- Email: [email protected]
Effects of active non-smoking programmes on smoking behaviour in oral precancer patients
Int. J. Oral Maxillofac. Surg. 2007; 36: 706–711 doi:10.1016/j.ijom.2007.03.001, available online at http://www.sciencedirect.com
Clinical Paper Head and Neck Oncology
Effects of active non-smoking programmes on smoking behaviour in oral precancer patients
O. Hamadah, S. Hepburn, P. J. Thomson Oral & MaxilloFacial Surgery, School of Dental Sciences, University of Newcastle upon Tyne, UK
O. Hamadah, S. Hepburn, P. J. Thomson: Effects of active non-smoking programmes on smoking behaviour in oral precancer patients. Int. J. Oral Maxillofac. Surg. 2007; 36: 706–711. # 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Smoking is the commonest risk factor for oral cancer and precancer. The objective of this study was to characterize smoking behaviour and attitude in a cohort of oral precancer patients in Newcastle upon Tyne, UK, and to determine changes in behaviour during diagnosis, treatment and follow-up. Twenty-seven consecutive, smoking patients with dysplastic oral lesions were recruited to the study and a detailed smoking history obtained, quantifying types and numbers of cigarettes smoked, length of smoking history, and changes in smoking behaviour during treatment episodes and long-term follow-up. All patients underwent an interventional management protocol comprising risk-factor education, histopathological diagnosis by incisional biopsy and laser excision of lesions. Patients were followed up for 5 years. Whilst there was a significant decrease in the number of cigarettes smoked at patients’ most recent follow-up compared with initial presentation (p < 0.001), 74% continued to smoke. Patients received advice from a smoking cessation adviser on support available to them from the local NHS (National Health Service) Stop Smoking services. Six out of 10 patients who set a ‘quit date’ and attended a programme had quit at the 4-week follow-up but only 5 remained non-smokers. Smoking remains a considerable problem in oral precancer patients even after interventional treatment, with the risk of further precancerous lesions and malignant transformation.
Cigarette smoking remains the leading cause of preventable morbidity and mortality in the UK, and is well documented as a primary aetiological agent in head and neck cancer15,18. Oral squamous cell carcinoma (OSCC) occurs more frequently in smokers than non-smokers, and a dose– 0901-5027/080706 + 06 $30.00/0
response relationship is recognised between risk of cancer development and the amount and duration of tobacco use2,14. Oral precancerous lesions (OPLs), which are clinically recognisable antecedents of OSCC comprising leukoplakia, erythroplakia and erythroleukoplakia, and which
Key words: oral precancer; smoking; carbon monoxide interventional treatment. Accepted for publication 1 March 2007 Available online 19 April 2007
exhibit variable dysplastic change and unpredictable malignant transformation rates, have been shown to occur up to six times more frequently in smokers6. The type and amount of tobacco consumption affects the size, number and location of oral precancers7,22.Measuring proliferative
# 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Non-smoking programmes for oral precancer patients activity of head and neck squamous cell carcinoma (HNSCC) specimens, using Ki 67, showed an increase in labelling index (LI) in both smokers and ex-smokers compared with non-smokers. Interestingly, ex-smokers (both HNSCC patients and healthy individuals) manifested a trend towards increased proliferative activity which may indicate permanent smokingrelated biological alterations in oral epithelium28. It is also known that treatment efficacy, patient survival, risk of recurrence and vulnerability to second primary neoplasms are all adversely affected by continued smoking following OSCC diagnosis and management11,25. Smoking cessation advice and treatment are therefore of considerable importance in the overall care of head and neck cancer patients31. Patients who stop smoking decrease their increased risk for OSCC within 5–10 years15, whilst a significant proportion of OPLs will disappear or become smaller within the first year of smoking cessation8,31. The aims of this study were: (1) to characterize smoking behaviour in a cohort of oral precancer patients attending the Oncology/Dysplasia clinic at the MaxilloFacial Unit at Newcastle General Hospital, Newcastle upon Tyne, UK; (2) to determine changes in behaviour during diagnosis, treatment and follow-up; and (3) to explore the beneficial role of the smoking cessation advisor as part of an oral precancer multidisciplinary team. Methods
Following local ethical committee approval and informed patient consent, patients attending the MaxilloFacial Oncology/Dysplasia clinic for review following treatment for OPLs were invited to take part in the study. Inclusion criteria required a first presentation of a newly diagnosed OPL (confirmed as dysplastic
by incisional diagnostic biopsy), with no previous history of OSCC or any surgical or radiotherapy treatment. All patients underwent an identical management protocol, coordinated by the same clinician, comprising education and advice regarding risk factors, and interventional laser surgery excision of lesions. Regular patient follow-up with known clinical outcome for 5 years post diagnosis was required. Histopathological examination of excised lesions was carried out by experienced oral pathologists working to standardized criteria. Dysplasia was graded as mild (atypia confined to the basal third of epithelium), moderate (involving up to two thirds) or severe (greater than two thirds), whilst carcinoma-in-situ was characterized as severe tissue dysmaturation extending to an intact basement membrane. Following recording of individual demographic and clinico-pathological data, patients were asked to complete a questionnaire detailing their smoking habits covering pre-diagnosis, perioperative behaviour and most recent follow-up appointment. Retrospective review of clinical records was carried out to document patients’ recorded smoking behaviour at 6-monthly intervals during their follow-up. At the 5-year follow-up appointment, smoking status was confirmed by patient interview. In addition, following brief opportunistic advice given to patients by the clinician in accordance with national evidencebased guidelines, patients were offered subsequent advice from a smoking cessation advisor, who attended the clinic and provided immediate consultations (minimum of 10 min per patient). Both the patient’s motivation to quit and their nicotine dependence were assessed, and the structured behavioural support and medication, such as nicotine replacement ther-
