The A-Z of Oral Cancer An Holistic Route

ORAL HEALTH GROUP THE ORAL HEALTH GROUP
The A-Z of Oral Cancer An Holistic Route
a report produced by
Royal Society of Edinburgh
The
Preface
Welcome by Sir David Carter
Sir David Carter, the Vice-President of the Royal Society of Edinburgh, welcomed the delegates to the meeting. He intimated that the RSE was very pleased to be associated with the programme of meetings on oral health. Sir David commented that he had alwasy been aware of what a significant problem oral cancer posed, but the days programme brought back to him the stark reality of the morbidity and mortality that this disease causes. There is a particular problem in Scotland so it was fitting that a meeting was being held in Edinburgh to discuss this disease. Oral cancer now accounts for 2-3% of all cancers in the UK and has an even higher incidence elsewhere in the world. There is also the frustration of late presentation of disease that is clearly, in part, preventable and is certainly eminently treatable if one could achieve early diagnosis and effective team work. The Royal Society of Edinburgh was very pleased that the event was multi-professional since establishing communication and effective team working were key purposes of the meeting. Sir David concluded his welcome by wishing the delegates an informative, stimulating and productive day.
The
Meeting Proceedings
The A to Z of Oral Cancer : An Holistic Route Oral Health Workshop Friday 25 January 2002
The Royal Society of Edinburgh 22-26 George Street EDINBURGH
Edited by Jeremy Bagg, T Wallace MacFarlane, Mary McCann and David Soutar
2003 The Royal Society of Edinburgh. ISBN 0 902198 63 7
CONTENTS
INTRODUCTION TO THE WORKSHOP Professor David Wray ..................................................................................................... 5 SESSION 1: Epidemiology, Diagnosis and Current Treatment .......................................... 7 Epidemiology The Extent of the Problem Mr David Soutar ........................................................................................................... 7 Presentation and Diagnosis The Clinicians View Professor Michael Lewis ............................................................................................... 9 Current Treatment of Oral Cancer An Overview ....................................................... 10 Mr Jeremy McMahon Patients Pathways Co-ordinating Care .................................................................... 14 Mrs Rosemary Kelly SESSION 2: NOVEL TREATMENTS AND SCREENING ........................................................... 17 Novel and Experimental Treatments Mr Ian Ganly .............................................................................................................. 17 Screening for Cancer Dr Vikki Entwistle ......................................................................................................... 21 SESSION 3: FOLLOW-UP AND REHABILITATION ................................................................ 25 The Patients Perspective Mr Michael Walton ..................................................................................................... 25 The Speech Therapists Role Mrs Mary Jackson ....................................................................................................... 27 Palliative Care for Head and Neck Cancer Dr Hugh MacDougall .................................................................................................. 29 Restorative Dentistry in Head and Neck Oncology Mr Arshad Ali............................................................................................................... 31 SUMMARY OF CONCLUSIONS ........................................................................................ 35 SUMMARY OF MAIN ISSUES RAISED IN THE WORKSHOPS ................................................. 37 ACKNOWLEDGEMENTS .................................................................................................. 39
The A to Z of Oral Cancer : An Holistic Route
INTRODUCTION TO THE WORKSHOP

Professor David Wray Professor of Oral Medicine and Dean, Glasgow Dental Hospital and School, University of Glasgow Professor Wray indicated that it would not be possible to cover all aspects of oral cancer in the space of one day. Whilst there have been enormous advances in surgical acumen over the years, this has not been matched by an improvement in the prognosis for those suffering from the disease. In addition, although something is known about the aetiology, for example factors such as tobacco and alcohol, it is a disease that is now also affecting younger people, and often individuals who do not smoke or drink. Clearly there is still significant morbidity associated with oral cancer, therefore the workshop would not just consider the current management of the disease, but also novel therapies. The wider holistic approach in the care of these patients, involving the whole of the care team, would also be a major consideration for the day. This would not be a symposium or a conference, but a workshop, with breakout sessions in the afternoon to which all delegates could contribute. Hopefully there would be a consensus to help drive forward the care and management of these patients.
SESSION1: E PIDEMIOLOGY, DIAGNOSIS AND CURRENT TREATMENT

Chair Professor Gordon MacDonald Professor of Oral Pathology, Glasgow Dental Hospital and School University of Glasgow
Epidemiology The Extent of the Problem__________ Mr David Soutar, Consultant in Plastic Surgery, Canniesburn Hospital, Glasgow Within the United Kingdom, there are about three and a half thousand new registrations of oral cancer per year. The overall survival rate at the present time is somewhere in the region of 50% (Fig. 1). Oral cancer has a very high death to registration index, which means that it is a bad cancer, similar to melanoma and cervix and almost as bad as breast disease. There are two different kinds of oral cancer, those based on premalignancy and those that arise de novo from what looks like normal oral epithelium. The premalignant lesions are usually superficial, slow growing, multifocal, some regress by changing the diet or by use of retinoids and other substances, they very rarely metastasise and they require non-radical treatment. So there is a spectrum of oral cancer in which those based on premalignancy tend to be less aggressive than the ones that arise de novo. The latter are rapidly growing, often deeply penetrating into bone, with a short time scale, often arising from a single focus, they show no regression whatsoever, they metastisise and they require radical treatment. These are the problem cases. Interpreting the statistics is made more difficult by the staging of oral cancer. Staging is determined by the TNM system, T being the tumour size, N being the nodal status and M being distant metastasis. The terms stage 1, stage 2, stage 3 and stage 4 disease are used. T1 is less than 2 cm and T2 is 2-4cm, but the size itself is not important the significant cut-off is when there is involvement of nodes. Spread to regional nodes indicates stage 3 and stage 4 disease. The prognosis depends on the stage of the disease. Stage 1 disease (T1N0) does reasonably well, whereas patients with stage 4 disease do very badly. Thus, when comparing mortality statistics between one country or another, or one set or another, particular attention must be paid to the staging of the disease. In addition, oral cancer is not a single entity, since some sites in the mouth have a better prognosis than others. Thus, lip cancer has a higher 5-year survival than any other site. Conversely, tongue cancers do particularly badly, with stage 2 disease having a 5-year survival rate of only 40% and advanced disease only 30%. The two important risk factors are tobacco (smoking, chewing or snuff) and alcohol. Alcohol and tobacco act synergistically. Thus, an individual who smokes 40 cigarettes a day and drinks 50 units of alcohol a week has a very high incidence of oral cancer. Alcohol itself is not carcinogenic but it may be that it irritates or somehow affects the protective cellular lining of the oral cavity to allow access of co-carcinogens like tobacco. It may also be the case that people whose livers have failed are less able to detoxify carcinogens. There are other recognised risk factors, such as deprivation and diets poor in fruit and vegetables. Anaemia is associated with oral cancer, as are certain vitamin deficiencies, particularly vitamins A, C and E. Candidal infections have an important role to play. The role of viral infections is unclear. Nasopharyngeal cancer is strongly linked to Epstein-Barr virus and some evidence supports human papilloma virus as being implicated in oral cancer. Lip cancer has a totally different aetiology from other forms of oral cancer. In the early 1900s lip cancer was associated with clay pipe smoking, but it is now sun exposure that is the major risk factor. Many would like to see lip cancer taken out of oral cancer and classified with skin cancer, because its aetiology is the same and many of the factors underlying lip cancer are the same as those related to skin squamous cell carcinoma. In Scotland, deprivation is a major player in the incidence of oral cancer. This may be related to tobacco and alcohol use, dietary
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Oral Health Workshop - 25 January 2002

deficiencies or chronic oral sepsis. The ratio of incidence is 4 to 1 from the most deprived to the least deprived in Scotland. In addition, survival of the most deprived is worse. Is this because they do not go to their dentist or their GP, is it because they present late, or is it because they have advanced disease when they present? There are changing trends in oral cancer. The incidence of oral cancer is increasing worldwide, but shows a geographical variation. Within Europe, two areas in France have a very high incidence of oral cancer. Scotland has a higher incidence than England and Wales. The incidence in Scotland is about 13 per 100,000, while the incidence in England and Wales is about 7 per 100,000. Within Scotland there was an alarming rise (over 40%) in the incidence during the period between 1985 and 1996, so Scotland has a particular problem with oral cancer. One of the great epidemiologists, Peter Boyle, has said that in 20 years time the incidence of oral cancer worldwide will have doubled. This is partly due to the increasing age of the population, because oral cancer is a disease primarily of the elderly. Most cases in the UK are 50-70 years of age (Fig. 2). There has also been a tremendous change in the sex incidence. The male to female ratio for oral cancer 50 years ago was 5 to 1, but this has now dropped to 2 to 1. In Scotland, there has also been a very sharp increase in the incidence amongst a younger age group, 35-50 years of age, particularly in men. This worrying change towards the younger population suggests that it is not only advancing age which is responsible for the increased incidence. One of the reasons why the prognosis for oral cancer has not improved may be that the common sites have changed. Over 70% of tumours are in the tongue or floor of mouth region. In Britain, palatal tumours and buccal mucosal tumours are uncommon. In Scotland, the incidence of lip cancer is reducing, but unfortunately it is the more aggressive cancers, tongue cancer in men and floor of mouth cancer in women, which are increasing. There has been no significant change in survival from about 1960 to the present day, despite advances in major surgery, in radiotherapy and in chemotherapy. In Scotland at present there is a rise in oral cancer in both males and females and an increased death rate in males and females. In summary, the mortality in Scotland for oral cancer is rising at an alarming rate. This is a disease that is not static. It is changing and unfortunately it is changing for the worse.
Figure 1. Trends in relative survival from oral cancer for Scotland
Figure 2. Age-specific incidence rates of oral cancer for Scotland for 1986-1995
Source: ISD Scotland: Scottish Cancer Intelligence Unit. Cancer Registration Statistics Scotland 1986-95
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The A-Z of Oral Cancer : An Holistic Route

