-
Head and Neck Pathology Sep 2019Leukoplakia and erythroplakia are two entities under the moniker of "oral potentially malignant disorders" that are highly associated with the presence of oral... (Review)
Review
Leukoplakia and erythroplakia are two entities under the moniker of "oral potentially malignant disorders" that are highly associated with the presence of oral epithelial dysplasia (OED) at first biopsy, while lesions of submucous fibrosis develop OED after being present for years. Importantly, traumatic/frictional keratoses are often mistaken clinically for leukoplakia and it is important for the pathologist to recognize and report them as such. The features of OED have been well-described and other architectural features will be discussed here, in particular verrucous and papillary architecture, bulky epithelial proliferation and epithelial atrophy. Proliferative leukoplakia, verrucous or otherwise, often show only hyperkeratosis in early lesions, with development of OED occurring over time, and squamous cell carcinoma developing in the majority of cases over time. The concept of hyperkeratosis without features of OED and that is not reactive, is likely a precursor to the dysplastic phenotype. Many cases of leukoplakia exhibiting OED are associated with a band of lymphocytes at the interface and these should not be mistaken for oral lichen planus.
Topics: Humans; Leukoplakia, Oral; Mouth Mucosa
PubMed: 30887394
DOI: 10.1007/s12105-019-01020-6 -
Oral Diseases Nov 2021Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated... (Review)
Review
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 potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with "oral lichenoid lesions" and among those diagnosed with oral manifestations of 'chronic graft-versus-host disease'. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer.
Topics: Cell Transformation, Neoplastic; Consensus; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Mouth Neoplasms; Precancerous Conditions; World Health Organization
PubMed: 33128420
DOI: 10.1111/odi.13704 -
Brazilian Journal of Otorhinolaryngology 2017Proliferative verrucous leukoplakia is a multifocal and progressive lesion of the oral mucosa, with unknown etiology, and commonly resistant to all therapy attempts with... (Review)
Review
INTRODUCTION
Proliferative verrucous leukoplakia is a multifocal and progressive lesion of the oral mucosa, with unknown etiology, and commonly resistant to all therapy attempts with frequent recurrences. It is characterized by a high rate of oral squamous cell carcinoma and verrucou carcinoma transformations.
OBJECTIVE
To analyze the studies about Proliferative verrucous leukoplakia and develop a concise update.
METHODS
A Pubmed search identifying studies (laboratory research, case series and reviews of literature) that examined patients with Proliferative verrucous leukoplakia was realized.
RESULTS
There are not enough studies about Proliferative verrucous leukoplakia in the literature. The few found studies not present a consensus about its etiology and diagnosis criteria. Although several treatment strategies have been proposed, most of them still show a high recurrence rate.
CONCLUSION
More research about Proliferative verrucous leukoplakia is necessary to understand and treat this disease.
Topics: Female; Humans; Leukoplakia, Oral; Male
PubMed: 28209441
DOI: 10.1016/j.bjorl.2016.12.005 -
The Indian Journal of Medical Research Jul 2018Smokeless tobacco (SLT) use has many oral effects including oral cancer, leukoplakia and erythroplakia, oral submucous fibrosis (if mixed with areca nut), loss of... (Review)
Review
Smokeless tobacco (SLT) use has many oral effects including oral cancer, leukoplakia and erythroplakia, oral submucous fibrosis (if mixed with areca nut), loss of periodontal support (recession) and staining of teeth and composite restorations. This review was aimed to provide information to identify oral lesions that occur due to the use of smokeless tobacco so that effective interventions can be undertaken to reduce morbidity and mortality from the use of SLT.
Topics: Areca; Humans; Leukoplakia, Oral; Mouth Neoplasms; Oral Health; Oral Submucous Fibrosis; Nicotiana; Tobacco, Smokeless
PubMed: 30264752
DOI: 10.4103/ijmr.IJMR_1793_17 -
Nature Communications Feb 2023Head and neck squamous cell carcinoma (HNSCC) undergoes stepwise progression from normal tissues to precancerous leukoplakia, primary HNSCC, and metastasized tumors. To...