707
apy (NRT) and Zyban, available through NHS Stop Smoking services were explained. Patients who requested close assistance were offered a 12-week Stop Smoking programme with the smoking cessation adviser, or referred to their local NHS Stop Smoking service if additional clinic attendance was inconvenient. The effectiveness of the use of NRT and Zyban was explained to patients who declined further assistance but appeared motivated to quit. At the smoking cessation clinic patients were seen by the advisor on a one-to-one basis. Typically, 1 or 2 ‘pre-quit’ sessions were followed by weekly sessions for 4 weeks after the ‘quit date’ with fortnightly sessions thereafter up to week 12. A patient was counted as a ‘self-reported 4 week quitter’ if they were assessed face to face or by telephone 4 weeks (minus 3 days or plus 14) after the designated quit date, and declared that they had not smoked even a single puff on a cigarette in the past 2 weeks. A smoker was counted as a ‘carbon monoxide (CO) verified 4 week quitter’ if they were a self-reported 4 week quitter and their expired air CO was assessed 4 weeks (minus 3 days or plus 14) after the designated quit date and found to be less than 10 parts per million. Telephone support was offered between sessions as necessary. Specific components of the cessation treatment programme9 are summarised in Table 1. Non-specific support and encouragement were also provided, and expired air CO readings measured to confirm abstinence (a reading <10 parts per million assuming abstinence). Non-parametric statistical analysis of results was carried out using x2 or Fisher’s exact test as appropriate. Pairedsample t-test was performed to investigate the difference in the number of cigarettes smoked during the follow-up intervals.
Table 1. One-to-one treatment programme summary Week 1 – preparation appointment Explain treatment programme Assess motivation to quit Explain nicotine withdrawal syndrome Assess level of tobacco dependence Measure carbon monoxide level in expired breath Discuss medications and arrange supply Set a quit date Advise on preparing to stop
Week 2 – quit day
Weeks 3 to 11 – post-quit sessions
Week 12 – end of treatment and relapse prevention
How client feels about quitting Discuss how the week went Medication use Measure carbon monoxide in Check for withdrawal discomfort Discuss potential relapse expired breath situations Discuss medication issues Measure carbon monoxide Advise on coping with potential relapse situations Explain importance of Check on medication use Discuss any ongoing support complete abstinence Advise on coping Discuss coming week Summarise
Summarise
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Hamadah et al.
Table 2. Site distribution of oral precancer lesions Oral precancer Lesion Sites
No.
%
Floor of mouth Buccal mucosa Ventral tongue Fauces Lateral tongue Buccal sulcus
14 6 3 2 1 1
51.9 22.2 11.1 7.0 3.7 3.7
Results Demographic and clinico-pathological data
Twenty-seven patients were recruited, 19 male and 8 female, with an age range of 31–76 years. Mean age of males and females was 52.7 (10.3) years and 60.2 (4.6) years, respectively. Overall, 70% of patients were greater than 50 years of age on presentation. The floor of mouth (39%) and the tongue (24.4%) were the commonest intraoral sites for OPLs (Table 2). Clinically, the majority of lesions were leukoplakias (63.4%), with erythroplakias (9.8%), erythroleukoplakias (22%), and exophytic lesions (4.9%) accounting for the rest. The most frequent histopathological diagnoses were moderate dysplasia (43.9%)
and carcinoma-in-situ (31.7%). Severe dysplasia was seen in 19.5% of cases with only 4.9% exhibiting mild dysplasia, reflecting the severity of disease in patients undergoing laser excision. Clinical outcome
Clinical outcome following laser surgery was determined as no recurrent disease (65.6% of patients), persistent disease (lesions recurring at the same site in 9.8%), further disease (development of dysplastic lesions at new intra-oral sites in 22.2%) or malignant transformation (2.4%). Smoking behaviour
At initial presentation, all patients were smokers and all reported regular alcohol consumption. Males were significantly heavier smokers than females (p < 0.001, Fig. 1). At the 5-year follow-up appointment a significant decrease in the number of cigarettes smoked per day was found compared with the number reported at initial presentation (p < 0.001). Fig. 2 illustrates smoking behaviour as recorded in patients’ clinical records over the follow-up period.
Fig. 1. Patients’ smoking behaviour according to gender distribution.
The percentage of patients who smoked fell from an initial presentation high of 100% to a low of 62% smoking at 36 months post treatment. Between 36 and 60 months postoperatively, there was an increase in smoking behaviour leading to a residual 74% of patients persistently smoking 5 years after laser surgery. Changes in smoking behaviour did not appear to influence clinical outcome in this group of patients (p = 0.28).
