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Oral Pre-malignancy: An Update on Novel Therapeutic Approaches

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Abstract

Purpose of Review

This review aims to provide a comprehensive overview of the current advances in managing and preventing progression of oral potentially malignant disorders (OPMDs), focusing on their histological and clinicopathological features, and management.

Recent Findings

Recent studies, including a multicenter cross-sectional study, have identified oral leukoplakia as the most prevalent form of OPMD, comprising over half of the cases examined. Advances in histological grading, specifically the World Health Organization’s three-tier system (mild, moderate, and severe dysplasia), have significantly enhanced the accuracy of risk assessment for malignant transformation. Additionally, treatments such as surgical interventions, photodynamic therapy, and chemopreventive and molecularly targeted agents are being evaluated for their safety and efficacy as well as, immune checkpoint inhibitors being evaluated as potential preventive strategies to halt the progression of OPMDs.

Summary

The management of OPMDs remains challenging due to the lack of standardized screening protocols and varied clinical management approaches. Despite this, recent advancements in diagnostic grading and therapeutic interventions provide a framework for improved treatment outcomes. Continued research into the molecular and cellular mechanisms driving development and progression of OPMDs and innovative treatment trials are essential to optimize strategies that prevent malignant progression and thereby reduce the global health burden of oral cancer.

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Fig. 1

Source: OPMD samples from patients biopsied/treated at MD Anderson Cancer Center

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Data Availability

No datasets were generated or analysed during the current study.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Shield KD, et al. The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA Cancer J Clin. 2017;67:51–64.

    Article  PubMed  Google Scholar 

  2. Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med. 2008;37:1–10.

    Article  PubMed  Google Scholar 

  3. Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma–an update. CA Cancer J Clin. 2015;65:401–21.

    Article  PubMed  Google Scholar 

  4. Neville BW, Day TA. Oral cancer and precancerous lesions. CA Cancer J Clin. 2002;52:195–215.

    Article  PubMed  Google Scholar 

  5. Mello FW, et al. Prevalence of oral potentially malignant disorders: a systematic review and meta-analysis. J Oral Pathol Med. 2018;47:633–40.

    Article  PubMed  Google Scholar 

  6. Chaturvedi AK, et al. Oral leukoplakia and risk of progression to oral Cancer: a Population-based Cohort Study. J Natl Cancer Inst. 2020;112:1047–54.

    Article  PubMed  Google Scholar 

  7. Moyer VA, Force US. P.S.T. screening for oral cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160:55–60.

    PubMed  Google Scholar 

  8. Speight PM, et al. Screening for oral cancer-a perspective from the global oral Cancer Forum. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123:680–7.

    Article  PubMed  Google Scholar 

  9. Lingen MW, et al. Evidence-based clinical practice guideline for the evaluation of potentially malignant disorders in the oral cavity: A report of the American Dental Association. J Am Dent Assoc. 2017;148:712-727e710.

    Article  PubMed  Google Scholar 

  10. Mehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia - a systematic review and meta-analysis. Head Neck. 2009;31:1600–9.

    Article  PubMed  Google Scholar 

  11. Kumari P, Debta P, Dixit A. Oral potentially malignant disorders: etiology, Pathogenesis, and Transformation into oral Cancer. Front Pharmacol. 2022;13:825266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Deng S, Wang S, Shi X, Zhou H. Microenvironment in oral potentially malignant Disorders: multi-dimensional characteristics and mechanisms of carcinogenesis. Int J Mol Sci 23(2022).

  13. Warnakulasuriya S, 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;27:1862–80. This work is important in the field of OPMD as it provides an updated and evidence-based classification and nomenclature, enhancing the identification and risk stratification of potentially malignant oral disorders to improve prevention and management of oral cancers.

    Article  PubMed  Google Scholar 

  14. Cai X, et al. Development and validation of a nomogram prediction model for malignant transformation of oral potentially malignant disorders. Oral Oncol. 2021;123:105619.

