Q J Med 2014; 107:283–290 doi:10.1093/qjmed/hct248 Advance Access Publication 11 December 2013
Cancer risk among gingivitis and periodontitis patients: a nationwide cohort study B.-W. WEN1*, C.-S. TSAI2*, C.-L. LIN3, Y.-J. CHANG4, C.-F. LEE5, C.-H. HSU6y and C.-H. KAO7y From the 1Department of Family Medicine, Buddhist Tzu Chi General Hospital, Taichung Branch, 2 Department of Otolaryngology, Tung’s Taichung MetroHarbor Hospital, 3Management Office for Health Data, China Medical University Hospital, Taichung, 4Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, 5Department of Oral and Maxillofacial Surgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung, 6Department of Nuclear Medicine, Taipei Medical University Hospital and School of Medicine, College of Medicine, Taipei Medical University, Taipei and 7Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, Taichung and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
Received 29 October 2013 and in revised form 29 November 2013
Summary Aim: Periodontal disease encompasses gingivitis and periodontitis, which exerts systemic effects. We conducted a population-based study to evaluate the association between periodontal disease and the risk of cancer. Methods: We used insurance claims data from 1997 to 2010, accessing a database of 1 million randomly selected insurants in Taiwan. All patients were older than 20 and newly diagnosed with periodontitis between 1 January 1997 and 31 December 2010. The comparison cohort comprised patients older than 20, who were newly diagnosed with gingivitis in the same period. Both cohorts were followed until
Introduction Periodontal disease is described as any inherited or acquired disorder of the tissues surrounding and supporting the teeth (periodontium).1 This disease can be classified into eight subcategories, including
a cancer diagnosis, lost to follow-up, death, termination of insurance, or the end of 2010. Results: The incidence rate of cancer was 1.14 times higher in the study cohort than in the comparison cohort [confidence interval (CI) = 1.11–1.17]. The adjusted hazard ratio (HR) was 1.05 (95% CI = 1.00–1.11). A multivariable analysis showed that the periodontitis patients exhibited an elevated risk of developing oral cancer (adjusted HR = 1.79, 95% CI = 1.42–2.25). Conclusion: The findings indicated that patients in the periodontitis cohort exhibited a higher risk of developing oral cancer than those in the gingivitis cohort.
gingival disease, chronic periodontitis and aggressive periodontitis.2,3 Gingivitis is primarily caused by accumulated dental-bacterial plaque2 and is the mildest form of periodontal disease.1 Unnoticed plaque requires 2–3 days to cause gingivitis;2
! The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: [email protected]
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Address correspondence to C.-H. Kao, M.D., Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 404, Taiwan. email: [email protected] *These authors contributed equally to this work. y These authors contributed equally to this work.
284
B.-W. Wen et al.
Materials and methods Data sources The National Health Insurance (NHI) program in Taiwan is a universal health insurance system that was implemented in March 1995 by the Bureau of National Health Insurance, Department of Health. At the end of 2009, the NHI program covered 99% of the 23.74 million people in Taiwan and was contracted with 97% of Taiwanese hospitals and clinics.6 The NHI program covers comprehensive medical services including inpatient and outpatient care, Chinese medicine, dental care, physical therapy, preventive care, prescription drugs and coverage at various medical institutions. The identifying factors in the patient registration files are scrambled to ensure patient anonymity. This study used a longitudinal, retrospective cohort design, assessing insurance claims data from 1997 to 2010 for 1 million people, who were randomly selected from
the insurants in Taiwan. All diagnoses were coded using the International Classification of Disease, ninth revision, Clinical Modification (ICD-9-CM). This study was approved by the Ethics Review Board of China Medical University (CMU-REC101-012). No written informed consent was obtained from the participants, because the identification numbers used in the National Health Insurance Research Database (NHIRD) assure patient anonymity.
Study participants The study patients were older than 20 and newly diagnosed with periodontitis (ICD-9-CM codes 523.3 and 523.4) between 1 January 1997 and 31 December 2010. The comparison cohort included selected patients older than 20 who were newly diagnosed with gingivitis (ICD-9-CM codes 523.0 and 523.1) in the same period. To ensure that periodontitis and gingivitis were accurately diagnosed, we selected patients who were admitted at least three times for related treatment. The index date was defined as the date of periodontitis or gingivitis diagnosis. Patients diagnosed with malignant cancer (ICD-9-CM codes 140–208) before the index date or lacking sex and age information were excluded.
Outcome measures By using the unique patient identification numbers, we linked to the Catastrophic Illness Patient Database to gather histological confirmation of cancer diagnoses. Both cohorts were followed until a malignant cancer diagnosis (ICD-9-CM codes 140–194, 200– 208), loss to follow-up, death, insurance termination, or the end of 2010. The baseline comorbidities were diabetes (ICD-9-CM code 250), hypertension (ICD-9CM codes 401–405) and hyperlipidemia (ICD-9-CM code 272).
