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Oral Dysplasia: Biomarkers, Treatment, and Follow-up

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Abstract

Dysplasia affecting the oral mucosa has a malignant potential. The options for treatment of oral dysplasia are limited. Surgery remains the mainstay of management, with no strong evidence for medical treatments currently available. Histological grading alone does not accurately predict which dysplastic lesions will progress to cancer, which poses the clinician with difficult decisions regarding the most appropriate treatment and may lead to some patients being overtreated, with potentially unnecessary morbidity. The use of biomarkers may help to improve prediction of which cases are likely to transform. The efficacy of individual markers for prediction will be discussed in this paper. There is also a lack of consensus on the optimal frequency and duration of follow-up for patients with oral dysplasia.

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References

Recently published papers of interest have been highlighted as • Of importance •• Of major importance

  1. Warnakulasuriya S, Johnson NW, Van Der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. Journal of Oral Pathology & Medicine. 2007;36(10):575–80.

    Article  CAS  Google Scholar 

  2. Organization GWH. World Health Organization. Report of a meeting of inves- tigators on the histological definition of precancerous lesions. . 1973 Can ⁄731.

  3. • Thomson P. Field change and oral cancer: new evidence for widespread carcinogenesis? International journal of oral and maxillofacial surgery. [10.1054/ijom.2002.0220]. 2002;31(12190131):262–6. This paper demonstrated that dysplastic change can occur in apparently normal-looking mucosa at a site distant from the obvious dysplastic lesion.

    Article  PubMed  CAS  Google Scholar 

  4. van der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral oncology. [10.1016/j.oraloncology.2010.02.016]. 2010;46(20308005):423–5.

    Article  PubMed  Google Scholar 

  5. Petti S. Pooled estimate of world leukoplakia prevalence: a systematic review. Oral Oncology. 2003;39(13679200):770–80.

    Article  PubMed  Google Scholar 

  6. Online I. ISD Online, 2010 Cancer Incidence and Mortality data, 2008.

  7. Agency NISaR. Northern Ireland Statistics and Research Agency 2010 Northern Ireland Mortality data, 2008.

  8. Statistics OfN. Office for National Statistics, 2010 Mortality Statistics: Cause, 2008.

  9. •• Lodi G, Sardella A, Bez C, Demarosi F, Carrassi A. Interventions for treating oral leukoplakia. Cochrane database of systematic reviews (Online). [10.1002/14651858.CD001829.pub3]. 2006(17054142):CD001829. This review demonstrated the lack of evidence that any treatments prevent malignant transformation of oral leukoplakia.

  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 Dec;31(12):1600–9. This is a thorough systematic review of the highest-quality evidence available on the treatment and follow-up of oral dysplasia.

    Article  PubMed  Google Scholar 

  11. Thomson P, Wylie J. Interventional laser surgery: an effective surgical and diagnostic tool in oral precancer management. International journal of oral and maxillofacial surgery. [10.1054/ijom.2001.0189]. 2002;31(12102411):145–53.

    Article  PubMed  CAS  Google Scholar 

  12. • Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med. 2008 Jan;37(1):1–10. This excellent review on the natural history of leukoplakia is part of a series of publications to come from a workshop coordinated by the WHO Collaborating Center for Oral Cancer and Precancer.

    Article  PubMed  Google Scholar 

  13. Vladimirov BS, Schiodt M. The effect of quitting smoking on the risk of unfavorable events after surgical treatment of oral potentially malignant lesions. Int J Oral Maxillofac Surg. 2009 Nov;38(11):1188–93.

    Article  PubMed  CAS  Google Scholar 

  14. Epstein JB, Wong FL, Millner A, Le ND. Topical bleomycin treatment of oral leukoplakia: a randomized double-blind clinical trial. Head Neck. 1994 Nov-Dec;16(6):539–44.

    Article  PubMed  CAS  Google Scholar 

  15. Sankaranarayanan R, Mathew B, Varghese C, Sudhakaran PR, Menon V, Jayadeep A, et al. Chemoprevention of oral leukoplakia with vitamin A and beta carotene: an assessment. Oral Oncol. 1997 Jul;33(4):231–6.

    Article  PubMed  CAS  Google Scholar 

  16. Lippman SM, Lee JJ, Martin JW, El-Naggar AK, Xu X, Shin DM, et al. Fenretinide activity in retinoid-resistant oral leukoplakia. Clinical cancer research : an official journal of the American Association for Cancer Research. [10.1158/1078-0432.CCR-05-2636]. 2006;12(16707609):3109–14.

