions (particularly in the tonsils and oropharynx). Screening for their presence may become a useful component of the early detection of patients and lesions at risk of malignant transformation. Anti-HPV vaccines are being developed and may become a novel therapy to eradicate HPV-associated mucosal lesions. There is no strong evidence to suggest that oral cancer is familial, although few hereditary syndromes are known. People with poor dental health such as sharp, broken teeth, dental sepsis or trauma from ill-fitting dentures are at slightly increased risk. Oral sepsis (commensal bacteria) in mouths of alcoholics might contribute to the metabolism of alcohol to acetaldehyde, a known carcinogen. Immunosuppression regimes, for example following renal or other organ transplantation, increase the risk of ultraviolet-induced cancer of skin and lip. There appears to be no increased risk of intra-oral squamous cell carcinoma in those with HIV disease, and there is as yet no evidence that the characteristic, so-called, oral hairy leukoplakia in HIV/AIDS patients has malignant potential. However other neoplasms such as Kaposi’s Sarcoma and NonHodgkin's lymphomas are certainly increased. Course design by The Dental Channel ©MMVII 4. How Do We Recognise and Treat Oral Cancer? A multitude of mucosal disorders and benign anomalies may be found when screening the oral mucosa. This makes it difficult to make a diagnosis unless the practitioner is familiar with the essential crireia to establish a diagnosis. Some malignant lesions seen in the early stage may be mistaken for a benign change. Key entities considered in this section to help the practitioner with a differential diagnosis are: Cancer and Potentially malignant disorders This latter group includes: Leukoplakia Erythroplakia Lichen planus Oral submucous fibrosis Discoid lupus erythematosus Tertiary syphilis Actinic keratosis Course design by The Dental Channel ©MMVII Clinical Presentations of Cancer of the Oral Cavity Any ulcer of the mucosa (a break in the surface lining) that fails to heal within two weeks with appropriate therapy (eg removal of a frictional source) and for which no other diagnosis can be established (eg major apthous ulcer - Fig 23) should be suspected of a malignancy until confirmed otherwise (Fig 24) Pain (deeper in the mucosa), could be an early symptom that differentiates a malignant ulcer particularly in the absence of erythema and acute infection of the surrounding area. Induration is the key clinical sign of malignancy. This means that the surrounding mucosa or base of the lesion is firm (Fig 25). It is therefore important that all areas with a visual abnormality are palpated to exclude the presence or absence of induration. A new growth for which there is no explanation (eg. trauma from teeth or denture trauma) should also be suspected of cancer. This may be an exophytic growth of tissue that produces a lump with a smooth, lobulated or corrugated surface covering (Fig 26). Fungation is common, due to central necrosis of a rapidly enlarging mass which outgrows its blood supply. The mucosa may be fixed to underlying tissues, with loss of normal mobility. Failure to heal of a tooth socket or any other wound may fail to heal. There may be tooth mobility or unexplained pain or paraesthesia with no apparent cause, Similarly dysphagia for which no other diagnosis can be made should be considered suspicious. White and red patches of the mucosa ((Fig 27) are commonly considered as potentially malignant lesions, but occasionally they may be the clinical presentation of a malignancy. In a large case series in the USA 6% of the lesions which were histologically squamous cell carcinomas presented to the clinician as a simple white patch, suggesting the significance of biopsy investigation to exclude malignancy. Red patches in particular could be cancerous even at the time of first presentation. The lymph nodes of the head and neck should always be palpated as part of the clinical Course design by The Dental Channel ©MMVII examination by every dentist. Enlargement of one or more nodes presenting with a primary in the mouth may indicate metastasis, especially if hard or fixed to skin or deeper structures (Fig 28). The precise group of nodes likely to be affected depends on the location of the primary cancer, but submandibular, then upper, middle and lower deep cervical nodes are most commonly involved with intra-oral lesions; these are often referred to as levels 1-4, level 5 being the posterior triangle of neck. The greater the size of the enlarged nodes and the number of node groups involved, the more serious is the prognosis for the patient. The lower the level in the neck, the more extensive is the spread (UICC 2002). Course design by The Dental Channel ©MMVII Clinical Presentations of Potentially Malignant Disorders Disorders of the oral mucosa that may progress to cancer with time but not frankly malignant at the time of presentation, may present in a number of ways. These are now referred to as Potentially Malignant Disorders (OPMD). Their clinical signs are likely to be less obvious than those from established carcinoma. Leukoplakia is the most common OPMD. The term leukoplakia has long been used rather loosely by clinicians specialising in oral, throat and even genital diseases. Dentists have tended to follow the WHO in 1977 defined leukoplakia as, 'a white patch which cannot be rubbed off and cannot be characterised clinically or histologically as any other lesion'. It is now recommended that the term is used as a clinical descriptor of a white patch or plaque that cannot be described as otherwise, and is confirmed by histological information to exclude other possible disorders. A more recent definition from ' the WHO Collaborating Centre for for oral cancer (2005) states: The term leukoplakia should be used to recognize predominantly white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer ’. It is recommended that the term be used as a clinical diagnosis. Biopsy of such lesions is essential to establish diagnosis and estimate the degree of epithelial dysplasia which has some value for predicting malignant potential. It will indicate whether the cancer is already present or not. Histology may lead to diagnosis of a specific lesion which can present as a white or red plaque, such as lichen planus, chronic candidiasis, or lupus erythematosis. The clinician should characterise tobacco-induced lesions and assist in differentiating these from the idiopathic white plaques in which no causal factor is evident from history or examination. Leukoplakia appears as a predominantly white patch of slightly raised mucosa and plaque anywhere in the mouth (Fig 29). The mucosal surface may be smooth or cracked. Most are benign in sites other than the floor of the mouth or ventral tongue. An example of idiopathic keratosis is a homogenous leukoplakia on the floor of the mouth and ventral surface of the tongue in a non-smoker; this is considered a high-risk lesion (Fig 30). Some leukoplakias have a white granular (nodular) surface. They may often be associated with Course design by The Dental Channel ©MMVII Candida albicans infection. A key to clinical diagnosis of oral leukoplakia is given by Warnakulasuriya et al (2007): A candidal leukoplakia) Fig 32) is a hyperkeratotic lesion that is superficially affected by fungus, most commonly Candida albicans. The term can only be used after histological examination. Most so-called candidal leukoplakias are clinically erythroleukoplakias (speckled). It is well established that the presence of fungi increases the long-term risk of malignant transformation. Appropriate anti-fungal therapy is therefore an important component of the management of such cases. A verrucous leukoplakia is a white lesion with a warty corrugated surface (Fig 33). Similarly a proliferative verrucous leukoplakia is a white lesion with a warty hyperplastic surface. However, multiple and widespread leukoplakias may be present in this condition that recur on removal. A high proportion of patients develop oral cancer. Erythroplakia appears as a well-defined fiery red, velvety patch of oral mucosa and situated 0.1-0.2 Course design by The Dental Channel ©MMVII mm suppressed than the surrounding oral mucosa. While some have a smooth surface others may have a granular appearance, interspersed with white or yellow nodules. Often there is a well defined margin to this red patch. Erythroplakias are not wide spread and appear localised. Generally soft to palpation unless transformed to malignancy. Common sites are the buccal mucosa, mandibular gingival and soft palate. Tongue is rarely affected by erythroplakia ANDREW I WOULD LIKE TO TAKE THIS TO A Second SECTION BELOW LEUKOPLAKIA Erythroplakia has a greater malignant potential than leukoplakia. Histologically there are changes ranging from moderate to severe dysplasia to micro invasive squamous cell carcinoma. An erythroleukoplakia has combined red and white elements in the plaque together with an irregular surface texture, and is most commonly found in the oral commisures (Fig 31). It is synonymous with but has replaced the term speckled leukoplakia in the new WHO definition (2005). Course design by The Dental Channel ©MMVII OTHER Potentially Malignant Conditions Lichen planus presents as keratotic striae; the characteristic reticular form is illustrated in Fig 36. The presentation is often bilateral. On the dorsal surface of the tongue lichen planus presents as white plaques (Fig 38). Erythematous lichen planus appears as atrophic, erosive red areas of the oral mucosa (Fig 37), particularly affecting gingivae- referred to as desquamatice gingivitis. . Ulcerative lesions can occur on buccal mucosa or lateral tongue and are often associated with surrounding keratotic striae. Ulcerative areas cause pain and discomfort to the patient, especially upon contact with acidic or spicy foodstuffs. Ulcerative lichen planus must be treated symptomatically. Lichen planus in whatever form should be monitored regularly (at least annually) as a small proportion of lesions may become malignant. Recent evidence suggests that the “plaque type” of lichen planus and lichenoid lesions may also carry an increased risk. Oral submucous fibrosis (OSF) (Fig 40) presents as a loss of elasticity of the mucosa, with fibrous bands causing limitation of opening of the mouth. Early signs may include blanching and stiffening of the mucosa and a leathery feeling. A burning sensation in the