Presentation and Diagnosis The Clinicians View__________ Professor Michael Lewis, Professor of Oral Medicine, Honorary Consultant in Oral Medicine, Dental School, University of Wales College of Medicine, Cardiff The clinical presentation of oral cancer is highly variable. It may appear as a colour change of the oral mucosa, typically a red or white patch, a swelling, ulceration or a combination of these features. Therefore the first problem is that if we are trying to diagnose these lesions while they are small, then we are looking not for one specific appearance, but a range of appearances. However, oral cancer does often have a characteristic rolled peripheral margin due to the fact that squamous cell carcinoma is cell replication out of control - these cells burrow down and under the mucosa, forcing away the surrounding normal tissues (Fig. 3). The majority of oral cancers arise within normal tissues, de novo. However, some
Figure 4. Leukoplakia
Figure 3. Oral squamous cell carcinoma
One of the major problems of oral cancer is late presentation. Mis-diagnosis may occur, for example confusion between cancer of the lip and a cold sore. The history is important in diagnosis. Thus, a cold sore is painful temporarily and relatively superficial whilst cancer of the lip is painless, persistent and indurated. The middle third of the lateral margin of the tongue and the floor of mouth are the most frequent sites for oral cancer. Unfortunately, unlike conditions such as aphthous ulceration which are painful, oral cancer is often painless. Because there is no pain, certainly until the cancer is quite advanced, people do not seek help. Thus, in contrast to extraoral lip lesions, intra-oral cancers are rarely detected whilst small. Small is beautiful small is a key message in relation to diagnosis and management of oral cancer. Unfortunately, most oral cancers present large, often with varied clinical appearances.
lesions are preceded by a leukoplakia an adherent white patch which cannot be diagnosed as any other disease process (Fig. 4). A more sinister lesion is erythroplakia (Fig. 5) - a red patch of the oral mucosa which cannot be diagnosed clinically as another disease. However, it is important to remember that the majority of these premalignant lesions do not progress. In the UK, 2 - 3% of white patches and 3 - 5% of red patches progress to oral cancer. Unfortunately, it is not possible to determine which of these lesions will progress therefore all patients with premalignant signs need to be kept under observation. Tissue biopsy is the only way to diagnose oral cancer. The biopsy specimen should be put on a piece of card or filter paper and placed into formalin. A biopsy specimen shrinks by 30% and will distort if not supported with card. The better the quality of specimen provided to the pathologist, the more
Figure 5. Erythroplakia

accurate the report. Other relevant investigations may include tests for candida, iron deficiency and levels of vitamins A, C and E. Vital staining, using tolonium chloride, has been heavily promoted commercially. This nuclear dye, which has been used to screen the cervix in women for squamous cell carcinoma, has also been suggested as a screening tool for oral squamous cell carcinoma. Unfortunately, in the mouth it seems to stain all tissues blue and is of limited value. It may be helpful in determining where to take a biopsy for a patient with multiple red and white patches. However, as a primary screening tool it is a waste of time. More recently, oral CDX, a brushing biopsy technique, which samples cells from the oral tissues, may prove to have a useful role in the diagnosis of oral cancer in the future. In summary, look for colour change, swelling and persistent ulceration. Examine soft tissues regularly and biopsy any suspicious or persistent lesions.
Current Treatment of Oral Cancer An Overview__________ Mr Jeremy McMahon, Consultant Oral and Maxillofacial Surgeon, Monklands Hospital, Airdrie
INTRODUCTION
The treatment goal in the management of the majority of patients who present with oral cancer is, self-evidently, to achieve cure. It is, however, worth reflecting on why we emphasise cure and how we measure the outcomes of treatment. Until recently success, or otherwise, of treatment was measured primarily in terms of disease specific survival at 5 years and this remains an important measure in clinical governance terms as well as in trials comparing alternative treatment strategies. However, it is also important to consider overall survival in analysing treatment success, and a discrepancy between the two survival curves is a consistent finding (Fig. 6). A small proportion of this discrepancy may be related to adverse effects of treatment, eg. the patient who chronically aspirates after a resection which involves the pharyngeal wall. The majority of the discrepancy is, however, accounted for by co-morbidity. Recognition of this results in a clearer understanding of treatment aims and a realisation that gauging efficacy of therapy solely in terms of survival curves is too narrow a view. A patient unlikely to survive more than 18-24 months because of a co-morbid condition may still undergo treatment with curative intent. The best way to give the majority of patients with oral cancer an improved quality of life is to achieve a cure. Oral cancer which persists or recurs leads to a progressive decline in quality of life and often a distressing death. Pain, impairment of basic and essential functions such as speech and swallowing, and significant disfigurement are all very real consequences of the disease. However, such adverse outcomes may also be adverse results of curative treatment. Circumstances arise whereby the functional impact of curative treatment is so high that a patient will choose a treatment strategy less likely to achieve locoregional control, or even cure,
Figure 6. Overall and disease specific survival curves for a series of patients presenting with metastatic SCC to the neck from an unknown primary source, demonstrating a lower overall survival compared with disease specific survival.
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rather than incur such a penalty. It is essential that we are able to provide patients with accurate information that allows such decision making to take place. Treatment outcomes must be measured in terms of disease specific survival and overall survival, but also functional status. Trials comparing results of treatment should incorporate a quality of life comparison of outcomes in addition to the traditional survival curves. Where survival outcomes do not differ significantly, it seems probable that any advantage in terms of quality of life or functional outcome will be the prime determinant of treatment strategy. Access to care which provides the best possible outcome must be irrespective of geography and social status. Recent Scottish data suggest inequalities on both counts (Figs. 7 and 8).
Survival 100 80 % survival 60 40 20 0 1 Least deprived 2 3
Incidence
Mortality 25 20 15 10 5 0
5 Most deprived
Deprivation quintile
Figure 7. ISD data demonstrating increased incidence and mortality from head and neck cancer with social deprivation.
Figure 8. Cause-specific survival by health board Incidence, unadjusted survival at 5 years and adjusted hazard ratio (with 95% CI) compared to Scotland (with 95% CI): patients diagnosed 1991-951
Survival analyses Health Board2 Argyll & Clyde Ayrshire & Arran Borders Dumfries& Galloway Fife Forth Valley Grampian Greater Glasgow Highland Lanarkshire Lothian Tayside Scotland5 Incidence rates3 16.1 13.3 11.6 10.8 13.8 13.8 13.8 20.1 14.5 14.3 15.2 12.9 15.2 No. included in analysis 347 259 76 97 250 186 349 889 153 366 565 273 3874 Unadjusted survival 56.9 64.0 68.7 62.0 56.0 56.7 64.0 54.6 61.6 55.8 52.7 49.4 56.7 Adjusted hazard ratio4 1.00 0.79 0.69 0.82 1.08 1.06 0.81 1.04 0.86 0.98 1.17 1.20 1.00 95% CI Lower 0.85 0.65 0.46 0.58 0.89 0.85 0.68 0.94 0.65 0.84 1.04 1.01 Upper 1.18 0.97 1.05 1.15 1.30 1.32 0.97 1.16 1.12 1.15 1.32 1.43 -
The hazard ratio is the ratio of the rate of death in a health board to the rate in Scotland as a whole. Health boards with higher survival usually have lower hazard ratios. However this is not always the case because the hazard ratios have been adjusted for difference in age, sex and deprivation category between health boards. See the ISD publication Trends in Cancer Survival in Scotland 1971-1995 for further information
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have 5 years follow-up 2 Mainland health boards only 3 Age-standardised incidence rates per 100 000 person-years at risk (European standard population) 4 Adjusted for age and 1991 Census Carstairs deprivation category 5 Figures for Scotland include Orkney, Shetland and Western Isles Source: ISD publication Trends in Cancer Survival in Scotland 1971-1995
Cases diagnosed in 1994 and 1995 do not
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incidence/mortality per 100 000

CURRENT TREATMENT
Modern cross-sectional imaging modalities have made treatment planning a much more precise process. This applies particularly to advanced tumours which extend into inaccessible anatomical regions. Examples include maxillary tumours which extend to involve the infratemporal fossa, skull base, and orbit. Tongue base tumours may involve the pre-epiglottic space and this has important treatment implications. Sagittal MRI scans provide useful images of this region. Evaluation of the extent of any nodal metastasis is also improved with CT and MR imaging. However, the addition of CT and MRI in assessment of the neck for occult metastasis offers only a modest improvement in accuracy (approximately 50%) over palpation alone. Only ultrasound-guided fine needle aspiration (FNA) biopsy is capable of reliably detecting a tumour volume of less than one cm 3. The use of ultrasound-guided FNA is time consuming and operator dependent, making it impracticable for most Head and Neck Cancer services in the UK. The information available to date suggests that Positron Emission Tomography has similar limitations to CT and MRI in detecting low volume nodal disease. The curative treatment modalities have, at least in name, remained unchanged for at least three decades. Surgery and radiotherapy remain the mainstays of treatment. This explains in large part the unchanged cancer registry survival rates for oral cancer over that 30 year period. However, substantial changes in management have occurred. These changes may be divided into two categories, a) those which have decreased the impact of treatment on patients and b) those which have led to incremental improvements in diseasespecific survival curves. Advances in surgical management have fallen mainly into the former category. However, improvements in anaesthesia and perioperative care have led to perioperative mortality rates falling to 1-2% in patients undergoing major surgery for oral cancer. This is a very real achievement in a population of patients having substantial comorbidity. Thirty years ago neck disease was managed solely with a classic radical neck dissection. This incurs significant disability with respect to shoulder function. Resection of oral cancer was frequently accompanied by a mandibular resection in the belief that spread occurred via permeation of
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periosteal lymphatics. Advances in our understanding of the mechanisms of tumour nodal metastasis, and the nodal echelons at risk in the neck, have led to mandiblesparing procedures and structure-preserving neck dissections respectively. Current investigation evaluating the efficacy of sentinel lymph node biopsy may lead to a further reduction in the morbidity for many patients at high risk of occult nodal metastasis. The use of access procedures to approach otherwise difficult areas has led to sparing of uninvolved structures whilst facilitating complete and controlled tumour resection. Reconstructive surgical techniques have made enormous strides over three decades. Mandibular reconstruction with free tissue transfer means that it is possible to maintain form and function for the large majority of patients requiring a jaw resection for direct invasion. The replacement of missing lining with local, pedicled, and particularly free flaps, means that oro-cutaneous fistula formation is an uncommon postoperative event, substantially decreasing duration of hospital stay. The replacement of resected oral lining means that secondary loss of function, particularly residual tongue, due to tethering is minimised. This optimises postoperative speech, mastication, and swallowing. Effective methods of reconstituting both the hard and soft palate partition are now widely utilised. Prosthodontic solutions remain the preferred option for some low level maxillary defects however. For early stage disease (T1N0, T2N0), radiotherapy with surgery for salvage is generally regarded as being equally efficacious, with surgery as the primary treatment modality, utilising post-operative radiotherapy where there are adverse pathological features. However, direct comparisons with randomised trials are lacking. The primary treatment modality is chosen on the basis of relative treatment associated morbidity, patient co-morbidity, logistics, and protocols designed to prevent relapse of disease in regional lymph nodes. Recently reported evidence from the West of Scotland demonstrates improved outcomes when treatment planning is protocol based, and this is probably the most important factor in treatment selection. Radiotherapy may be delivered in the form of external beams of particles (photons and electrons) generated by linear accelerators (teletherapy), or in the form of radioactive implants (interstitial or brachytherapy).

