Periodontitis and the risk of oral cancer: a meta-analysis of case-control studies
DOI:
https://doi.org/10.2340/aos.v83.40478Keywords:
Periodontal diseases, periodontitis, oral cancer, missing teeth, clinical attachment loss, meta-analysisAbstract
Objective: The current studies have yielded inconclusive findings regarding the connection between periodontitis and oral cancer (OC). Therefore, our goal is to elucidate this relationship.
Materials and methods: We conducted a thorough search of electronic databases (EMBASE, PubMed, Web of Science, and Cochrane Library) up to September 2023. The Newcastle-Ottawa Scale (NOS) was applied to assess study quality. To evaluate potential publication bias, both a funnel plot and Egger’s test were employed. Additionally, a sensitivity analysis was conducted to explore the source of heterogeneity when the I2 statistic exceeded 50%.
Results: This systematic review encompassed 16 studies, involving a total of 6,032 OC patients and 7,432 healthy controls. Our meta-analysis, incorporating data from nine studies, revealed a significant correlation between periodontitis and the risk of OC (OR [odds ratio] = 2.94, 95% CI [confidence interval] (2.13, 4.07); five studies, 6,927 participants; low certainty of evidence). Findings also suggested that individuals with more than 15 missing teeth may have a heightened risk of OC (OR = 1.91, 95% CI (1.01, 3.62)). Furthermore, clinical attachment loss (CAL) and decayed, missing, and filled teeth (DMFT) in OC patients were more pronounced compared to the control group (CAL, SMD = 1.94, 95% CI (0.22, 3.66); DMFT, SMD = 0.65, 95% CI (0.12, 1.18)).
Conclusion: Periodontitis may serve as a potential risk factor for OC. However, caution is warranted in interpreting these findings due to the substantial level of heterogeneity.
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References
Papapanou PN, Sanz M, Buduneli N, et al. Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. J Clin Periodontol. 2018;45(Suppl 20):S162–70.
Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet (London, England). 2005;366:1809–20. https://doi.org/10.1016/S0140-6736(05)67728-8 DOI: https://doi.org/10.1016/S0140-6736(05)67728-8
Arigbede AO, Babatope BO, Bamidele MK. Periodontitis and systemic diseases: a literature review. J Indian Soc Periodontol 2012;16:487–91. https://doi.org/10.4103/0972-124X.106878 DOI: https://doi.org/10.4103/0972-124X.106878
Sanz M, Ceriello A, Buysschaert M, et al. Scientific evidence on the links between periodontal diseases and diabetes: consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. J Clin Periodontol. 2018;45:138–49. https://doi.org/10.1111/jcpe.12808 DOI: https://doi.org/10.1111/jcpe.12808
Liccardo D, Cannavo A, Spagnuolo G, et al. Periodontal disease: a risk factor for diabetes and cardiovascular disease. Int J Mol Sci. 2019;20(6):1414. https://doi.org/10.3390/ijms20061414 DOI: https://doi.org/10.3390/ijms20061414
Figuero E, Han YW, Furuichi Y. Periodontal diseases and adverse pregnancy outcomes: mechanisms. Periodontol 2000. 2020;83:175–88. https://doi.org/10.1111/prd.12295 DOI: https://doi.org/10.1111/prd.12295
Katz J, Onate MD, Pauley KM, et al. Presence of Porphyromonas gingivalis in gingival squamous cell carcinoma. Int J Oral Sci. 2011;3:209–15. https://doi.org/10.4248/IJOS11075 DOI: https://doi.org/10.4248/IJOS11075
Al-Hebshi NN, Nasher AT, Maryoud MY, et al. Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas aeruginosa identified in association with oral squamous cell carcinoma. Sci Rep. 2017;7:1834. https://doi.org/10.1038/s41598-017-02079-3 DOI: https://doi.org/10.1038/s41598-017-02079-3