Statistical analysis The data analysis involved comparing demographic characteristics and comorbidities by using the chisquare test for categorical variables and the t-test for continuous variables between the study and comparison cohorts. The follow-up time (in personyears) was used to estimate the incidence density rates, comparing the incidence rate ratio (IRR) of the study and comparison cohorts at a 95% confidence interval (CI) based on demographic characteristics and comorbidities. The multivariable Cox proportional-hazard regression model was used to assess the risk of developing malignant cancer associated with periodontitis and gingivitis, and to adjust the demographic characteristics and comorbidities.
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adults who exhibit normal gingiva can develop biofilm on the teeth 24 h after conducting oral hygiene procedures (e.g. tooth-brushing) and form gingivitis 10–21 days after these procedures.1,4 The worldwide prevalence of periodontal disease as high as 90% and gingivitis affects 50–90% of the adult population.1 Common symptoms include bleeding and tenderness.2 Similar symptoms occur in periodontitis,3 which is an inflammatory disease of the supporting tissues of the teeth caused by specific microorganisms or groups of specific microorganisms, resulting in progressive destruction of the periodontal ligament and alveolar bone with increased probing depth formation, recession, or both.3 Periodontitis is always preceded by gingivitis,3 but differs from gingivitis regarding its irreversible course.2 Approximately 10–15% of gingivitis patients progress to chronic periodontitis; in addition to bleeding and tenderness,3 this causes tooth mobility and eventually tooth loss if left untreated.1 The pathogenic bacteria causing periodontitis include Porphyromonas gingivalis, Tannerella forsythia (formerly Bacteroides forsythus) and Treponema denticola.3 Emerging evidence has suggested that periodontal disease correlates with an increased cancer risk.5 Population-based studies evaluating the association between periodontal disease and cancer are lacking in Taiwan. Because of the high prevalence of gingivitis and the short time required to progress from normal gingiva to gingivitis, we performed a retrospective study to evaluate the risk of cancer among gingivitis and periodontitis patients.
Cancer, gingivitis and periodontitis
285
Table 1 Demographic characteristics in periodontal disease patientsa Periodontal disease
Gender Women Men Age stratified 20–49 50–64 565 Age, mean SD Comorbidity Diabetes Hypertension Hyperlipidemia
P-value
Gingivitis (N = 96 375)
Periodontitis (N = 51 791)
45 583 (50.7) 47 522 (49.3)
25 503 (49.2) 26 288 (50.8)
Cancer risk among gingivitis and periodontitis patients: a nationwide cohort study B.-W. WEN1*, C.-S. TSAI2*, C.-L. LIN3, Y.-J. CHANG4, C.-F. LEE5, C.-H. HSU6y and C.-H. KAO7y From the 1Department of Family Medicine, Buddhist Tzu Chi General Hospital, Taichung Branch, 2 Department of Otolaryngology, Tung’s Taichung MetroHarbor Hospital, 3Management Office for Health Data, China Medical University Hospital, Taichung, 4Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, 5Department of Oral and Maxillofacial Surgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung, 6Department of Nuclear Medicine, Taipei Medical University Hospital and School of Medicine, College of Medicine, Taipei Medical University, Taipei and 7Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, Taichung and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
Received 29 October 2013 and in revised form 29 November 2013
Summary Aim: Periodontal disease encompasses gingivitis and periodontitis, which exerts systemic effects. We conducted a population-based study to evaluate the association between periodontal disease and the risk of cancer. Methods: We used insurance claims data from 1997 to 2010, accessing a database of 1 million randomly selected insurants in Taiwan. All patients were older than 20 and newly diagnosed with periodontitis between 1 January 1997 and 31 December 2010. The comparison cohort comprised patients older than 20, who were newly diagnosed with gingivitis in the same period. Both cohorts were followed until
Introduction Periodontal disease is described as any inherited or acquired disorder of the tissues surrounding and supporting the teeth (periodontium).1 This disease can be classified into eight subcategories, including
a cancer diagnosis, lost to follow-up, death, termination of insurance, or the end of 2010. Results: The incidence rate of cancer was 1.14 times higher in the study cohort than in the comparison cohort [confidence interval (CI) = 1.11–1.17]. The adjusted hazard ratio (HR) was 1.05 (95% CI = 1.00–1.11). A multivariable analysis showed that the periodontitis patients exhibited an elevated risk of developing oral cancer (adjusted HR = 1.79, 95% CI = 1.42–2.25). Conclusion: The findings indicated that patients in the periodontitis cohort exhibited a higher risk of developing oral cancer than those in the gingivitis cohort.
gingival disease, chronic periodontitis and aggressive periodontitis.2,3 Gingivitis is primarily caused by accumulated dental-bacterial plaque2 and is the mildest form of periodontal disease.1 Unnoticed plaque requires 2–3 days to cause gingivitis;2
! The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: [email protected]
Downloaded from by guest on November 15, 2015
Address correspondence to C.-H. Kao, M.D., Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 404, Taiwan. email: [email protected] *These authors contributed equally to this work. y These authors contributed equally to this work.
