Recognition of oral potentially malignant disorders and transformation to oral cancer.

Oral potentially malignant disorders refer to oral mucosal disorders with increased risk for malignant transformation, primarily to oral squamous cell carcinoma (SCC). Leukoplakia and erythroplakia are the most common of these disorders, but others have been identified. Transformation rates to oral cancer vary based on multiple factors. Healthcare providers should be aware of risk factors and clinical manifestations of these disorders and should intervene early to monitor and/or treat them to reduce the potential for malignant transformation.

Oral erythroplakia-What is it?

Oral erythroplakia is a rare type of lesion, and little is known about the origin of the lesion. It has traditionally been described as the red counterpart of oral leukoplakia, which implies that it is a red lesion that cannot be characterized clinically or pathologically as any other definable lesion. A definition by exclusion is less satisfactory than a positive description to define a lesion, and as erythroplakia probably is related to lichenoid lesions, a new approach to perceive the lesion is proposed based on the clinical features of a fiery red, sharply demarcated lesion situated at a slightly lower level than the surrounding mucosa. Such a definition would probably help clinicians distinguish erythroplakia from other red lesions of the oral mucosa. Although the course of such lesions varies, a significant proportion will develop malignancy, which is why they should be followed at short intervals.

Avaliação clínica e histopatológica e hábitos associados ao surgimento de leucoplasias e eritroplasias orais / Clinical and histopathological evaluation and habits associated with the onset of oral leukoplakia and erythroplakia

Objective: This research aims to establish the prevalence, factors associated with the onset, and clinical and histopathological features of oral leukoplakia and erythroplakia, so that these data can contribute to the prevention of these lesions and, consequently, of oral cancer. Material and method: A retrospective study was conducted at a reference service of Universidade Federal do Rio Grande do Norte (UFRN) from 2000 to 2012. To verify the association of variables, Pearson's chi-squared test and Fisher's exact test (p ≤ 0.05) were used. Results: Among 6,560 investigated records, 54 cases were selected, of which 44.4% were male and 55.6% female, with mean age of 56.93 years. Regarding habits, 72.2% were smokers and 25% were alcohol users; 17.9% showed association of both habits. Oral leukoplakia lesions were the most prevalent (0.65%) and oral erythroplakia showed greater association with malignancy in the histopathological presentation (p = 0.001). Most lesions showed no symptoms (p = 0.004). The most frequent was oral leukoplakia in smoking women, with mean age of 57 years. Conclusion: Knowledge of associated factors and clinical characteristics of oral leukoplakia and erythroplakia is essential for establishing the correct diagnosis and treatment...

Objetivo: Esta pesquisa objetiva estabelecer a prevalência, os fatores associados ao surgimento e as características clínicas e histopatológicas das leucoplasias e eritroplasias orais, a fim de que estes dados possam contribuir na estratégia de prevenção ao desenvolvimento dessas lesões e, consequentemente, do câncer oral. Material e método: Foi realizado estudo retrospectivo em um serviço de referência da Universidade Federal do Rio Grande do Norte (UFRN) no período de 2000 a 2012. Para verificar a associação das variáveis foi utilizado o teste qui-quadrado e o exato de Fisher (p ≤ 0,05). Resultados: Foram investigados 6.560 prontuários, tendo sido selecionados 54 casos, dos quais 44,4% do sexo masculino e 55,6% do feminino, com idade média de 56,93 anos. Com relação aos hábitos, 72,2% eram fumantes e 25% usuários de álcool, sendo que 17,9% exibiam associação dos dois hábitos. As leucoplasias orais foram as lesões mais prevalentes (0,65%), e as eritroplasias orais apresentaram maior associação com apresentação maligna no diagnóstico histopatológico (p = 0,001). A maioria das lesões não apresentou sintomatologia (p = 0,004). A leucoplasia oral foi mais frequente em mulheres fumantes com média de idade de 57 anos. Conclusão: O conhecimento dos fatores associados e das características clínicas das eritroplasias e leucoplasias orais é essencial para o estabelecimento do correto diagnóstico e tratamento...

Evidence for a possible anatomical subsite-mediated effect of tobacco in oral potentially malignant disorders and carcinoma.