Considerable progress has been made in radiation oncology. CT imaging as an aid to planning allows greater precision in the planning of radiation fields. Computer software development has led to the introduction of Intensity Modulated Radiotherapy in many units worldwide. This technology allows delivery of the prescribed therapeutic dose to the tumour whilst minimising dose to adjacent uninvolved tissues. The aim is to ensure tumour cell kill while reducing unwanted effects. A number of trials have demonstrated improved treatment efficacy with alternative fractionation techniques of teletherapy dose delivery. Standard fractionation regimens have comprised once-daily dosing of 1.8 to 2 Gy five days a week typically up to doses of 70 Gy. This strategy has the theoretical disadvantages of allowing tumour re-population, increasing the total dose required and thus late toxicity. These effects increase the required total dose and thus long-term toxicity. Schedules have been designed which seek to overcome these problems in two ways. One strategy is to accelerate the radiotherapy so that the treatment is given over a shorter period of time. A further strategy is hyperfractionation of the dosing schedule so that the total dose is given in a greater number of fractions, generally twice daily. Late toxicity is a function of total dose but also dose per fraction. Hyperfractionation allows a higher total dose without increased toxicity. These two strategies have been combined. The penalty for both is increased acute toxicity. It is this increased toxicity as well as the logistic requirements of such regimens that have led to the slow widespread adoption of alternative fractionation regimens as standard. The substantial adverse functional consequences of surgery have led to the search for alternative treatment strategies in those with advanced oral cancer. This particularly applies to cancer involving the tongue base where total glossectomy plus or minus laryngectomy would be necessary to obtain clear surgical margins. Brachytherapy as an organ preservation approach has undergone evaluation in a number of centres worldwide, including Glasgow. It has been employed as the sole treatment of the primary site or as a boost to the primary following external beam radiotherapy. Reports detailing functional outcomes give mixed results, emphasising that organ preservation does not necessarily imply preservation of function. Problems include chronic severe pain, soft tissue necrosis, and osteoradionecrosis. Concurrrent chemotherapy with radiotherapy is currently receiving considerable attention. Meta-analysis suggests concurrent chemoradiation improves survival by approximately 10% compared with radiotherapy alone. An alternative approach has been to use a highly selective intra-arterial chemotherapy regime, concurrent with external beam radiotherapy, for advanced cancer of the head and neck including oral cancer. A high rate of complete response has been reported and encouraging survival rates. However all concurrent chemotherapy radiation therapy regimens are associated with significant acute and late toxicity. They require that patients have reasonable cardiac and renal function and are thus not applicable to all patients. More work is required to better define the population of patients most likely to benefit. Studies are required which compare organ preservation treatment strategies with surgery and postoperative radiotherapy where the adverse functional consequences of surgery are not so severe. In these subsites the use of organ preservation strategies remains investigational. Overall, it seems probable that, given appropriate resources, we can hope to achieve a few percentage point incremental improvements in survival, as well as quality of life for survivors, with the use of these refined treatment strategies. Within Scotland it seems likely that improvement in outcomes (both survival and quality of life) can, in the short term, be most dramatically affected by ensuring equitable access to dedicated head and neck cancer multidisciplinary teams with adequate resources. The current situation in which there are multiple small teams, working more or less independently of each other, often deficient in key resources, is neither desirable nor sustainable. Other than re-organisation and investment, any major advance in the treatment of oral cancer awaits the development of novel therapeutic strategies.
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Patients Pathways Co-ordinating Care___________________ Mrs Rosemary Kelly, Support/Liaison Sister, Head and Neck Unit, Canniesburn Hospital The abstracts for the workshop contain a number of recurring words: variation, increasing, challenge, individualised needs, information, resources and quality of care. All are wrapped up in a package of care. Quality of life is a major issue for patients suffering from cancer. Quality of life for a person with oral cancer may be affected on three fronts: visual functional emotional
THE JOURNEY
Although it is no holiday, I would like to relate our patients pathway to todays more conventional journey a package holiday. Many professionals can be likened to those who help to make the journey possible during the book-in, check-in, in-flight and ground support all the way to the destination. In order to deliver seamless care we want to get the traveller to the point of departure without unnecessary delays. So at prediagnosis or the booking-in, we want rapid access. Do we offer the local bus service which calls in to every village square, or do we go Inter-city? Has our traveller got the necessary documents? For treatment planning we need to know that the patient is fit to make the journey, so we are the insurance company. If he cannot fly, then we need to arrange an alternative route with the travel agent. But what kind of service does our travel brochure offer? Is it a small outfit which offers limited options, but good personal service, or is it a bigger company, where service is spread more thinly, and where even a short journey needs a big team. In a combined regional oral cancer unit, there must be co-ordination; the bed coordinator, transport co-ordinator, just to start, and there are numerous other co-ordinators along the different stages of the journey. With so many different units involved there must be good communication between ground control and the flight-deck.
Quality of life questionnaires are often complicated and time-consuming to administer successfully. Simply asking your patient What do you want to do that you can no longer do? may quickly give some measure of what is important to his / her quality of life. For example, how often do dentures figure in quality of life questionnaires? And yet, how many of us hear these recurring questions, When will I get my dentures? or Of course, Ill be able to eat, once I get my dentures. How can we guide patients along the pathway to ensure optimum quality of life? Patient pathways are fashionable at the moment, but the care of the oral cancer patient is so individualised and involves so many different disciplines that to design a standardised care pathway is incredibly difficult. What kind of journey is it for the oral cancer sufferer? It is often a one-way ticket, with no turning round. It is usually to a life that will never be the same again, and a successful life depends on how adaptable the traveller proves to be. It is a challenge. In bygone days, it was often a journey without support - dependent on luck, a frontiersman perhaps - dependent on a watering hole, with hopefully no Indians along the way. Perhaps nowadays, it is more like climbing a mountain; for some an afternoon up Ben Lomond, but for others it is more like Mount Everest. Although there may be some support from base camp the hardest stretch must be done alone or perhaps with one close companion - then there is always the descent.
THE TRAVELLERS
The patient journey may be illustrated by some case histories. The question posed is whether their journey was first class or economy class in terms of support. Happy Harry is 75 and he has an early cancer. He is generally well in himself but he is the sole carer for a disabled wife. There are no other family members and he is edentulous. Bingo Betty has multifocal oral dysplasia and she needs yet another small excision. She smokes and takes social alcohol, enjoys her socialising and would not dream of facing the world without her teeth.
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Pretty Penny is 40, has a fairly early tumour and is a teacher with a young family. She is a non-smoker, takes occasional alcohol, eats well and goes to the gym. There is a family history of cancer. She is absolutely devastated by this diagnosis. Why me? What will happen to the children? Will I be able to work again? Anxious Alan is 55, and has an advanced tumour. He has a history of past alcohol abuse but is doing his best and had been dry for nine months. He lives in a rehabilitation hostel and attends AA meetings. He still smokes, is separated but his wife is still very supportive. Aimless Alex is also 55, an alcoholic and smoker with no intentions of even trying to stop. He has not been near a GP for years. He is homeless and steals scrap metal to buy his food. In addition to the treatment of oral disease according to the local protocol, all of these people require assessment of any co-morbid conditions and support from a wide range of disciplines. In order to deliver seamless, efficient care to the increasing numbers and wide variety of patients with oral cancer, adequate assessment of needs is required at all stages of the patient journey. Efficient assessment with appropriate action as an insurance policy might help to reduce complications and be cost-effective in terms of bed occupancy. Having identified these needs, sufficient knowledge is required as to when, to whom and how to refer. Which health care or social service will be available to them to deliver long-term efficient care? Happy Harry can we treat him as a day case and hope that he will have no problems so that we can let him home at the end of the day to look after his wife? For them life goes on as before - if we are lucky. Option two may be to alert the GP or social worker to arrange short-term respite care arrangements for his wife. Harry could then be kept in hospital for a couple of days until nutrition is established and perhaps then initiate a future care package for the couple. Whilst the second option might sound excessive, it may save on long-term costs if it transpires that Harry cannot cope with himself, let alone his wife. Who will coordinate all of this activity? Bingo Betty feels that each time they excise a lesion she looks like less of the person she once was. Will she have access to a dental rehabilitation service? Without dentures will
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she still socialise? Will she be able to go out of the house? Will she become depressed? A study in the early 1990s by Espie showed that at least one third of oral cancer patients suffer from significant depression. Eleven years on, are we any more skilled in identifying this fact and doing something about it? Pretty Penny has a good chance of cure but she needs psychological support now. Will she be lucky and have access to a counsellor now or will she be one of the thousands of cancer patients who have to draw lots for consultations with psychologists? Will she have support from a member of the MacMillan or a Marie Curie home care team now, or does she live ten miles further down the road where reduced resources mean that the waiting time is six weeks just for a home visit? Will she routinely have ongoing services with a speech therapist so that she can return to work with confidence? Anxious Alan is doing his best and is keen to get back to his computer course. He wants to co-operate with everyone who tries to help him. He has been given sufficient understanding of the proposed treatment. He would like to give up smoking, but no one has actually told him to stop, so he feels like a lost cause. Who will advise on smoking cessation? During treatment, either radiotherapy or chemotherapy, he may have to fend for himself in a hostel. Who will recognise his need for continued support from a dietitian during treatment? Will there be one available to him? He needs help with re-housing, but he feels that he was treated like low-life by the housing officials because is an alcoholic. Who will he confide in? Who will liaise with his social worker or key worker? Aimless Alex has had numerous problems. Several co-morbid conditions were discovered. He has had endless complications including DTs and respiratory infections to name a few. He has received care from every member of the in-house team and from other specialities during all stages of treatment. He especially needs the social work department to find him suitable accommodation so that he can be discharged from hospital, but despite all of this support he still blames everyone else, not least the doctor who did this to him. He can now no longer eat his favourite pie and chips nor manipulate the scrap metal. He is noncompliant and fails to keep appointments. Eventually he is lost to follow-up until he presents to A & E with advanced recurrence.

These patients are fictitious but you will probably recognise them. To end with a very positive traveller and a true story, Gladys had treatment 10 years ago for a very advanced tumour and at that time her quality of life score was rock bottom. Now, her score has changed very little but she can speak on the phone and although she has a pharyngostomy tube in place she regularly goes abroad. She has documents to cover her continued use of opiates and her excess baggage requirements. When she arrives at her destination, thanks to hospital-to-home nutrition services, she finds that all her feeding requirement have been delivered to her hotel. Gladys has used many different companies. All have gone out of their way to assist her. Can we deliver healthcare services so efficiently? For Gladys there has been a long period of very hard work, but without the continued support of a wide range of health professionals she would perhaps not have learned to adapt to a life which has changed considerably since her diagnosis. In conclusion, at every stage of the patients journey from preventive health education, through first presentation, to rehabilitation or palliative care and in every setting, be it hospital or community, nurses are well placed to make assessment of patients needs and to co-ordinate services. Working in conjunction with other professionals allied to medicine in nurse-led clinics would free up some consultant or registrar time at clinics. This would provide a wider service to the patient. Such an approach would surely prove cost-effective in terms of reducing the morbidity associated with all forms of treatment. However, have nurses the means to communicate with one another and with all members of the multidisciplinary team on a day-to-day basis? Nurses in some Trusts have little access to IT. Team meetings do fulfil a need but what if the problem cannot wait until the next meeting? Are there enough specialist nurses in post? More resources are required to enable nurses and others to develop specialist skills and the opportunity to gain knowledge. To sum up, adequate resources are required to provide an increasing number of oral cancer patients, who have very varying needs, with adequate support and information to ensure optimum quality of life. Anything less risks economy class syndrome.
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SESSION 2 : N OVEL TREATMENTS AND SCREENING

