Chronic inflammation as a diagnostic modifier in oral potentially malignant disorders: a clinical perspective

Authors

DOI:

https://doi.org/10.5327/2525-5711.499

Keywords:

Oral potentially malignant disorders, chronic inflammation, oral epithelial dysplasia, chronic mechanical irritation, Candida

Abstract

This study examines how local chronic inflammatory conditions, particularly oral dysbiosis, Candida-associated inflammation, and chronic mechanical irritation, may modify the clinical and histopathological presentation of oral potentially malignant disorders (OPMDs) and complicate their assessment in routine practice. This expert clinical perspective, supported by selected literature and representative clinical scenarios, addresses clinicopathological gray zones arising when OPMDs coexist with inflammatory and microbial disturbances. These conditions may accentuate erythema, ulceration, hyperkeratosis, epithelial hyperplasia, and reactive cytological atypia, potentially complicating the distinction between inflammation-associated changes and true oral epithelial dysplasia (OED). Oral dysbiosis and Candida-associated inflammation may further modify the local inflammatory microenvironment and lesion phenotype. Recognition of these modifiers may inform biopsy timing and site selection, histopathological interpretation, and communication between clinicians and pathologists. Local inflammatory and microbial modifiers should be considered when evaluating OPMDs, particularly when clinical and histopathological findings are equivocal or discordant. Careful clinicopathological correlation and further prospective studies are needed to clarify the interactions among oral dysbiosis, chronic inflammation, and epithelial alterations in OPMDs.

References

1. Warnakulasuriya S, Kujan O, Aguirre-Urizar JM, et al. Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis. 2021;27(8):1862-80. https://doi.org/10.1111/odi.13704

2. Celentano A, Cirillo N. Diseases with oral malignant potential: Need for change to inform research, policy, and practice. J Oral Pathol Med. 2024;53(8):495-501. https://doi.org/10.1111/jop.13573

3. Speight PM, Khurram SA, Kujan O. Oral potentially malignant disorders: risk of progression to malignancy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125(6):612-27. https://doi.org/10.1016/j.oooo.2017.12.011

4. Odell E, Kujan O, Warnakulasuriya S, Sloan P. Oral epithelial dysplasia: Recognition, grading and clinical significance. Oral Diseases. 2021;27(8):1947-76. https://doi.org/10.1111/odi.13993

5. Feller L, Altini M, Lemmer J. Inflammation in the context of oral cancer. Oral Oncol. 2013;49(9):887-92. https://doi.org/10.1016/j.oraloncology.2013.07.003

6. Woo SB. Oral Epithelial Dysplasia and Premalignancy. Head Neck Pathol. 2019;13:423-39. https://doi.org/10.1007/s12105-019-01020-6

7. Gerardo G, Eduardo P, René P. Oral epithelial reactive atypia/dysplasia: An underestimated true atypia/dysplasia? Med Hypotheses. 2020;144:110217. https://doi.org/10.1016/j.mehy.2020.110217

8. Lazos JP, Piemonte ED, Lanfranchi HE, Brunotto MN. Characterization of Chronic Mechanical Irritation in Oral Cancer. Int J Dent. 2017;2017:6784526. https://doi.org/10.1155/2017/6784526

9. Piemonte E, Lazos J, Belardinelli P, Secchi D, Brunotto M, Lanfranchi-Tizeira H. Oral cancer associated with chronic mechanical irritation of the oral mucosa. Med Oral Patol Oral Cir Bucal. 2018;23(2):e151-e160. https://doi.org/10.4317/medoral.22017

10. Piemonte ED, Lazos JP, Gilligan GM, Panico RL, Werner LC, Yang YH, et al. Chronic mechanical irritation enhances the effect of tobacco and alcohol on the risk of oral squamous cell carcinoma: a case-control study in Argentina. Clin Oral Investig. 2022;26:6317-26. https://doi.org/10.1007/s00784-022-04584-w

11. Yoithapprabhunath TR, Ganapathy N, Renugadevi S, Rafath JM, Aparna V, Dineshshankar J. Cytogenetic analysis of genetic damage in young individuals exposed to chronic mechanical irritation in the lateral border of the tongue due to sharp teeth - a novel study. Med Pharm Rep. 2021;94(1):88-93. https://doi.org/10.15386/mpr-1567