mouth or throat may be an early symptom. The tongue shows loss of papillae, firmness and a lack of mobility. This condition is found in Asian patients who chew areca nut, whether chewed alone or as a component of quids with or without tobacco. Prevalence of OSF is increasing in Asian communities due to the availability and use of betel quid in commercially packaged freeze-dried forms (pan masala/gutkha). Hundreds of thousands of people suffer from this condition world wide, particularly in south Asia and in immigrant communities from that region. A large reservoir of undetected disease exists amongst Asian populations who chew areca products. It has one of the highest rates of malignant transformation amongst potentially malignant oral disorders. Discoid lupus erythematosus of the oral mucosa may or may not be associated with skin lesions elsewhere on the body. Oral lesions appear as an area of atrophy or erosion, surrounded by a white keratotic halo (Fig 41). Soreness is often present. This is an uncommon condition but when present the buccal mucosa and lips are most likely to be involved. Biopsy of a representative site is essential to confirm the diagnosis, coupled with haematological examination to exclude systemic lupus erythematosus (SLE). There is little quantitative information on the risk of malignant transformation, but most reports of cancer development in cases with DLE often involve the lips. Syphilis is seen less frequently these days because the earlier stages are amenable to treatment with Course design by The Dental Channel ©MMVII antibiotics. Nevertheless syphilis is still a common disease worldwide. The keratotic plaque of tertiary syphilis appears on the dorsum of the tongue and may occasionally be associated with the development of oral cancer at this site (Fig 42). Special investigations are essential to establish a diagnosis. Actinic keratosis may be characterised by atrophy, erosion and white or brown crusting of the vermilion of the lower lip (Fig 42). It is caused by exposure to ultraviolet light, particularly from strong sunlight. This condition and cancer of the lip itself is thus more common in outdoor workers such as fishermen and farmers, particularly in latitudes close to the equator, and in those with fair complexions. Avoidance of sunburn and chronic exposure by the wearing of broad-brimmed hats and the use of topical sunscreens should be advised. The world is experiencing an epidemic of skin cancer, particularly malignant melanoma due to an over exposure to sun. Mucosal atrophy is often a feature with pallor as a clinical sign and may be associated with malignant change in the oral cavity and pharynx. The condition may predispose to candidiasis and ulceration of the oral mucosa. Paterson Kelly (Plummer-Vinson) Syndrome is the combination of iron deficiency anaemia (Fig 35) with dysphasia and glossitis. Spooning of finger nails (koilonychia) may be seen. Indeed, correction of anaemia whatever its type, and of any other nutritional deficiencies present in the patient, is a fundamental aspect of management. Course design by The Dental Channel ©MMVII Management of Potentially Malignant Lesions and Conditions Management of potentially malignant lesions and conditions should be considered under the following categories: Establish the correct diagnosis Control of risk factors Systemic treatments Local measures & surgical intervention where indicated) Improvement of diet Follow up Establish correct diagnosis At the moment this is limited to morphological (histological) evaluation of oral dysplasia in the biopsy (Fig 44). Control of risk factors Every effort must be made to help the patient quit tobacco and areca nut use, and to moderate alcohol consumption. Patients with oral dysplasias could be assisted with tobacco cessation by referring to a smoker’s clinic (Poate & Warnakulasariya 2006). Advice on diet and nutrition is important to reduce the risk of recurrence or progression. Systemic treatments These include: Elimination of chronic trauma to the affected site Topical anti-fungals such as miconazole gels, amphoteracin or nystatin lozenges for the control of Candidiasis Topical retinoids (synthetic vitamin A derivatives designed to suppress keratinisation and aberrant epithelial differentiation) or topical cytotoxic agents (such as bleomycin and methotrexate, designed to suppress excess cell proliferation and malignant transformation). Such approaches are, Course design by The Dental Channel ©MMVII however, still experimental Excision or ablation of a localised potentially malignant lesion. Surgical excision with a margin of normal tissue allowing submission of the specimen to histological examination remains the method of choice. CO2 lasers may also be used to excise tissue (Fig 44). Laser ablation, with or without photodynamic sensitisation, is not recommended because the tissue is not available for microscopy. However laser excision has recently been reported as a useful intervention (van der Hem et al 2004.) Cryotherapy for ablation of this type of lesion has been popular in some centres but cannot be recommended for widespread use for the same reasons. Irrespective of the combination of methods of management, long-term follow-up is essential to monitor general health, compliance with advice on risk factors and or with medication, and to observe the mouth for regression, recurrence or progression of the potentially malignant lesion or condition. The interval between visits will vary: patients with severely dysplastic lesions, conditions and or continuing bad habits may be seen in intervals as short as 3 months; those with less worrying lesions and who are compliant, perhaps once a year. At each visit the oral cavity should be subjected to a systematic examination, noting any changes in colour, consistency and size compared with the original tumour, and any new incidence of tumours elsewhere in the oral cavity. Clinical observations should be carefully recorded, preferably on well-designed proformas and lesions measured and photographed. Course design by The Dental Channel ©MMVII Management of Invasive Oral Cancer This lies in the hands of specialists from many different disciplines and dentists are important members Course design by The Dental Channel ©MMVII of the team. An ideal head and neck cancer management team would include those personnel listed in Table 1. Technical details of surgical and/or radio/chemo therapeutic procedures are beyond the scope of this program and their choice and application depends on the site, signs and complications of the individual case and the availability of staff and resources. In most modern centres the approach is by combination therapy: either surgery followed within a few weeks by radiotherapy to kill any residual or spilled malignant cells or by primary radiotherapy followed by necessary salvage surgery. Survival curves published by the Yorkshire Cancer Registry are shown as an example. It has to be appreciated that lesions treated primarily by surgery, which seems to produce the best results, will include a large proportion of small lesions inherently easier to cure: conversely those primarily managed by radiotherapy will include palliative treatment of a number of advanced and inoperative cases. Lip cancer is clearly a much less lethal disease than intra-oral cancer. There are no striking differences by sex or age. The benefit of chemotherapy (Cisplatin and 5FU) as an adjunct to surgery or radiotherapy in the management of oral and other head and neck cancers is being studied in randomised clinical trials all around the world. At the present time no large beneficial effect in the form of significant improvement of overall or disease-free survival has been found sufficient to justify a recommendation of this approach, particularly in view of the toxic side effects. Other phase III trials include new models of therapy using monoclonal antibodies, an agent that binds to the cell surface on growth factor receptors activated in cancer. Nevertheless some studies have produced encouraging results. Particular note should be taken of the following encouraging aspects: Small lesions are more easily cured with less morbidity. This emphasises the importance of diagnosing cases as early as possible in the natural history. Cure rates, at least in four highly expert treatment institutions, show improved survival rates in recent years. This is based on knowledge gained from experience of a large number of cases, including recognition of the importance of adjunctive radiotherapy and definitive treatment of lymph nodes in the neck. However many cancer treatment units cannot reproduce these results and the outcome remains poor. Techniques and skills in reconstructive surgery have improved vastly, often reducing physical and functional morbidity compared to the past.Speech and swallowing therapy adds considerably to quality of life for patients. This emphasises the need for the incorporation of prosthodontists and Course design by The Dental Channel ©MMVII speech therapists in the oncology team. Dentists have important roles in control of caries, dry mouth and other complications following irradiation of the head and neck. Restorative dentists and prosthodontists are fundamental to rehabilitation of form and function. Social, psychological and spiritual support is increasingly recognised as important and is increasingly available. Techniques in palliative care, in particular pain control, and in managing the terminally ill have advanced considerably. Nevertheless, once invasive carcinoma is present, the patient has a life-threatening disease, which even if he or she survives, inevitably causes serious damage to the quality of life. The strengths, weaknesses and future improvements required in maximising quality of life for oral cancer patients should be discussed with patients and their carers by the professionals involved in their management (Edwards BM, 1998). The central message for the dental profession remains: Prevention of oral of cancer is our first priority. Course design by The Dental Channel ©MMVII 5. Diagnosing Oral Cancer Early diagnosis of oral cancer lies mainly in the hands of primary dental care professionals. However, patients with oral cancer symptoms may present to a medical practitioner and family physicians should therefore be aware of the anatomy , including normal structures of the oral cavity and abnormal signs that indicate cancer. Let’s now consider: the role of those working