Smoking cessation
All patients in the study were seen by the smoking cessation adviser in the Oncology/Dysplasia Clinic. Twelve patients accepted the offer of a further appointment at the smoking cessation clinic, whilst 9 preferred referral to their local NHS Stop Smoking service. Three patients decided that they did not want formal assistance and would try to quit without behavioural support, with a further three not motivated to quit. Fig. 3 summarises patients’ adherence and attitude to smoking. Of the 12 who attended the smoking cessation clinic, most had a daily cigarette consumption of 20 and over. Ten patients agreed a ‘quit date’ and received NRT, with six successfully quitting at the 4week follow-up. For five patients nonsmoking status was confirmed by use of a CO monitor; the other patient who quit was followed up by telephone. At 5-year follow-up, only five of these patients remained non-smokers. Only one patient from the nine referred to local smoking cessation services was successful in quitting. Similarly, only one patient from the three who decided to quit independently managed to stop smoking. All three patients not motivated to stop smoking were still smoking at 5-year follow-up, resulting in a total of only seven patients (26%) who successfully quit. Discussion
Fig. 2. Changes in smoking behaviour of oral precancer patients through follow-up intervals.
The third National Health and Nutrition Examination Survey (NHANES III), investigated clinical risk factors for oral leukoplakia in a representative sample of the US population. Smoking was the most independent risk factor in oral leukoplakia. This damaging role of smoking was not affected by the alcohol consumption status of the participants5. The management of risk factors in OPL patients remains poorly documented, as does the treatment of OPLs where there is little evidence base and no agreed management protocols19, although the efficacy of inter-
Non-smoking programmes for oral precancer patients
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Fig. 3. Outcome of smoking cessation advice.
ventional laser surgery in OPL treatment has previously been demonstrated27. Tobacco smoking, particularly in combination with excessive alcohol consumption, is a major risk factor for both oral precancer and subsequent lesion transformation into invasive carcinoma13,30. A cohort study investigating risk factors among patients diagnosed with leukoplakia in Taiwan demonstrated that frequent alcohol users were nine times more likely to develop leukoplakia compared with nondrinkers. Similarly, heavier smokers were five-fold more likely to develop leukoplakia compared with non-smokers16.Patient education regarding oral cancer risk factors and the provision of smoking cessation advice is an important component of treatment protocols for patients with OPLs. Nevertheless, more than one-third of head and neck cancer patients continue to smoke during and after treatment23. The population of north-east England has one of the worst health and deprivation indicators in the UK, with approximately 33% of men and 26% of women identified as smokers17. This study is unique in that it characterizes for the first time smoking habits in a cohort of patients presenting in this area with histologically confirmed dysplastic OPLs treated to a standard protocol by the same clinical team and with documented 5-year clinical outcome data. All patients in the study population were smokers at their initial presentation, and smoking remained a considerable problem even following laser surgery, risking development of further precancerous lesions and malignant transformation. Although not
statistically significant, the two patients who developed carcinoma continued to smoke postoperatively. Overall, changes in smoking behaviour did not appear to influence clinical outcome in this group over a 5-year follow-up period. All dysplastic lesions were formally excised in this study, but other studies in which lesions were not removed have demonstrated some clinical regression of lesions up to 10–15 years following tobacco cessation12. The relevance of patients’ use of alcohol, potential dietary and nutritional deficiencies and probably most importantly the accuracy of smoking data provided by subjects are all highly significant factors in trying to determine the true relationship between changes in smoking behaviour and treatment outcomes. Unfortunately, the reliability of patientreported data is highly variable, although all patients in this study stated that they continued to consume regular alcohol (despite risk-factor counselling). Further research into the role of alcohol in OPL patients is clearly warranted. A decrease in smoking behaviour was seen at patients’ 5-year follow-up appointments compared with their initial presentation, but 74% of patients ultimately continued to smoke despite surgical intervention. Taking into consideration that the study did not demonstrate that alteration in patients’ reported smoking behaviour affected the clinical treatment outcomes, a differentiation needs to be made between smokers who appear to reduce their smoking but continue to ‘compensatory’ smoke by inhaling more deeply to maintain nico-