PURPOSE: To test the hypothesis that cigarette smokers develop oral potentially malignant disorders or carcinomas in preferential anatomical subsites. METHODS: The association of smoking habit with the presence of oral lesions in specific anatomical subsites was assessed in 123 patients using the odds ratio analysis. RESULTS: When compared to all the other subsites, the relative frequency of smokers with lesions was higher in the buccal mucosa and in the floor of the mouth (FOM) (P=0.002 and P=0.005), while it was lower in the tongue (P<0.0005). Smokers were about 7 years younger than non-smokers (P=0.008). CONCLUSIONS: The association of smoking and age suggests that smoking may contribute to generate a field of injury that leads to lesions in shorter periods than other causes. The stronger relationship of smoking with lesions in the buccal mucosa and FOM than in the tongue suggests that tissue characteristics mediate the effects of tobacco.

Is workplace screening for potentially malignant oral disorders feasible in India?

BACKGROUND: Because of delays in diagnosis, oral cancer usually presents for therapy at a late stage. Patients are unaware of having lesions as they are mostly asymptomatic and physicians generally do not examine the mouth sufficiently. People in rural areas or are underserved may not frequently visit the dentist who can easily pick up these lesions early. Screening programs are useful in that regard. Such programs in general are conducted by either inviting people to come to a screening center or by health care workers visiting the individual households. However, those who work during the day may not visit screening centers or be at home during the day of the screening by a visiting health care worker. Workplace screening overcomes these challenges. METHODS: To assess the feasibility of a screening program to detect potentially pre-malignant oral disorders in a workplace in India, clinically visible mucosal lesions were compared with the clinical photographs of the same lesions assessed by an expert. Role of smoking, alcohol, and chewing betel quid and tobacco in the etiology of those lesions were assessed. RESULTS: Sixty-nine percent of the eligible subjects participated in the screening (n=1613). Prevalence of leukoplakia was 5%. Bidi (OR=35.6), and cigarette smoking (OR=22.8), alcohol (OR=17.6), and tobacco and areca nut chewing (OR=7.5), were significantly associated with leukoplakia and erythroplakia (all P< 0.05). CONCLUSIONS: Conduction of a screening program by valid visual inspection to detect potentially malignant oral disorders within a workplace is not only feasible but also effective.

[Oral erythroplakia and erythroleukoplakia: red and red-white dysplastic lesions of the oral mucosa--part 1: epidemiology, etiology, histopathology and differential diagnosis]. / Erythroplakie und Erythroleukoplakie: Rote und rot-weisse Risikoläsionen der Mundhöhlenschleimhaut. Teil 1: Epidemiologie, Atiologie, Histopathologie und Differenzialdiagnose.

Oral erythroplakia (OE) and oral erythroleukoplakia (OEL; synonym: speckled leukoplakia) are working diagnoses for red and red-white lesions of the oral mucosa after exclusion of all other possible diagnoses for lesions with a similar clinical appearance. A good knowledge of oral medicine and possible differential diagnoses of oral mucosal pathologies is mandatory to correctly detect OE and OEL on this exclusion basis. In the present review article in a series of two, epidemiologic data, etiologic factors, possible differential diagnoses, and the histopathologic characteristics of OE and OEL will be presented and discussed regarding the current literature. A thorough histopathologic examination of these epithelial precursor lesions is mandatory to recognise the presence and the severity of epithelial dysplasia, which is a decisive factor for the subsequent treatment planning.

Natural history of potentially malignant oral lesions and conditions: an overview of the literature.

At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Pre-cancer in the UK issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers. In this report we review the literature on the epidemiology and natural history of potentially malignant disorders (PMD), detailing those characteristics of the patients and lesions thought to be associated with future development of oral squamous cell carcinoma (OSCC). Older patients, particularly females are more at risk than younger patients; the duration of PMD may be important. Those who have never used tobacco seem at greater risk than smokers. OSCC is more likely with PMD on the lateral and ventral tongue, floor of mouth and retromolar/soft palate complex than with those elsewhere. The vast majority of PMD in which OSCC develop are non-homogenous although 5% of homogenous PMD will develop carcinoma. Large lesions covering several intraoral subsites also appear more at risk.

Long-term treatment outcome of oral premalignant lesions.