in primary care using detecting systems to aid early detection toluidine blue autofluorescence Chemiluminescence and the brush biopsy technique Course design by The Dental Channel ©MMVII Early Detection: Primary Care Roles As seen in previous sections, the prevention and early diagnosis of oral cancer lies mainly in the hands of primary dental care professionals: Dentists are important in early detection through opportunistic screening and planned screening of populations at high risk. Physicians can attempt a targeted approach on high risk subjects (smokers and heavy alcohol drinkers), directing them for regular check-ups by a local dental practitioner. Dental hygienists should bring to the attention of the supervising dentists any suspicious lesions they might notice during hygiene visits Receptionists in dental practices can help allay the fears of those seeking opinions and encourage them to attend the dentist Pharmacists should encourage people requesting over the counter medications for suspicious ulcers to attend their general practitioner or dentist for an opinion Course design by The Dental Channel ©MMVII Using Detecting Systems to Aid Early Diagnosis Thorough visual and digital examination of all the oral soft tissues, along with the careful examination of the head, neck and cervical lymph nodes, followed by biopsy of suspicious areas, remains the mainstay of diagnosis. Adjuncts to conventional methods of detection include: Toluidine blue test Autofluorescence. Chemiluminescence Brush biopsy Course design by The Dental Channel ©MMVII How Useful is Toluidine Blue? The use of toluidine blue dye as a mouthwash or topical application has been tried as an aid to the diagnosis of oral cancer and potentially malignant lesions. It certainly has a place, with appropriate training, in screening high-risk subjects and in helping to define the site for biopsy. Figure 49shows an area of atrophic mucosa with a distinctive lesion. Figure 1b shows that the mucosa took up the dye and which proved, on biopsy, to show epithelial dysplasia, indicating an increased risk of progressing to malignancy if untreated. The FDI Commission, through its report after Project on Oral Cancer, has recently agreed a statement on the use of toluidine blue, supporting its use in appropriately experienced hands, and urging further research on its clinical utility in primary care settings. FDI Statement - Toluidine Blue Mouthwash 1% Toluidine Blue Mouthwash is being promoted as an adjunct to oral cancer diagnosis - for use on high risk individuals and groups only and explicitly not as a tool for population screening. The sensitivity and specificity of toluidine blue as a test for early detection of oral cancer is adequate. However, the sensitivity and specificity are given for both overtly malignant lesions and potentially malignant lesions (particularly severe epithelial dysplasia) under the umbrella oral cancer. Although 100% of cancers may stain, most studies show that only 50% or less of dysplasias are detected by this technique. The use of toluidine blue in expert and experienced hands is recommended: in the monitoring of suspicious lesions over time in screening for oral mucosal malignancy and potentially malignant lesions in high risk individuals and population groups in the follow-up of patients already treated for upper aero digestive tract cancer in helping to determine an optimal site for biopsy when a suspicious lesion or condition is present; and intraoperatively during surgery of upper aero digestive tract malignancy. For clinicians in primary care settings, specific training is required for correct application of the test and correct interpretation of the results. Toluidine blue shall not be considered a replacement for a detailed visual and digital examination, but as an extra tool for the identification of patients who should be referred to specialists or centres experienced in the diagnosis Course design by The Dental Channel ©MMVII and treatment of oral cancer and potentially malignant lesions or conditions. Course design by The Dental Channel ©MMVII Brush Biopsy Technique A transepitelial biopsy obtained using a Cytospin brush has been advocated for reporting on cellular atypia by computer assisted diagnosis. Brush biopsy samples transported in a liquid medium could also be used for ploidy analysis. Course design by The Dental Channel ©MMVII Course design by The Dental Channel ©MMVII Autofluoresence The presence of cellular alterations will change the concentrations of fluorophores, which affect the scattering and absorption of light in the tissue, thereby resulting in change in colour that can be observed visually. The potential application of fluorescence visualisation as an adjunctive tool in identifying high-risk lesions has recently been investigated. Visually Enhanced Lesion Scope (VELscope) is a hand held device that is based on the direct visualization of tissue fluorescence and the changes in fluorescence that occurs when abnormalities are present. The VELscope hand-piece emits a safe blue light into the oral cavity, which excites the tissue from the surface of the epithelium through to the basement membrane and into the stroma beneath, causing it to fluoresce. The clinician is then able to immediately view the different fluorescence responses and the manufacturer claims that this tool helps to differentiate between normal and abnormal tissue. Typically, healthy tissue appears as a bright apple-green glow while suspicious regions are identified by a loss of fluorescence, which thus appear dark. Figure 53 shows loss of fluorescence in a suspect area when an exciting light wave is applied using a fluoroscope. Chemiluminescence Chemiluminescence was developed for use in detecting abnormal growths on the uterine cervix. The technique has been adapted for use in the oral cavity with the development of two hand held devices, namely ViziLiteTM & MicroLux/DLTM system. These devices function under the assumption that mucosal tissue undergoing abnormal metabolic or structural changes have different absorbance and reflectance profiles when exposed to various forms of light sources – as a result enhancing the identification of oral mucosal abnormalities. The ViziLite system involves an oral rinse with 1% acetic acid solution for 1 minute to help remove surface debris and slightly desiccate the oral mucosa. This is followed by direct visual examination of the oral cavity using the chemiluminescent blue-white light stick with an average wavelength of 490 to 510 nm. Normal cells absorb the illumination and appear lightly bluish, whereas abnormal cells having higher nuclear-cytoplasmic ratio Course design by The Dental Channel ©MMVII reflects the illumination and appear “aceto-white” with brighter, sharper, more distinct margins. 6. Practical Prevention Approaches to disease prevention are often classified at three levels: Primary prevention is the approach which concentrates on removing risk factors from the community with the intention of minimising the number of new cases of the disease which arise in that community: viz reducing the incidence of disease. This is effective at an affordable cost and is clearly the best approach in terms of both public and personal health gain. Secondary prevention refers to the detection of cases with the disease in question at an earlier stage in its history at which intervention is likely to lead cure, or to minimise morbidity and reduce eventual mortality. This is the category which encompasses screening. It is a complex area of science and the risks, benefits and cost of screening need careful evaluation in every situation. Based on the incidence in a particular population and available manpower, the optimal approach i.e. opportunistic, high-risk, or population screening should be adopted. Tertiary prevention refers to interventions designed to reduce recurrence of disease after treatment or to minimise the morbidity rising from treatment. Course design by The Dental Channel ©MMVII Primary Prevention of Oral Cancer The major risk factors for oral cancer are well understood. Taken together, the effects of tobacco use, heavy alcohol consumption and poor diet probably explain over 90% of cases. The preventive approach is therefore clear and dentists, along with all other primary health care professionals, have excellent opportunities to contribute. Disease prevention or health promotion messages can be directed at whole communities, targeted at sectors of the population such as youth, prepared specifically for defined populations such as employees of a business or factory, or delivered to individual dental patients. There will be much common ground in the materials suitable for these approaches. Dentists can obtain literature suitable for use in their practices from many sources including national dental associations, health development agencies and cancer prevention organisations. The FDI also offers courses on oral cancer detection at the annual conference. Course design by The Dental Channel ©MMVII Deaths Through Tobacco Use Every 10 seconds another person dies somewhere in the world as a result of tobacco use. In developed countries as a whole tobacco is responsible for 24 % of all male deaths and 7% of female deaths, rising to over 40 % for men in Eastern European countries and 17% for women in the USA. This has been calculated to represent an average loss of eight years of life for cigarette smokers, directly attributed to tobacco. The proportion of cancer deaths attributed to smoking in developing countries as a whole are lower, being about 21% for men and only 4% for women. However these figures are rising, the fall in global tobacco consumption in the west being matched by growth in developing countries. Indeed the vast majority of the estimated 1100 million smokers in the world, some 800 million are in developing countries, 300 million in China alone! Globally some 3 million deaths a year have been estimated to be attributable to smoking, rising to 10 million year in 30-40 years time when some 7 million will be in developing countries. When the use of oral smokeless tobacco is added to these figures, and the deaths it contributes through oral, pharyngeal and oesophageal cancer, the seriousness of the global epidemic of tobacco related diseases is even more staggering. We all share a responsibility to help quell this epidemic. According to Doll et al using data from a long-term study on male British doctors, about half of all regular