tine levels, and smokers who achieve actual cutting down3. It is essential for clinical relevance to utilize validated methods to evaluate smoking status among OPL patients, as the unreliability of self-reported smoking habits is well known26. In this study, CO measurement in expired air was used as an objective parameter to verify smoking cessation adherence. This parameter is indicative of true smoking status, since smoking is the main source of environmental CO10. CO monitoring confirmed the quitting-smoking data reported by five participants in this investigation, but it was difficult to get patients to make the additional clinical visits necessary for CO monitoring. There are very few studies which examine the determinants of smoking behaviour in head and neck cancer patients, although SCHNOLL & LERMAN23 suggested that patients with low levels of quit motivation or those with a high self-blame/low perceived control ratio were at greatest risk of continuing to smoke following diagnosis and treatment. Balancing the ‘pros and cons’ of quitting, individuals‘ perception of vulnerability to disease and their level of emotional distress were thought to influence patient behaviour. It is also speculated that HNSCC patients diagnosed with advance disease or those undergoing extensive treatment are less likely to continue smoking20,24. Offering frequent, short duration advice at the time of cancer diagnosis has previously been found to be effective in achieving smoking cessation in head and neck cancer patients20,29. An integral
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component of oral precancer treatment protocols should be one-to-one consultations aimed at: (1) educating patients about specific health benefits of quitting smoking, (2) encouraging patients to make quitting attempts, (3) demonstrating practical skills that reinforce smoking cessation, and (4) managing acute nicotine withdrawal20. The efficacy of a dedicated smoking cessation advisor in OPL management is clearly demonstrated in this study, as the highest number of non-smokers at 5 years was seen in the smoking cessation clinic/CO monitoring group. POATE & WARNAKULASURIYA21 have recently emphasized the importance of studies to investigate the effectiveness of both interventional therapies and smoking cessation advice in the management of OPLs. Indeed, the need for such research seems imperative according to AL-SHAM1 MARI et al. who reported a significant lack of awareness of the deleterious oral health effects of smoking in smokers, compared with non-smokers. Although the number of patients in this study was relatively small, results compare favourably with regional and national NHS Stop Smoking service 4-week quit rates. In 2003/04 in the North East Government Office region, 53% of those setting a quit date had successfully quit (based on self-report), with the number confirmed by CO validation being 40%. Nationally, the NHS Stop Smoking service 4-week quit rate was 57% with 35% being CO validated4. Further research is required into the longer-term outcomes for oral precancer patients accessing smoking cessation services. In conclusion, smoking remains a considerable problem in oral precancer patients even after interventional treatment, and risks further precancerous lesion development and malignant transformation. Smoking cessation advice in combination with oral health instruction is an essential component of oral precancer treatment protocols.
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Acknowledgements. We wish to acknowledge the help of colleagues in the Pathology department at the Royal Victoria Infirmary, Newcastle for the histopathological examination of all tissue specimens in this study, and the Regional Medical Physics department in Newcastle for their assistance with the CO2 laser.
12.
13.
References 1. Al-Shammari KF, Moussa MA, AlAnsari JM, Al-Duwairy YS, Honkala
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EJ. Dental patient awareness of smoking effects on oral health: comparison of smokers and non-smokers. J Dent 2006: 34: 173–178. Banoczy J, Gintner Z, Dombi C. Tobacco use and oral leukoplakia. J Dent Educ 2001: 65: 322–327. Binnie V, McHugh S, Macpherson L, Borland B, Moir K, Malik K. The validation of self-reported smoking status by analysing cotinine levels in stimulated and unstimulated saliva, serum and urine. Oral Dis 2004: 10: 287–293. Department of Health: Statistical Bulletin – Statistics on NHS Stop Smoking Services in England, April 2003 to March 2004, 2004. Dietrich T, Reichart PA, Scheifele C. Clinical risk factors of oral leukoplakia in a representative sample of the US population. Oral Oncol 2004: 40: 158– 163. Franceschi S, Barra S, La Vecchia C, Bidoli E, Negri E, Talamini R. Risk factors for cancer of the tongue and the mouth. A case–control study from northern Italy. Cancer 1992: 70: 2227– 2233. Freitas MD, Blanco-Carrion A, Gandara-Vila P, Antunez-Lopez J, Garcia-Garcia A, Gandara Rey JM. Clinicopathologic aspects of oral leukoplakia in smokers and nonsmokers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006: 102: 199–203. Gupta PC, Mehta FS, Pindborg JJ, Aghi MB, Bhonsle RB, Daftary DK, Murti PR, Shah HT, Sinor PN. Intervention study for primary prevention of oral cancer among 36 000 Indian tobacco users. Lancet 1986: 1: 1235– 1239. HAJEK P, WEST R. One-to-one smoking cessation advice. Setting up and running specialist smoking cessation services. In: HAJEK P, WEST R, eds: Smoking Cessation Training and Research Programme. London, 2003. Hald J, Overgaard J, Grau C. Evaluation of objective measures of smoking status—a prospective clinical study in a group of head and neck cancer patients treated with radiotherapy. Acta Oncol 2003: 42: 154–159. Hiyama T, Sato T, Yoshino K, Tsukuma H, Hanai A, Fujimoto I. Second primary cancer following laryngeal cancer with special reference to smoking habits. Jpn J Cancer Res 1992: 83: 334–339. Jaber MA, Porter SR, Gilthorpe MS, Bedi R, Scully C. Risk factors for oral epithelial dysplasia—the role of smoking and alcohol. Oral Oncol 1999: 35: 151– 156. Johnson NW. Tobacco use and oral cancer: a global perspective. J Dent Educ 2001: 65: 328–339. Johnson NW. Aetiology and risk factors for oral cancer. In: Shah Jatin P, John-