The purpose of the present retrospective study was to learn the long-term outcome of oral premalignant lesions, leukoplakia and erythroplakia, with or without surgical intervention and to relate the outcome to factors supposed to be significant for malignant development including clinical type, demarcation, size, site, presence of epithelial dysplasia, smoking and surgery. A total of 269 lesions in 236 patients were included. Ninety-four lesions were surgically removed, 39 lesions (41%) being homogenous and 46 (49%) non-homogenous leukoplakias whereas nine (5%) were erythroplakias. Seventy-three percent of the lesions were associated with tobacco habits. The mean size of the lesions was 486 mm(2), and 71% of the lesions showed a degree of epithelial dysplasia. After excision the defects were closed primarily by transposition of mucosal flaps or they were covered by free mucosal or skin grafts. A few defects were left for secondary healing. After surgical treatment the patients were followed (mean 6.8 yrs, range 1.5-18.6 yrs), and new biopsies taken in case of recurrences. One hundred and seventy five lesions had no surgical intervention, 149 lesions (85%) being homogenous and 20 (11%) non-homogenous leukoplakias, and 6 (3%) erythroplakias. Eighty-one percent of the lesions were associated with smoking. The mean size of the lesions was 503 mm(2) and 21 of the lesions (12%) exhibited epithelial dysplasia. Sixty-five lesions were not biopsied. These patients were also followed (mean 5.5 yrs, range 1.1-20.2 yrs), and biopsies taken in case of changes indicative of malignant development. All patients were encouraged to quit smoking and candidal infections were treated. The possible role of different variables for malignant development was estimated by means of logistic regression analysis. Following surgical treatment 11 lesions (12%) developed carcinoma after a mean follow-up period of 7.5 yrs. Non-homogenous leukoplakia accounted for the highest frequency of malignant development, i.e. 20%, whereas 3% of the homogenous leukoplakias developed carcinomas. Surgically treated lesions with slight, moderate, severe and no epithelial dysplasia developed carcinoma with similar frequencies, i.e. 9-11%. Without surgical intervention 16% of the 175 lesions disappeared whereas seven lesions (4%) developed carcinoma after a mean observation period of 6.6 yrs. The highest frequency of malignant development (15%) was seen for non-homogenous leukoplakias, this figure being 3% for homogenous leukoplakias. Fourteen percent of lesions with slight epithelial dysplasia developed malignancy and 2% of lesions with no dysplasia showed malignant transformation. Logistic regression analysis showed a seven times increased risk (OR = 7.0) of non-homogenous leukoplakia for malignant development as compared with homogenous leukoplakia and a 5.4 times increased risk for malignant development for lesions with a size exceeding 200 mm(2). No other examined variables including presence of any degree of epithelial dysplasia, site, demarcation, smoking and surgical intervention were statistically significant factors for malignant development.

Oral medicine--update for the dental practitioner: red and pigmented lesions.

This series provides an overview of current thinking in the more relevant areas of oral medicine for primary care practitioners, written by the authors while they were holding the Presidencies of the European Association for Oral Medicine and the British Society for Oral Medicine, respectively. A book containing additional material will be published. The series gives the detail necessary to assist the primary dental clinical team caring for patients with oral complaints that may be seen in general dental practice. Space precludes inclusion of illustrations of uncommon or rare disorders, or discussion of disorders affecting the hard tissues. Approaching the subject mainly by the symptomatic approach--as it largely relates to the presenting complaint--was considered to be a more helpful approach for GDPs rather than taking a diagnostic category approach. The clinical aspects of the relevant disorders are discussed, including a brief overview of the aetiology, detail on the clinical features and how the diagnosis is made. Guidance on management and when to refer is also provided, along with relevant websites which offer further detail.

Oral precancerous disorders associated with areca quid chewing, smoking, and alcohol drinking in southern Taiwan.

OBJECTIVE: To investigate the prevalence and the associated risk factors of oral precancerous disorders in southern Taiwan. METHODS: We conducted a cross-sectional community survey interviewing 1075 adult subjects, 15 years of age and over, gathered from randomly selected 591 households, and spanning five villages in southern Taiwan. The study protocol included a visual oral soft tissue examination and a questionnaire-based interview. The chi-square test was used to test the differences in prevalence of oral precancerous lesions and conditions by different "life styles" relating to current risk habits of current areca quid chewing, smoking, and alcohol drinking. To control for possible confounding, a logistic regression model was used to estimate the Odds Ratios (OR) for leukoplakia and oral submucous fibrosis (OSF). RESULTS: 136 precancerous lesions and conditions were detected among 1075 subjects (12.7%). The analysis of the spectrum of oral precancerous disorders detected, leukoplakia (n = 80), OSF (n = 17) and verrucous lesions (n = 9), demonstrated an association with gender (P < 0.001). There were statistically significant associations among leukoplakia (P < 0.01), OSF (P < 0.0001), and verrucous lesions (P < 0.0001) and the life style of current areca quid chewing, smoking, and alcohol drinking. The synergistic effect of smoking and areca quid chewing habit on leukoplakia and OSF was demonstrated. CONCLUSION: This study reinforces the association of current areca quid chewing without tobacco, cigarette smoking, and alcohol drinking to leukoplakia, OSF, and verrucous lesions in Taiwan.