Bracci PM. Oral health and the oral microbiome in pancreatic cancer: an overview of epidemiological studies. Cancer J. 2017;23:310–14. https://doi.org/10.1097/PPO.0000000000000287 DOI: https://doi.org/10.1097/PPO.0000000000000287
Bawaskar HS, Bawaskar PH. Oral diseases: a global public health challenge. Lancet (London, England). 2020;395:185–6. https://doi.org/10.1016/S0140-6736(19)33016-8 DOI: https://doi.org/10.1016/S0140-6736(19)33016-8
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30. https://doi.org/10.3322/caac.21166 DOI: https://doi.org/10.3322/caac.21166
Sarode G, Maniyar N, Sarode SC, et al. Epidemiologic aspects of oral cancer. Dis Mon. 2020;66:100988. https://doi.org/10.1016/j.disamonth.2020.100988 DOI: https://doi.org/10.1016/j.disamonth.2020.100988
Ramos-Garcia P, Roca-Rodriguez MDM, Aguilar-Diosdado M, et al. Diabetes mellitus and oral cancer/oral potentially malignant disorders: a systematic review and meta-analysis. Oral Dis. 2021;27:404–21. https://doi.org/10.1111/odi.13289 DOI: https://doi.org/10.1111/odi.13289
Kapila YL. Oral health’s inextricable connection to systemic health: special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions. Periodontol 2000. 2021;87:11–16. https://doi.org/10.1111/prd.12398 DOI: https://doi.org/10.1111/prd.12398
Katsanos KH, Roda G, Brygo A, et al. Oral cancer and oral precancerous lesions in inflammatory bowel diseases: a systematic review. J Crohns Colitis. 2015;9:1043–52. https://doi.org/10.1093/ecco-jcc/jjv122 DOI: https://doi.org/10.1093/ecco-jcc/jjv122
Seymour RA. Is oral health a risk for malignant disease? Dent Update. 2010;37:279–80, 82–3. https://doi.org/10.12968/denu.2010.37.5.279 DOI: https://doi.org/10.12968/denu.2010.37.5.279
Meyer MS, Joshipura K, Giovannucci E, et al. A review of the relationship between tooth loss, periodontal disease, and cancer. Cancer Causes Control. 2008;19:895–907. https://doi.org/10.1007/s10552-008-9163-4 DOI: https://doi.org/10.1007/s10552-008-9163-4
Fitzpatrick SG, Katz J. The association between periodontal disease and cancer: a review of the literature. J Dent. 2010;38:83–95. https://doi.org/10.1016/j.jdent.2009.10.007 DOI: https://doi.org/10.1016/j.jdent.2009.10.007
Maisonneuve P, Amar S, Lowenfels AB. Periodontal disease, edentulism, and pancreatic cancer: a meta-analysis. Ann Oncol. 2017;28:985–95. https://doi.org/10.1093/annonc/mdx019 DOI: https://doi.org/10.1093/annonc/mdx019
Mei T, Noguchi H, Kuraji R, et al. Effects of periodontal pathogen-induced intestinal dysbiosis on transplant immunity in an allogenic skin graft model. Sci Rep. 2023;13:544. https://doi.org/10.1038/s41598-023-27861-4 DOI: https://doi.org/10.1038/s41598-023-27861-4
Momen-Heravi F, Babic A, Tworoger SS, et al. Periodontal disease, tooth loss and colorectal cancer risk: results from the nurses’ health study. Int J Cancer. 2017;140:646–52. https://doi.org/10.1002/ijc.30486 DOI: https://doi.org/10.1002/ijc.30486
Shi T, Min M, Sun C, et al. Periodontal disease and susceptibility to breast cancer: a meta-analysis of observational studies. J Clin Periodontol. 2018;45:1025–33. https://doi.org/10.1111/jcpe.12982 DOI: https://doi.org/10.1111/jcpe.12982
Michaud DS, Liu Y, Meyer M, et al. Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study. Lancet Oncol. 2008;9:550–8. https://doi.org/10.1016/S1470-2045(08)70106-2 DOI: https://doi.org/10.1016/S1470-2045(08)70106-2
Ahn J, Chen CY, Hayes RB. Oral microbiome and oral and gastrointestinal cancer risk. Cancer Causes Control. 2012;23:399–404. https://doi.org/10.1007/s10552-011-9892-7 DOI: https://doi.org/10.1007/s10552-011-9892-7