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son Newell W, Batsakis John G, eds: Oral Cancer. London: Martin Dunitz 2003: 33–75. Kerawala CJ. Oral cancer, smoking and alcohol: the patients’ perspective. Br J Oral Maxillofac Surg 1999: 37: 374– 376. Lee JJ, Hung HC, Cheng SJ, Chen YJ, Chiang CP, Liu BY, Jeng JH, Chang HH, Kuo YS, Lan WH, Kok SH. Carcinoma and dysplasia in oral leukoplakias in Taiwan: prevalence and risk factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006: 101: 472–480. RICKARDS L, FOX K, ROBERTS C, FLETCHER L, GODDARD E. Living in Britain ‘‘General Household Survey 2002’’. National Statistics: London, 2004. http://www.sta tistics.gov.uk/downloads/theme_com pendia/lib2002.pdf. Llewellyn CD, Linklater K, Bell J, Johnson NW, Warnakulasuriya S. An analysis of risk factors for oral cancer in young people: a case–control study. Oral Oncol 2004: 40: 304– 313. LODI G, SARDELLA A, BEZ C, DEMAROSI F, CARRASSI A. Interventions for treating oral leukoplakia. Cochrane Database Syst Rev 2006:CD001829. Ostroff JS, Jacobsen PB, Moadel AB, Spiro RH, Shah JP, Strong EW, Kraus DH, Schantz SP. Prevalence and predictors of continued tobacco use after treatment of patients with head and neck cancer. Cancer 1995: 75: 569– 576. Poate TW, Warnakulasuriya S. Effective management of smoking in an oral dysplasia clinic in London. Oral Dis 2006: 12: 22–26. Schepman KP, Bezemer PD, van der Meij EH, Smeele LE, van der Waal I. Tobacco usage in relation to the anatomical site of oral leukoplakia. Oral Dis 2001: 7: 25–27. Schnoll RA, Lerman C. Smoking behaviour and smoking cessation among head and neck cancer patients. In: Ensley J, Salivio Gutkind J, Jacobs J, Lippman S, eds: Head and Neck Cancer : Emerging Perspectives. US: Academic Press Inc. 2002. Silverman Jr S, Gorsky M, Greenspan D. Tobacco usage in patients with head and neck carcinomas: a follow-up study on habit changes and second primary oral/ oropharyngeal cancers. J Am Dent Assoc 1983: 106: 33–35. Silverman Jr S, Griffith M. Smoking characteristics of patients with oral carcinoma and the risk for second oral primary carcinoma. J Am Dent Assoc 1972: 85: 637–640. Stanton WR, McClelland M, Elwood C, Ferry D, Silva PA. Prevalence, reliability and bias of adolescents’ reports of smoking and quitting. Addiction 1996: 91: 1705–1714.
Non-smoking programmes for oral precancer patients 27. Thomson PJ, Wylie J. Interventional laser surgery: an effective surgical and diagnostic tool in oral precancer management. Int J Oral Maxillofac Surg 2002: 31: 145–153. 28. van Oijen MG, Gilsing MM, Rijksen G, Hordijk GJ, Slootweg PJ. Increased number of proliferating cells in oral epithelium from smokers and ex-smokers. Oral Oncol 1998: 34: 297–303.
29. Vander Ark W, DiNardo LJ, Oliver DS. Factors affecting smoking cessation in patients with head and neck cancer. Laryngoscope 1997: 107: 888–892. 30. Warnakulasuriya S, Sutherland G, Scully C. Tobacco, oral cancer, and treatment of dependence. Oral Oncol 2005: 41: 244–260. 31. Winn DM. Tobacco use and oral disease. J Dent Educ 2001: 65: 306–312.
Address: Omar Hamadah Oral & MaxilloFacial Surgery School of Dental Sciences Framlington Place Newcastle upon Tyne NE2 4BW UK Tel: +44 191 222 8290 Fax: +44 191 222 6137 E-mail: [email protected]
711
Clinical Paper Head and Neck Oncology
Effects of active non-smoking programmes on smoking behaviour in oral precancer patients
O. Hamadah, S. Hepburn, P. J. Thomson Oral & MaxilloFacial Surgery, School of Dental Sciences, University of Newcastle upon Tyne, UK
O. Hamadah, S. Hepburn, P. J. Thomson: Effects of active non-smoking programmes on smoking behaviour in oral precancer patients. Int. J. Oral Maxillofac. Surg. 2007; 36: 706–711. # 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Smoking is the commonest risk factor for oral cancer and precancer. The objective of this study was to characterize smoking behaviour and attitude in a cohort of oral precancer patients in Newcastle upon Tyne, UK, and to determine changes in behaviour during diagnosis, treatment and follow-up. Twenty-seven consecutive, smoking patients with dysplastic oral lesions were recruited to the study and a detailed smoking history obtained, quantifying types and numbers of cigarettes smoked, length of smoking history, and changes in smoking behaviour during treatment episodes and long-term follow-up. All patients underwent an interventional management protocol comprising risk-factor education, histopathological diagnosis by incisional biopsy and laser excision of lesions. Patients were followed up for 5 years. Whilst there was a significant decrease in the number of cigarettes smoked at patients’ most recent follow-up compared with initial presentation (p < 0.001), 74% continued to smoke. Patients received advice from a smoking cessation adviser on support available to them from the local NHS (National Health Service) Stop Smoking services. Six out of 10 patients who set a ‘quit date’ and attended a programme had quit at the 4-week follow-up but only 5 remained non-smokers. Smoking remains a considerable problem in oral precancer patients even after interventional treatment, with the risk of further precancerous lesions and malignant transformation.
