One of the goals of the fourth meeting of The World Workshop on Oral Medicine (WWOM
IV) included a review of the pathophysiology and future directions for the clinical
management of patients with oral epithelial dysplasia, excluding the lips and oropharynx.
In the pathophysiology review of dysplasia since WWOM III (1998-2006), a wide range
of molecular changes associated with progression of dysplasia to squamous cell carcinoma
were found. These include loss of heterozygosity, dysregulation of apoptosis, aberrant
DNA expression, and altered expression of numerous tissue markers. Based on the literature
search, no single molecular pathway has been identified as the primary factor in progression
of dysplasia to squamous cell carcinoma. A systematic review of medical (i.e., nonsurgical)
management strategies for the treatment of dysplastic lesions has shown promising
results in short-term resolution of dysplasia in the small number of studies that
met eligibility criteria for review. However, because of the limited periods of follow-up
reported in these studies, it remains unclear as whether resolution of dysplasia would
actually be a long-term benefit of these interventions. This question is particularly
germane when it is considered in the context of prevention of future development of
squamous cell carcinoma. Because of the lack of randomized controlled trials that
have shown effectiveness in the prevention of malignant transformation, no recommendations
can be provided for specific surgical interventions of dysplastic oral lesions either.
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References
- Definition of leukoplakia and related lesions: an aid to studies on oral precancer.Oral Surg Oral Med Oral Pathol. 1978; 46: 518-539
- World Health Organization classification of tumours. Pathology & genetics. Head and neck tumours. International Agency for Research on Cancer (IARC). IARC Press, Lyon, France2005
- Histological typing of cancer and precancer of the oral mucosa. Springer-Verlag, Berlin1997
- Prognosis of oral pre-malignant lesions: significance of clinical, histopathological, and molecular biological characteristics.Crit Rev Oral Biol Med. 2003; 14: 47-62
- Effect of cessation of tobacco use on the incidence of oral mucosal lesions in a 10-yr follow-up study of 12,212 users.Oral Dis. 1995; 1: 54-58
- Chemoprevention of oral leukoplakia with vitamin A and beta carotene: an assessment.Oral Oncol. 1997; 33: 231-236
- Potentially malignant oral lesions in northern Ireland: a 20-year population perspective of malignant transformation.Oral Dis. 2001; 7: 18-24
- Long-term treatment outcome of oral premalignant lesions.Oral Oncol. 2006; 42: 461-474
- Observer variability in the histologic assessment of oral premalignant lesions.J Oral Pathol Med. 1995; 24: 198-200
- Intraexaminer and interexaminer reliability in the diagnosis of oral epithelial dysplasia.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995; 80: 188-191
- Observer agreement in the grading of oral epithelial dysplasia.Community Dent Oral Epidemiol. 2003; 31: 300-305
- Identification of genes and molecular pathways involved in the progression of premalignant oral epithelia.Mol Cancer Ther. 2005; 4: 865-875
- Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia.Clin Cancer Res. 2000; 6: 357-362
- Accumulative increase of loss of heterozygosity from leukoplakia to foci of early cancerization in leukoplakia of the oral cavity.Cancer. 2001; 92: 2349-2356
- Patterns of CDKN2A gene loss in sequential oral epithelial dysplasias and carcinomas.Cancer Res. 2001; 61: 2371-2375
- Alterations of p16(INK4a) and p14(ARF) in patients with severe oral epithelial dysplasia.Cancer Res. 2002; 62: 5295-5300
- Changes in apoptosis and mitotic index, p53 and Ki67 expression in various types of oral leukoplakia.Oncology. 2003; 65: 331-336
- The overexpression of p53 and proliferative activity in precancerous and cancerous lesions of oral squamous epithelium.J Exp Clin Cancer Res. 1997; 16: 141-146