Yao QW, Zhou DS, Peng HJ, et al. Association of periodontal disease with oral cancer: a meta-analysis. Tumour Biol. 2014;35:7073–7. https://doi.org/10.1007/s13277-014-1951-8 DOI: https://doi.org/10.1007/s13277-014-1951-8
Ye L, Jiang Y, Liu W, et al. Correlation between periodontal disease and oral cancer risk: a meta-analysis. J Cancer Res Ther. 2016;12:C237–40. https://doi.org/10.4103/0973-1482.200746 DOI: https://doi.org/10.4103/0973-1482.200746
Gonde N, Rathod S, Kolte A, et al. Association between tooth loss and risk of occurrence of oral cancer – a systematic review and meta-analysis. Dent Res J. 2023;20:4. https://doi.org/10.4103/1735-3327.367903 DOI: https://doi.org/10.4103/1735-3327.367903
Slee VN. The international classification of diseases: ninth revision (ICD-9). Ann Intern Med. 1978;88:424–6. https://doi.org/10.7326/0003-4819-88-3-424 DOI: https://doi.org/10.7326/0003-4819-88-3-424
Trott PA. International classification of diseases for oncology. J Clin Pathol. 1977 Aug;30(8):782. https://doi.org/10.1136/jcp.30.8.782-c DOI: https://doi.org/10.1136/jcp.30.8.782-c
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5. https://doi.org/10.1007/s10654-010-9491-z DOI: https://doi.org/10.1007/s10654-010-9491-z
Luchini C, Veronese N, Nottegar A, et al. Assessing the quality of studies in meta-research: review/guidelines on the most important quality assessment tools. Pharm Stat. 2021;20:185–95. https://doi.org/10.1002/pst.2068 DOI: https://doi.org/10.1002/pst.2068
Lo CK, Mertz D, Loeb M. Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments. BMC Med Res Methodol. 2014;14:45. https://doi.org/10.1186/1471-2288-14-45 DOI: https://doi.org/10.1186/1471-2288-14-45
Laprise C, Shahul HP, Madathil SA, et al. Periodontal diseases and risk of oral cancer in Southern India: results from the HeNCe Life study. Int J Cancer. 2016;139:1512–19. https://doi.org/10.1002/ijc.30201 DOI: https://doi.org/10.1002/ijc.30201
Moraes RC, Dias FL, Figueredo CM, et al. Association between chronic periodontitis and oral/oropharyngeal cancer. Braz Dent J. 2016;27:261–6. https://doi.org/10.1590/0103-6440201600754 DOI: https://doi.org/10.1590/0103-6440201600754
Chang JS, Lo HI, Wong TY, et al. Investigating the association between oral hygiene and head and neck cancer. Oral Oncol. 2013;49:1010–17. https://doi.org/10.1016/j.oraloncology.2013.07.004 DOI: https://doi.org/10.1016/j.oraloncology.2013.07.004
Zheng TZ, Boyle P, Hu HF, et al. Dentition, oral hygiene, and risk of oral cancer: a case-control study in Beijing, People’s Republic of China. Cancer Causes Control. 1990;1:235–41. https://doi.org/10.1007/BF00117475 DOI: https://doi.org/10.1007/BF00117475
Tezal M, Sullivan MA, Hyland A, et al. Chronic periodontitis and the incidence of head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prevent. 2009;18:2406–12. https://doi.org/10.1158/1055-9965.EPI-09-0334 DOI: https://doi.org/10.1158/1055-9965.EPI-09-0334
Komlos G, Csurgay K, Horvath F, et al. Periodontitis as a risk for oral cancer: a case-control study. BMC Oral Health. 2021;21:640. https://doi.org/10.1186/s12903-021-01998-y DOI: https://doi.org/10.1186/s12903-021-01998-y
Shin YJ, Choung HW, Lee JH, et al. Association of periodontitis with oral cancer: a case-control study. J Dent Res. 2019;98:526–33. https://doi.org/10.1177/0022034519827565 DOI: https://doi.org/10.1177/0022034519827565
Narayan TV, Revanna GM, Hallikeri U, et al. Dental caries and periodontal disease status in patients with oral squamous cell carcinoma: A screening study in urban and semiurban population of Karnataka. J Maxillofac Oral Surg. 2014;13:435–43. https://doi.org/10.1007/s12663-013-0540-5 DOI: https://doi.org/10.1007/s12663-013-0540-5