smokers will be killed by their habit. The major causes of such deaths are shown. Among men in industrialised countries, smoking is estimated to be the cause of 40 to 50% of all cancer deaths, 90-95% of lung cancer deaths, over 85 % of oral cancer deaths, 75% of chronic obstructive lung disease deaths, and further 5% of cardiovascular disease deaths in those aged 35-69 years. Thus, oral and pharyngeal cancers figure prominently. Lung cancer, other pulmonary diseases and cardiovascular diseases should all be the starting points for anti-tobacco counselling. Data available from the WHO ranks smoking prevalence in 100 countries from which the top 20 are presented. There has been a good deal of scientific evidence on the cost-effectiveness of approaches to tobacco (principally smoking) prevention or intervention. Table 2 ranks these and indicates that individual action by doctors and dentists is clearly important. Course design by The Dental Channel ©MMVII Dentists and Tobacco Control Members of the dental profession can be active in influencing politicians and community leaders to adopt appropriate legislative approaches. All National Dental Association's are urged to adopt a policy on tobacco and health and the FDI policy statement could form the basis for such national statements. Recent parliamentary bills introducing a smoking ban in public places should contribute to public awareness. Most importantly, dentists can work within their clinical environment to great effect. There is ample evidence that general medical practitioner advice to quit tobacco use is respected by a majority of patients, and several recent studies show the dentist can be equally effective. This is achieved by following the simple scheme of the 5 A's: Ask patients about their tobacco habits, Advise them on the importance of quitting, Assess their willingness to stop Assist them in achieving this (e.g. agree a quit date or provide/direct them to use NRT) Arrange follow up. Dentists have a natural entree to the discussion of tobacco-related diseases with their patients because of the oral signs of tobacco use and its influence on many oral diseases and conditions. Malignant and potentially malignant lesions and conditions have been covered earlier in this program. The socially important changes-bad breath and tooth staining-are often sufficient to focus dentists and patients alike on the desirability of quitting. Increased severity and extent of periodontal disease, and limitations in response to periodontal treatment, is another important hook for involving an affected patient in tobacco control. Knowledge in this area is growing rapidly and has recently been summarised in a position paper from the American Academy of Periodontology Course design by The Dental Channel ©MMVII The British Dental Association has produced pertinent literature to help train dentists and their teams in antitobacco counselling. “Helping Smokers to Stop: a Guide for the Dental Team”, by the UK Health Education Authority and British Dental Association (Fig 56), is especially recommended. Other countries have produced similar literature. A recent review addressing tobacco cessation with particular reference to oral cancer can be found in the update by Scully and Warnakulasuriya (2005) Even in the absence of oral stigmata of tobacco use, dentists should ask and advise in order to prevent young people starting to smoke. This is a particular challenge with young people. Statistics from many Western countries show encouraging falls in the proportion of adults smoking, but rises in teenagers. Almost all countries in the world have educational material designed for professionals and health promotion material designed for the public: these should be easily accessed by approaching the appropriate agencies, perhaps starting with your national dental association. Surveys of dental practitioner knowledge, attitudes and behaviour towards tobacco control, have been conducted in a number of countries with, unsurprisingly, variable results. In the UK this knowledge has gradually risen between 1995 and 2005. It is clear that a substantial proportion, usually a majority, of dentists are inhibited from asking and reluctant to advise. Barriers include uncertainty as to patient response and lack of training in counselling techniques. Education efforts are thus required for both the public and for the profession in the hope of developing a growing awareness of the appropriateness of dentists addressing these issues. At present it is likely that many practitioners will opt to refer interested dental patients to smoking cessation clinics: the AA-R approach (Ask, Advise, Refer) rather than the 5As approach. Advice leaflets which include telephone numbers and addresses of such resources should be available in every dental clinic. Dentists are increasingly willing to receive training in tobacco control methods. This may involve advising patients on the use of nicotine replacement therapy (NRT) to help over the period of withdrawal. As an active substance nicotine, on a milligram for milligram basis, is 10 times more potent than heroin. It has been shown that the use of nicotine skin patches can double the rate of smoking cessation handled through a medical practitioner or pharmacist, from around 5% to around 10% of recruits. A demonstration programme with dentists achieved a comparable 11% quit rate. NRT is available as skin patches, chewing gum, lozenges, nasal sprays or inhalators. Advice on their appropriate use, including dosages and contraindications, are included in the training literature referred to below, and from the manufacturers. In some countries these products are available over the counter, with detailed instructions: pharmacists can also be consulted by a dentist or pvatient for advice. Course design by The Dental Channel ©MMVII Oral Smokeless Tobacco There is no doubt that the addition of tobacco to areca nut (betel) quids, consumed by millions in south and south-east Asia and the pacific islands, confers a major increase in risk to carcinogenicity. The habitués must therefore be encouraged to quit. Indeed the benefits of doing so are clear. The tobacco used in mixtures such as Nass, Niswar or Toombak in North Africa, the Middle East or northern part of the Indian sub-continent contain high levels of nitrosamines and are dangerous. Fig 57 shows a snuff-induced carcinoma caused by smokeless tobacco use. Controversy exists, however, as to the danger of moist loose or portion-packed snuff in the West, notably Scandinavia and the USA. It appears that the risk of oral cancer is low with these products; up to about 30% of that attributable to smoked tobacco. There is even the suggestion that smokers should be encouraged to take up oral smokeless tobacco as a less dangerous means of coping with nicotine addiction. This however is an unproven and potentially dangerous approach; there are safer forms of nicotine replacement available, and the cardiovascular effects and risks of cancer at other organs with oral smokeless tobacco (e.g. pancreas) are reported. The IARC (2006) concluded an evaluation that confirms that oral smokeless tobacco is carcinogenic to man. Course design by The Dental Channel ©MMVII Passive Smoking Recent critical meta-analyses of the world literature from the Wolfson Institute of Preventive Medicine in London and reviews from the USA show conclusively that exposure to environmental tobacco smoke is a major cause of serious illness. In the USA alone it is calculated to be responsible for 3000 deaths from lung cancer each year, 35,000-62,000 deaths from ischaemic heart disease (tobacco smoke has a marked effect on platelet biology even at low doses), 150,000-300,000 cases of bronchitis or pneumonia in infants and children up to 18 months of age (of whom a proportion die), 8000-26,000 new cases of asthma, and exacerbation of asthma in up to a million children, 9700-18,600 cases of low birth weight and 1900-2700 sudden infant deaths. Any association with oral cancer has not been shown to date. We, as members of a health profession, should set an example by not smoking ourselves (seeking help if we are current smokers), and by ensuring that the whole dental team and work environment are smoke-free. Course design by The Dental Channel ©MMVII Dentists and the Management of Heavy Alcohol Consumption Dentists are even more inhibited from taking alcohol histories from their patients, but excessive alcohol consumption is a major cause of individual morbidity, mortality and contributes much damage to society. Dentists are not alone amongst health professionals in their inability to address concerns on alcohol misuse. Studies on GP practices regarding tackling alcohol –related issues show limited enthusiasm to discuss the subject (Beich BMJ 2002). With tact, dentists ought to be able to help their patients see that such questioning is directed at genuine concerns for their general health and that this is relevant to their oral health. Oral and other aero-digestive tract cancers and potentially malignant lesions are obviously our major concerns as dentists. As explained previously, many epidemiologists believe that the rise in both incidence and mortality of these cancers seen in a number of countries (particularly in Europe) is related to rising alcohol consumption over recent years. Differences in alcohol consumption (particularly among those who also smoke) explain most of the increasingly high rates of oral cancer amongst blacks, as opposed to whites in the USA. Projections of disease levels based on trends in alcohol consumption lead to disturbing predictions of future cancers at these sites. In addition, alcohol contributes to dental and maxillo-facial injuries, by secondary effects following liver damage and, often, under-nutrition, and compromises periodontal health, wound healing and resistance to infection. Dentists can often see these facial and intra-oral signs in their patients, and suspicion may be aroused because of patient behaviour. A policy of Ask, Advise ought to be followed by dentists, accepting that referral is probably then wise for patients with a suspected alcohol problem. A wide variety of dedicated groups, agencies and clinics exist in most countries, and practitioners are advised to be aware of what networks exist locally. Moderate alcohol consumption is not harmful, and may even be beneficial in reducing the risk of cardiovascular diseases. Indeed protector substances have been identified in