    Article  PubMed  Google Scholar 

  15. Khan AS, et al. Description of clinicopathological characteristics of oral potentially malignant disorders with special focus on two histopathologic grading systems and subepithelial inflammatory infiltrate. J Cancer Res Ther. 2023;19:S724–30.

    Article  PubMed  Google Scholar 

  16. Zhang X, et al. Deep learning-based pathology image analysis predicts cancer progression risk in patients with oral leukoplakia. Cancer Med. 2023;12:7508–18. This work is important because it uses AI, specifically convolutional neural networks, to improve the prediction of oral leukoplakia progression to oral cancer, facilitating early intervention and potentially reducing cancer morbidity and mortality.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Cossa F, Piastra A, Sarrion-Perez MG, Bagan L. Oral manifestations in drug users: a review. J Clin Exp Dent. 2020;12:e193–200.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cressey D. The cannabis experiment. Nature. 2015;524:280–3.

    Article  PubMed  Google Scholar 

  19. Izumchenko E, et al. Notch1 mutations are drivers of oral tumorigenesis. Cancer Prev Res (Phila). 2015;8:277–86.

    Article  CAS  PubMed  Google Scholar 

  20. Martins-de-Barros AV, et al. High prevalence of oral potentially malignant disorders and risk factors in a semi-urban Brazilian city: a population-based cross-sectional study. Med Oral Patol Oral Cir Bucal. 2021;26:e778–85.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Al-Hashimi I, et al. Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(Suppl):e21–12.

    Google Scholar 

  22. Rodriguez-Fonseca L, Llorente-Pendas S, Garcia-Pola M. Risk of Prediabetes and diabetes in oral Lichen Planus: a case-control study according to current diagnostic criteria. Diagnostics (Basel) 13(2023).

  23. Tsushima F, et al. Malignant transformation of oral lichen planus: a retrospective study of 565 Japanese patients. BMC Oral Health. 2021;21:298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gillenwater A, Papadimitrakopoulou V, Richards-Kortum R. Oral premalignancy: new methods of detection and treatment. Curr Oncol Rep. 2006;8:146–54.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Svistun E, et al. Vision enhancement system for detection of oral cavity neoplasia based on autofluorescence. Head Neck. 2004;26:205–15.

    Article  PubMed  Google Scholar 

  26. Vedtofte P, Holmstrup P, Hjorting-Hansen E, Pindborg JJ. Surgical treatment of premalignant lesions of the oral mucosa. Int J Oral Maxillofac Surg. 1987;16:656–64.

    Article  CAS  PubMed  Google Scholar 

  27. Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer. 1953;6:963–8.

    Article  CAS  PubMed  Google Scholar 

  28. van der Hem PS, Nauta JM, van der Wal JE, Roodenburg JL. The results of CO2 laser surgery in patients with oral leukoplakia: a 25 year follow up. Oral Oncol. 2005;41:31–7.

    Article  PubMed  Google Scholar 

  29. Sudbo J, et al. The influence of resection and aneuploidy on mortality in oral leukoplakia. N Engl J Med. 2004;350:1405–13.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang L, et al. Impact of localized treatment in reducing risk of progression of low-grade oral dysplasia: molecular evidence of incomplete resection. Oral Oncol. 2001;37:505–12.

    Article  CAS  PubMed  Google Scholar 

  31. Chandu A, Smith AC. The use of CO2 laser in the treatment of oral white patches: outcomes and factors affecting recurrence. Int J Oral Maxillofac Surg. 2005;34:396–400.

    Article  CAS  PubMed  Google Scholar 

  32. Pandey A, et al. Cryotherapy for oral potentially malignant disorders. Bioinformation. 2023;19:1377–82.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sako K, Marchetta FC, Hayes RL. Cryotherapy of intraoral leukoplakia. Am J Surg. 1972;124:482–4.

    Article  CAS  PubMed  Google Scholar 

  34. Yeh CJ. Simple cryosurgical treatment for oral lesions. Int J Oral Maxillofac Surg. 2000;29:212–6.

    Article  CAS  PubMed  Google Scholar 

  35. Yu CH, Lin HP, Cheng SJ, Sun A, Chen HM. Cryotherapy for oral precancers and cancers. J Formos Med Assoc. 2014;113:272–7.