Moergel M, Kämmerer P, Kasaj A, et al. Chronic periodontitis and its possible association with oral squamous cell carcinoma – a retrospective case control study. Head Face Med. 2013;9:39. https://doi.org/10.1186/1746-160X-9-39 DOI: https://doi.org/10.1186/1746-160X-9-39
Guha N, Boffetta P, Wünsch Filho V, et al. Oral health and risk of squamous cell carcinoma of the head and neck and esophagus: results of two multicentric case-control studies. Am J Epidemiol. 2007;166:1159–73. https://doi.org/10.1093/aje/kwm193 DOI: https://doi.org/10.1093/aje/kwm193
Bundgaard T, Wildt J, Frydenberg M, et al. Case-control study of squamous cell cancer of the oral cavity in Denmark. Cancer Causes Control. 1995;6:57–67. https://doi.org/10.1007/BF00051681 DOI: https://doi.org/10.1007/BF00051681
De Rezende CP, Ramos MB, Daguíla CH, et al. Oral health changes in patients with oral and oropharyngeal cancer. Braz J Otorhinolaryngol. 2008;74:596–600. https://doi.org/10.1016/S1808-8694(15)30609-1 DOI: https://doi.org/10.1016/S1808-8694(15)30609-1
Tezal M, Sullivan MA, Reid ME, et al. Chronic periodontitis and the risk of tongue cancer. Arch Otolaryngol Head Neck Surg. 2007;133:450–4. https://doi.org/10.1001/archotol.133.5.450 DOI: https://doi.org/10.1001/archotol.133.5.450
Rosenquist K, Wennerberg J, Schildt EB, et al. Oral status, oral infections and some lifestyle factors as risk factors for oral and oropharyngeal squamous cell carcinoma. A population-based case-control study in southern Sweden. Acta Oto-laryngol. 2005;125:1327–36. https://doi.org/10.1080/00016480510012273 DOI: https://doi.org/10.1080/00016480510012273
Chen PJ, Chen YY, Lin CW, et al. Effect of periodontitis and scaling and root planing on risk of pharyngeal cancer: a nested case – control study. Int J Environ Res Public Health. 2021;18:1–12. https://doi.org/10.3390/ijerph18010008 DOI: https://doi.org/10.3390/ijerph18010008
Hiraki A, Matsuo K, Suzuki T, et al. Teeth loss and risk of cancer at 14 common sites in Japanese. Cancer Epidemiol Biomarkers Prevent. 2008;17:1222–7. https://doi.org/10.1158/1055-9965.EPI-07-2761 DOI: https://doi.org/10.1158/1055-9965.EPI-07-2761
Garrote LF, Herrero R, Reyes RM, et al. Risk factors for cancer of the oral cavity and oro-pharynx in Cuba. Br J Cancer. 2001;85:46–54. https://doi.org/10.1054/bjoc.2000.1825 DOI: https://doi.org/10.1054/bjoc.2000.1825
Javed F, Warnakulasuriya S. Is there a relationship between periodontal disease and oral cancer? A systematic review of currently available evidence. Crit Rev Oncol Hematol. 2016;97:197–205. https://doi.org/10.1016/j.critrevonc.2015.08.018 DOI: https://doi.org/10.1016/j.critrevonc.2015.08.018
Meisel P, Holtfreter B, Biffar R, et al. Association of periodontitis with the risk of oral leukoplakia. Oral Oncol. 2012;48:859–63. https://doi.org/10.1016/j.oraloncology.2012.02.022 DOI: https://doi.org/10.1016/j.oraloncology.2012.02.022
Michaud DS, Fu Z, Shi J, et al. Periodontal disease, tooth loss, and cancer risk. Epidemiol Rev. 2017;39:49–58. https://doi.org/10.1093/epirev/mxx006 DOI: https://doi.org/10.1093/epirev/mxx006
Dhingra K. Is periodontal disease a risk factor for oral cancer? Evidence-based dentistry. Evid Based Dent. 2022;23:20–1. https://doi.org/10.1038/s41432-022-0245-z DOI: https://doi.org/10.1038/s41432-022-0245-z
Karin M, Lawrence T, Nizet V. Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell. 2006;124:823–35. https://doi.org/10.1016/j.cell.2006.02.016 DOI: https://doi.org/10.1016/j.cell.2006.02.016
Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7. https://doi.org/10.1038/nature01322 DOI: https://doi.org/10.1038/nature01322