several beverages, such as polyphenols and the antioxidants in wine derived from grape skins. What therefore constitutes potentially unhealthy levels of alcohol consumption? Many governments and agencies suggest a healthy level of 21 units of alcohol a week for men and 14 for women, with at least two alcohol-free days a week. A unit of alcohol is taken to be half a pint of average strength beer or lager (284 ml), a single measure (25 ml) of spirits or a single standard (113 ml) glass of wine or aperitif (50 ml). Course design by The Dental Channel ©MMVII Dentists and Healthy Eating Dentists will enquire routinely about the dietary habits of their patients, usually because they are interested in the likely cariogenicity of their diets. However, adequate (neither under nor over) nutrition is essential to host resistance against all diseases. Cancer is no exception, and the protective role of diets adequate in trace elements, minerals and vitamins (particularly the antioxidant scavenging vitamins A, C, and E) has been emphasised in section 3. An extensive literature has been reviewed by La Vecchai et al (1997). The advice which we should give to our patients is part of every nation's promotion guidelines, well summarised by the American Cancer Society. This incorporates the recommendation that 5-6 portions of fresh fruit or vegetables should be consumed daily. Course design by The Dental Channel ©MMVII 7. Dentists and Smoking Cessation This section is important for all members of the dental and other primary care teams. It discusses: The widespread use of tobacco Its relationship with oral cancer The role of nicotine Practical advice on how to help smokers quit And a conclusion Course design by The Dental Channel ©MMVII Tobacco Use Tobacco use is the leading preventable cause of premature death worldwide (Brundtland G H, 2000). Possibly 4.9 million people died of tobacco-related illness in the year 2000. Tobacco is a major independent risk factor for the development of oral and pharyngeal cancer and is related causally to at least 16 types of human cancer. It is consumed in a variety of ways, with manufactured cigarettes being the most prevalent. In most countries at least one quarter of the population smoke; approximately 25% of the US and 27% of the UK are smokers. The highest reported rates are from China, with around 63% of males smoking. The number of male smokers generally outnumbers the female. The exceptions are Denmark, New Zealand and the United Kingdom, where the gender distribution is almost equivalent. Aside from cigarettes hundreds of millions of people world-wide are addicted to smokeless tobacco. Course design by The Dental Channel ©MMVII Tobacco and Oral Cancer The main cause of oral cancer has long been known to be cigarette smoking. Several casecontrol studies from Europe and USA show an increased risk varying from 3 to 35-fold, particularly in the presence of other synergistic factors. Over 90% of the patients diagnosed with oral cancer use tobacco, either smoking or chewing it. Population surveys amongst adults on oral cancer have demonstrated an alarming lack of knowledge on tobacco as a risk factor and, despite some recent campaigns, knowledge deficits remain. Course design by The Dental Channel ©MMVII Nicotine Dependence Nicotine affects mood and performance, and is a drug of addiction. Either smoking or chewing tobacco gives rise to physical and psychological dependency. Nicotine withdrawal symptoms, which are believed to be the reason why tobacco users relapse in the short-term, have been studied more thoroughly in smokers than in smokeless tobacco users. They include irritability, impatience, restlessness, difficulty sleeping, increased appetite particularly for sweet high carbohydrate foods, weight gain, anxiety and depressed mood. The craving or urges to smoke cigarettes, the increased appetite and weight gain, can continue for many months after quitting. Although 70% of smokers want to quit and 35% attempt to do so each year, less than 5% succeed. This low success rate is related to the effect of nicotine addiction. Course design by The Dental Channel ©MMVII Diagnosis, Screening and Brief Interventions In the UK around 40% of smokers attempt to quit after recommendation by their doctor. Unfortunately about 95% of these will fail because although the smoker leaves the consultation motivated to stop but then embarks on a poorly planned quit attempt alone, without support or medication. The challenge is to harness this now-motivated population and ensure that they receive sufficient help with their quit attempt so as to maximize their chance of success. Dental clinics are obvious locations for tobacco cessation programmes, but few interventions by dentists are reported. Recommendations for a successful intervention for tobacco users were proposed in several papers. There are five crucial steps in motivating people to stop smoking, known as the “5 A’s”: Ask Advise Assess Assist Arrange It is very important that every patient who is seen in a dental practice is asked about the status of their tobacco use and the finding noted on clinical records and the information kept as up to date as possible. Such a record should cover whether the patient is a smoker and if so, the frequency of smoking and for how long the patient has smoked. Other forms of tobacco use should also be noted. Every smoker must be told of the value that stopping smoking will have for them, and of the dangers that exist in continuing. It is important to discuss the sequelae of continuing smoking and give plain, precise and personalised advice to them, particularly when a risk lesion such as a white or red patch of the oral mucosa is found. The advice where appropriate should include directions to use nicotine replacement therapy (NRT) or, if appropriate, Zyban (buproprion) through their medical practitioner. Other reasons for quitting, for example preventing other cancers or heart disease, should be included in the overall advice. The dentist should inquire whether the patient is keen to quit. Information about previous attempts to quit should be noted, including whether any aids had been used. This will assist in identifying the best Course design by The Dental Channel ©MMVII means of quitting. Other clinic staff in the practice should be encouraged to help any smoker who wishes to stop. Setting a date for quitting and arranging to remind a smoker through reception staff may be helpful. In the UK, the patient could be provided with the telephone number to call NHS smoking helpline (0800 169 0 169) or information for visiting an appropriate website (e.g http://www.gosmokefree.co.uk). Useful leaflets should be available in the surgery for distribution (Fig 65). Lack of leaflets and information in dental practices to take away was identified as a barrier in engaging in cessation activities in a recent study (Johnson et al 2006). Arranging a follow-up is important, preferably within 1 week of quitting. This may fit in with a subsequent dental appointment or a visit to the hygienist. Heavy smokers may also be referred to local smoking cessation services and help lines. This is important since studies show that people are twice as likely to quit successfully with intensive counselling. There is now a very convincing evidence base indicating that both short- and long-term abstinence rates are significantly increased by both counselling and pharmacotherapy (Fiore et al 2000). Course design by The Dental Channel ©MMVII Intensive Clinical Interventions Intensive interventions produce higher success rates than brief ones. Ideally when faced with a motivated tobacco user who wishes to make a serious quit attempt, referral should be made to a local smokers’ clinic if available. Specialist clinics in the UK are usually staffed by psychologists and nurses who have had specialist training in the treatment of tobacco dependence. Intensive interventions differ from minimal ones primarily in the intensity of the programme. Treatment may be provided in a group format. Particular types of counselling, including psychoeducational, behavioural skills training and cognitive behavioural therapy are utilized in this setting, along with strong encouragement to use appropriate pharmacotherapy. Course design by The Dental Channel ©MMVII Conclusions Tobacco is the major risk factor for oral cancer (and many other cancers). Oral cancer is, to a great degree, preventable. The disease has a long developmental period during which secondary prevention could reduce risk; early interventions could alter the natural history of the disease limiting the malignant transformation. Dentists, through their individual efforts, could improve the oral health of the public by engaging in tobacco education. Primary care dentists could contribute to preventing cancer, saving lives and diminishing suffering through education, advocacy and clinical care. Other cancer prevention approaches related to alcohol moderation, quitting betel quid use and improving diet are also important and providing such advice should be undertaken in the primary care setting. Course design by The Dental Channel ©MMVII 8. Screening for Oral Cancer and Potentially Malignant Lesions Screening for disease is a very precise science. This section considers: Secondary prevention Systematic examination of the oral mucosa Referral guidelines Population screening Targeting screening Opportunistic screening Tertiary prevention Advances in the basis science of oncology. Course design by The Dental Channel ©MMVII Secondary Prevention of Oral Cancer Screening for disease is a very precise science and must follow established principles. Oral cancer meets some, but not all, of these criteria and, although there are clear potential advantages they are also potential disadvantages. The rationale for screening for cancer based on the fact that these malignancies are asymptomatic, localised for a period of the natural history, and are often preceded by potentially malignant lesions and conditions such as leukoplakia, erythroplakia and submucous fibrosis,. They can be detected by a simple systematic oral examination. This is important because habit intervention, dietary intervention and surgical treatment can result in the resolution or elimination of dysplastic changes. Course design by The Dental Channel ©MMVII Thorough Systematic Examination of All Oral Soft Tissue A thorough systematic examination is mandatory every time a dentist sees one of his or her patients. A