Chair Dr Gerry Robertson Consultant Radiation Oncologist, Beatson Oncology Centre Western Infirmary, Glasgow
Novel and Experimental Treatments__________ Mr Ian Ganly, Specialist Registrar in Otolaryngology, Royal Alexandra Hospital, Paisley One of the main causes of treatment failure in oral cancer is local and regional recurrence, due to minimal residual disease. This is due to inadequate or incomplete surgical resection. The second cause of failure, which is becoming more important, is distant metastatic disease. This is due to clinically and radiologically undetectable micro-metastases. Patients successfully go through surgery and radiotherapy, then six months to one year later present with clinically evident metastatic disease. The third cause of treatment failure is the development of second primaries of the aero-digestive tract. It is estimated that two thirds of patients with oral cancer present with stage 3 or stage 4 disease, i.e. advanced disease. In these patients, the incidence of loco-regional recurrence after treatment is 50% and the incidence of developing distant metastases is 25%. The incidence of recurrence and metastases is directly related to the number of positive neck nodes. The present treatment for recurrence is very poor. Reirradiating patients is seldom possible because the patients have had the full dose of radiation therapy. Brachytherapy is possible for patients with recurrent tongue tumours but results are less good than for primary tumours. Chemotherapy is also of limited benefit. For distant metastatic disease, chemotherapy is usually the only treatment of choice. In both recurrence and distant metastases, the overall response to chemotherapy is only 35%. Rarely is such treatment curative and the duration of response is 6-9 months. In essence, once there is recurrence or distant metastases, the prognosis for patients is extremely poor. The possible clinical situations where novel therapies might be useful are as follows. First, novel therapies could play a role in the treatment of loco-regional recurrence by intra-tumoral injection or by systemic therapy. Secondly, distant metastases, once they have occurred, could be treated by systemic therapy. Thirdly, the prevention of loco-regional recurrence could be undertaken at the time of surgery by treating minimal residual disease, possibly by injecting surgical resection beds to mop up residual cells. Fourthly, it may be possible to prevent distant disease that cannot be detected clinically or radiologically, again by giving systemic therapy. Lastly, there is the treatment of premalignant lesions such as leukoplakia. The types of novel therapies that will be considered are gene therapy, viral oncolytic therapies and antibody therapy. Gene therapy is the transfer of foreign DNA into cells to produce a therapeutic effect. There are three different ways in which DNA or genes can be transferred into cells chemical, physical and viral. DNA can be incorporated into a chemical transporter such as a liposome, enabling transfer across the cell membrane. An example of physical transfer of DNA is to apply an electric current to the tumour cells, which temporarily liquefies the cell membrane, allowing DNA to transfer across. This method is called electroporation, and electroporation guns are now available that can be used to deliver injections to patients. The third and currently most important method is by using viral vectors, such as adenoviruses. These vectors have had a significant amount of their genetic machinery removed from them, which makes them non-replicating. The gene of interest is inserted into these viral vectors and the virus then carries the gene into the cells. There are two ways of doing this. The first is in vivo, where the virus containing the DNA is injected directly into the patient. Alternatively, it can be undertaken ex vivo, by taking cells out of a patient, injecting the virus into the cells and
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then injecting the cells back into the patient. What genes should be transferred? Carcinogenesis is a multi-step process, which involves accumulation of multiple genetic events. At least ten genetic alterations are required to convert a normal cell into a squamous cancer cell. Many of these genetic alterations involve over-expression of oncogenes or loss of tumour suppressor genes. Oncogenes and tumour suppressor genes are normal genes present in every cell. When oncogenes are over-expressed they stimulate cell proliferation. The normal function of tumour suppressor genes is to inhibit cell proliferation, and if they are lost there is an increase in cell proliferation. If there is over-expression of oncogenes or loss of tumour suppressor genes then there is uncontrolled cell proliferation leading to cancer formation. In head and neck cancer the two most important tumour suppressor genes are p53 and p16. It is estimated that 55 to 80% of oral cancers have lost p53 and over 80% will have lost p16. The most important oncogene in oral cancer is called cyclin D, which is over-expressed in 33% of cases. When these events occur together, there is increased cell proliferation, loss of cell cycle control and cancer formation (Fig. 9).
Cyclin D amplification Oncogene
this phase one study, the researchers were able to inject up to 1011 virus particles into the patients without producing any toxic side effects. In a phase 2 trial with 101 patients, they were able to produce seven complete responses, ten partial responses and twenty-nine stable diseases. The work has now progressed to a phase 3 trial, the first gene therapy trial in cancer that has reached phase 3.
Adenoviral vector p53 transgene
Unresectable HNSCC Mutant p53
Tumour cells transfected with wt p53 p53 mediated apoptosis Regression of tumour (wtp53 is dominant)
Figure 10a. Gene Replacement Therapy
Autologous tumour cells
Patient
RV IL-2 Il-2 stimulates cytotoxic T cells against tumour cells
Rb loss p53 loss p16 loss
Inject s/c
G1 S Loss of cell cycle control
Transfect IL-2 in-vitro
Tumour suppressor genes Cancer
Figure 10b. Immunotherapy
Figure 9. Cyclin D in oral cancer
Adenoviral vector tk transgene
Thus, the genes that we would want to transfer, are those which have been lost i.e. tumour suppressor genes. This type of gene therapy is called gene replacement therapy. This has been attempted in clinical trials where the p53 transgene has been injected into patients with recurrent head and neck cancer (Fig. 10a). In 1997, at the MD Anderson Cancer Institute in America, patients with un-resectable tumours in their necks and with a non-functioning p53, had the gene injected back into the tumours. These tumour cells then started expressing the normal gene, became more like normal cells and the cells actually began to die. In
Tumour cells transfected with tk gene
Ganciclovir injection
Ganciclovir activated by tk
Tumour killed selectively (nontransduced cells killed by bystander effect)
Figure 10c. Gene directed prodrug therapy
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The second type of gene therapy is called anti-oncogene therapy. Here the aim is to try to suppress the over-expression of oncogenes using anti-sense therapy. In head and neck cancer, the gene to target would be cyclin D since this is amplified in 33% of cancers. This therapy has yet to be evaluated in clinical trials. The third type of gene therapy is immunotherapy. In this therapy genes which enhance immune recognition and immune mediated killing are tranfected into the tumour cells. There are two ways of doing this. First, we can transfect a gene into the tumour cell which allows the tumour to be recognised more efficiently by the immune system. Secondly, we can transfect a gene into the tumour cell, which stimulates the immune system to proliferate and increase the number of cytotoxic lymphocytes. One example is to insert a gene called B7 into tumours. B7 is a co-stimulatory molecule, which enhances lymphocyte proliferation. These tumours will then express B7, which is expressed on the cell membrane of the tumour cell and this is recognised by tumourinfiltrating lymphocytes. There is better recognition of the tumour and therefore the tumour is more efficiently destroyed by the tumour-infiltrating lymphocytes. This type of therapy has shown partial responses in patients in a phase 1 trial, and is now progressing into phase 2. An example of the second type of immunotherapy is the transfer of the gene for interleukin 2 (IL2) into the tumour. The tumour will then express IL2, which in turn stimulates cytotoxic T cells to proliferate, attack the tumour and kill it (Fig. 10b). This has been carried out in a phase 1 study, but the results were very poor for head and neck cancer compared with melanoma, which has shown good responses in comparison. The fourth type of gene therapy is the most promising and is called gene directed enzyme prodrug therapy (GDEPT). Here we transfect a gene into the tumour, which codes for an enzyme that can activate a drug into an active chemotherapy agent. One example of such a gene codes for thymidine kinase (tk). The tumour will express the tk gene and this converts the drug ganciclovir, which is non-toxic, into a toxic agent by phosphorylation. The active drug then acts on the tumour, causing tumour regression. Because the tk gene is only expressed in the tumour and not in normal tissue, selective tumour destruction is achieved (Fig. 10c). The advantage of this method is that it has a bystander effect, i.e. only 10% of the tumour cells need to express this gene to get a good response, because once this agent is activated, it can then diffuse through the cells via gap junctions and kill the surrounding cells. There are several different types of enzymes and prodrugs that can be used. The second type of novel treatment is called selectively replicating oncolytic viral therapy. The requirement in this therapy is for a virus that can infect, replicate and cause cytolysis selectively in tumour cells but not normal cells. The first virus that was used was called Onyx 015, which is an adenovirus. This adenovirus has been genetically altered such that it recognises cells that have a nonfunctioning p53 gene. Therefore in normal cells, which have functional p53, this virus does not replicate. However, when it infects a tumour cell, which has a non-functioning p53 gene, the virus will replicate causing cytolysis of infected cells (Fig. 11). Phase 1 and phase 2 trials in head and neck cancer have been carried out. Patients were treated by multiple intra-tumour injections on a daily basis for five days. The overall response rate was approximately 33%, with a complete response of 8%, but unfortunately these responses were of a very short duration (three to six months), similar to chemotherapy. A later study examined the effect of intratumoural viral injection in combination with systemic chemotherapy. In this study, the response rate increased to 63% and overall a complete response rate of 27% was observed. The patients also appeared to survive longer, with 83% progression-free at six months. The current area of interest in our group is in the use of a genetically modified herpes simplex virus called HSV 1716. Tumour cells divide more rapidly than normal cells. This virus replicates most efficiently in rapidly dividing cells and therefore HSV1716 will replicate selectively in tumour cells rather than normal cells. The mechanism is still unclear but is believed to be dependent upon a molecule called PCNA Proliferating Cell Nuclear Antigen; rapidly dividing cells have high levels of PCNA and normal cells have low levels. A phase 2 clinical trial is due to start in patients with oral cancer by direct intratumoural injection. Lastly, there are antibody therapies. Here there is a requirement for an antibody, which recognises the tumour or tissue-specific antigen. There are two types, unconjugated
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and conjugated antibody therapy. In unconjugated antibody therapy the antibody inhibits tumour growth by blocking a growth factor receptor or signal transduction factor. Head and neck cancers over-express epidermal growth factor receptor (EGFR). The antibody C225 binds to this receptor and blocks it, therefore preventing epidermal growth factor from stimulating growth and thus inhibiting the tumour. A recent (2001) study in head and neck cancer patients using this antibody alone produced 11 stable diseases. Interestingly, when this therapy was combined with cis-platin, 6 out of 9 had a response. When combined with radiotherapy all patients had a response, including 13 complete responses. The second method is conjugated antibody therapy. An example of this is to link a radionucleotide onto the antibody. In this case, the antibody targets the radionucleotide to the tumour where the radiation then kills the tumour cells. In one study, carried out in Amsterdam, the radionucleotide Renium, which kills tumour cells by emitting beta particles, was linked to an antibody to CD44, which is expressed in squamous cell cancers. Encouraging results were achieved in the phase 1 study and this therapy is now proceeding to phase 2. In summary, treatment failure in oral cancer is due to loco-regional recurrence and distant disease. The current treatment for this has only limited success and therefore new novel treatments will have a role to play in the treatment and prevention of these two conditions. The current studies, in gene therapy, viral therapy and antibody therapy, are all promising but they are only in the early stages and as yet, there are no commercially-available novel therapies for use in the treatment of oral cancer.
Ad2 infection of normal cell
virus infects cell Ad2 has E1B gene p5
virus produces 55k p53 55k
viral replication p5 55
p5 normal cell has functional p53
55k inactivates p53
cell lysis
Onyx-015 infection of normal cell
virus infects cell Onyx-015 has no E1B gene p53
virus cannot produce 55k p5
abortive infection
p53
p53 prevents viral replication
normal cell has functional p53
Onyx-015 infection of p53(-) cells
virus infects cell Onyx-015 has no E1B gene
virus can replicate
cancer cell cannot produce p53 cancer cell lacks p53
cell lysis
Figure 11. Selectively replicating oncolytic viral therapy
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Screening for Cancer__________ Dr Vikki Entwistle, Health Services Research Unit, Medical School, University of Aberdeen Oral cancer is nasty and is getting more common. People often do not know they have got the disease until it is advanced, so treatment often starts late. If treatment had been started earlier, the treatment itself might not have been so unpleasant and the outcomes might be better. Many reasonably intelligent people, armed with that knowledge, would suggest that surely a screening programme is needed. But is it? In this paper, I will consider and encourage you to think about the types of criteria that should be used to decide whether and how screening programmes should be introduced. I will also ask how, if a national screening programme were established, individuals should be enabled to make decisions about whether or not to participate in that screening programme. In order to answer the question would the introduction of a screening programme for oral cancer be good or bad for the population? there are five basic subquestions that should be considered: 1. Is the target condition (oral cancer) serious? 2. Is the screening test accurate in detecting early stage disease? 3. Does early detection (of oral cancer) improve outcomes? 4. What are the harms of screening and treatment? 5. Do the benefits outweigh the harms? Some of the knowledge that is required to answer these questions in respect of oral cancer is available, but some is apparently lacking. The UK has a National Screening Committee. It was established in 1997 and continues to serve all of the UK health departments, including the Scottish Executive Health Department. Its main roles are to appraise screening technologies and to assure the quality of screening programmes. When appraising screening technologies, the Committee asks questions about the condition of interest, about the screening test or tests that might be used, about the available treatment and about the form that the programme might take. We can apply these questions to the case of oral cancer. First in relation to the condition: Is oral cancer an important health problem? Do we understand enough about its epidemiology and natural history? Is there a detectable risk factor, disease marker, latent period or early symptomatic stage for this disease? The National Screening Committee considers possible screening programmes in the context of broader healthcare activities, and we must also ask whether all the known cost-effective primary prevention interventions for oral cancer have been implemented. Second in relation to the screening test that might be used: Is there a simple, safe, precise test available? Do we know what kind of pattern of responses or results we would get if we were to apply this test to a population? Do we know where we should apply the cut-off to refer people on for further diagnosis or treatment? Is the test actually acceptable to the population? Is it something people would have if it were offered to them? Is there an agreed policy on what will happen to people who screen positive? Third in relation to the question about available treatment: Are there effective treatments and interventions available? Is there research evidence to demonstrate that early treatment of oral cancer does lead to better outcomes than later treatment? The intuitive opinion of clinicians is not sufficient to justify the introduction of a screening programme. The National Screening Committee would want to know whether there were agreed evidence-based policies about which treatment option(s) should be offered and to whom. Before sanctioning the introduction of a screening programme, they would want to know that the provision of care for people with oral cancer was as good as it could be. Fourth, considering the potential screening programme as a whole: Is there evidence from randomised controlled trials that the whole screening programme actually does reduce mortality or morbidity? If we look across the different cancer screening programmes that are or might be used for different types of cancer, there is quite clear evidence for some that the screening programme as a whole can reduce mortality and morbidity. In other cases, there might be a promising screening
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test that is quite sensitive and good at picking up the condition, but the introduction of a screening programme into the messy day-to-day practice of a national healthcare system might not, on balance, be effective in terms of reducing mortality and morbidity. Is there evidence that the whole screening programme would be acceptable? Would people use it if it were introduced? Would the benefit from the programme outweigh the physical and psychological harm? It is important to remember that with screening we are talking about possibly doing good or harm to a lot of healthy people. As well as thinking of the benefits that a screening programme might give to the people in whom early stage disease is detected, we have to consider its impact on others. We have to ask about the consequences of a screening programme for those who have false positive results and for those who screen negative. For those who have false positive screening results, there might be morbidity associated with the biopsy they have for diagnosis. For them and others the psychological consequences of screening also need to be considered. Substantial psychological harms have been demonstrated from screening programmes for other cancers. The National Screening Committee considers whether the cost of introducing a screening programme is balanced in relation to spending on healthcare as a whole. If there is a limited pot of money, we have to consider whether it should be spent on a screening programme or whether it could be better spent on something else. So even if a screening programme seems to have some overall benefit it might not be the best use of the available resources. Before a national programme can be introduced, there must be agreed quality standards for the programme and a plan for monitoring the programme against these. Within a national programme, there should be equity of access, with consistent high quality standards wherever people attend for screening. There must also be adequate staffing and resources for all of the diagnostic, treatment and programme management work that a screening programme generates. So before a national screening programme is introduced, a tough set of questions must be given serious consideration. If it is decided that from a population perspective it would be a good thing to introduce a national screening programme for a particular health problem, questions must be asked about how people should be encouraged to take up the screening programme. I will consider here two different approaches: a traditional public health approach and an informed individual choice approach. Most of the national screening programmes, when they have been introduced to date, have followed a traditional public health approach. A mass screening programme has been introduced on a nationwide basis and procedures have been standardised to try to ensure quality and to maximise the efficiency of the system. The assumption has been that all eligible people should participate and efforts have been directed to maximise uptake. Within the traditional public health approach, communications from the healthcare system to the population or the individuals being invited for screening can be caricatured as: The disease is pretty horrific. The benefits of screening are X, Y and Z and basically screening can save you. The messages given about screening are very positive. People are told: When you come for screening, this is what we will do to you, dont worry about it. In terms of ensuring high quality procedures for a programme and wide uptake, this approach has been very effective. However it has also caused some problems. People have got the message that screening for cancer is a good thing, but they have also developed unrealistic expectations about what it can deliver, and the limitations of screening are generally not very well known. The fact that there are false negatives and false positives in any screening programme is not striking home. Thus people who receive false negative or false positive results are unprepared for them and some of these inevitable events get reported in the media as disasters that should not have happened. This can dent public confidence in screening programmes. For these and other reasons, the National Screening Committee became interested in adopting a slightly different approach to communication between the screening programme and potential participants. Within the informed individual choice approach, as in the traditional public health approach, a mass screening programme is organised for the whole population and procedures are standardised to ensure
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quality. Within the informed individual choice approach, however, more emphasis is placed on the individualisation of decisions about screening. The idea is that all eligible people should be given an option and enabled to participate. Efforts are directed to promoting informed choice about the screening process and to ensuring that people understand the issues relating to screening so they can make a more active contribution to their own decision about whether they participate or not. Within the informed individual choice approach, communication from the healthcare system would still explain that this disease is horrific, and point out the benefits of screening. However, it would also explain the limitations of screening. It would probably explain what procedures are involved in screening, but perhaps in a sentence that invites a person to be screened rather than assumes that they will. The general message would be that you are now eligible for screening and you are being given this information to help you to think about it. The information provided would be geared to help the individual make up his or her mind. The informed individual choice approach places demands on individuals and on health care providers. It requires everyone to think for him or herself, regardless of what decision has been made about whether this screening programme is good for the population as a whole. It asks health service users to appreciate the limitations of screening programmes, to grapple with population averages and to apply their own values to those. It asks people to think about their understanding of and attitudes towards the disease, the screening tests and the treatment. It asks people to consider, for example, If I had the screening test, what would I do if I got a positive result? Would I want to go on to the diagnostics? If I was offered these treatment options what would I do? It requires people to be able to discuss their values and negotiate their own decisions with healthcare professionals, which a lot of people do not feel very able to do. The informed individual choice approach also places demands on the healthcare system and on healthcare professionals. It requires them to provide information and support for individuals facing their own decisions. It requires that people are given time to consider their options. It requires health care professionals to accept that people might make choices that they disagree with. Although the national breast screening programme has officially adopted a more informed choice type of approach, some of the health professionals who deliver this service are uncomfortable when a woman makes a decision that screening is not for her. Are these efforts and discomforts worthwhile? If we are committed to respecting peoples autonomy and to ensuring that decisions about health care are well informed and reflect the personal values and preferences of individuals, then we have to say that they are. The question of whether, if a national screening programme were introduced for oral cancer, communication about it should follow a traditional public health or an informed choice approach is at present difficult to answer. However some of the issues relating to informed individual choice in screening apply to informed individual choice in all sorts of treatment and diagnostic decision making. The general question of how health care professionals should be working with patients to help them make decisions about healthcare interventions is one that can be asked about all aspects of care relating to oral cancer. In conclusion, I suggest that a screening programme for oral cancer might, but would not necessarily, be a good thing. Research evidence relating to a range of questions will need to be carefully considered before that judgement can be made.
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SESSION3: F OLLOW U P AND REHABILITATION

