n Pye, Andrew David (2015) Investigations into oral health and dental care factors associated with oral cancer risk and management. MSc(R) thesis. http://theses.gla.ac.uk/6483/ Copyright and moral rights for this thesis are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the Author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the Author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Glasgow Theses Service http://theses.gla.ac.uk/ [email protected] Investigations into oral health and dental care factors associated with oral cancer risk and management Mr Andrew David Pye BDS MFDS RCS(Ed) FDS (Rest.Dent.) RCPS(Glasg) Submitted in fulfilment of the requirements for the Degree of Master of Science (by Research) Glasgow Dental School College of Medical, Veterinary and Life Sciences University of Glasgow ©Andrew Pye 2 Abstract Introduction In Scotland in 2010, 460 new cases of cancer of the oral cavity were reported with a crude rate of 8.8 per 100,000 person/year risk (ISD Scotland). Worldwide, oral cancer (also known as lip and oral cavity cancer) is the 15th most common cancer, with more than 300,000 new cases diagnosed in 2012 (2% of the total). Oral cancer is the 15th most common cancer in Europe, with around 61,400 new cases diagnosed in 2012 (2% of the total) (GLOBOCAN 2012). In order to reduce the incidence of oral cancer, risk factors need to be identified and appropriate preventative strategies developed. In addition to significant mortality, there is significant morbidity associated with oral cancer. Patients can suffer from disfigurement, pain, reduced function and depressive illness as a result of the disease and its treatment. Guidelines state that oral cancer patients should receive pre- and post-operative dental assessments and management as part of their cancer treatment to reduce complications and improve outcomes (British Association of Head and Neck Oncologists, 2009, National Institute for Clinical Excellence, 2004, Scottish Intercollegiate Guidelines Network, 2006). Aims To carry out a systematic review and meta-analysis of the world-wide literature regarding oral health and dental care factors associated with oral cancer risk. To examine the level and degree of clinical dental care for patients diagnosed with and treated for head and neck/ oral cancer. Materials and Methods A systematic review and meta-analysis of the world literature was undertaken assessing the association between oral health and dental care factors and the incidence risk of oral cancer. Studies were included if they reported odds ratios 3 and corresponding 95% Confidence Intervals of oral cancer with respect to oral health or a dental care factor or if the estimates could be calculated or obtained. Meta-analyses were performed to quantify the risk associated with each factor. Included studies were assessed regarding heterogeneity and meta- analysis were carried out using a random effects model where heterogeneity was significant and a fixed effects model where heterogeneity was not significant. Included studies were also assessed regarding their methodological quality and sensitivity analyses and publication bias assessments were conducted. Case records for head and neck cancer patients diagnosed 2002-2004 were examined and assessed for evidence of dental assessments in parallel to a large multi-centre case-control study. Data were compared to audit data collected from patients diagnosed with head and neck cancer 2013-2014. Results The systematic search retrieved 8534 articles (after removal of duplicates, books and patents) which were screened against the inclusion criteria. This resulted in 18 studies that met the inclusion criteria. The overall estimate for general oral health associated with increased risk of oral cancer comparing the best oral health score with the worst was OR 3.91 (95% CI 2.29, 6.67) based on 3 studies. The overall estimate for gum bleeding associated with increased risk of oral cancer comparing the absence of gum bleeding with the worst score was 1.76 (95% CI 1.20, 2.58) based on 6 studies. The overall estimate for poor oral hygiene associated with increased risk of oral cancer was 3.56 (95% CI 2.52, 5.04) based on 2 studies. The overall estimate for 6 or more missing teeth associated with increased risk of oral cancer was OR 2.3 (95% CI 1.27, 4.18) based on 6 studies. The overall estimate for non-attendance at the dentist associated with increased risk of oral cancer was 1.45 (95% CI 1.12, 1.87) based on 3 studies. The overall estimate for denture-wearing associated with increased risk of oral cancer was 1.08 (95% CI 0.80, 1.46) based on 5 studies. The overall estimate for reduced frequency of toothbrushing associated with increased risk of oral cancer was reported as OR 1.75 (95% CI 1.21, 2.53) based on 6 studies. Regarding dental assessment of head and neck cancer patients, 6 out of 43 (14%; 95% CI 4%, 24%) dentate patients from the 2002-2004 cohort had a pre-operative 4 dental assessment compared to 45 out of 71 (63%; 95% CI 52%, 74%) of the dentate patients in the 2013-2014 cohort, which was a significant improvement. In the 2002-2004 cohort, 14 (18%; 95% CI 9%, 27%) patients out of 76 had a post- operative dental assessment compared to 19 (26%; 95% CI 16%, 36%) out of 74 patients were identified as having had some form of post-operative assessment or management, which was not a significant