Head and neck squamous cell carcinoma (HNSCC) undergoes stepwise progression from normal tissues to precancerous leukoplakia, primary HNSCC, and metastasized tumors. To delineate the heterogeneity of tumor cells and their interactions during the progression of HNSCC, we employ single-cell RNA-seq profiling for normal to metastasized tumors. We can identify the carcinoma in situ cells in leukoplakia lesions that are not detected by pathological examination. In addition, we identify the cell type subsets of the Galectin 7B (LGALS7B)-expressing malignant cells and CXCL8-expressing fibroblasts, demonstrating that their abundance in tumor tissue is associated with unfavorable prognostic outcomes. We also demonstrate the interdependent ligand-receptor interaction of COL1A1 and CD44 between fibroblasts and malignant cells, facilitating HNSCC progression. Furthermore, we report that the regulatory T cells in leukoplakia and HNSCC tissues express LAIR2, providing a favorable environment for tumor growth. Taken together, our results update the pathobiological insights into cell-cell interactions during the stepwise progression of HNSCCs.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Gene Expression Profiling; Leukoplakia
PubMed: 36828832
DOI: 10.1038/s41467-023-36691-x -
Critical Reviews in Oral Biology and... 2003Chronic hyperplastic candidosis/candidiasis (CHC; syn. candidal leukoplakia) is a variant of oral candidosis that typically presents as a white patch on the commissures... (Review)
Review
Chronic hyperplastic candidosis/candidiasis (CHC; syn. candidal leukoplakia) is a variant of oral candidosis that typically presents as a white patch on the commissures of the oral mucosa. The major etiologic agent of the disease is the oral fungal pathogen Candida predominantly belonging to Candida albicans, although other systemic co-factors, such as vitamin deficiency and generalized immune suppression, may play a contributory role. Clinically, the lesions are symptomless and regress after appropriate antifungal therapy and correction of underlying nutritional or other deficiencies. If the lesions are untreated, a minor proportion may demonstrate dysplasia and develop into carcinomas. This review outlines the demographic features, etiopathogenesis, immunological features, histopathology, and the role of Candida in the disease process. In the final part of the review, newer molecular biological aspects of the disease are considered together with the management protocols that are currently available, and directions for future research.
Topics: Antifungal Agents; Candida; Candidiasis, Oral; Chronic Disease; Diabetes Complications; Disease Susceptibility; Humans; Hyperplasia; Leukoplakia, Oral
PubMed: 12907694
DOI: 10.1177/154411130301400403 -
CA: a Cancer Journal For Clinicians 2002In the United States, cancers of the oral cavity and oropharynx represent approximately three percent of all malignancies in men and two percent of all malignancies in... (Review)
Review
In the United States, cancers of the oral cavity and oropharynx represent approximately three percent of all malignancies in men and two percent of all malignancies in women. The American Cancer Society estimates that 28,900 new cases of oral cancer will be diagnosed in 2002, and nearly 7,400 people will die from this disease. Over 90 percent of these tumors are squamous cell carcinomas, which arise from the oral mucosal lining. In spite of the ready accessibility of the oral cavity to direct examination, these malignancies still are often not detected until a late stage, and the survival rate for oral cancer has remained essentially unchanged over the past three decades. The purpose of this article is to review the clinical features of oral cancer and premalignant oral lesions, with an emphasis on early detection.
Topics: Carcinoma, Squamous Cell; Carcinoma, Verrucous; Diagnosis, Differential; Erythroplasia; Humans; Leukoplakia, Oral; Mouth Neoplasms; Neoplasm Staging; Precancerous Conditions; Risk Factors; Nicotiana
PubMed: 12139232
DOI: 10.3322/canjclin.52.4.195 -
The Cochrane Database of Systematic... Jul 2016Oral leukoplakia is a relatively common oral lesion that, in a small proportion of people, precedes the development of oral cancer. Most leukoplakias are asymptomatic;... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral leukoplakia is a relatively common oral lesion that, in a small proportion of people, precedes the development of oral cancer. Most leukoplakias are asymptomatic; therefore, the primary objective of treatment should be to prevent onset of cancer. This review updates our previous review, published in 2006.
OBJECTIVES
To assess the effectiveness, safety and acceptability of treatments for leukoplakia in preventing oral cancer.
SEARCH METHODS
We searched the following electronic databases: Cochrane Oral Health's Trials Register (to 16 May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 4), MEDLINE Ovid (1946 to 16 May 2016), Embase Ovid (1980 to 16 May 2016) and CancerLit via PubMed (1950 to 16 May 2016). We searched the metaRegister of Controlled Trials (to 10 February 2015), ClinicalTrials.gov (to 16 May 2016) and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (to 16 May 2016). We placed no restrictions on the language or date of publication when searching electronic databases.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that enrolled people with a diagnosis of oral leukoplakia and compared any treatment versus placebo or no treatment.
DATA COLLECTION AND ANALYSIS
We collected data using a data extraction form. Oral cancer development, demonstrated by histopathological examination, was our primary outcome. Secondary outcomes were clinical resolution of the lesion, improvement of histological features and adverse events. We contacted trial authors for further details when information was unclear. When valid and relevant data were available, we conducted a meta-analysis of the data using a fixed-effect model when we identified fewer than four studies with no heterogeneity. For dichotomous outcomes, we calculated risk ratios (RRs) and 95% confidence intervals (CIs). We assessed risk of bias in studies by using the Cochrane tool. We assessed the overall quality of the evidence by using standardised criteria (Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE)).