Chair Professor T W MacFarlane, FRSE Formerly Glasgow Dental Hospital and School University of Glasgow The Patients Perspective__________ Mr Michael Walton, The Ben Walton Trust, West Linton My only qualification for standing here today is that our son Ben died from oral cancer five years ago. Are things different now? I think, in terms of what we are hearing today, that things are improving on certain levels. One of my concerns and one of the things I am going to talk about today is considering the emotional context and needs of the patient. After our son died, we decided to set up the Ben Walton Trust, really as a response to the way he had tackled the disease and faced up to it within the period of the year that he survived from his first diagnosis. He was very insistent that something must be done and that people should be shocked that first, individuals can contract a disease which is so little known and second, at what the disease can do in a short space of time if not rapidly treated. The Trust, which was set up in his name, has a particular interest in why oral cancer occurs in the under 45s. My views have not changed since my initial response, that a lot needs to be done to improve the current situation. My feeling is that increased public awareness is a key issue which would pay dividends. Also rapid detection, referral, diagnosis and treatment are necessary if improved outcomes are to be achieved. It is gratifying now, five years later, to see events like todays workshop and many new initiatives that have taken place in Scotland and elsewhere. We are at last moving towards raising the profile of this disease. What I have to offer you is a personal story and our response and reaction to it, which might be thought provoking. I want to tell you a little about Bens journey. Ben was healthy, reasonably fit, did not smoke, drank moderately and had excellent oral hygiene so he did not fit the normal stereotype for an oral cancer patient. He had earlier, however, experienced two bad bouts of glandular fever. At one point, two years prior to his illness, he had a mouth ulcer large enough for the GP to measure it. That subsequently disappeared entirely. When the tumour presented it was in the same site. He was studying honours psychology at the time of his illness. He took a year out and then returned for the final term. He was an accomplished pianist and trombone player. He loved singing and had a great sense of humour. His sense of humour, I think, served him very well throughout the disease. Today, no one has directly said, but some have alluded to, what an awful disease oral cancer is. It is a sort of minefield where it is very easy to lose ones direction along the way. Ben was amazed and horrified that something that starts potentially so innocuously can go on and kill within a year. In addition, the process and the potential compromise to quality of life can be enormous and the nature of the death can be very traumatic. Elsewhere I have described this disease as medieval, and I think that is an appropriate term. Ben chose not to have surgery as it would not cure but it would reduce his ability to communicate. He wanted to be able to talk and sing as long as possible, which he did. He did have some radiotherapy and a little chemotherapy and a great deal of emotional support. In retrospect, he was probably a classic case of late referral. His GP had seen him over a period of time but it took a while to refer him, about ten to twelve weeks. His pathway was probably, as for many oral cancer patients, one of ups and downs, improvements, periods of relative normality, periods of never being free from pain and, finally, death. I would like to look initially at some of the critical problems with this particular disease. There is poor public and professional knowledge, with a lot of blame around oral cancer: too much drinking, too much smoking, perhaps cannabis and recently, I have heard, oral sex. Thus, an individual
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getting the disease starts with a great disadvantage, although many that have it do none of these things or not all of them. Conversely, many people who do indulge heavily do not succumb to oral cancer. In Bens case, because he had a compromised immune system in the hospital he first attended, they thought he had AIDS. This caused great consternation to him and his girlfriend but it meant that due to patient confidentiality his family could not find out what was going on. The only way that we discovered that there was something very seriously wrong, was when I asked the nurse whether we should stay over the weekend for his first clinic, and the nurse burst into tears. In relation to public knowledge of this disease, a paper published in the British Dental Journal in 1999 reported a study of 2000 UK adults. Of these 2000, 96% had heard of lung cancer, 86% of cervical cancer and only 56% of oral cancer. Interestingly, the knowledge of oral cancer was highest in areas where incidence was low. In a recent study in the West of Scotland, carried out in 2001, 1000 individuals were questioned and only 6% were spontaneously aware of oral cancer. We can easily begin to see why delay in referral can occur. With regard to professional awareness, the real problem for general medical practitioners is that they may see very few cases in their working lifetimes or perhaps are less well equipped to examine the mouth than dentists, yet there is a patient charge to see a dentist. During oral cancer awareness week this year, 100 regional and national newspapers covered the subject, 22 dental magazines and only 2 medical publications, one of which was the BMJ. No single profession detects, diagnoses and treats oral cancer, hence the importance of a team approach. However, the difficulty is that all those people involved in the team have different remits, different involvement and there has not been a single profession that has actually argued the case for the disease. I feel that there is a need for a very clear message to the public about what the signs are for this disease, who to refer to and when. But before that, there is a need for clear professional agreement over the ownership of the disease and what part each profession plays. Communication is never particularly easy and is an important issue in the context of oral cancer. Much depends on what the patient absorbs and whether they respond to verbal information, visual material, their emotional state at the time and the complexity of the information. It is also important to remember that the average reading age in the UK is equivalent to an 810 year old. So one must be very clear, very honest, very direct and tailor much to individual needs, always being supportive. How does the patient feel at diagnosis? Well, things have changed for them in their world, things are beginning to shift and fall apart, they may be disorientated, they may be shocked. Their perception of the world may be changed forever. What is commonplace to most of those who have spoken at todays workshop is very unfamiliar territory to most patients. We know that there is not only a high mortality rate but there is also high morbidity. Isolation and withdrawal can occur and oral cancer patients are statistically seven times more likely to commit suicide than other cancer patients. Because of frequent communication difficulties that patients experience, they tend not to join groups such as those for patients with breast cancer. Additionally, as most oral cancers and their treatments vary greatly from patient to patient, it is not easy for them to interchange accurate information in terms of treatment or how their tumour might progress. So what do patients want? An honest diagnosis, kindly and compassionately delivered. They need providers who listen, direct answers to questions and also to participate in decision making regarding all aspects of treatment. Two other major factors are first, to hopefully get better or to fully understand their future and second, quality of life, which has been touched upon today. Quality of life can become the single most important factor to a patient for whom only palliative care is appropriate. How can they function most effectively and get the best possible out of life, depending on their individual circumstances? I want to mention diet in relation to Bens case. In the hospice, which was excellent in many ways, his dietary needs were not understood. He survived initially on spaghetti hoops for about three days and never had enough liquid. The frustration and anger that this caused at a critical time for him was real. You also find with oral cancer patients that eating out becomes an interesting activity. Although not disfigured by surgery, Ben had great difficulty swallowing and he had to have everything liquidized. For an evening out, I had arranged with a restaurant, via a personal conversation with the manager, that all the food had to be liquidized. We arrived on the evening with Ben on one of his
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first social occasions out and he was looking forward to it. We were then told that we do not do things like that here. For Ben it was a difficult moment. Some simple things that can help patients enormously are often things that do not cost very much but can make a real difference, particularly someone showing that they care. It does not matter who it is in the process, but it needs to be done. It may seem to be unprofessional to some, but for the patient it is critical an arm around a shoulder, hugging and expressing emotion can make the patient feel cared for. One such instance I can give from our own experience happened just after Ben had received the news that his situation was terminal and that he was not going to recover. Spontaneously, as a group, several young nurses came together, they hugged him and they wept and he wept. He came away and said that was one of the most important things that happened to him because it showed that people really did care and that was important. This was a contrast to the attention of the hospice, where although there was excellent care with nurses trained in palliative care, there was no emotion. There was no sense that this person does feel and does care about the patient. It may be about simple things like moving a bed into a ward so that a patients partner or relative can be close at critical times. It may be massage, reflexology, prayer, meditation and visualisation, anything that relaxes or encourages a positive mental attitude. This has the The Speech Therapists Role__________ Mrs Mary S. Jackson, Senior Speech & Language Therapist, Canniesburn Hospital, Glasgow The complexity of oral cancer requires multidisciplinary management. The importance of the Speech and Language Therapist in the team is recognised by our governing body and is included in the consensus document for Effective Head and Neck Cancer Management. The defined role of the speech therapist involved in the care of oral cancer patients is to assess, diagnose and treat the speech and/or swallowing problems caused by the disease itself or treatment of the disease. Counselling, or perhaps more accurately, the listening skills of the therapist, should also be included in this role. If the ability to communicate effectively is compromised, the patient needs time and help to deal with the loss of function and his/her perceived
27
potential to actually help the immune system. It now has the grand title of psychoneuroimmunology and has produced some interesting and positive results in breast cancer patients. We felt that there were certain things that happened on our pathway that really did help. We were fortunate in having, at that time, the only non-medical fully trained counsellor in Scotland working with oral cancer patients. This meant that not only did we have a translator at consultations but also we were encouraged to write things down, to ask questions and to come away with the answers to them. This allowed us to have both practical and emotional support when we needed it. We had someone to encourage us so that we could make informed decisions and come away feeling that we had done the best we could and perhaps most importantly it helped our morale. We came away sure that generally we understood the future and importantly that the team that looked after us showed us that they cared and were doing everything in their power to get the best result under poor circumstances. They ensured that they were there for us through the good and bad. We never felt excluded or abandoned, even when all their useful treatment was exhausted, and for what more can one ask? To sum up, increased public awareness, sustained professional development and rapid detection, fast track referral to a centre of excellence for diagnosing and treating oral cancer, will save lives.
change of role within the family and society. Although survival, disease-free interval and symptom-free period are the prime concern of patients, the quality of life and functional implications should be carefully considered prior to treatment. Pre-treatment contact with the patient and family enables the therapist to establish a speech profile and to discuss post-treatment outcomes. Although the exact details of the functional effects generally cannot be provided pre-operatively, the focus is on informing the patient that there are likely to be changes in speech and swallowing. The patient can be reassured that although intelligibility may be compromised, he will be able to speak.