12. Gilligan GM, Panico RL, Di Tada C, Piemonte ED, Brunotto MN. Clinical and Immunohistochemical epithelial profile of non-healing chronic traumatic ulcers. Med Oral Patol Oral Cir Bucal. 2020;25(5):e706-13. https://doi.org/10.4317/medoral.23729

13. Lazos JP, Hernandez Rios M, Astorga J, Panico RL, Piemonte ED, Zárate AM. p16 and MGMT Methylation in Chronic Traumatic Ulcers: A Plausible Link Between Chronic Mechanical Irritation and Oral Carcinogenesis? J Oral Pathol Med. 2026;55(6):669-75. https://doi.org/10.1111/jop.70128

14. Yoithapprabhunath TR, Ganapathy N, Renugadevi S, Rafath JM, Aparna V, Dineshshankar J. Cytogenetic analysis of genetic damage in young individuals exposed to chronic mechanical irritation in the lateral border of the tongue due to sharp teeth - a novel study. Med Pharm Rep. 2021;94(1):88-93. https://doi.org/10.15386/mpr-1567

15. Pandiar D, Krishnan RP. Plausible mechanisms in malignisation of non-habit related chronic nonhealing traumatic ulcers of oral cavity. Ind J Pathol Microbiol. 2024;67(3):725-8. https://doi.org/10.4103/ijpm.ijpm_800_23

16. Eisen D. Evaluating and treating patients with oral lichen planus. Dermatol Ther. 2002;15(3):206-17. https://doi.org/10.1046/j.1529-8019.2002.01529.x

17. Camargo CM dos S, Brotas AM, Ramos-e-Silva M, Carneiro S. Isomorphic phenomenon of Koebner: facts and controversies. Clin Dermatol. 2013;31(6):741-9. https://doi.org/10.1016/j.clindermatol.2013.05.012

18. Shan D, Long H, Lai W. TRPA1 may contribute to the exacerbation of oral lichen planus through Koebner phenomenon. Oral Dis. 2017;23(6):809-10. https://doi.org/10.1111/odi.12636

19. Holmstrup P. Oral erythroplakia-What is it? Oral Dis. 2018;24(1-2):138-43. https://doi.org/10.1111/odi.12709

20. Pérez MA, Raimondi AR, Itoiz ME. An experimental model to demonstrate the carcinogenic action of oral chronic traumatic ulcer. J Oral Pathol Med. 2005;34(1):17-22. https://doi.org/10.1111/j.1600-0714.2004.00249.x

21. Ashrafi F, Velte L, Schriber M, Baumhoer D, Bornstein MM. Oral squamous cell carcinoma misinterpreted as reaction to chronic mechanical trauma: report of two cases and critical review of the literature. Swiss Dent J. 2025;135(4):27-36. https://doi.org/10.61872/sdj-2025-04-03

22. Karpiński TM. Role of Oral Microbiota in Cancer Development. Microorganisms. 2019;7(1):20. https://doi.org/10.3390/microorganisms7010020

23. Choi YS, Kim Y, Yoon HJ, Baek KJ, Alam J, Park HK, et al. The presence of bacteria within tissue provides insights into the pathogenesis of oral lichen planus. Sci Rep. 2016;6:29186. https://doi.org/10.1038/srep29186

24. Khor B, Snow M, Herrman E, Ray N, Mansukhani K, Patel KA, Said-Al-Naief N, et al. Interconnections Between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance Between Systemic Health and Disease. Microorganisms. 2021;9(3):496. https://doi.org/10.3390/microorganisms9030496

25. Chattopadhyay I, Verma M, Panda M. Role of Oral Microbiome Signatures in Diagnosis and Prognosis of Oral Cancer. Technol Cancer Res Treat. 2019;18:1533033819867354. https://doi.org/10.1177/1533033819867354