    Article  PubMed  Google Scholar 

  36. Kawczyk-Krupka A, et al. Comparison of cryotherapy and photodynamic therapy in treatment of oral leukoplakia. Photodiagnosis Photodyn Ther. 2012;9:148–55.

    Article  PubMed  Google Scholar 

  37. Hamadah O, Thomson PJ. Factors affecting carbon dioxide laser treatment for oral precancer: a patient cohort study. Lasers Surg Med. 2009;41:17–25.

    Article  CAS  PubMed  Google Scholar 

  38. Thomson PJ, Wylie J. Interventional laser surgery: an effective surgical and diagnostic tool in oral precancer management. Int J Oral Maxillofac Surg. 2002;31:145–53.

    Article  CAS  PubMed  Google Scholar 

  39. Brandon MS, Strauss RA. Complications of CO(2) laser procedures in oral and maxillofacial surgery. Oral Maxillofac Surg Clin North Am. 2004;16:289–99.

    Article  PubMed  Google Scholar 

  40. Goodson ML, Sugden K, Kometa S, Thomson PJ. Complications following interventional laser surgery for oral cancer and precancerous lesions. Br J Oral Maxillofac Surg. 2012;50:597–600.

    Article  CAS  PubMed  Google Scholar 

  41. Tan YQ, Li ZT, Zhou G. Developmental synergism in the management of oral potentially malignant disorders. Photodiagnosis Photodyn Ther. 2023;42:103563.

    Article  PubMed  Google Scholar 

  42. Steward WP, Brown K. Cancer chemoprevention: a rapidly evolving field. Br J Cancer. 2013;109:1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Stich HF, Hornby AP, Mathew B, Sankaranarayanan R, Nair MK. Response of oral leukoplakias to the administration of vitamin A. Cancer Lett. 1988;40:93–101.

    Article  CAS  PubMed  Google Scholar 

  44. Hong WK, et al. 13-cis-retinoic acid in the treatment of oral leukoplakia. N Engl J Med. 1986;315:1501–5.

    Article  CAS  PubMed  Google Scholar 

  45. Lippman SM, et al. Comparison of low-dose isotretinoin with beta carotene to prevent oral carcinogenesis. N Engl J Med. 1993;328:15–20.

    Article  CAS  PubMed  Google Scholar 

  46. Papadimitrakopoulou VA, et al. Low-dose isotretinoin versus beta-carotene to prevent oral carcinogenesis: long-term follow-up. J Natl Cancer Inst. 1997;89:257–8.

    Article  CAS  PubMed  Google Scholar 

  47. William WN Jr., Heymach JV, Kim ES, Lippman SM. Molecular targets for cancer chemoprevention. Nat Rev Drug Discov. 2009;8:213–25.

    Article  CAS  PubMed  Google Scholar 

  48. Alpha-Tocopherol B. .G. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994;330:1029–35.

    Article  Google Scholar 

  49. Scardina GA, Carini F, Maresi E, Valenza V, Messina P. Evaluation of the clinical and histological effectiveness of isotretinoin in the therapy of oral leukoplakia: ten years of experience: is management still up to date and effective? Methods Find Exp Clin Pharmacol. 2006;28:115–9.

    Article  PubMed  Google Scholar 

  50. Singh M, Krishanappa R, Bagewadi A, Keluskar V. Efficacy of oral lycopene in the treatment of oral leukoplakia. Oral Oncol. 2004;40:591–6.

    Article  CAS  PubMed  Google Scholar 

  51. Papadimitrakopoulou VA, et al. Pilot randomized phase II study of celecoxib in oral premalignant lesions. Clin Cancer Res. 2008;14:2095–101.

    Article  CAS  PubMed  Google Scholar 

  52. Mulshine JL, et al. Randomized, double-blind, placebo-controlled phase IIb trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia. Clin Cancer Res. 2004;10:1565–73.