    CAS  Google Scholar 

  17. Chiesa F, Tradati N, Grigolato R, Boracchi P, Biganzoli E, Crose N, et al. Randomized trial of fenretinide (4-HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: long-term results. International journal of cancer Journal international du cancer. [10.1002/ijc.20923]. 2005;115(15700313):625–9.

    Article  PubMed  CAS  Google Scholar 

  18. William WN, Lee JJ, Lippman SM, Martin JW, Chakravarti N, Tran HT, et al. High-dose fenretinide in oral leukoplakia. Cancer prevention research (Philadelphia, Pa). [10.1158/1940-6207.CAPR-08-0100]. 2009;2(19139014):22–6.

    Article  CAS  Google Scholar 

  19. Renkonen J, Wolff H, Paavonen T. Expression of cyclo-oxygenase-2 in human tongue carcinoma and its precursor lesions. Virchows Arch. 2002 Jun;440(6):594–7.

    Article  PubMed  CAS  Google Scholar 

  20. Shaheen NJ, Straus WL, Sandler RS. Chemoprevention of gastrointestinal malignancies with nonsteroidal antiinflammatory drugs. Cancer. 2002 Feb 15;94(4):950–63.

    Article  PubMed  CAS  Google Scholar 

  21. Papadimitrakopoulou VA, William WN, Dannenberg AJ, Lippman SM, Lee JJ, Ondrey FG, et al. Pilot randomized phase II study of celecoxib in oral premalignant lesions. Clinical cancer research : an official journal of the American Association for Cancer Research. [10.1158/1078-0432.CCR-07-4024]. 2008;14(18381950):2095–101.

    CAS  Google Scholar 

  22. Wirth LJ, Krane JF, Li Y, Othus M, Moran AE, Dorfman DM, et al. A pilot surrogate endpoint biomarker study of celecoxib in oral premalignant lesions. Cancer prevention research (Philadelphia, Pa). [10.1158/1940-6207.CAPR-07-0003]. 2008;1(19138978):339–48.

    Article  Google Scholar 

  23. Mulshine JL, Atkinson JC, Greer RO, Papadimitrakopoulou VA, Van Waes C, Rudy S, 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 Mar 1;10(5):1565–73.

    Article  PubMed  CAS  Google Scholar 

  24. Zhang S, Li Y, Li L, Zhang Y, Gao N, Zhang Z, et al. Phase I study of repeated intraepithelial delivery of adenoviral p53 in patients with dysplastic oral leukoplakia. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. [10.1016/j.joms.2008.06.079]. 2009;67(19375021):1074–82.

    Google Scholar 

  25. Rigual NR, Thankappan K, Cooper M, Sullivan MA, Dougherty T, Popat SR, et al. Photodynamic therapy for head and neck dysplasia and cancer. Archives of otolaryngology--head & neck surgery. [10.1001/archoto.2009.98]. 2009;135(19687399):784–8.

    Article  Google Scholar 

  26. Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S, et al. Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res. 1996 Jun;56(11):2488–92.

    PubMed  CAS  Google Scholar 

  27. Barnes L EJ, Reichart P, Sidransky D. World Health Organization classification of tumours. Pathology and genetics of tumours of the head and neck: IARC Press: Lyon; 2005.

    Google Scholar 

  28. Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. [10.1111/j.1600-0714.2007.00584.x]. 2008;37(18251935):127–33.

    CAS  Google Scholar 

  29. Fleskens S, Slootweg P. Grading systems in head and neck dysplasia: their prognostic value, weaknesses and utility. Head Neck Oncol. 2009;1(1):11.

    Article  PubMed  Google Scholar 

  30. Smith J, Rattay T, McConkey C, Helliwell T, Mehanna H. Biomarkers in dysplasia of the oral cavity: a systematic review. Oral Oncol. 2009 Aug;45(8):647–53.

    Article  PubMed  CAS  Google Scholar 

  31. Lo Muzio L, Pannone G, Leonardi R, Staibano S, Mignogna MD, De Rosa G, et al. Survivin, a potential early predictor of tumor progression in the oral mucosa. J Dent Res. 2003 Nov;82(11):923–8.

    Article  PubMed  CAS  Google Scholar 

  32. Jordan RC, Macabeo-Ong M, Shiboski CH, Dekker N, Ginzinger DG, Wong DT, et al. Overexpression of matrix metalloproteinase-1 and -9 mRNA is associated with progression of oral dysplasia to cancer. Clin Cancer Res. 2004 Oct 1;10(19):6460–5.