routine which is comprehensive, effective and should not take more than three minutes to perform is illustrated here. Screening of the oral mucosa is most effective if a methodical examination procedure is followed. The system described here is quick and easy to use. It minimises the risk of missing any particular area and of oral mucosa that could harbour a risk lesion. When perfected, the time taken for a routine mucosa examination is less than three minutes. Two mouth mirrors are preferable when retracting the tissues. This visual inspection should be supplemented by palpation with a gloved finger of any suspicious area. The examination should commence with a general appraisal of the well-being of the patient on entering the surgery. Observe the face for asymmetry, swellings, skin blemishes, moles and pigmentation. Palpate lymph nodes of face and neck. Examine the vermilion border of the lips and corners of the mouth, note any change in colour and texture If the patient is wearing dentures request that these be removed Examine the labial mucosa and sulcus with the mouth half open With the mouth open wide, retract for cheek on one side and examine the colour and texture of the buccal mucosa. Then, with the mouth half open, observe the maxillary and mandibular sulci. Repeat this sequence for the other side of the mouth. Inspect the tongue at rest and protruded, note any aberrations in colour, texture, distribution of papillae, symmetry or mobility To facilitate inspection of the lateral borders, hold the tip of the tongue with a gauze square and move it to one side, whilst also retracting the cheek to the opposite side. Repeat for the other side of the mouth. Examine the floor of the mouth and ventral surface of the tongue with the tip of the tongue Course design by The Dental Channel ©MMVII raised to the palate. Depress the tongue and inspect the hard and soft palate, then request the patient to say "Ah" and examine the pillars of a fauces, tonsils, uvula and oropharynx. Finally palpate any abnormal areas. If any oral mucosa lesion is found during the visual screening examination it is essential that the examination is extended to include palpation of the lesion. Where there is a suspicion of malignancy or infection, the regional lymph nodes must be palpated. The clinician should request an urgent hospital appointment for any patient who presents with a lesion which is suspected of malignancy upon clinical examination, or is associated with enlargement or hardness of regional lymph nodes. Guidelines for referral are given in the next topic, and a referral form 'RefForm' for oral mucosal lesions may be downloaded from the resources section of this course. This may be printed and used as a referral pro-forma. Course design by The Dental Channel ©MMVII Referral Guidelines (ANDREW Please Move this to the Third Section What to do) If any abnormality is discovered, the patient should be referred to a specialist To allay fears at this stage the dentist should be sensitive to the words used to describe what was observed, and explain that it is best to obtain a second opinion from a specialist. Referrals should be categorised as non-urgent, prompt or urgent. Of course if cancer is suspected the referral must be marked “Urgent” so that the hospital can prioritize this referral to be placed on their “2 week wait programme” available for this purpose. Conditions and symptoms that fall under Urgent referral of suspected Head and Neck cancers – referred to as NICE guidelines in the UK- are given below. (ANDREW PLEASE COPY FROM PAPERWORK WE PREPARED FOR CANCER NETWORK) . Dentists must be familiar with these and use them in consultation with the local hospital and country guidelines. Potentially Malignant Disorders that should be referred to a specialist following a mucosal examination include leukoplakia, erythroplakia, erythroleukoplakia, submucous fibrosis, lichen planus, discoid lupus erythematosis and actinic keratosis. The referring practitioner should inform the patient that at a hospital visit a small piece of tissue may be removed under local anaesthesia, referred to as a biopsy, in order to confirm the health or otherwise of the mucosa. Course design by The Dental Channel ©MMVII Population Screening Population screening for oral cancer in low risk countries (such as the UK and Japan) cannot be recommended because there is insufficient evidence for its utility or cost-effectiveness. Oral cancer screening programmes have been carried out on several hundreds of thousands of individuals in developing countries (mostly Sri Lanka, India and Cuba) and several thousands in developed countries (mostly the USA, UK, Italy, Sweden, Hungary and Japan). The evidence from these is reviewed by Warnakulasuriya and Johnson, 1996 and by Franceschi et al, 1997. In the high incidence parts of the world a substantial proportion of suspicious lesions has been found (ranging from 2 to 16% in South Asia), but compliance of patients to attend follow-up was less than desirable (5472%). In the West the yield is substantially lower. For example the larger study group in Minnesota whose mouths were examined by dentists between 1957 and 1972 consisted of over 23,000 adults over the age of 30. Although more than 10% of those screened had oral lesions these were mostly benign: ‘precancer’ was encountered in 2.9% and cancer in less than 0.1%. A recent study under the auspices of the IARC and conducted in India has shown a reduction in mortality of the screened population (among tobacco users) after 5 years of follow-up in comparison with a neighbouring unscreened population. This gives evidence for the first time that visual screening could contribute to reduction in mortality. Course design by The Dental Channel ©MMVII Targeting Screening Logically, a stronger case can be made for targeted screening of at-risk populations. In the context of oral cancer this might be smokers and heavy drinkers over the age of 40. Such individuals can be identified from the records of family medical practitioners or occupational health records. Even so, studies of this kind conducted in the UK have shown high non-attendance rates for the initial oral examination. This, together with the still low prevalence of lesions makes even this type of screening of dubious utility. In a series of studies conducted by ENT specialists in northern Italy between 1994 and 1998 the yield was substantially increased by adding inspections of the pharynx and larynx (with appropriate instrumentation), and aiming the programme at smokers and/or heavy drinkers, relying on general practitioners for the identification of these high risk groups. Even so, only 1564 out of 4469 (35%) individuals complied with the examination: this yielded 152 (9.7%) precancerous lesions (mostly low risk, flat leukoplakias), and 20 (1.3%) cancers at any of these upper aero-digestive sites. The sensitivity and specificity of lesion detection by artificial intelligence is comparable to that of any oral examination. By use of artificial intelligence systems it is possible to direct limited resources to examine selected cases picked by the computer as high risk. This is an exciting way forward, though bringing these individuals to early treatment will remain a problem. Course design by The Dental Channel ©MMVII Opportunistic screening Opportunistic screening, viz. offering a screening test for an unsuspected disorder at a time when a person presents to a doctor-or a dentist or any other suitably trained primary health care professional for another reason, is rational and cost-effective. This is the basis of the screening examination of the oral soft issues in the UK. The required manpower is available in most Eurpean countries- dentists are trained as examiners in the detection of what constitutes normal and abnormal tissues - and it need take only approximately three minutes. This we have a duty to perform. The clinical identification of suspicious lesions by visual observation and manual palpation is a skill which can be learned and updated. The most encouraging outcome of such studies so far published comes in the oral cancer case finding programme in Cuba, where a down-staging of the disease is reported with an approach to national screening utilising stomatologists. Opportunistic screening was reviewed by the Working Group for Screening for Oral Cancer and Precancer (1991). Only one study has so far been repeated using this approach in UK practices. The study (Lim et al 2004) shows opportunistic screening can detect mucosal lesions in patients attending for routine care, Course design by The Dental Channel ©MMVII Tertiary Prevention Tertiary prevention is concerned with preventing recurrence or further primary cancers and minimising morbidity. A patient treated for an oral cancer could develop further cancer in the mouth months or years after apparently successful treatment. The new lesion could be a recurrence arising because of incomplete removal of the primary lesion, failure of margins, a loco-regional failure due to micrometastasis, or a second primary lesion, arising in the field of altered mucosa. The concept of field cancerisation is that the patient's genetic predisposition, plus the lifelong accumulation of potentially carcinogenic insults from known and unknown risk factors, renders the patient, and the anatomical area most affected, at increased risk of cancer. This applies whether the second cancer is synchronous with the first, or arises later (metachronous). An alternative view is a clone of genetically damaged and therefore premalignant cells migrates in the anatomical area and may give rise to second tumours. Either way, it is clear that with oral cancer the whole of the upper aero-digestive tract can be regarded as the susceptible field. Unsurprisingly, therefore, the risk of a further cancer is high once a patient has been treated for oral cancer, amounting to some 20% over a twenty-year period. This is especially so if tobacco, alcohol and dietary risk factors continue to be present. All of the above primary prevention approaches are therefore especially important at time of treatment of the first cancer, including supplementation with antioxidants such as vitamin A, retinoids, or carotene in the form of chemoprevention. Further secondary prevention (by screening) is also especially important. Treated patients should be monitored regularly in order to insure that their mastication, swallowing, speaking, smiling and other functions, their