284
B.-W. Wen et al.
Materials and methods Data sources The National Health Insurance (NHI) program in Taiwan is a universal health insurance system that was implemented in March 1995 by the Bureau of National Health Insurance, Department of Health. At the end of 2009, the NHI program covered 99% of the 23.74 million people in Taiwan and was contracted with 97% of Taiwanese hospitals and clinics.6 The NHI program covers comprehensive medical services including inpatient and outpatient care, Chinese medicine, dental care, physical therapy, preventive care, prescription drugs and coverage at various medical institutions. The identifying factors in the patient registration files are scrambled to ensure patient anonymity. This study used a longitudinal, retrospective cohort design, assessing insurance claims data from 1997 to 2010 for 1 million people, who were randomly selected from
the insurants in Taiwan. All diagnoses were coded using the International Classification of Disease, ninth revision, Clinical Modification (ICD-9-CM). This study was approved by the Ethics Review Board of China Medical University (CMU-REC101-012). No written informed consent was obtained from the participants, because the identification numbers used in the National Health Insurance Research Database (NHIRD) assure patient anonymity.
Study participants The study patients were older than 20 and newly diagnosed with periodontitis (ICD-9-CM codes 523.3 and 523.4) between 1 January 1997 and 31 December 2010. The comparison cohort included selected patients older than 20 who were newly diagnosed with gingivitis (ICD-9-CM codes 523.0 and 523.1) in the same period. To ensure that periodontitis and gingivitis were accurately diagnosed, we selected patients who were admitted at least three times for related treatment. The index date was defined as the date of periodontitis or gingivitis diagnosis. Patients diagnosed with malignant cancer (ICD-9-CM codes 140–208) before the index date or lacking sex and age information were excluded.
Outcome measures By using the unique patient identification numbers, we linked to the Catastrophic Illness Patient Database to gather histological confirmation of cancer diagnoses. Both cohorts were followed until a malignant cancer diagnosis (ICD-9-CM codes 140–194, 200– 208), loss to follow-up, death, insurance termination, or the end of 2010. The baseline comorbidities were diabetes (ICD-9-CM code 250), hypertension (ICD-9CM codes 401–405) and hyperlipidemia (ICD-9-CM code 272).
Statistical analysis The data analysis involved comparing demographic characteristics and comorbidities by using the chisquare test for categorical variables and the t-test for continuous variables between the study and comparison cohorts. The follow-up time (in personyears) was used to estimate the incidence density rates, comparing the incidence rate ratio (IRR) of the study and comparison cohorts at a 95% confidence interval (CI) based on demographic characteristics and comorbidities. The multivariable Cox proportional-hazard regression model was used to assess the risk of developing malignant cancer associated with periodontitis and gingivitis, and to adjust the demographic characteristics and comorbidities.
Downloaded from by guest on November 15, 2015
adults who exhibit normal gingiva can develop biofilm on the teeth 24 h after conducting oral hygiene procedures (e.g. tooth-brushing) and form gingivitis 10–21 days after these procedures.1,4 The worldwide prevalence of periodontal disease as high as 90% and gingivitis affects 50–90% of the adult population.1 Common symptoms include bleeding and tenderness.2 Similar symptoms occur in periodontitis,3 which is an inflammatory disease of the supporting tissues of the teeth caused by specific microorganisms or groups of specific microorganisms, resulting in progressive destruction of the periodontal ligament and alveolar bone with increased probing depth formation, recession, or both.3 Periodontitis is always preceded by gingivitis,3 but differs from gingivitis regarding its irreversible course.2 Approximately 10–15% of gingivitis patients progress to chronic periodontitis; in addition to bleeding and tenderness,3 this causes tooth mobility and eventually tooth loss if left untreated.1 The pathogenic bacteria causing periodontitis include Porphyromonas gingivalis, Tannerella forsythia (formerly Bacteroides forsythus) and Treponema denticola.3 Emerging evidence has suggested that periodontal disease correlates with an increased cancer risk.5 Population-based studies evaluating the association between periodontal disease and cancer are lacking in Taiwan. Because of the high prevalence of gingivitis and the short time required to progress from normal gingiva to gingivitis, we performed a retrospective study to evaluate the risk of cancer among gingivitis and periodontitis patients.
Cancer, gingivitis and periodontitis
285
Table 1 Demographic characteristics in periodontal disease patientsa Periodontal disease
Gender Women Men Age stratified 20–49 50–64 565 Age, mean SD Comorbidity Diabetes Hypertension Hyperlipidemia
P-value
Gingivitis (N = 96 375)
Periodontitis (N = 51 791)
45 583 (50.7) 47 522 (49.3)
25 503 (49.2) 26 288 (50.8)