Cigarette smoking remains the leading cause of preventable morbidity and mortality in the UK, and is well documented as a primary aetiological agent in head and neck cancer15,18. Oral squamous cell carcinoma (OSCC) occurs more frequently in smokers than non-smokers, and a dose– 0901-5027/080706 + 06 $30.00/0
response relationship is recognised between risk of cancer development and the amount and duration of tobacco use2,14. Oral precancerous lesions (OPLs), which are clinically recognisable antecedents of OSCC comprising leukoplakia, erythroplakia and erythroleukoplakia, and which
Key words: oral precancer; smoking; carbon monoxide interventional treatment. Accepted for publication 1 March 2007 Available online 19 April 2007
exhibit variable dysplastic change and unpredictable malignant transformation rates, have been shown to occur up to six times more frequently in smokers6. The type and amount of tobacco consumption affects the size, number and location of oral precancers7,22.Measuring proliferative
# 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Non-smoking programmes for oral precancer patients activity of head and neck squamous cell carcinoma (HNSCC) specimens, using Ki 67, showed an increase in labelling index (LI) in both smokers and ex-smokers compared with non-smokers. Interestingly, ex-smokers (both HNSCC patients and healthy individuals) manifested a trend towards increased proliferative activity which may indicate permanent smokingrelated biological alterations in oral epithelium28. It is also known that treatment efficacy, patient survival, risk of recurrence and vulnerability to second primary neoplasms are all adversely affected by continued smoking following OSCC diagnosis and management11,25. Smoking cessation advice and treatment are therefore of considerable importance in the overall care of head and neck cancer patients31. Patients who stop smoking decrease their increased risk for OSCC within 5–10 years15, whilst a significant proportion of OPLs will disappear or become smaller within the first year of smoking cessation8,31. The aims of this study were: (1) to characterize smoking behaviour in a cohort of oral precancer patients attending the Oncology/Dysplasia clinic at the MaxilloFacial Unit at Newcastle General Hospital, Newcastle upon Tyne, UK; (2) to determine changes in behaviour during diagnosis, treatment and follow-up; and (3) to explore the beneficial role of the smoking cessation advisor as part of an oral precancer multidisciplinary team. Methods
Following local ethical committee approval and informed patient consent, patients attending the MaxilloFacial Oncology/Dysplasia clinic for review following treatment for OPLs were invited to take part in the study. Inclusion criteria required a first presentation of a newly diagnosed OPL (confirmed as dysplastic
by incisional diagnostic biopsy), with no previous history of OSCC or any surgical or radiotherapy treatment. All patients underwent an identical management protocol, coordinated by the same clinician, comprising education and advice regarding risk factors, and interventional laser surgery excision of lesions. Regular patient follow-up with known clinical outcome for 5 years post diagnosis was required. Histopathological examination of excised lesions was carried out by experienced oral pathologists working to standardized criteria. Dysplasia was graded as mild (atypia confined to the basal third of epithelium), moderate (involving up to two thirds) or severe (greater than two thirds), whilst carcinoma-in-situ was characterized as severe tissue dysmaturation extending to an intact basement membrane. Following recording of individual demographic and clinico-pathological data, patients were asked to complete a questionnaire detailing their smoking habits covering pre-diagnosis, perioperative behaviour and most recent follow-up appointment. Retrospective review of clinical records was carried out to document patients’ recorded smoking behaviour at 6-monthly intervals during their follow-up. At the 5-year follow-up appointment, smoking status was confirmed by patient interview. In addition, following brief opportunistic advice given to patients by the clinician in accordance with national evidencebased guidelines, patients were offered subsequent advice from a smoking cessation advisor, who attended the clinic and provided immediate consultations (minimum of 10 min per patient). Both the patient’s motivation to quit and their nicotine dependence were assessed, and the structured behavioural support and medication, such as nicotine replacement ther-
707
apy (NRT) and Zyban, available through NHS Stop Smoking services were explained. Patients who requested close assistance were offered a 12-week Stop Smoking programme with the smoking cessation adviser, or referred to their local NHS Stop Smoking service if additional clinic attendance was inconvenient. The effectiveness of the use of NRT and Zyban was explained to patients who declined further assistance but appeared motivated to quit. At the smoking cessation clinic patients were seen by the advisor on a one-to-one basis. Typically, 1 or 2 ‘pre-quit’ sessions were followed by weekly sessions for 4 weeks after the ‘quit date’ with fortnightly sessions thereafter up to week 12. A patient was counted as a ‘self-reported 4 week quitter’ if they were assessed face to face or by telephone 4 weeks (minus 3 days or plus 14) after the designated quit date, and declared that they had not smoked even a single puff on a cigarette in the past 2 weeks. A smoker was counted as a ‘carbon monoxide (CO) verified 4 week quitter’ if they were a self-reported 4 week quitter and their expired air CO was assessed 4 weeks (minus 3 days or plus 14) after the designated quit date and found to be less than 10 parts per million. Telephone support was offered between sessions as necessary. Specific components of the cessation treatment programme9 are summarised in Table 1. Non-specific support and encouragement were also provided, and expired air CO readings measured to confirm abstinence (a reading <10 parts per million assuming abstinence). Non-parametric statistical analysis of results was carried out using x2 or Fisher’s exact test as appropriate. Pairedsample t-test was performed to investigate the difference in the number of cigarettes smoked during the follow-up intervals.