physical appearance and their social integration are as good as the cancer care team can manage, but also to screen for the possibility of new lesions. In this latter respect toluidine blue application may have particular utility. Nowhere is teamwork in cancer care more important than with treated patients, in order to maximise the quality of life for those afflicted and to insure the best possible quality of death. Dentists have a significant role to play for those patients who survive mouth cancer, helping them to maintain their oral health and adjust their exposure to risk factors. Course design by The Dental Channel ©MMVII Advances in the Basic Science of Oncology It is beyond the scope of this program to detail the many exciting but complex advances in cell molecular biology, which are revolutionising modern medicine. However a taste of what the future may hold is appropriate. Cancer is a genetic disease. It is a form of uncontrolled slow-growth chatter and inherited defect in the constituent cells. The epithelia which line the aero-digestive tract give rise to most cancers. In health they are a constantly renewing cell population, where the rate of production of new cells is exactly matched by losses of cells through two mechanisms: shedding or desquamation of cells from the surface, and programmed cell death - a process called apoptosis. Thus the balance between proliferation and apoptosis is critical, and is it the accumulation of defects in these pathways which give rise to cancer. Fig 77 shows these pathways and some of the factors and genes which control them. It is possible to analyse tissue, and indeed a variety of body fluids (increasingly including saliva), for markers of aberrations in these genes or their protein product. It is also possible to screen chromosomes for signs from oral epithelial cells in health, from potentially malignant lesions and from overt cancers and record abnormalities such as loss, amplification a transposition of parts of the genome thought to be important in carcinogenesis. Specific chromosomes that harbour mutations so far known to be involved in the mutagenic stage of the carcinogenic process are shown. It is not known precisely how many hits or aberrations are necessary to render a clone of cells malignant, though a figure of around six is often quoted. Recent research of the above kind has led to genetic models for the development of head and neck cancer. Such models should not be taken to imply that precisely this series of abnormalities, in precisely that order, are necessary or sufficient for cancer to develop: the number, type and order may differ from patient to patient. Nevertheless the accumulation of such changes indicates an increase in risk of malignant transformation and this information will, in the future, be put to use in: Screening clinically normal patients who are heavy smokers and drinkers to determine their risk of a future cancer Screening potentially malignant lesions and conditions in order to assess how far along the path to malignancy has been reached, and thus to focus intervention for the individual patient Determining completeness of excision/killing by radiotherapy/chemotherapy, by sampling tissue in situ after treatment for an overt cancer, in order to assess the risk of recurrence or second primary. This encompasses the concept of a 'residual disease' Course design by The Dental Channel ©MMVII Screening peripheral blood or bone marrow for malignant cells disseminated from the primary lesion. Finally, this knowledge opens the possibility of gene therapy for human oral cancer: viz. Correcting a critical genetic abnormality in the clone of epithelial cells giving rise to the cancer. This can be done by carrying a copy of the gene into the cells with a vector such as an adenovirus, or physically shooting them into cells with a 'gene gun' - a device which fires fine gold particles coated with the relevant DNA. The principles are well-established in the laboratory experiments, and human clinical trials are now beginning. Course design by The Dental Channel ©MMVII Resources The following resources are available for download: Referral proforma (courtesy Department of Oral Medicine, King’s College London Dental Institute) Referral guidleines for dentists (courtesy Cancer Research UK) Referral guidelines for doctors (courtesy Cancer Research UK) Referral guidelines for pharmacists (courtesy Cancer Research UK) Helping Smokers to Quit – Resource for the Dental Team (courtesy Department of Health/British Dental Association) Websites Cancer Research UK Department of Health (United Kingdom) The Dental Channel World Health Organisation Course design by The Dental Channel ©MMVII Program Acknowledgements Subject expert Professor K A A S Warnakulasariya, BDS, PhD, FDSRCS, DSc Professor of Oral Medicine and Experiment Oral Pathology, King's College London Dental Institute. Program design, authoring and production Dr APS Gould BSc., BDS, LDSRCS, AKC. European Collaborators Xxxxxx Xxxxxx xxxxxxx The authors would like to thank the many people who have participated in the production of this program. They include: D Smith, S Smellie The people who kindly agreed to agreed to be photographed or filmed. Course design by The Dental Channel ©MMVII References EPIDEMIOLOGY OF ORAL CANCER Conway DI, Stockton DL, Warnakulasuriya KAAS, Ogden G, Macpherson LMD. Incidence of oral and oropharyngeal cancer in United Kingdom (19901999) – recent trends and regional variation. Oral Oncology 2006; 42:586-592. CANCER RESEARCH UK. Cancer Stats Oral Cancer – UK April 2005. La Vecchia C, Tavani A, Franceschi S, Levi F, Corrao G, Negri E. Epidemiology and prevention of oral cancer. Oral Oncol. 1997 ; 33 (5):302-312 Johnson N W. A global view of the epidemiology of oral cancer. In Johnson N W, ed. Risk Markers for Oral Diseases, Vol 2 pp 3-26. Oral Cancer Detection of Patients and Lesions at Risk, 1991Cambridge: Cambridge University Press TOBACCO AND ALCOHOL US Surgeon General Annual Report 1995. National Institute of Health, Bethesda, Md. Warnakulasuriya KAAS, Sutherland G, Scully C. Tobacco, oral cancer and treatment of dependence. Oral Oncology 2005;41:244-260. Gupta P C, Murti P R, Bhonsle R B et al. Effect of cessation of tobacco use on the incidence of oral mucosal lesions in a 10-year follow up study of 12,212 users. Oral Dis 1995 1: 54-58. Warnakulasariya K A A S, Johnson N W. Dentists and oral cancer prevention in the UK: opinions, attitudes and practices to screening for mucosal lesions and to counselling patients on tobacco and alcohol use: baseline data from 1991. Oral Diseases (1999) 5; 10-14. Jaber MA, Porter SR, Gilthorpe MS, Bedi R, Scully C. Risk factors for oral epithelial dysplasia – the role of smoking and alcohol. Oral Oncology 1999;35:151-156. Franceschi S. Oesophageal and oral cancer: aetiological factors. Euro J Cancer Prev 1993 2:23. Blot W J, Mclaughlin I N, Winn D M, et al. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 1988 48: 3282- 3287. Bundgaard T, Wildt J, Frydenberg M, EIbrond 0, Nielsen J E. Case-control study of squamous cell carcinoma of the oral cavity in Denmark. Cancer Causes Control 1995 6: 56-67. Winn D M, Blot W J, McLaughlin J K, Sustin D F, Greenberg R 5, Preston-Martin 5, et al. Mouthwash use and oral conditions in the risk of oral and pharyngeal cancer. Cancer Res 1991 51: 3044-3047. Course design by The Dental Channel ©MMVII Beich A, Gannik D, Malerud K. Screening and brief intervention for excessive alcohol use: qualitative interview study of the experiences of general practitioners. BMJ.2002 Oct 19;325 Harris CK, Warnakulasuriya KAAS, Cooper DJ, Peters TJ, Gelbier S. Prevalence of oral mucosal lesions in alcohol misusers in South London. Journal Oral Pathology Medicine 2004;33:253-9. Harris C K, Warnakulasuriya KAAS, Johnson N W et al. Oral health in alcohol misusers. Community Dental Health 1996 13: 199-203. Day G L, Blot W J, Austin D F et aI. Racial differences in risk of oral and pharyngeal cancer: alcohol, tobacco and other determinants. J Nat Cancer Inst 1993 85: 465-473. Macfarlane G J, Macfarlane TV. Lowenfels A B. The influence of alcohol consumption on world wide trends in mortality from upper aerodigestive tract cancers in males. J Epidemiol Community Health 1996 13: 199-203. ORAL SMOKELESS TOBACCO Cogliano V, Straif K, Baan R, Grosse Y, Secretan B, El Ghissassi F. Smokeless tobacco and tobacco-related nitrosamines. Lancet Oncol. 2004 ; 5 (12):708 Lewin F, Norell S E, Johansson H et al. Smoking tobacco, oral snuff and alcohol in the aetiology of squamous cell carcinoma of the head and neck. A population-based case-referent study in Sweden. Cancer 1998; 82: 1367-1375. Rosenquist K, Wennerberg J, Schildt E-B, Bladstrom A, Hansson G, Anderson G. Use of Swedish moist snuff, smoking and alcohol consumption in the aetiology or oral and oropharyngeal squamous cell carcinoma. A population-based case-control study in southern Sweden. Acta Oto-Laryngologica 2005;125:991-998. Warnakulasuriya KAAS. Smokeless tobacco and oral cancer. Oral Diseases.2004;10:1-4. Idris A M, Warnakulasuriya KAAS, Ibrahim Y E et aI. Toombak-associated oral mucosal lesions in Sudanese show a low prevalence of epithelial dysplasia. J Oral Pathol Med 1996 25: 239-244. ARECA NUT and BETEL QUID Thomas S, Wilson A. A quantitative evaluation of the aetiological role of betel quid in oral carcinogenesis. Oral Oncology Eur J Cancer 1993 29B: 265-271. Maher R, Lee A J, Warnakulasuriya K A A S et al. Role of areca nut in the causation of oral submucous fibrosis a case-control study in Pakistan. J Oral Pathol Med 1994 23: 65-69. Course design by The Dental Channel ©MMVII Murti P R, Bhonsle R B, Gupta P C, et al. Aetiology of oral submucous fibrosis with special reference to the role of areca nut chewing. J Oral Pathol Med 1995 24: 45-152. DIET Enwonwu C 0, Meeks V I. Bionutrition and oral cancer in humans. Crit Rev Oral Biol Med 1995 6:5-17. Scully C. Oral precancer: preventive and medical approaches to management. Oral Oncol Euro J Cancer 1995 31B: 16-26. Maher R, Aga P, Johnson N W et al. Evaluation of multiple micronutrient supplementation in the management of oral submucous fibrosis in Karachi, Pakistan. Nutrition and Cancer 1997 27: 4147. Winn D M. Diet and nutrition the aetiology of oral cancer. Am J Clin Nutr 1995 61: 473S-475S. Tavani A, Gallus S, La Vecchia C, Talamini R, Barbone F, Herrero R, Franceschi S. Diet and risk of oral and pharyngeal cancer. An Italian case-control study. Eur.J Cancer Prev 2001 