    Article  CAS  PubMed  Google Scholar 

  53. William WN Jr., et al. Erlotinib and the risk of oral Cancer: the Erlotinib Prevention of oral Cancer (EPOC) randomized clinical trial. JAMA Oncol. 2016;2:209–16.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Tsao AS, et al. Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions. Cancer Prev Res (Phila). 2009;2:931–41.

    Article  CAS  PubMed  Google Scholar 

  55. Kuriakose MA, et al. A Randomized double-blind placebo-controlled phase IIB trial of curcumin in oral Leukoplakia. Cancer Prev Res (Phila). 2016;9:683–91.

    Article  CAS  PubMed  Google Scholar 

  56. Epstein JB, Wong FL, Millner A, Le ND. Topical bleomycin treatment of oral leukoplakia: a randomized double-blind clinical trial. Head Neck. 1994;16:539–44.

    Article  CAS  PubMed  Google Scholar 

  57. Mallery SR, et al. Topical application of a mucoadhesive freeze-dried black raspberry gel induces clinical and histologic regression and reduces loss of heterozygosity events in premalignant oral intraepithelial lesions: results from a multicentered, placebo-controlled clinical trial. Clin Cancer Res. 2014;20:1910–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gutkind JS et al. Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions. JCI Insight 6(2021).

  59. Pang X, et al. Myeloid derived suppressor cells contribute to the malignant progression of oral squamous cell carcinoma. PLoS ONE. 2020;15:e0229089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kouketsu A, et al. Regulatory T cells and M2-polarized tumour-associated macrophages are associated with the oncogenesis and progression of oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2019;48:1279–88.

    Article  CAS  PubMed  Google Scholar 

  61. Yagyuu T, et al. Programmed death ligand 1 (PD-L1) expression and tumor microenvironment: implications for patients with oral precancerous lesions. Oral Oncol. 2017;68:36–43.

    Article  CAS  PubMed  Google Scholar 

  62. Grgurevic J, Knezevic G, Kobler P, Krmpotic I. An alternative method of fixation of alveolar ridge mucosa during the vestibuloplasty procedure. Br J Oral Maxillofac Surg. 1988;26:370–4.

    Article  CAS  PubMed  Google Scholar 

  63. Chen XJ, Tan YQ, Zhang N, He MJ, Zhou G. Expression of programmed cell death-ligand 1 in oral squamous cell carcinoma and oral leukoplakia is associated with disease progress and CD8 + tumor-infiltrating lymphocytes. Pathol Res Pract. 2019;215:152418.

    Article  CAS  PubMed  Google Scholar 

  64. Foy JP, et al. Immunological and classical subtypes of oral premalignant lesions. Oncoimmunology. 2018;7:e1496880.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Hanna GJ, et al. Comprehensive immunoprofiling of high-risk oral proliferative and localized Leukoplakia. Cancer Res Commun. 2021;1:30–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hanna GJ et al., Nivolumab for Patients With High-Risk Oral Leukoplakia: A Nonrandomized Controlled Trial. JAMA Oncol. (2023).  This work provides strong evidence that immune checkpoint therapy, specifically anti-PD-1 therapy, may offer a promising treatment for high-risk proliferative verrucous leukoplakia, a precancerous condition with a high risk of progression to oral squamous cell carcinoma. Additionally, the study identifies critical immunogenomic associations that could guide future research and treatment strategies for this aggressive disease.

  67. Girolami I, et al. Prevalence of PD-L1 expression in head and neck squamous precancerous lesions: a systematic review and meta-analysis. Head Neck. 2020;42:3018–30.

    Article  PubMed  Google Scholar 

  68. Mascaux C, et al. Immune evasion before tumour invasion in early lung squamous carcinogenesis. Nature. 2019;571:570–5.