improvement (p= 0.28). Conclusions The available evidence indicates that general oral health, gum bleeding, oral hygiene, missing teeth, dental attendance and frequency of toothbrushing are all risk factors for oral cancer. Denture use per se is not associated with an increased risk of oral cancer. Oral health factors and, more widely, dental care factors should be acknowledged alongside traditional smoking and alcohol behaviours as important risk factors for oral cancer. An improvement in the frequency of pre-operative dental assessments has been seen. However, guidelines and standards that state that all oral cancer patients should receive a pre-operative dental assessment are not being met (British Association of Head and Neck Oncologists, 2009, National Institute for Clinical Excellence, 2004, Scottish Intercollegiate Guidelines Network, 2006) and we don’t appear to have achieved the quality performance indicator (Healthcare Improvement Scotland, 2014) stating that at least 90% of oral cancer patients should receive a pre-operative dental assessment. Post-operative dental assessments have not seen a significant improvement and compliance is difficult to assess against other research as there is little published work in this area. As standards have not been met, further efforts should be made to attempt to ensure dental assessment and management are integrated as part of the multidisciplinary team approach for patients with oral cancer. 5 6 Table of Contents Abstract ...................................................................................... 2 List of Tables ................................................................................ 9 List of Figures .............................................................................. 10 List of Accompanying Material ........................................................... 11 Preface ...................................................................................... 12 Acknowledgements ........................................................................ 13 Author’s Declaration ...................................................................... 14 Definitions/Abbreviations ................................................................ 15 1 Introduction ........................................................................... 16 1.1 Background ....................................................................... 16 1.1.1 Oral cancer .................................................................. 16 1.2 Risk factors for developing oral cancer ...................................... 19 1.2.1 Smoking ...................................................................... 20 1.2.2 Alcohol ....................................................................... 21 1.2.3 Oral health and dental care factors ..................................... 21 1.3 Oral Cancer guidelines, standards and targets .............................. 23 1.4 Oral Health assessment and oral cancer care ............................... 25 1.4.1 Oral health of patients presenting with oral cancer .................. 25 1.4.2 Rationale for pre-treatment oral health assessment as part of cancer care 25 1.4.3 Post-cancer oral and dental rehabilitation ............................. 27 1.4.4 Frequency of oral health assessment as part of oral cancer care ... 28 1.5 Gaps in the literature and rationale for research .......................... 28 1.5.1 Oral health and dental care as risk factors for oral cancer .......... 28 1.5.2 The role of dental assessment and care in the management of patients with oral cancer ........................................................... 29 2 Aims and objectives ................................................................. 31 3 Systematic Review Chapter ......................................................... 32 3.1 Introduction ...................................................................... 32 3.1.1 Aim ........................................................................... 32 3.1.2 Definition .................................................................... 32 3.2 Methods ........................................................................... 33 3.2.1 Search strategy ............................................................. 33 3.2.2 Inclusion criteria ............................................................ 34 3.2.3 Methodological assessment of included studies ........................ 34 3.2.4 Data extraction ............................................................. 35 7 3.2.5 Meta-analysis ................................................................ 36 3.2.6 Publication bias ............................................................. 37 3.3 Results ............................................................................ 37 3.3.1 Search Strategy ............................................................. 37 3.3.2 Study Characteristics ....................................................... 38 3.3.3 Methodological characteristics ........................................... 41 3.3.4 General oral health and risk associated with oral cancer ............ 42 3.3.5 Gum bleeding and periodontal disease and risk associated with oral cancer ................................................................................ 44 3.3.6 Oral hygiene and risk associated with oral cancer..................... 