Apr;10(2):191-5. Jang M, Cai L, Udeani G 0 et.al. Cancer chemopreventive effect of resveratrol, a natural product derived from grapes. Science 1995 275: 218-220. VIRUSES Sugerman P, Shillitoe E. Evidence for and against a role for Human Papilloma Viruses in the aetiology of oral cancer. Oral Dis 1997 3. Herrero R, et al IARC Multicenter Oral Cancer Study Group.. Human papillomavirus and oral cancer: The International Agency for Research on Cancer multicenter study. J Natl Cancer Inst. 2003 ; 95(23):1772-83. OTHER FACTORS Zheng T, Boyle P, Hu H et al. Dentition, oral hygiene and risk of oral cancer a case-control study in Beijing, Peoples Republic of China. Cancer Causes Control 1990 1:235-241. King G N, Healy C M, Glover M T et al. Increased prevalence of dysplastic and malignant lip lesions in renal-transplant recipients. N EngI J Med 1995 332: 1052-1057. Field E A, Field J K, Martin M V. Does Candida have a role in oral epithelial neoplasia? J Med Vet Mycol 1989 27: 277-294. ORAL CANCER and PRECANCER Course design by The Dental Channel ©MMVII van der Waal I, Schepman K P, van der Meij E H et al. 1997. Oral leukoplakia clinicopathological review. Oral Oncology, 33: 291-301. Woolgar J A, Brown J S Scott J et al. Survival, metastasis and recurrence of oral cancer in relation to pathological features. Ann R Coll Surg EngI 1995 77: 325-331. Holmstrup P. The controversy of a premalignant potential of oral lichen planus is over. Oral Surg Oral Med Oral Pathol 1992 73: 704-706 Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakularsuriya KAAS. Oral submucous fibrosis: Review on aetiology and pathogenesis. Oral Oncology 2006;42:561-568. Eisenberg E, Krutchkoff D I. Diagnostic criteria and their importance in the alleged relationship to oral cancer. Oral Surg Oral Med Oral Pathol 1992 73: 699704. ORAL CANCER IN YOUNG PEOPLE Llewellyn CD, Johnson NW, Warnakulasuriya KAAS. Risk factors for squamous cell carcinoma of the oral cavity in young people - a comprehensive literature review. Oral Oncology.2001;37:401-418. MANAGEMENT OF POTENTIALLY MALIGNANT LESIONS AND CONDITIONS Lodi G, Sardella A, Bez C, Demarosi F, Carassi A. Systematic review of randomised trial for the treatment of oral leukoplakia. J Dent Education 2002; 66: 896-902 Tradati N, Grigolat R, Calabrese L et al. Oral leukoplakias: to treat or not? Oral Oncology ; 1997: 33:317-321. Holmstrup P, Vedtofte P, Reibel J, Stoltze. Long-term treatment outcome or oral premalignant lesions. Oral Oncology 2005; 42:461-474. Lippman S M, Spitz M R, Huber M H et al. Strategies for chemo-prevention study of premalignancy and second primary tumours in the head and neck. Curr Opin Oncol 1995 7: 234-241. Tanaka J. Chemoprevention of oral carcinogenesis. Oral Oncol Eur J Cancer 1995 1B: 3-15. Khuri F R, Lippman S M, Spitz M R et al. Molecular epidemiology and retinoid chemoprevention of head and neck cancer. J Nat Cancer Inst 1997 89:199211. Epstein J B, Wong F L W, Millher A et al. Topical bleomycin treatment of oral leukoplakia: a randomised double-blind clinical trial. Head and Neck 1994 16: 539-544. Roodenburg J L, Panders A K, Vermey A. Carbon dioxide laser in the treatment of oral leukoplakia. Oral Surg Oral Med Oral Pathol 1991 71: 670-674. Course design by The Dental Channel ©MMVII van der Hem PS, Nauta JM, van der Wal JE, Roodenburg JL. The results of CO2 laser surgery in patients with oral leukoplakia: a 25 year follow up. Oral Oncol. 2005 Jan;41(1):31-7. Lamey P-J. Management options in potentially malignant and malignant oral epithelial lesions. Community Dent Health 1993 10: Supplement 1, 53-62. Marley J J, Cowan C G, Lamey P-J et al. Management of potentially malignant oral mucosal lesions by consultant UK oral and maxillofacial surgeons. Br J Oral Maxfac Surg 1996 34: 28-36. Maher R, Aga P, Johnson NW, Sankaranarayanan R, Warnakulasuriya KAAS. Evaluation of multiple micronutrient supplementation in the management of oral submucous fibrosis in Karachi, Pakistan. Nutr Cancer. 1997; 27(1): 41-7 PROGNOSTIC FACTORS FOR ORAL CANCER Woolgar JA. Histopathological prognosticators in oral and oropharyngeal squamous cell carcinoma. Oral Oncology 2006;42:229-239. Kademani D, Bryan-Bell R, Bagheri S, Holmgren E, Dierks E, Potter B, Homer L. Prognostic Factors in Intraoral Squamous Cell Carcinoma: The Influence of Histologic Grade. J Oral Maxillofac Surg 2005;63:1599-1605. MANAGEMENT OF INVASIVE ORAL CANCER Ord RA. Current management of oral cancer. A multidisciplinary approach JADA 2001; 132 S: 24-30 Rapidis A D, Angelopoulos A P, Langdon J D. The team approach in the management of oral cancer. Ann R Coll Surg EngI 1980 62:116-119. Cancer in Yorkshire: Head and Neck Cancers, Special Report Series 2. Yorkshire Cancer Organisation 1994. Shah J P. Chemotherapy in head and neck cancer: an unfulfilled promise and a continued challenge. J Surg Oncol 1994 55: 69-70. Tobias J 5, Edwards W G, Grant H R, Monson K M, Houghton J. Brit J Cancer 1994 70: Supp xxii, 10. Grau J J, Estape J, Blanch A et al. Neoadjuvant and adjuvant chemotherapy in the multidisciplinary treatment of oral cancer stage III or IV. Oral Oncol Eur J Cancer 1996 32B: 238241. Shaha A R. Spiro R H, ShahJ P, Strong E W. Squamous carcinoma of the floor of the mouth. Am J Surg 1984 148: 455-459. Hughes C J, Gallo 0, Spiro R H, Shah J P. Management of occult neck metastases in oral cavity squamous carcinoma. Am J Surg 1993 166: 380-383. Franceschi D, Gupta R. Spiro R H, Shah J P. Improved survival in treatment of squamous carcinoma of the oral tongue. Am J Surg1993 166: 360-365. Brown A E, Langdon J D. Management of Oral Cancer, Ann R Coll Surg EngI 1 995 77: 404-408. Course design by The Dental Channel ©MMVII Edwards D. Face to face Head and neck cancer services London: The Kings Fund, 1997. Edwards D. Head and neck cancer services: views of patients, their families and professionals. Br J Oral Maxillofac Surg.1998 Apr;36(2):99-102 TOLUIDINE BLUE, BRUSH BIOPSY and AUTOFLUORESCENCE Warnakulasariya K A A S, Johnson N W. Sensitivity and specificity of OraScan toluidine blue mouthrinse in the detection of oral cancer and precancer. J Oral Pathol Med 1996; 25:97-103. Gandolfo S, Pentenero M, Broccoletti R et al., Toluidine blue uptake in potentially malignant oral lesions in vivo: clinical and histological assessment. Oral Oncology 2006; 42: 89-95 De Veld DLG, Witjis MJH, Sterenborg HJCM, Roodenburg JLN. The status of in vivo autofluorescence spectroscopy and imaging for oral oncology. Oral Oncology 2005; 41: 117-132. DEATHS THROUGH TOBACO USE Peto-R, Lopez A D et aI. Mortality from smoking worldwide. Br Med Bul 1996 52: 12-21. World Health Organization. Tobacco or Health: A Global Status Report. 1997, Geneva. Doll R, Peto R, Wheatley K et aI. Mortality n relation to smoking. 40 years observations on male British doctors. Br Med J 1994 309: 901-911. TOBACCO CONTROL Brundtland GH. Achieving worldwide tobacco control. JAMA 2000;284:750-1 Russell M A, Stapleton J A, Feyeraband C, et aI. Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. Br Med J 1993 306: 1308-1312. Gupta P C, Murti P R, Bhonsle R B et aI. Effect of cessation of tobacco use on the incidence of oral mucosal lesions in a ten year follow up study of 12,212 users. Oral Diseases 1995 1: 54-58. West R. Assessment of tobacco dependence and motivation to stop smoking. Br Med J 2004; 328:338-9. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. The Cochrane Database of Systematic Reviews 2004; Issue 3. Course design by The Dental Channel ©MMVII West R. Addressing regulatory barriers to licensing nicotine products for smoking reduction. Addiction 2000; 95(Suppl 1):S29-34. DENTISTS AND TOBACCO CONTROL. Warnakulasuriya KAAS. Effectiveness of tobacco counselling in the dental office: an overview. J Dent Ed 2002;66:1080-9. Tomar S. Dentistry’s role in tobacco control . J Dent Ed 2002;66:1080-9. Watt R G, Jonhson N W, Warnakulasariya K A A S. Action on smoking - opportunities for the dental team. Br Dent J 2000; 189: 357-360. Position paper: Tobacco use and the periodontal patient. J Periodontol 1996 67: 51-56. Warnakulasariya K A A S, Jonhson N W. Dentists and oral cancer prevention in the UK: opinions, attitudes and practices to screening for mucosal lesions and to counselling patients on tobacco and alcohol use: baseline data from 1991. Oral diseases 1999; 5: 10-14. Smith S E, Warnakulasuriya K A A S, Feyerabend C et aI. A successful feasibility study of smoking cessation for patients in a general dental practice environment. Br Dent J 1998 185: 299- 303. Scully C, Warnakulasuriya KAAS. The role of the dental team in preventing and diagnosing cancer: 4. Risk factor reduction: tobacco cessation. Dent Update 2005 Sept; 32(7)394-6m 399-401. Johnson NW, Lowe JC, Warnakulasuriya KAAS. Tobacco cessation activities of UK dentists in primary care: signs of improvement. Br Dent J 2006 ;200 (2):85-9. Poate TW, Warnakulasuriya KAAS. Effective management of smoking in an oral dysplasia clinic in London. Oral Dis.2006 Jan;12(1):22-6 Ramseier CA, Mattheos N, Needleman I, Watt R, Wickholm S. Concensus report: First European Workshop on Tobacco Use Prevention and Cessation for Oral Health Professionals. Oral Health Prev Dent.2006;4(1):7-18 MANAGEMENT OF HEAVY ALCOHOL CONSUMPTION. UK Health Education Authority That's the limit: a guide to sensible drinking., 1992 London. SECONDARY PREVENTION OF ORAL CANCER Wilson J M G, Jungner G. Principles and practice of screening for disease. Public Health Paper No. 34, Geneva, WHO, 1968. Gupta P C, Murti P R, Bhonsle R B et al. 1995, Effect of cessation of tobacco use on the incidence of oral lesions in a ten year follow up study of 12,212 users. Oral Dis 1: 5458. Course design by The Dental Channel ©MMVII Sankaranarayanan R, Matthew B, Varghese P R et al. 1977. Chemo prevention of oral leukoplakia with vitamin A and beta carotene: an assessment. Oral Oncology 33: 231-236. POPULATION SCREENING Speight P M, Downer M C, Zakrzewska J M eds. 1993, Screening for oral cancer and precancer: report of a UK working group. Community Dental Health; 10: (Suppl 1): 1-89. Downer M C, Jullien J A, Speight P M, 1997. An interim determination of health gain from oral cancer and precancer screening. 1. Obtaining health state utilities. Community Dental Health; 14:139-142. Warnakulasuriya K A A S, Johnson N W. 1996. Strengths and weaknesses of screening programmes for oral malignancies and potentially malignant lesions. European J Cancer Prevention, 5:93-98. 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