    Article  PubMed  CAS  Google Scholar 

  33. Yoon AJ, Shen J, Santella RM, Zegarelli DJ, Chen R, Weinstein IB. Activated checkpoint kinase 2 expression and risk for oral squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2768–72.

    Article  PubMed  CAS  Google Scholar 

  34. Hall GL, Shaw RJ, Field EA, Rogers SN, Sutton DN, Woolgar JA, et al. p16 Promoter methylation is a potential predictor of malignant transformation in oral epithelial dysplasia. Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):2174–9.

    Article  PubMed  CAS  Google Scholar 

  35. Torres-Rendon A, Roy S, Craig GT, Speight PM. Expression of Mcm2, geminin and Ki67 in normal oral mucosa, oral epithelial dysplasias and their corresponding squamous-cell carcinomas. Br J Cancer. 2009 Apr 7;100(7):1128–34

    Article  PubMed  CAS  Google Scholar 

  36. Taoudi Benchekroun M, Saintigny P, Thomas SM, El-Naggar AK, Papadimitrakopoulou V, Ren H, et al. Epidermal growth factor receptor expression and gene copy number in the risk of oral cancer. Cancer Prevention Research. [10.1158/1940-6207.CAPR-09-0163]. 2010;3(20570883):800–9.

    Article  PubMed  Google Scholar 

  37. Saintigny P, El-Naggar AK, Papadimitrakopoulou V, Ren H, Fan YH, Feng L, et al. DeltaNp63 overexpression, alone and in combination with other biomarkers, predicts the development of oral cancer in patients with leukoplakia. Clin Cancer Res. 2009 Oct 1;15(19):6284–91.

    Article  PubMed  CAS  Google Scholar 

  38. Kawaguchi H, El-Naggar AK, Papadimitrakopoulou V, Ren H, Fan YH, Feng L, et al. Podoplanin: a novel marker for oral cancer risk in patients with oral premalignancy. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. [10.1200/JCO.2007.13.4072]. 2008;26(18202409):354–60.

    Google Scholar 

  39. Ogbureke KU, Abdelsayed RA, Kushner H, Li L, Fisher LW. Two members of the SIBLING family of proteins, DSPP and BSP, may predict the transition of oral epithelial dysplasia to oral squamous cell carcinoma. Cancer. 2010 Apr 1;116(7):1709–17.

    Article  PubMed  Google Scholar 

  40. Rosin MP, Cheng X, Poh C, Lam WL, Huang Y, Lovas J, et al. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clinical cancer research : an official journal of the American Association for Cancer Research. 2000;6(10690511):357–62.

    CAS  Google Scholar 

  41. Zhou X, Jordan RC, Li Y, Huang BL, Wong DT. Frequent allelic imbalances at 8p and 11q22 in oral and oropharyngeal epithelial dysplastic lesions. Cancer Genet Cytogenet. 2005 Aug;161(1):86–9.

    Article  PubMed  CAS  Google Scholar 

  42. Partridge M, Emilion G, Pateromichelakis S, A’Hern R, Phillips E, Langdon J. Allelic imbalance at chromosomal loci implicated in the pathogenesis of oral precancer, cumulative loss and its relationship with progression to cancer. Oral Oncol. 1998 Mar;34(2):77–83.

    Article  PubMed  CAS  Google Scholar 

  43. Hogmo A, Lindskog S, Lindholm J, Kuylenstierna R, Auer G, Munck-Wikland E. Preneoplastic oral lesions: the clinical value of image cytometry DNA analysis, p53 and p21/WAF1 expression. Anticancer Res. 1998 Sep-Oct;18(5B):3645–50.

    PubMed  CAS  Google Scholar 

  44. Torres-Rendon A, Stewart R, Craig GT, Wells M, Speight PM. DNA ploidy analysis by image cytometry helps to identify oral epithelial dysplasias with a high risk of malignant progression. Oral Oncol. 2009 Jun;45(6):468–73.

    Article  PubMed  CAS  Google Scholar 

  45. Tsui IF, Poh C, Garnis C, Rosin M, Zhang L, Lam W. Multiple pathways in the FGF signaling network are frequently deregulated by gene amplification in oral dysplasias. International journal of cancer Journal international du cancer. [10.1002/ijc.24611]. 2009;125(19623652):2219–28.

    Article  PubMed  CAS  Google Scholar 

  46. Sundvall M, Karrila A, Nordberg J, Grenman R, Elenius K. EGFR targeting drugs in the treatment of head and neck squamous cell carcinoma. Expert Opin Emerg Drugs. 2010 Jun;15(2):185–201.