MAIN RESULTS
We included 14 studies (909 participants) in this review. Surgical interventions, including laser therapy and cryotherapy, have never been studied by means of an RCT that included a no treatment or placebo arm. The included trials tested a range of medical and complementary treatments, in particular, vitamin A and retinoids (four studies); beta carotene or carotenoids (three studies); non-steroidal anti-inflammatory drugs (NSAIDs), specifically ketorolac and celecoxib (two studies); herbal extracts (four studies), including tea components, a Chinese herbal mixture and freeze-dried black raspberry gel; bleomycin (one study); and Bowman-Birk inhibitor (one study).We judged one study to be at low risk of bias, seven at unclear risk and six at high risk. In general, we judged the overall quality of the evidence to be low or very low, so findings are uncertain and further research is needed.Five studies recorded cancer incidence, only three of which provided useable data. None of the studies provided evidence that active treatment reduced the risk of oral cancer more than placebo: systemic vitamin A (RR 0.11, 95% CI 0.01 to 2.05; 85 participants, one study); systemic beta carotene (RR 0.71, 95% CI 0.24 to 2.09; 132 participants, two studies); and topical bleomycin (RR 3.00, 95% CI 0.32 to 27.83; 20 participants, one study). Follow-up ranged between two and seven years.Some individual studies suggested effectiveness of some proposed treatments, namely, systemic vitamin A, beta carotene and lycopene, for achieving clinical resolution of lesions more often than placebo. Similarly, single studies found that systemic retinoic acid and lycopene may provide some benefit in terms of improvement in histological features. Some studies also reported a high rate of relapse.Side effects of varying severity were often described; however, it seems likely that interventions were well accepted by participants because drop-out rates were similar between treatment and control groups.
AUTHORS' CONCLUSIONS
Surgical treatment for oral leukoplakia has not been assessed in an RCT that included a no treatment or placebo comparison. Nor has cessation of risk factors such as smoking been assessed. The available evidence on medical and complementary interventions for treating people with leukoplakia is very limited. We do not currently have evidence of a treatment that is effective for preventing the development of oral cancer. Treatments such as vitamin A and beta carotene may be effective in healing oral lesions, but relapses and adverse effects are common. Larger trials of longer duration are required to properly evaluate the effects of leukoplakia treatments on the risk of developing oral cancer. High-quality research is particularly needed to assess surgical treatment and to assess the effects of risk factor cessation in people with leukoplakia.
Topics: Humans; Leukoplakia, Oral; Mouth Neoplasms; Randomized Controlled Trials as Topic
PubMed: 27471845
DOI: 10.1002/14651858.CD001829.pub4 -
Atencion Primaria Jan 2020
Topics: Female; Humans; Leukoplakia, Oral; Middle Aged
PubMed: 31029457
DOI: 10.1016/j.aprim.2019.02.008 -
Journal of the National Cancer Institute Oct 2020The optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion,...
BACKGROUND
The optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion, to estimate the relative and absolute risks of progression to cancer, the predictive accuracy of a clinician's decision to biopsy a leukoplakia vis-à-vis progression, and histopathologic predictors of progression.
METHODS
We conducted a retrospective cohort study (1996-2012) of patients with oral leukoplakia (n = 4886), identified using electronic medical records within Kaiser Permanente Northern California. Among patients with leukoplakia who received a biopsy (n = 1888), we conducted a case-cohort study to investigate histopathologic predictors of progression. Analyses included indirect standardization and unweighted or weighted Cox regression.
RESULTS
Compared with the overall Kaiser Permanente Northern California population, oral cancer incidence was substantially elevated in oral leukoplakia patients (standardized incidence ratio = 40.8, 95% confidence interval [CI] = 34.8 to 47.6; n = 161 cancers over 22 582 person-years). Biopsied leukoplakias had a higher oral cancer risk compared with those that were not biopsied (adjusted hazard ratio = 2.38, 95% CI = 1.73 to 3.28). However, to identify a prevalent or incident oral cancer, the biopsy decision had low sensitivity (59.6%), low specificity (62.1%), and moderate positive-predictive value (5.1%). Risk of progression to oral cancer statistically significantly increased with the grade of dysplasia; 5-year competing risk-adjusted absolute risks were: leukoplakia overall = 3.3%, 95% CI = 2.7% to 3.9%; no dysplasia = 2.2%, 95% CI = 1.5% to 3.1%; mild-dysplasia = 11.9%, 95% CI = 7.1% to 18.1%; moderate-dysplasia = 8.7%, 95% CI = 3.2% to 17.9%; and severe dysplasia = 32.2%, 95% CI = 8.1%-60.0%. Yet 39.6% of cancers arose from biopsied leukoplakias without dysplasia.
CONCLUSIONS
The modest accuracy of the decision to biopsy a leukoplakia vis-à-vis presence or eventual development of oral cancer highlights the need for routine biopsy of all leukoplakias regardless of visual or clinical impression. Leukoplakia patients, particularly those with dysplasia, need to be closely monitored for signs of early cancer.
Topics: Adult; Aged; California; Cohort Studies; Disease Progression; Female; Humans; Leukoplakia, Oral; Male; Middle Aged; Mouth Neoplasms; Precancerous Conditions; Retrospective Studies; Risk
PubMed: 31860085
DOI: 10.1093/jnci/djz238