Pre-treatment assessment should include an examination of the oral cavity, movements of the articulators and dental status. Speech intelligibility should be assessed and any preexisting articulation problems or voice abnormalities noted. An informal or bedside swallowing assessment should be carried out and videofluroscopy if clinically appropriate. Swallowing can be effectively assessed objectively in a number of ways, the gold standard being videofluroscopy. Jeri Logemann has researched this extensively in the United States. The modified barium swallow is designed to assess not only whether the patient is aspirating but also the reason for the aspiration so that appropriate treatment can be initiated. Scoring systems for assessing function can be quick and easy to use. The Functional Intraoral Glasgow Scale (FIGS) was developed at Canniesburn and has been in use for a number of years. This is a 5-point ordinal scale for assessing speech, going from 5 (fully intelligible) to 1 (completely unintelligible), chewing, 5 (having no difficulty) to 1 (unable to chew at all) and swallowing 5 (normal swallow) to 1 (has or should have nasogastric or PEG feeding). FIGS has shown statistically significant reliability between assessors but is, as yet, unpublished. Enderbys Therapy Outcome Measures is also a 5-point scale assessing disability and handicap in addition to impairment and these measures have been standardised. There is, however, a lack of objective assessment for speech. Many objective speech assessments are actually based on subjective assessments by either trained or untrained listeners. Computer analysis should provide a consistent and objective appraisal of segmental speech quality related to function. A personal computer-based workstation that provides an objective and quantitative method for characterising the speech of oral cancer patients has been developed at Canniesburn. The system applies signal-processing techniques that can automatically analyse selected acoustic phonetic features and provide consistent measurements. The application of spectral analysis algorithms maps the speech of each patient into a universal feature space. The speech distance metrics are tolerant of patient-specific characteristics such as vocal tract size, but are sensitive to the position and movement of the articulators. Pre-treatment, each patient who is enrolled in the study records six sentences, one of which is dense in fricative segments. The others contain a range of potentially problematic sounds. By selecting each sentence in turn the therapist is presented with a waveform, spectrogram and a voiced/unvoiced decision chart, all calculated in real time. The fricative analysis is automated so that all voiced frames are rejected. Analysing six pre-treatment segments and storing their accumulated mean and convariance matrix determines the target. By repeating the procedure the metric is able to quantify the distance between each post-treatment speech segment and the patients own pretreatment target. At present the metric is limited to fricative segments i.e. s, sh and f. S is used for comparison, as accurate muscular co-ordination is required for this phoneme. The system has a number of advantages. It is non-invasive and less expensive than electro-palatography. It is non-demanding, unlike conventional assessments that can be time-consuming. The patient acts as his own control. Patient reaction has been favourable being able to chart his/her progress and having visual feedback is beneficial. The programme can also identify subtle changes in speech that may be an early indication of recurrent disease. Indirect therapy and speech rehabilitation can start almost immediately with gentle exercises to maximise range of movement, but care needs to be taken to avoid tension following surgical reconstruction. Compensatory tongue positions may need to be taught to achieve the closest possible approximation for consonants. Although the ability to maintain intelligible speech is important to post-operative quality of life, the inability to swallow must be devastating. Support is essential and the successful first swallow attempts under the direction of an experienced therapist can make all the difference to the patients progress and to his confidence. The type and severity of swallowing problems experienced by the patient depends on the structures removed and extent of the excision. It has been reported that in general one half to one third of the mobile tongue can be removed without serious swallowing disability. Slow healing and oro-cutaneous fistulae can result in delay in starting orally. Reduced oral control with delayed oral transit times means the patient may take a long time to eat a meal. Drooling may occur if the tongue is swollen
28