    Article  PubMed  CAS  Google Scholar 

  47. Cruz IB, Snijders PJ, Meijer CJ, Braakhuis BJ, Snow GB, Walboomers JM, et al. p53 expression above the basal cell layer in oral mucosa is an early event of malignant transformation and has predictive value for developing oral squamous cell carcinoma. J Pathol. 1998 Apr;184(4):360–8.

    Article  PubMed  CAS  Google Scholar 

  48. Cruz I, Napier SS, van der Waal I, Snijders PJ, Walboomers JM, Lamey PJ, et al. Suprabasal p53 immunoexpression is strongly associated with high grade dysplasia and risk for malignant transformation in potentially malignant oral lesions from Northern Ireland. J Clin Pathol. 2002 Feb;55(2):98–104.

    Article  PubMed  CAS  Google Scholar 

  49. Regezi JA, Zarbo RJ, Regev E, Pisanty S, Silverman S, Gazit D. p53 protein expression in sequential biopsies of oral dysplasias and in situ carcinomas. J Oral Pathol Med. 1995 Jan;24(1):18–22.

    Article  PubMed  CAS  Google Scholar 

  50. Rich AM, Kerdpon D, Reade PC. p53 expression in oral precancer and cancer. Aust Dent J. 1999 Jun;44(2):103–5.

    Article  PubMed  CAS  Google Scholar 

  51. Shahnavaz SA, Regezi JA, Bradley G, Dube ID, Jordan RC. p53 gene mutations in sequential oral epithelial dysplasias and squamous cell carcinomas. J Pathol. 2000 Mar;190(4):417–22.

    Article  PubMed  CAS  Google Scholar 

  52. Nankivell P WM, McConkey C, Paleri V, Mehanna H. Biomarkers in laryngeal dysplasia: a systematic review. Accepted to Head and Neck. 2010.

  53. Schaaij-Visser TB, Bremmer JF, Braakhuis BJ, Heck AJ, Slijper M, van der Waal I, et al. Evaluation of cornulin, keratin 4, keratin 13 expression and grade of dysplasia for predicting malignant progression of oral leukoplakia. Oral Oncol. 2010 Feb;46(2):123–7.

    Article  PubMed  CAS  Google Scholar 

  54. •• McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, et al. REporting recommendations for tumour MARKer prognostic studies (REMARK). British journal of cancer. [10.1038/sj.bjc.6602678]. 2005;93(16106245):387–91. This paper suggests guidelines to enable more standardized and transparent reporting of biomarker studies.

    Article  PubMed  CAS  Google Scholar 

  55. Fleskens S, Takes R, Otte-H√∂ller I, Van Doesburg L, Smeets A, Speel E, et al. Simultaneous assessment of DNA ploidy and biomarker expression in paraffin-embedded tissue sections. Histopathology. [10.1111/j.1365-2559.2010.03599.x]. 2010;57(20653778):14–26.

    Article  PubMed  Google Scholar 

  56. Epstein JB, Gorsky M, Fischer D, Gupta A, Epstein M, Elad S. A survey of the current approaches to diagnosis and management of oral premalignant lesions. Journal of the American Dental Association (1939). 2007;138(18056099):1555–62; quiz 614.

    Google Scholar 

  57. Marley JJ, Linden GJ, Cowan CG, Lamey PJ, Johnson NW, Warnakulasuriya KA, et al. A comparison of the management of potentially malignant oral mucosal lesions by oral medicine practitioners and oral & maxillofacial surgeons in the UK. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1998;27(9831962):489–95.

    CAS  Google Scholar 

  58. Spielmann P, Palmer T, McClymont L. 15-Year review of laryngeal and oral dysplasias and progression to invasive carcinoma. European Archives of Oto-Rhino-Laryngology. [10.1007/s00405-009-1013-9]. 2010;267(19543904):423–7.

    Article  PubMed  Google Scholar 

  59. Mehanna H, Paleri V, Robson A, Wight R. Consensus statement on the management of Laryngeal Dysplasia. Clinical Otolaryngology. 2010;in print.

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  1. Institute of Head and Neck Studies and Education (InHANSE), University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry, CV2 2DX, UK

    Paul Nankivell & Hisham Mehanna

  2. Department of Otorhinolaryngology/Head and Neck Surgery, University Hospitals Coventry and Warwick, Coventry, UK

    Paul Nankivell & Hisham Mehanna

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Correspondence to Hisham Mehanna.

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Nankivell, P., Mehanna, H. Oral Dysplasia: Biomarkers, Treatment, and Follow-up. Curr Oncol Rep 13, 145–152 (2011). https://doi.org/10.1007/s11912-010-0150-z

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