Table 1. One-to-one treatment programme summary Week 1 – preparation appointment Explain treatment programme Assess motivation to quit Explain nicotine withdrawal syndrome Assess level of tobacco dependence Measure carbon monoxide level in expired breath Discuss medications and arrange supply Set a quit date Advise on preparing to stop
Week 2 – quit day
Weeks 3 to 11 – post-quit sessions
Week 12 – end of treatment and relapse prevention
How client feels about quitting Discuss how the week went Medication use Measure carbon monoxide in Check for withdrawal discomfort Discuss potential relapse expired breath situations Discuss medication issues Measure carbon monoxide Advise on coping with potential relapse situations Explain importance of Check on medication use Discuss any ongoing support complete abstinence Advise on coping Discuss coming week Summarise
Summarise
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Hamadah et al.
Table 2. Site distribution of oral precancer lesions Oral precancer Lesion Sites
No.
%
Floor of mouth Buccal mucosa Ventral tongue Fauces Lateral tongue Buccal sulcus
14 6 3 2 1 1
51.9 22.2 11.1 7.0 3.7 3.7
Results Demographic and clinico-pathological data
Twenty-seven patients were recruited, 19 male and 8 female, with an age range of 31–76 years. Mean age of males and females was 52.7 (10.3) years and 60.2 (4.6) years, respectively. Overall, 70% of patients were greater than 50 years of age on presentation. The floor of mouth (39%) and the tongue (24.4%) were the commonest intraoral sites for OPLs (Table 2). Clinically, the majority of lesions were leukoplakias (63.4%), with erythroplakias (9.8%), erythroleukoplakias (22%), and exophytic lesions (4.9%) accounting for the rest. The most frequent histopathological diagnoses were moderate dysplasia (43.9%)
and carcinoma-in-situ (31.7%). Severe dysplasia was seen in 19.5% of cases with only 4.9% exhibiting mild dysplasia, reflecting the severity of disease in patients undergoing laser excision. Clinical outcome
Clinical outcome following laser surgery was determined as no recurrent disease (65.6% of patients), persistent disease (lesions recurring at the same site in 9.8%), further disease (development of dysplastic lesions at new intra-oral sites in 22.2%) or malignant transformation (2.4%). Smoking behaviour
At initial presentation, all patients were smokers and all reported regular alcohol consumption. Males were significantly heavier smokers than females (p < 0.001, Fig. 1). At the 5-year follow-up appointment a significant decrease in the number of cigarettes smoked per day was found compared with the number reported at initial presentation (p < 0.001). Fig. 2 illustrates smoking behaviour as recorded in patients’ clinical records over the follow-up period.
Fig. 1. Patients’ smoking behaviour according to gender distribution.
The percentage of patients who smoked fell from an initial presentation high of 100% to a low of 62% smoking at 36 months post treatment. Between 36 and 60 months postoperatively, there was an increase in smoking behaviour leading to a residual 74% of patients persistently smoking 5 years after laser surgery. Changes in smoking behaviour did not appear to influence clinical outcome in this group of patients (p = 0.28).
Smoking cessation
All patients in the study were seen by the smoking cessation adviser in the Oncology/Dysplasia Clinic. Twelve patients accepted the offer of a further appointment at the smoking cessation clinic, whilst 9 preferred referral to their local NHS Stop Smoking service. Three patients decided that they did not want formal assistance and would try to quit without behavioural support, with a further three not motivated to quit. Fig. 3 summarises patients’ adherence and attitude to smoking. Of the 12 who attended the smoking cessation clinic, most had a daily cigarette consumption of 20 and over. Ten patients agreed a ‘quit date’ and received NRT, with six successfully quitting at the 4week follow-up. For five patients nonsmoking status was confirmed by use of a CO monitor; the other patient who quit was followed up by telephone. At 5-year follow-up, only five of these patients remained non-smokers. Only one patient from the nine referred to local smoking cessation services was successful in quitting. Similarly, only one patient from the three who decided to quit independently managed to stop smoking. All three patients not motivated to stop smoking were still smoking at 5-year follow-up, resulting in a total of only seven patients (26%) who successfully quit. Discussion
Fig. 2. Changes in smoking behaviour of oral precancer patients through follow-up intervals.
The third National Health and Nutrition Examination Survey (NHANES III), investigated clinical risk factors for oral leukoplakia in a representative sample of the US population. Smoking was the most independent risk factor in oral leukoplakia. This damaging role of smoking was not affected by the alcohol consumption status of the participants5. The management of risk factors in OPL patients remains poorly documented, as does the treatment of OPLs where there is little evidence base and no agreed management protocols19, although the efficacy of inter-
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Fig. 3. Outcome of smoking cessation advice.