Oral erythroplakia--a review.

Oral erythroplakia (OE) is considered a rare potentially malignant lesion of the oral mucosa. Reports entirely devoted to OE are very few, and only two reviews none of which are of recent date have been published. Only the true, velvety, red homogeneous OE has been clearly defined while the terminology for mixed red and white lesions is complex, ill-defined and confusing. A recent case control study of OE from India reported a prevalence of 0.2%. A range of prevalences between 0.02% and 0.83% from different geographical areas has been documented. OE is predominantly seen in the middle aged and elderly. One study from India showed a female:male ratio of 1:1.04. The soft palate, the floor of the mouth and the buccal mucosa is commonly affected. A specific type of OE occurs in chutta smokers in India. Lesions of OE are typically less than 1.5 cm in diameter. The etiology of OE reveals a strong association with tobacco consumption and the use of alcohol. Histopathologically, it has been documented that in OE of the homogenous type, 51% showed invasive carcinoma, 40% carcinoma in situ and 9% mild or moderate dysplasia. Recently, genomic aberrations with DNA aneuploidy has been demonstrated. p53 mutations with different degrees of dysplasia may play a role in some cases of OE. Transformation rates are considered to be the highest among all precancerous oral lesions and conditions. Surgical excision is the treatment of choice. Data on laser excision are not available. Recurrence rates seem to be high, reliable data are, however, missing. More studies on OE are strongly needed to evaluate a number of so far unanswered questions. The natural history of OE is unknown. Do OEs develop de novo or are they developing from oral leukoplakia through several intermediate stages of white/red lesions? The possible role of fungal infection (Candida micro-organisms) is not clear as is the possible role of HPV co-infection in the development of OE. More data on incidence and prevalence, biological behaviour and adequate treatment are urgently needed.

Risk factors for multiple oral premalignant lesions.

Oral leukoplakia, oral submucous fibrosis and erythroplakia are 3 major types of oral premalignant lesions. Multiple oral premalignant lesions may possibly develop due to field cancerization, where carcinogenic exposures can cause simultaneous genetic defects to the upper aerodigestive tract epithelium, putting the epithelium at high risk for development of premalignant lesions at different stages of carcinogenesis. There have been no epidemiological studies on risk or protective factors of the disease. A case-control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. A total of 115 subjects with multiple oral premalignant lesions (8-10% of oral premalignant lesions in our case series) were included: 64 subjects with oral leukoplakia and oral submucous fibrosis, 19 subjects with oral leukoplakia and erythroplakia, 22 subjects with oral submucous fibrosis and erythroplakia and 10 subjects with all 3 lesions. Individuals without oral lesions were considered controls (n=47,773). The odds ratio (OR) for ever tobacco chewers was 37.8 (95% confidence interval (CI)=16.2-88.1) when adjusted for age, sex, education, BMI, smoking, drinking and fruit/vegetable intake. Dose-response relationships were seen for the frequency (p<0.0001) and duration of tobacco chewing (p<0.0001) with the risk of multiple oral premalignant lesions. Whereas alcohol drinking may possibly be a risk factor for multiple oral premalignant lesions, smoking was not associated with the risk of multiple oral premalignant lesions (OR=0.9, 95%CI=0.5-1.7). The results suggest that tobacco chewing was the most important risk factor for multiple oral premalignant lesions and may be a major source of field cancerization on the oral epithelium in the Indian population.

Oral precancerous and malignant lesions associated with graft-versus-host disease: report of 2 cases.