or if there has been a lip split for access. Nasal leakage or regurgitation can be very unpleasant for the patient especially following palatal resections. Food can be lost to the sides or over the base of the tongue. There can be delay or difficulty initiating the swallow and possibly aspiration. During swallowing rehabilitation adequate analgesia is most important. If a patient anticipates that the swallow is going to be painful he will be more likely to delay swallowing with increased potential for aspiration. Postural changes or different swallowing techniques may be suggested. Small sips of clear fluid are normally given first, but following some resections a larger bolus may be needed to trigger the swallow. Liquid may always be needed to propel the bolus backwards. Eating is slow. Swallowing is no longer automatic and attention may always be necessary to avoid aspiration. Although our aim is to encourage patients to progress to soft diet prior to the start of radiotherapy, this treatment usually results in further problems. Xerostomia, mucositis and pain from inflamed tissues can result in the patient reverting to fluid diet only. In some cases tube feeding may be re-introduced. Loss of taste and xerostomia take time to resolve. Some patients simply give up and nutritional intake may be grossly inadequate for weight maintenance. In an attempt to minimise the devastating effects of surgery for advanced tongue cancer, organ preservation or brachytherapy may be the preferred option. In a small study carried out at Canniesburn Hospital, speech results were found to be better following brachytherapy, but swallowing disability was slightly greater. Weight loss was more than double that following surgery and external beam radiotherapy. Rehabilitation can be complex and time consuming as it takes time to adapt to the altered oral anatomy and to become comfortable and confident with the resultant speech patterns. Quality of life is often referred to when discussing treatments for oral cancer. We need to remember that it is the patient and his familys perceived level of disability that is important. The involvement of the Speech Therapist in the multi-disciplinary team is essential to maximise functional recovery.
Palliative Care for Head and Neck Cancer___________________ Dr Hugh MacDougall, Consultant Clinical Oncologist, The Edinburgh Cancer Centre, Western General Hospital, Edinburgh What is palliative care in head and neck cancer? There is a speciality called palliative care and it is a very important one, but palliative care is a generality for all care in this field. It is often thought to be about relief of pain and suffering and, particularly, the holistic approach to death and dying espoused by the hospice movement over the last decades. As opposed to that view, there is another concept, which arose at the Christie Hospital, Manchester, in the 1930s and 40s where Ralston Patterson worked. He developed the simple but important concept of the decision as to whether to treat patients in a palliative sense or in a radical sense. He had a fairly straightforward and clear feeling that he could assess a patient. If the patient had a curable tumour they were appropriate for radical treatment with surgery or radiotherapy. If they did not have a curable tumour they were appropriate only for palliative treatment and palliative treatment was only appropriate if the patients had symptoms. In other words,
29
there was a group of patients who were relatively asymptomatic who did not need to be treated. Nowadays, we think about skilled symptom control, the appropriate supportive nurse, social and pastoral support and the quote which comes from Cicely Saunders to enable the patient to live until they die. Head and neck cancer accounts for 2% of cancers in the UK, but is very common in the Third World. Both there and here, advanced disease is very common. The clinical problems reflect the anatomical importance of the structures affected. There is a critical interface of the air passages, the food passages and the vital senses. Head and neck cancers are heterogeneous anatomically and histologically and are not one subject. Palliative therapy in head and neck cancer has not been subject to systematic analysis, but the sorts of symptoms that cause problems reflect the pathophysiology. The obstructive symptoms are associated with the obstruction of the airways and food passages. Haemorrhage is

common in very advanced cases, and the erosion of the carotid artery with carotid artery blow-out can be particularly devastating. Fistulae may form, pharyngocutaneous fistula being the most common. Loss of sensory functions, vision, smell, taste and hearing, all essential components in terms of communication, may occur. Communication may not only be directly physical - there may be psychological barriers to communication in these patients. They may feel uncomfortable about relating to other people because of the physical appearance of their cancers. In terms of investigating the patient with advanced cancer of the head and neck, diagnostic imaging, CT scanning and MRI are important and can often differentiate the operable from the inoperable. Endoscopy and assessment of swallowing are also valuable adjuncts. The illnesses of two American presidents illustrate two extremes in the management of head and neck cancer. General Ulysses S. Grant, hero of the Civil War was found, in October 1884, to have a squamous carcinoma of the tonsil. His doctors decided that his disease was fatal and that all they could do was to relieve the suffering. Opiates and cocaine were prescribed. In his lucid moments the general dictated his memoirs, the income from which would be essential for the financial security of his family. In one sitting alone he dictated 10,000 words. When they were eventually published his memoirs earned his widow $500,000. General Grant died on the morning of 23rd July 1885. In 1893, President Grover Cleveland was found to have a carcinoma of the maxilla. On 1st July in secret, on a yacht sailing slowly off the coast, surgeons performed a partial maxillectomy. A second operation followed twelve days later and a rubber prosthesis was constructed. On 7th August the president was able to give a reassuring speech to congress on the state of the economy. No one suspected that he had recently had surgery for cancer. Grover Cleveland died in 1917 of heart disease. The treatment of Sigmund Freud exemplifies a clinical course intermediate between the strictly palliative care for Grant and the successful cure enjoyed by Cleveland. Freud was first found to have a carcinoma of the palate in 1923. This was treated initially by surgery. He had further operations in 1931 and 1938 and had radium treatment in 1936 and in 1939. On 23rd September 1939 Freud died with uncontrolled carcinoma fungating through his cheek.
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It would be comforting to think that management of head and neck cancer had moved forward greatly since those days of Grant, Cleveland and Freud. Techniques may have improved, and local control rates may have advanced a little, but our decision-making often remains subjective. The decision on whether to treat is crucial in terms of the advanced care of cancer. On many occasions, such decisions are not made for good scientific or clinical reasons and there is little in the literature about this subject. We know that fewer than 40% of oral cancer patients survive in advanced disease and 50% die of local disease progression. Some of the major complaints are pain, dysphagia, airway obstruction, fungating wounds, nausea, vomiting and mucosal dryness. What are the treatment options? Multidisciplinary assessment is vital, even in the advanced cases where palliative treatment is appropriate. It is an easy decision to actively treat and a very difficult decision not to treat. It is still too common to be presented with a patient who has been told by a surgeon outside the unit that he/ she is going to be treated with a course of radiotherapy, when it is probably not in the patients best interest. That makes a decision not to treat even more problematic. In relation to interventions, pain control is becoming more sophisticated. Xerostomia, and associated candidal infections, can be managed medically. Managing speech and communication disorders is an important aspect of palliative treatment. For the treatment of swallowing disorders, the assistance of speech therapists is important. Increasing numbers of patients are being fed by gastric tubes, which is probably appropriate, but there is a little explicit thinking about whether to feed the patient or not to feed the patient. These issues need to be faced up to in terms of explicit decision-making. Radiotherapy does not have a vast role in the palliative treatment itself. Surgery may have a role in many cases in advanced cancer. Photo-dynamic therapy is said to have a role, but current data are inconclusive. On occasion, laser or cryotherapy can help to keep the patient more comfortable than no treatment. In conclusion, palliative care is a significant challenge in head and neck cancer. There are no clear-cut rules and guidelines and lack of good studies. There is, too often, dependence on the experience of clinicians and that can be systematically flawed. It remains unclear to me whether we have made progress since Grover Cleveland, Ulysses Grant and Sigmund Freud.

Restorative Dentistry in Head and Neck Oncology__________ Mr Arshad Ali, Consultant / Honorary Clinical Senior Lecturer in Restorative Dentistry, Glasgow Dental Hospital and School Treatment of head and neck cancer involves surgery, radiotherapy, chemotherapy or combinations of the above. There is no doubt that the main treatment objective has to be elimination of disease, but restoration of function and aesthetics are also important. A number of reports by expert groups have stated clearly that all patients should have access to a uniformly high quality of care wherever they may live, and expect maximum cure rates and best quality of life. The head and neck cancer team, as defined by the British Association of Head and Neck Oncologists, is extensive. The dental input is important, not only from the general dental practitioner and restorative dentist but also the dental hygienist and the maxillofacial technologist. Clinical guidelines on the oral management of oncology patients have been produced by the Faculty of Dental Surgery of the Royal College of Surgeons of England. The guidelines suggest that there should be pre-treatment dental assessment for these patients, that dental staff should see them during the acute phase of cancer therapy and guidelines are provided on restorative dental care. Every relevant oncology protocol should include an early pre-treatment oral assessment. In a study of 49 patients at the Beatson Oncology Centre, 16 patients had no general dental practitioner; 20 of those patients were dentate; a number of the patients required pre-therapy treatment, but for various reasons only two of them received this treatment. Unfortunately, this is not unusual in cancer centres world-wide. With regard to extractions prior to cancer therapy, teeth in direct association with the tumour or teeth with dubious prognosis have to be extracted. The site of the lesion is important, dependent on whether radiotherapy is going to involve mandible or the major salivary glands. It should also be remembered that many of our patients are not very well motivated, and in such cases, keeping teeth can cause major problems in the postoperative period. Following radiotherapy to the head and neck, there will often be a reduced salivary flow and an increase in cariogenic organisms. Cervical carious lesions can develop soon after treatment. Dietary advice is important together with use of chlorhexidine and fluoride. Again, achieving co-operation can be very difficult with some of these patients.
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In relation to periodontal disease, very often after surgery there will be an altered oral anatomy, which may result in difficult access for oral hygiene. There is a reduced vascularity and an impaired capacity of the supporting tissues to re-model and repair following radiotherapy. The reduced salivary flow will also increase plaque accumulation. Osteoradionecrosis of the mandible may arise from sites of periodontal disease. Clearly, pre-treatment assessment is extremely important to try to avoid these situations arising. Another major problem in regard to restorative dentistry is trismus, which is often seen postoperatively and post radiotherapy. This may be reduced by use of jaw exercises at an early stage after treatment, using either patients fingers, tongue spatula or a trismus screw. Osteoradionecrosis can be a real problem in these cases. There are different guidelines as to when teeth should be extracted. The optimal period would be about three weeks prior to radiotherapy. Ill-fitting prostheses after radiotherapy can also cause osteoradionecrosis. In one study of osteoradionecrosis, 23 out of 78 episodes affecting the mandible required fairly radical resection. With regard to rehabilitation, one has to consider all of the functions, namely mastication, speech, swallowing, and control of saliva and respiratory secretions. In some cases there will be cosmetic disfigurement and we also have to consider the psychological rehabilitation. In relation to the maxilla (Figs. 12a-c), there are some surgical aspects which will help in the prosthodontic rehabilitation: retaining as
Figure 12a. Exophytic carcinoma of the mandible