    Article  CAS  PubMed  Google Scholar 

  69. Pennycuick A, et al. Immune Surveillance in Clinical Regression of Preinvasive squamous cell Lung Cancer. Cancer Discov. 2020;10:1489–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Rangel R, Pickering CR, Sikora AG, Spiotto MT. Genetic changes driving immunosuppressive microenvironments in oral Premalignancy. Front Immunol. 2022;13:840923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Shi Y, et al. Local Anti-PD-1 delivery prevents progression of Premalignant lesions in a 4NQO-Oral carcinogenesis mouse model. Cancer Prev Res (Phila). 2021;14:767–78.

    Article  CAS  PubMed  Google Scholar 

  72. Spira A, et al. Leveraging premalignant biology for immune-based cancer prevention. Proc Natl Acad Sci U S A. 2016;113:10750–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Wang T, Sun S, Zeng X, Li J. ICI-based therapies: a new strategy for oral potentially malignant disorders. Oral Oncol. 2023;140:106388.

    Article  CAS  PubMed  Google Scholar 

  74. Hanna GJ, et al. Nivolumab for patients with high-risk oral leukoplakia: a Nonrandomized Controlled Trial. JAMA Oncol. 2024;10:32–41.

    Article  PubMed  Google Scholar 

  75. Novaes MdeO. Targeting of CD40 and PD-L1 pathways inhibits progression of oral premalignant lesions in a carcinogen-induced model of oral squamous cell carcinoma. Cancer Prev Res (Phila). 2021;14:313–24.

    Article  Google Scholar 

  76. Wang Z, et al. Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4. Nat Commun. 2019;10:5546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Liu JF, et al. T-cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer. Mol Oncol. 2017;11:235–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Shayan G, et al. Adaptive resistance to anti-PD1 therapy by Tim-3 upregulation is mediated by the PI3K-Akt pathway in head and neck cancer. Oncoimmunology. 2017;6:e1261779.

    Article  PubMed  Google Scholar 

  79. Deng WW, et al. LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma. Oncoimmunology. 2016;5:e1239005.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Mishra AK, et al. Squamous cell carcinomas escape immune surveillance via inducing chronic activation and exhaustion of CD8 + T cells co-expressing PD-1 and LAG-3 inhibitory receptors. Oncotarget. 2016;7:81341–56.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Triebel F, et al. LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med. 1990;171:1393–405.

    Article  CAS  PubMed  Google Scholar 

  82. Igor Samoylenko OVK, Zabotina T. Demidov. Intralesional anti-PD1 treatment in patients with metastatic melanoma: the pilot study. J Clin Oncol. 2018;36:188–188.

    Article  Google Scholar 

  83. Epstein JB, Guneri P, Boyacioglu H, Abt E. The limitations of the clinical oral examination in detecting dysplastic oral lesions and oral squamous cell carcinoma. J Am Dent Assoc. 2012;143:1332–42.

    Article  PubMed  Google Scholar 

  84. Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med. 2008;37:127–33.

    Article  CAS  PubMed  Google Scholar 

  85. Shafirstein G, et al. Using 5-aminolevulinic acid and pulsed dye laser for photodynamic treatment of oral leukoplakia. Arch Otolaryngol Head Neck Surg. 2011;137:1117–23.

    Article  PubMed  Google Scholar 

  86. Civantos F. Photodynamic therapy for head and neck lesions in the subtropics. J Natl Compr Canc Netw. 2012;10(Suppl 2):S65–68.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. The Department of Head and Neck Surgery, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Shorook Naara, Clara Andrews, Andrew Sikora, Mark Chambers, Jeffrey Myers & Moran Amit

  2. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Michelle Williams

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  1. Shorook Naara
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Contributions

S.N. and C.A. wrote the main manuscript and prepared the table. M.A, A.S., J.M., M.S. and M.W. reviewed and revised the manuscript. all authors reviewed the manuscript.

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Correspondence to Moran Amit.

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Naara, S., Andrews, C., Sikora, A. et al. Oral Pre-malignancy: An Update on Novel Therapeutic Approaches. Curr Oncol Rep (2024). https://doi.org/10.1007/s11912-024-01562-1

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