- Expression of p53 protein in oral submucous fibrosis, oral epithelial hyperkeratosis, and oral epithelial dysplasia.J Formos Med Assoc. 2000; 99: 229-234
- Histopathological and immunohistochemical study of malignant transformation of oral leukoplakia, with special reference to apoptosis-related gene products and proliferative activity.Acta Otolaryngol. 2003; 123: 767-775
- Evaluation of p53 and bcl-2 oncoprotein expression in precancerous lesions of the oral cavity.Neoplasma. 2001; 48: 94-98
- Proteic expression of p53 and cellular proliferation in oral leukoplakias.Med Oral Patol Oral Cir Bucal. 2005; 10: 1-8
- Two-phase appearance of oral epithelial dysplasia resulting from focal proliferation of parabasal cells and apoptosis of prickle cells.J Oral Path Med. 2005; 34: 140-149
- Molecular changes associated with oral dysplasia progression and acquisition of immortality: potential for its reversal by 5-azacytidine.Cancer Res. 2002; 62: 4757-4766
- Senescing oral dysplasias are not immortalized by ectopic expression of hTERT alone without other molecular changes, such as loss of INK4A and/or retinoic acid receptor-beta: but p53 mutations are not necessarily required.Oncogene. 2003; 22: 7804-7808
- Immunohistochemical study of syndecan-1 down-regulation and the expression of p53 protein or Ki-67 antigen in oral leukoplakia with or without epithelial dysplasia.J Oral Pathol Med. 2003; 32: 513-521
- Expression of p27 and apoptosis in oral leukoplakia.Anticancer Res. 2003; 23: 1265-1270
- Flow cytometric analysis of nuclear DNA content in oral leukoplakia: relation to clinicopathologic findings.Int J Oral Maxillofac Surg. 1995; 24: 44-47
- Flow cytometric analysis of cell cycle fractions in oral leukoplakia.Int J Oral Maxillofac Surg. 1998; 27: 217-221
- Chromosomal aneuploidy precedes morphological changes and supports multifocality in head and neck lesions.Laryngoscope. 2001; 111: 1853-1858
- DNA cytometry of oral leukoplakia and oral lichen planus.Med Oral Pathol Oral Cir Bucal. 2005; 10: E9-E14
- Flow cytometric analysis of nuclear DNA content in oral leukoplakia.Clin Otolaryngol. 1998; 23: 136-140
- Overexpression of matrix metalloproteinase-1 and −9 mRNA is associated with progression of oral dysplasia to cancer.Clin Cancer Res. 2004; 10: 6460-6465
- Increased EMMPRIN (CD 147) expression during oral carcinogenesis.Exp Mol Pathol. 2006; 80: 147-159
- Stromelysin 3, Ets-1, and vascular endothelial growth factor expression in oral precancerous and cancerous lesions: correlation with microvessel density, progression, and prognosis.Clin Cancer Res. 2005; 11: 2272-2284
- Differential expression of the keratin-4, −13, −14, −17 and transglutaminase 3 genes during the development of oral squamous cell carcinoma from leukoplakia.Oral Oncol. 2005; 41: 607-613
- Expression of alpha(v)beta6 integrin in oral leukoplakia.Br J Cancer. 2000; 82: 1433-1440
- Expression of CD44s, CD44v5, CD44v6 and CD44v7-8 in betel quid chewing-associated oral premalignant lesions and squamous cell carcinomas in Taiwan.J Oral Pathol Med. 1998; 27: 428-433
- Expression of granulocyte colony-stimulating factor receptor and platelet-derived endothelial cell growth factor in oral and oropharyngeal precancerous lesions.Anticancer Res. 2001; 21: 2901-2906
- Evaluation of TGF-· and EGFR expression in oral leukoplakia and oral submucous fibrosis by quantitative immunohistochemistry.Oral Oncol. 2001; 61: 284-292
- Frequent allelic imbalances at 8p and 11q22 in oral and oropharyngeal epithelial dysplastic lesions.Cancer Genet Cytogenet. 2005; 161: 86-89
- Allelic imbalance at chromosomal loci implicated in the pathogenesis of oral precancer, cumulative loss and its relationship with progression to cancer.Oral Oncol. 1998; 34: 77-83
Curfman GD, Morrissey S, Drazen JM. Expression of concern: Sudbo J et al. DNA content as a prognostic marker in patients with oral leukoplakia. N Engl J Med 2001;344:1270-8 and Sudbo J, et al. The Influence of resection and aneuploidy on mortality in oral leukoplakia. N Engl J Med 2004;350:1405-13. N Engl J Med 2006;354:638.