issue. Do we wait for a year or two or do we put the implants in early so that patients get maximum benefit from them? For mandibular defects implants can be placed in the anterior mandible, which has the highest success rate, or in posterior mandible or bone-grafted sites. There must be an optimal design of prosthesis over the implants. The role of the technician to assist and provide optimal rehabilitation must be emphasised. Similarly the role of the hygienist and the long-term maintenance are also crucial. Dental implants can also help with rehabilitation for maxillary defects. The anterior maxilla has the highest success rate (Figs. 13a-c). If implants are to be placed further back, then it may be necessary to
Figure 12b. Modifications at surgery can help prostho-denture rehabilitation
much of the hard palate as possible, retaining key teeth, using the palatal mucosa to cover the margins of the resection and skin grafting the cheek flap. A skin graft provides more flexibility of the cheek flap, it helps to retain the obturator and it is not as sensitive as respiratory mucosa. With regard to the mandible, there are certain factors which aid prosthodontic rehabilitation. These include mandibular continuity and retention of some teeth. Tongue function is very much better now with the modern surgical techniques involving flaps such as the radial forearm flap. Ridge and soft tissue contours are important and implants will be discussed later.
Figure 13a. Extensive maxillary defect with associated functional problems
consider bone grafting. Other implants can be placed in the tuberosity, pterygoid plates and the zygomatic arch. Success rates with implants are higher in non-irradiated patients. It may be necessary to consider the use of hyperbaric oxygen in patients who have had radiotherapy to the jaws.
Figure 12c. Good function with obturator in place
The Royal College of Surgeons of England has produced guidelines for selecting cases suitable for osseointegrated implants. There are difficulties with funding, but one of the priorities for implants within the NHS is for patients requiring replacements of hard and soft tissues. In the main, implants have been used where conventional treatment has been unsuccessful, but where there is sufficient bone and adequate access for implant placement. Patients must also be motivated. Timing of placement is also an
Figure 13b. Implant-retained obturator in place
The other major area for implant use is extraoral rehabilitation. Implants are used now to
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Excellence. The NICE guideline for head and neck cancer is currently out for peer review. It indicates that multidisciplinary teams are to meet weekly to discuss new and follow-up patients. The teams should be based at the same hospital site. They should include a restorative dentist with an interest in head and neck cancer, heading a team involving PCDs, and all patients will need to be seen by the dental staff pre-operatively. If these guidelines are to be implemented, there will need to be major changes in the way we work and the way we approach these cases. Such changes will need to be funded, which may require dis-investment in some other areas of current activity. Teamwork is the key patients with oral cancer cannot be managed in isolation. We must work closely together as an interdisciplinary team to provide optimal care for patients with oral cancer.
Figure 13c. Good post-implant function
rehabilitate patients with ear, nose and eye defects (Figs. 14a-b). Before the advent of implants, adhesives were used to retain these extra-oral prostheses. National guidelines are being produced for treatment of cancers. This is under the auspices of the National Institute of Clinical
Figure 14a. Traumatic loss of the left ear
Figure14b. Rehabilitation with an implant-retained prosthesis

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SUMMARY OF CONCLUSIONS
The mortality in Scotland for oral cancer is rising at an alarming rate The disease is not static and is changing for the worse Despite advances in medicine and science, there has been no improvement in survival across Scotland as a whole Early disease can be successfully treated but there remains a high proportion of cases presenting with advanced disease Clinical diagnosis can be difficult Routine examination of the oral cavity during physical examination should be encouraged, looking for colour changes, swelling and persistent ulceration Suspicious or persistent lesions should be biopsied There is a need for education in oral examination techniques and clinical features of oral cancer for a variety of healthcare professionals working in primary care Oral cancer patients have varying needs and require adequate support and information to ensure optimum quality of life Specialist teams are required to provide complete care for oral cancer patients
Rapid access in to the care system for diagnosis, investigation and treatment of oral cancer is required Equity of access can be provided by regionalisation of oral cancer services and by the establishment of managed clinical networks Improvements in outcomes (both survival and quality of life) can most dramatically be affected by ensuring early presentation and rapid access to dedicated head and neck cancer multi-disciplinary teams Such teams are complex involving many health care professionals involved in the diagnosis and assessment, treatment planning, rehabilitation, palliation, and communication Multidisciplinary teams require adequate resourcing Novel therapies in the treatment of oral cancer are in their infancy and are unlikely to impact on the disease for many years Increased public awareness should ensure earlier presentation Widespread use of screening programmes for oral cancer requires further investigation
Increased public awareness, sustained professional development, rapid detection, and fast track referral to a centre of excellence for diagnosing and treating oral cancer will save lives
35
SUMMARY OF MAIN ISSUES RAISED IN WORKSHOPS
Delegates considered two questions. WHY IS LATE PRESENTATION OF ORAL CANCER A CONTINUING PROBLEM? PUBLIC AWARENESS Ignorance of the problem among members of the general public Patients with no recognized risk factors Lack of knowledge about potential for treatment POSSIBLE SOLUTIONS . . . Enhanced publicity, including television activity e.g. Eastenders Need to consider carefully the key messages for publicity Consider deprivation, culture and attitudes PATIENT PATHWAYS Much depends on the patients first port of call Delays within the system if the patient does not enter the correct pathway Lack of equity of service provision POSSIBLE SOLUTIONS . Service re-design with rapid access clinics fast track referral . Regionalisation of oral cancer care in specialist centres . Establishing managed clinical networks EDUCATION Lack of public knowledge and awareness Variability of facilities for examination and investigation Variable expertise among medical and dental practitioners and other healthcare professionals POSSIBLE SOLUTIONS . Increase public awareness and education . Increase funding for primary care education . Improve access for adequate examination and investigation . Develop defined patient pathways
CLINICAL DETECTION . The cohorts of patients most at risk of oral cancer are more likely to be irregular dental attenders Oral cancer is often symptomless in its early stages and diagnosis can be difficult Older patients attend for dental care less often than the young Fear and anxiety surrounding dental attendance Costs of attendance for dental examinations and treatment POSSIBLE SOLUTIONS . . . Free dental examination for patients at risk Targeted screening of patients at risk Opportunistic screening of patients undergoing clinical or dental examination
37

WHAT ARE THE PRIORITIES FOR CHANGE IN PROVISION OF ORAL CANCER SERVICES, IF PATIENTS ARE TO RECEIVE SEAMLESS, HIGH QUALITY CARE AT ALL STAGES OF THEIR DISEASE? THE PATIENTS JOURNEY Often slow and unpredictable Variable treatment options dependent on path of referral Poor understanding of oral cancer Lack of systematic research to support differing treatment options POSSIBLE SOLUTIONS . Re-design care system with clearly defined patient pathway . Develop rapid access clinics for diagnosis and investigation . Regionalise oral cancer care to specialist centres and managed clinical networks . Develop protocol driven treatment plans . Invest in audit to improve clinical effectiveness of treatment FUNDING Lack of a co-ordinated approach to oral cancer Variability for examination and investigation, particularly imaging POSSIBLE SOLUTIONS Significant funding is required to target: . Service redesign for oral cancer . Access to imaging and other diagnostic facilities . . . . . Re-organisation into specialist centres and managed clinical networks Primary care education Public education awareness, prevention and screening Systematic research and audit Clinical effectiveness of treatment
LACK OF PUBLIC AND PROFESSIONAL AWARENESS Poor public perception of oral cancer Variable knowledge amongst health care professionals POSSIBLE SOLUTIONS . Public education campaign . Increase funding for primary care education . Encourage research, development of protocols and audit
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ACKNOWLEDGEMENTS Pfizer Ltd and CellPath are thanked for their support of this Oral Health Workshop. Mr Ray Watkins, Chief Dental Officer for Scotland, kindly provided financial assistance with the production costs for the published proceedings of the Workshop, as did NHS Education for Scotland. The expert secretarial assistance of Mrs Joanna McGrory is gratefully acknowledged.
Printed and Bound by Mackay & Inglis Limited, 19 Polmadie Street, Glasgow, G42 0PQ Layout by Jennifer Cameron, RSE
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Oral Health Workshop 25 January 2002
The
For further information, please contact: The Royal Society of Edinburgh 22-26 George Street Edinburgh, EH2 2PQ Tel 0131 240 5000 Fax 0131 240 5024 e-mail oralhealth@royalsoced.org.uk web www.royalsoced.org.uk 2003 The Royal Society of Edinburgh. ISBN 0 902198 63 7

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ORAL HEALTH GROUP THE ORAL HEALTH GROUP

The A-Z of Oral Cancer An Holistic Route

Royal Society of Edinburgh

Royal Society of Edinburgh

The Royal Society of Edinburgh 22-26 George Street EDINBURGH

The A to Z of Oral Cancer : An Holistic Route

INTRODUCTION TO THE WORKSHOP

The A to Z of Oral Cancer : An Holistic Route

SESSION1: E PIDEMIOLOGY, DIAGNOSIS AND CURRENT TREATMENT

Oral Health Workshop - 25 January 2002

Figure 1. Trends in relative survival from oral cancer for Scotland

The A-Z of Oral Cancer : An Holistic Route

Figure 3. Oral squamous cell carcinoma

Oral Health Workshop - 25 January 2002

The A-Z of Oral Cancer : An Holistic Route

Survival 100 80 % survival 60 40 20 0 1 Least deprived 2 3

Cases diagnosed in 1994 and 1995 do not

incidence/mortality per 100 000

Oral Health Workshop - 25 January 2002

The A-Z of Oral Cancer : An Holistic Route

Oral Health Workshop - 25 January 2002

The A-Z of Oral Cancer : An Holistic Route

Oral Health Workshop - 25 January 2002

The A-Z of Oral Cancer : An Holistic Route

SESSION 2 : N OVEL TREATMENTS AND SCREENING

Oral Health Workshop - 25 January 2002

Adenoviral vector p53 transgene

Unresectable HNSCC Mutant p53

Figure 10a. Gene Replacement Therapy

Autologous tumour cells

Rb loss p53 loss p16 loss

Transfect IL-2 in-vitro

Tumour suppressor genes Cancer

Figure 10b. Immunotherapy

Figure 9. Cyclin D in oral cancer

Adenoviral vector tk transgene

Tumour cells transfected with tk gene

Tumour killed selectively (nontransduced cells killed by bystander effect)

Figure 10c. Gene directed prodrug therapy

The A-Z of Oral Cancer : An Holistic Route

Oral Health Workshop - 25 January 2002

Ad2 infection of normal cell

virus infects cell Ad2 has E1B gene p5

virus produces 55k p53 55k

p5 normal cell has functional p53

55k inactivates p53

Onyx-015 infection of normal cell

virus infects cell Onyx-015 has no E1B gene p53

virus cannot produce 55k p5

p53 prevents viral replication

normal cell has functional p53

Onyx-015 infection of p53(-) cells

virus infects cell Onyx-015 has no E1B gene

virus can replicate

cancer cell cannot produce p53 cancer cell lacks p53

Figure 11. Selectively replicating oncolytic viral therapy

The A-Z of Oral Cancer : An Holistic Route

Oral Health Workshop - 25 January 2002

The A-Z of Oral Cancer : An Holistic Route

The A to Z of Oral Cancer : An Holistic Route

SESSION3: F OLLOW U P AND REHABILITATION

Oral Health Workshop - 25 January 2002

The A-Z of Oral Cancer : An Holistic Route

Oral Health Workshop - 25 January 2002