The development of secondary malignancies has been recognized as a potential iatrogenic complication in patients who have graft-versus-host disease secondary to bone marrow transplantation. Lymphohematopoietic cancer is most frequent, although solid malignancies have also been reported. We describe 2 patients with graft-versus-host disease who developed oral precancerous and malignant lesions. The first patient, a 24-year-old white man, had erythroplakia of the buccal mucosa that proved to be carcinoma in situ histopathologically. The second patient, a 14-year-old Hispanic boy, developed synchronous cutaneous and lingual squamous cell carcinomas. The current cases and similar sporadic case reports found in the literature highlight the susceptibility of patients with graft-versus-host disease to the development of oral cancer. Therefore, it is recommended that thorough evaluation of the oral mucosa and close follow-up be offered to all patients treated with bone marrow transplantation and particularly to those who develop graft-versus-host disease.

Chewing tobacco, alcohol, and the risk of erythroplakia.

Although chewing tobacco, smoking, and alcohol drinking have been suggested as risk factors for oral cancer, no study has examined the relationship between those factors and the risk of erythroplakia, an uncommon but severe oral premalignant lesion. In this study, we have analyzed the effects of chewing tobacco, smoking, alcohol drinking, body mass index, and vegetable, fruit, and vitamin/iron intake on the risk of erythroplakia and explored potential interactions between those factors in an Indian population. A case-control study including 100 erythroplakia cases and 47,773 controls was conducted, as part of an on-going randomized oral cancer screening trial in Kerala, India. The analysis was based on the data from the baseline screening for the intervention group, where the diagnostic information was available. The information on epidemiological risk factors was collected with interviews conducted by trained health workers. The erythroplakia cases were identified by health workers with oral visual inspections, and then confirmed by dentists and oncologists who made the final diagnosis. The odds ratios (OR) and their 95% confidence intervals (CIs) were calculated by the logistic regression model using SAS software. The adjusted OR for erythroplakia was 19.8 (95% CI, 9.8-40.0) for individuals who had ever chewed tobacco, after controlling for age, sex, education, body mass index, smoking, and drinking. The adjusted OR for ever-alcohol-drinkers was 3.0 (95% CI, 1.6-5.7) after controlling for age, sex, education, body mass index, chewing tobacco, and smoking. For ever-smokers, the adjusted OR was 1.6 (95% CI, 0.9-2.9). A more than additive interaction on the risk of erythroplakia was suggested between tobacco chewing and low vegetable intake, whereas a more than multiplicative interaction was indicated between alcohol drinking and low vegetable intake, and between drinking and low fruit intake. We concluded that tobacco chewing and alcohol drinking are strong risk factors for erythroplakia in the Indian population. Because the CIs of interaction terms were wide and overlapping with those of the main effects, only potential interactions are suggested.

Oral mucosal changes and associated factors among male industrial workers with or without access to subsidized dental care.

Oral mucosal changes and associated factors were studied among male industrial workers in southern Finland. Two groups, with or without access to an employer-provided dental benefit scheme, were compared. A multiple-choice questionnaire followed by clinical examinations was completed by 325 (81%) subsidized workers and 174 (69%) controls. In both groups 52% of the subjects had some oral mucosal change, and there were no significant differences between the groups in the location distribution of the changes. Smoking was significantly associated with redness of the oral mucosa (p < 0.001), coating (p < 0.001), and leukoplakia (p < 0.01), whereas denture wearing was associated with ulcers (p < 0.05), hyperplasia (p < 0.001), and redness (p < 0.001). Among denture wearers non-acceptable dentures were significantly associated with hyperplasia (p < 0.001). The subsidized group had better dentures, although this did not significantly benefit their oral mucosal status.

Erythroplakia: the dangerous red mucosa.

Erythroplakia is an uncommon and subtly innocuous change of the oral mucosa, but it has very specific and identifiable clinical characteristics, therapies, and prognostic features. It is the most dangerous of all the oral cancer precursor lesions, and a search for erythroplakia should be a part of every oral soft tissue examination in persons aged 35 years and older. No erythroplakia lesions should ever be left untreated. Much has been written about the malignant potential of oral leukoplakia, but too often the dental profession has ignored the more dangerous discoloration, erythroplakia, which carries a much greater cancer risk than the white lesions. A clear understanding of this lesion may save lives by identifying oral cancers prior to invasion or at an early stage, thereby avoiding extensive surgery and spread of the disease to other parts of the body. The learning objective of this article is to review and familiarize the reader with the terminology, diagnosis, etiology, treatment, and the prognosis of this disease.