ventional laser surgery in OPL treatment has previously been demonstrated27. Tobacco smoking, particularly in combination with excessive alcohol consumption, is a major risk factor for both oral precancer and subsequent lesion transformation into invasive carcinoma13,30. A cohort study investigating risk factors among patients diagnosed with leukoplakia in Taiwan demonstrated that frequent alcohol users were nine times more likely to develop leukoplakia compared with nondrinkers. Similarly, heavier smokers were five-fold more likely to develop leukoplakia compared with non-smokers16.Patient education regarding oral cancer risk factors and the provision of smoking cessation advice is an important component of treatment protocols for patients with OPLs. Nevertheless, more than one-third of head and neck cancer patients continue to smoke during and after treatment23. The population of north-east England has one of the worst health and deprivation indicators in the UK, with approximately 33% of men and 26% of women identified as smokers17. This study is unique in that it characterizes for the first time smoking habits in a cohort of patients presenting in this area with histologically confirmed dysplastic OPLs treated to a standard protocol by the same clinical team and with documented 5-year clinical outcome data. All patients in the study population were smokers at their initial presentation, and smoking remained a considerable problem even following laser surgery, risking development of further precancerous lesions and malignant transformation. Although not
statistically significant, the two patients who developed carcinoma continued to smoke postoperatively. Overall, changes in smoking behaviour did not appear to influence clinical outcome in this group over a 5-year follow-up period. All dysplastic lesions were formally excised in this study, but other studies in which lesions were not removed have demonstrated some clinical regression of lesions up to 10–15 years following tobacco cessation12. The relevance of patients’ use of alcohol, potential dietary and nutritional deficiencies and probably most importantly the accuracy of smoking data provided by subjects are all highly significant factors in trying to determine the true relationship between changes in smoking behaviour and treatment outcomes. Unfortunately, the reliability of patientreported data is highly variable, although all patients in this study stated that they continued to consume regular alcohol (despite risk-factor counselling). Further research into the role of alcohol in OPL patients is clearly warranted. A decrease in smoking behaviour was seen at patients’ 5-year follow-up appointments compared with their initial presentation, but 74% of patients ultimately continued to smoke despite surgical intervention. Taking into consideration that the study did not demonstrate that alteration in patients’ reported smoking behaviour affected the clinical treatment outcomes, a differentiation needs to be made between smokers who appear to reduce their smoking but continue to ‘compensatory’ smoke by inhaling more deeply to maintain nico-
tine levels, and smokers who achieve actual cutting down3. It is essential for clinical relevance to utilize validated methods to evaluate smoking status among OPL patients, as the unreliability of self-reported smoking habits is well known26. In this study, CO measurement in expired air was used as an objective parameter to verify smoking cessation adherence. This parameter is indicative of true smoking status, since smoking is the main source of environmental CO10. CO monitoring confirmed the quitting-smoking data reported by five participants in this investigation, but it was difficult to get patients to make the additional clinical visits necessary for CO monitoring. There are very few studies which examine the determinants of smoking behaviour in head and neck cancer patients, although SCHNOLL & LERMAN23 suggested that patients with low levels of quit motivation or those with a high self-blame/low perceived control ratio were at greatest risk of continuing to smoke following diagnosis and treatment. Balancing the ‘pros and cons’ of quitting, individuals‘ perception of vulnerability to disease and their level of emotional distress were thought to influence patient behaviour. It is also speculated that HNSCC patients diagnosed with advance disease or those undergoing extensive treatment are less likely to continue smoking20,24. Offering frequent, short duration advice at the time of cancer diagnosis has previously been found to be effective in achieving smoking cessation in head and neck cancer patients20,29. An integral
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component of oral precancer treatment protocols should be one-to-one consultations aimed at: (1) educating patients about specific health benefits of quitting smoking, (2) encouraging patients to make quitting attempts, (3) demonstrating practical skills that reinforce smoking cessation, and (4) managing acute nicotine withdrawal20. The efficacy of a dedicated smoking cessation advisor in OPL management is clearly demonstrated in this study, as the highest number of non-smokers at 5 years was seen in the smoking cessation clinic/CO monitoring group. POATE & WARNAKULASURIYA21 have recently emphasized the importance of studies to investigate the effectiveness of both interventional therapies and smoking cessation advice in the management of OPLs. Indeed, the need for such research seems imperative according to AL-SHAM1 MARI et al. who reported a significant lack of awareness of the deleterious oral health effects of smoking in smokers, compared with non-smokers. Although the number of patients in this study was relatively small, results compare favourably with regional and national NHS Stop Smoking service 4-week quit rates. In 2003/04 in the North East Government Office region, 53% of those setting a quit date had successfully quit (based on self-report), with the number confirmed by CO validation being 40%. Nationally, the NHS Stop Smoking service 4-week quit rate was 57% with 35% being CO validated4. Further research is required into the longer-term outcomes for oral precancer patients accessing smoking cessation services. In conclusion, smoking remains a considerable problem in oral precancer patients even after interventional treatment, and risks further precancerous lesion development and malignant transformation. Smoking cessation advice in combination with oral health instruction is an essential component of oral precancer treatment protocols.
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Acknowledgements. We wish to acknowledge the help of colleagues in the Pathology department at the Royal Victoria Infirmary, Newcastle for the histopathological examination of all tissue specimens in this study, and the Regional Medical Physics department in Newcastle for their assistance with the CO2 laser.
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Address: Omar Hamadah Oral & MaxilloFacial Surgery School of Dental Sciences Framlington Place Newcastle upon Tyne NE2 4BW UK Tel: +44 191 222 8290 Fax: +44 191 222 6137 E-mail: [email protected]
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