- Cytologic and DNA-cytometric very early diagnosis of oral cancer.J Oral Pathol Med. 2004; 33: 398-404
- Alterations of Rb pathway components are frequent events in patients with oral epithelial dysplasia and predict clinical outcome in patients with squamous cell carcinoma.Oncology. 2005; 68: 314-325
- Dysregulated cyclin D1 expression early in head and neck tumorigenesis: In vivo evidence for an association with subsequent gene amplification.Oncogene. 1998; 17: 2313-2322
- Relationship of p53 overexpression to other cell cycle regulatory proteins in oral squamous cell carcinoma.J Oral Pathol Med. 1998; 27: 376-381
- Reduced level of the cell cycle inhibitor p27 in epithelial dysplasia and carcinoma of the oral cavity.Am J Pathol. 1998; 142: 585-590
- Frequent inactivation of p16INK4α in oral premalignant lesions.Oncogene. 1997; 14: 1799-1803
- Potential diagnostic use of p16INK4A, a new marker that correlates with dysplasia in oral squamoproliferative lesions.Am J Pathol. 2005; 29: 792-796
- P53 expression in oral precancer as a marker for malignant potential.J Oral Pathol Med. 1998; 27: 191-196
- Interventions for treating oral leukoplakia.Cochrane Database Syst Rev. 2004; 3 (CD001829)
- Topical bleomycin treatment of oral leukoplakia: a randomized double-blind clinical trial.Head Neck. 1994; 16: 539-544
- Acitretin and treatment of the oral leucoplakias.J Eur Acad Dermatol Venereol. 2000; 14: 473-478
- 13-cis-retinoic acid in the treatment of oral leukoplakia.N Engl J Med. 1986; 315: 1501-1505
- The chemopreventive effects of tea on human oral precancerous mucosa lesions.Proc Soc Exp Biol Med. 1999; 220: 218-224
- bcl-2 expression and apoptotic bodies in 13-cis-retinoic acid (isotretinoin)-topically treated oral leukoplakia: a pilot study.Oral Oncol. 1999; 35: 314-320
- Oral proliferative verrucous leukoplakia (PVL); open trial of surgery compared with combined therapy using surgery and methisoprinol in papillomavirus-related PVL.Int J Oral Maxillofac Surg. 2001; 30: 318-322
- Efficacy of oral lycopene in the treatment of oral leukoplakia.Oral Oncol. 2004; 40: 591-596
- 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: 1565-1573
- Cytologic and DNA-cytometric follow-up of oral leukoplakia after CO2- and Er:YAG-laser assisted ablation: a pilot study.Lasers Surg Med. 2005; 37: 29-36
- Comparison of electrodessication with CO2 laser for the treatment of actinic cheilitis.Dermatol Surg. 2000; 26: 349-353
- 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
- Evaluation of surgical excision of non-homogeneous oral leukoplakia in a screening intervention trial, Kerala, India.Oral Oncol. 2001; 37: 103-109
- The results of CO2 laser surgery in patients with oral leukoplakia: a 25-year follow-up.Oral Oncol. 2005; 41: 31-37
- Response of oral leukoplakias to the administration of vitamin A.Cancer Lett. 1988; 40: 93-101
- Successful treatment of oral verrucous hyperplasia with topical 5-aminolevulinic acid-meditated photodynamic therapy.Oral Oncol. 2004; 40: 630-637
- Photodynamic therapy (PDT) using topically applied B-aminolevulinic acid (ALA) for the treatment of oral leukoplakia.J Oral Pathol Med. 2003; 32: 330-336
- 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: 1565-1573
- Selection of topically applied non-steroidal anti-inflammatory drugs for oral cancer chemoprevention.Oral Oncology. 2005; 41: 562-567
- An attenuated adenovirsus, ONYX-015, as mouthwash therapy for premalignant oral dysplasia.J Clin Oncol. 2003; 21: 4546-4552
- Lack of molecular markers to predict malignant potential of oral precancer.J Pathol. 2000; 190: 407-409
- Toluidine blue staining identifies high-risk primary oral premalingant lesions with poor outcome.Cancer Res. 2005; 65: 8017-8021
- Toluidine blue uptake in potentially malignant oral lesions in vivo: clinical and histological assessment.Oral Oncology. 2006; 42: 89-95
- An audit of the efficacy of the oral brush biopsy technique in a specialist Oral Medicine unit.Oral Oncol. 2004; 40: 829-834
- Fluorescence spectroscopy combined with 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in detectinh oral premalignany.J Photochem Photobiol B. 2006; 83: 27-33
- Assessment of oral premalignancy using elastic scattering spectroscopy.Oral Oncol. 2006; 42: 343-349
- Potentially malignant lesions of the mouth and oropharynx: natural history—cellular and molecular markers of risk.Eur J Cancer Prev. 1993; 2: 31-51
- Oral leukoplakia: a proposal for uniform reporting.Oral Oncol. 2002; 38: 521-526
- Effect of cessation of tobacco use on the incidence of oral lesions in a 10-year follow-up study of 12212 users.Oral Dis. 1995; 1: 54-58
- Effective management of smoking in an oral dysplasia clinic in London.Oral Dis. 2005; 12;: 22-26
Article info
Publication history
Published online: January 26, 2007
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© 2007 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