Dholam KP, Sharma MR, Gurav SV, et al. Oral and dental health status in patients undergoing neoadjuvant chemotherapy for locally advanced head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021;132:539–48. https://doi.org/10.1016/j.oooo.2021.07.018 DOI: https://doi.org/10.1016/j.oooo.2021.07.018
Takahashi N, Nyvad B. The role of bacteria in the caries process: ecological perspectives. J Dent Res. 2011;90:294–303. https://doi.org/10.1177/0022034510379602 DOI: https://doi.org/10.1177/0022034510379602
Kõll-Klais P, Mändar R, Leibur E, et al. Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity. Oral Microbiol Immunol. 2005;20:354–61. https://doi.org/10.1111/j.1399-302X.2005.00239.x DOI: https://doi.org/10.1111/j.1399-302X.2005.00239.x
Teanpaisan R, Piwat S, Dahlén G. Inhibitory effect of oral Lactobacillus against oral pathogens. Lett Appl Microbiol. 2011;53:452–9. https://doi.org/10.1111/j.1472-765X.2011.03132.x DOI: https://doi.org/10.1111/j.1472-765X.2011.03132.x
Tezal M, Scannapieco FA, Wactawski-Wende J, et al. Dental caries and head and neck cancers. JAMA Otolaryngol Head Neck Surg. 2013;139:1054–60. https://doi.org/10.1001/jamaoto.2013.4569 DOI: https://doi.org/10.1001/jamaoto.2013.4569
Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: framework and proposal of a new classification and case definition. J Periodontol. 2018;89(Suppl. 1):S159–72. https://doi.org/10.1002/JPER.18-0006 DOI: https://doi.org/10.1002/JPER.18-0006
Caton JG, Armitage G, Berglundh T, et al. A new classification scheme for periodontal and peri-implant diseases and conditions – introduction and key changes from the 1999 classification. J Clin Periodontol. 2018;45(Suppl. 20):S1–8. https://doi.org/10.1111/jcpe.12935 DOI: https://doi.org/10.1002/JPER.18-0157
Erriu M, Genta G, Pili FM, et al. Probing depth in periodontal pockets: in vitro evaluation of contributions to variability due to probe type and operator skill. Proc Inst Mech Eng H. 2015;229:743–9. https://doi.org/10.1177/0954411915606170 DOI: https://doi.org/10.1177/0954411915606170
Al Shayeb KN, Turner W, Gillam DG. Periodontal probing: a review. Prim Dent J. 2014;3:25–9. https://doi.org/10.1308/205016814812736619 DOI: https://doi.org/10.1308/205016814812736619
Tezal M, Grossi SG, Genco RJ. Is periodontitis associated with oral neoplasms? J Periodontol. 2005;76:406–10. https://doi.org/10.1902/jop.2005.76.3.406 DOI: https://doi.org/10.1902/jop.2005.76.3.406
Holtfreter B, Albandar JM, Dietrich T, et al. Standards for reporting chronic periodontitis prevalence and severity in epidemiologic studies: proposed standards from the Joint EU/USA Periodontal Epidemiology Working Group. J Clin Periodontol. 2015;42:407–12. https://doi.org/10.1111/jcpe.12392 DOI: https://doi.org/10.1111/jcpe.12392
Page RC, Eke PI. Case definitions for use in population-based surveillance of periodontitis. J Periodontol. 2007;78(Suppl. 7S):1387–99. https://doi.org/10.1902/jop.2007.060264 DOI: https://doi.org/10.1902/jop.2007.060264
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Natural Science Foundation of Xinjiang Uygur Autonomous Region
Grant numbers 2022D01C265
Acta Odontologica Scandinavica publishes original research papers as well as critical reviews relevant to the diagnosis, epidemiology, health service, prevention, aetiology, pathogenesis, pathology, physiology, microbiology, development and treatment of diseases affecting tissues of the oral cavity and associated structures including papers on cause and effect or explanatory/associative relationships for experimental or observational studies.