26. Botero JE, Posada-López A, Mejía-Vallejo J, Pineda-Tamayo RA, Bedoya-Giraldo E. Effects of nonsurgical periodontal therapy in patients with rheumatoid arthritis: a prospective before and after study. Colomb Med (Cali). 52(3):e2095051. https://doi.org/10.25100/cm.v52i3.5051

27. Hongal BP, Kulkarni VV, Deshmukh RS, Joshi PS, Karande PP, Shroff AS. Prevalence of fungal hyphae in potentially malignant lesions and conditions-does its occurrence play a role in epithelial dysplasia? J Oral Maxillofac Pathol. 2015;19(1):10-7. https://doi.org/10.4103/0973-029X.157193

28. Gainza-Cirauqui ML, Nieminen MT, Novak Frazer L, Aguirre-Urizar JM, Moragues MD, Rautemaa R. Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders. J Oral Pathol Med. 2013;42(3):243-9. https://doi.org/10.1111/j.1600-0714.2012.01203.x

29. Gupta SR, Xess I, Singh G, Sharma A, Gupta N, Mani K, et al. Therapeutic implications of candida phenotypes, virulence factors and antifungal sensitivity in Oral leukoplakia. J Oral Biol Craniofac Res. 2021;11(2):354-60. https://doi.org/10.1016/j.jobcr.2021.03.006

30. Shukla K, Vun I, Lov I, Laparidis G, McCamley C, Ariyawardana A. Role of Candida infection in the malignant transformation of oral leukoplakia: A systematic review of observational studies. Translational Research in Oral Oncology. 2019;4:2057178X19828229. https://doi.org/10.1177/2057178X19828229

31. Müller S. Oral epithelial dysplasia, atypical verrucous lesions and oral potentially malignant disorders: focus on histopathology. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125(6):591-602. https://doi.org/10.1016/j.oooo.2018.02.012

32. Tilakaratne WM, Sherriff M, Morgan PR, Odell EW. Grading oral epithelial dysplasia: analysis of individual features. J Oral Pathol Med. 2011;40(7):533-40. https://doi.org/10.1111/j.1600-0714.2011.01033.x

33. Lorenzo-Pouso AI, Pérez-Jardón A, Caponio VCA, Spirito F, Chamorro-Petronacci CM, Álvarez-Calderón-Iglesias Ó, et al. Oral Chronic Hyperplastic Candidiasis and Its Potential Risk of Malignant Transformation: A Systematic Review and Prevalence Meta-Analysis. J Fungi. 2022;8(10):1093. https://doi.org/10.3390/jof8101093

34. Hankinson P, Mahmood H, Walsh H, Speight PM, Khurram SA. Demystifying oral epithelial dysplasia: a histological guide. Pathology. 2024;56(1):11-23. https://doi.org/10.1016/j.pathol.2023.10.002

35. Nitya K, Madhushankari GS, Basandi PS, Mohan Kumar KP, Priya NK, Ramakrishna A. Bcl-2 expression in reactive oral lesions with atypical epithelium and in oral epithelial dysplasia associated with carcinogen exposure. J Oral Maxillofac Pathol. 2019;23(2):306. https://doi.org/10.4103/jomfp.JOMFP_195_18

36. Lissoni A, Agliardi E, Peri A, Marchioni R, Abati S. Oral microbiome and mucosal trauma as risk factors for oral cancer: beyond alcohol and tobacco. A literature review. J Biol Regul Homeost Agents. 2020;34(6 Suppl. 3):11-8. PMID: 33386052

37. Chen Q, Dan H, Pan W, Jiang L, Zhou Y, Luo X, et al. Management of oral leukoplakia: a position paper of the Society of Oral Medicine, Chinese Stomatological Association. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021;132(1):32-43. https://doi.org/10.1016/j.oooo.2021.03.009

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Published

2026-09-04

How to Cite

1.
Gilligan G, Garola F, Costa MFG, Lazos J, Piemonte E, Panico RL. Chronic inflammation as a diagnostic modifier in oral potentially malignant disorders: a clinical perspective. J Oral Diagn [Internet]. 2026 Sept. 4 [cited 2026 Oct. 27];11. Available from: https://jordi.com.br/revista/article/view/499

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Review Article