46 3.3.7 Missing teeth and risk associated with oral cancer .................... 47 3.3.8 Dental attendance and risk associated with oral cancer ............. 49 3.3.9 Association between oral cancer and the use of a denture .......... 50 3.3.10 Association between frequency of toothbrushing and oral cancer 52 3.3.11 Publication bias .......................................................... 53 3.4 Discussion ......................................................................... 57 3.4.1 Summary ..................................................................... 57 3.4.2 Advantages of systematic review ........................................ 57 3.4.3 Limitations of systematic review and meta-analysis .................. 58 3.4.4 Search Strategy strengths ................................................. 59 3.4.5 Search Strategy limitations ............................................... 59 3.4.6 Inclusion criteria limitations .............................................. 60 3.4.7 Methodological assessment ............................................... 61 3.4.8 Explanations ................................................................. 61 3.5 Conclusion ........................................................................ 69 4 Dental Assessment and Dental Care of Oral Cancer Patients .................. 70 4.1 Introduction ...................................................................... 70 4.2 Aims ............................................................................... 70 4.3 Methods ........................................................................... 70 4.3.1 Interviews 2004 ............................................................. 71 4.3.2 ARCAGE Follow-up study 2002-2004 ..................................... 71 4.3.3 Dental assessment of ARCAGE 2002-2004 cohort ...................... 71 4.3.4 Dental assessment of 2013-2014 Cohort................................. 73 4.3.5 Statistical analysis .......................................................... 74 4.4 Results ............................................................................ 75 4.4.1 Data collection .............................................................. 75 4.4.2 Summary of dental assessment ........................................... 75 4.4.3 Dental status ................................................................ 77 4.4.4 Oral Health Assessment .................................................... 77 8 4.4.5 Pre-operative dental assessment ......................................... 78 4.4.6 Post-operative Dental Assessment ....................................... 79 4.4.7 Pre-treatment and post-treatment dental assessment ............... 80 4.4.8 Radiotherapy ................................................................ 80 4.4.9 Interviews .................................................................... 81 4.5 Discussion ......................................................................... 82 4.5.1 Summary of findings........................................................ 82 4.5.2 Explanation of findings .................................................... 85 4.5.3 Comparison with literature ............................................... 86 4.5.4 Strengths ..................................................................... 87 4.5.5 Limitations ................................................................... 87 4.5.6 Intervention ................................................................. 88 4.6 Conclusions ....................................................................... 88 5 Discussion ............................................................................. 89 5.1 Oral health and dental care risk association with oral cancer ............ 89 5.1.1 Published literature ........................................................ 89 5.1.2 Contribution to current evidence ........................................ 92 5.1.3 What could have been done differently? ................................ 92 5.2 Dental Care Treatment Pathway .............................................. 93 5.2.1 Previous literature ......................................................... 93 5.2.2 Contribution to current evidence ........................................ 93 5.2.3 What could have been done differently? ................................ 94 5.3 Conclusions ....................................................................... 94 5.4 Recommendations for research ............................................... 95 References .................................................................................. 97 Appendices ................................................................................ 110 9 List of Tables Table 3.2-1 Methodological assessment of included studies ........................ 35 Table 3.3-1 Characteristics of included studies ....................................... 39 Table 3.3-2 Summary of meta-analysis and sensitivity analysis for oral health factors ....................................................................................... 44 Table 4.4-1 Data retrieved from oral cancer patients and source 2002-2004 cohort ....................................................................................... 75 Table 4.4-2 Oral Health assessment in 1st (2002-2004) and 2nd (2013-2014) cohorts ...................................................................................... 75