Development Of Oral Leukoplakia Research Articles

Effect of the gut microbiome and inflammation-related proteins on oral leukoplakia: a Mendelian randomization study and mediation analysis.

Oral leukoplakia (OL) is the most common potentially malignant disease of the oral cavity. In recent years, studies have identified a correlation between the gut microbiota (GM) and oral cancer, in addition, inflammation-related proteins have been reported to play an important role in the development of OL. However, the causal relationship between gut microbiota and OL, as well as whether cytokines play a mediating role, remain unclear. In this Mendelian randomization (MR) study, the genome-wide association studies (GWAS) (n=18340) of the MiBioGen consortium microbiome was used as exposure data. Genetic variation data related to OL were extracted from the Finngen R9 project (513 cases of OL and 411668 controls). The 91 inflammation-related proteins obtained in the literature serve as potential mediators. Two-sample Mendelian randomization analysis was applied to infer causality using Inverse Variance Weighted (IVW), MR Egger, weighted media, simple mode and weighted mode method. Subsequently, sensitivity analysis was conducted to ensure the robustness of the MR results. In addition, we conducted reverse MR analysis to alleviate reverse causality. Finally, we used mediation analysis to determine the pathway mediated by inflammation-related proteins from the gut microbiota to OL. The five bacterial taxa in the gut microbiota indicate a potential causal relationship with the development of OL. Notably, family Clostridiaceae1 was negatively correlated with the risk of OL development, while genus Dorea, genus Ruminococcus1, genus Senegalimasilia and genus Veillonella were positively associated with the risk of OL development. In addition, this study identified a potential causal relationship between interleukin-10 receptor subunit alpha (IL-10RA), interleukin-18 receptor 1(IL18-R1) and the occurrence of OL. In addition, intermediary analysis indicates that IL18-R1 mediated the pathway between the gut microbiota genus Senegalimasilia and OL. In summary, our research emphasize the complex relationship between gut microbiota, inflammation-related proteins and OL. The identified associations and mediating effects provide new insights into potential therapeutic approaches for targeting the gut microbiota in the management of OL, and contribute to its prevention, diagnosis and treatment.

Role of human papillomavirus infection in the development of oral leukoplakia and oral squamous cell carcinoma

BACKGROUND: The annual global oral cancer morbidity is more than 650,000 cases. Between 2007 and 2017 in the Russian Federation, the absolute number of first-ever diagnosed oral cavity malignant neoplasms is constantly increasing. According to many authors, oral squamous cell carcinoma is associated with pre-existing leukoplakia. This disease is the most common and prone to malignant precancerous oral mucosa disease. Human papillomaviruses (HPV) are crucial players in this process. However, the relationship between HPV infection in leukoplakia and oral squamous cell carcinoma remains unclear.
 AIM: To establish the HPV role in the development of leukoplakia and squamous cell carcinoma of the oral mucosa.
 MATERIAL AND METHODS: The study included 39 patients with verified various forms of oral leukoplakia and oral squamous cell carcinomas. The squamous cell carcinoma group included 19 patients. The oral leukoplakia group is consisted of 20 patients. The control group of healthy volunteers is represented by 22 patients with clinically healthy oral mucosa. HPV deoxyribonucleic acid (DNA) was detected and quantified in clinical materials by polymerase chain reaction with hybridization-fluorescence detection AmpliSense HPV HRS screen-titer-FL for HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 and AmpliSense HPV 6/11-FL for HPV types 6 and 11.
 RESULTS: HPV types 6 and 11 DNA were isolated in three cases with insignificant clinical disease from 19 samples taken from patients with oral squamous cell carcinoma. In groups of leukoplakia and healthy volunteers, no high oncological risk was identified. Despite a HPV-positive expression in squamous cell carcinoma samples is detected, no significant difference was found between the squamous cell carcinoma group and control group (p=0.09).
 CONCLUSION: No significant association was noted between HPV and oral squamous cell carcinoma; however, a low carcinogenic-risk HPV was detected in 15.7% of carcinoma samples. No HPV contamination was detected in patients with leukoplakia and healthy groups.

Expression of Ki-67, Cyclin D1, P53, and P16 in patients with oral leukoplakia and leukoplakia cancerization with spicy diet in Chengdu.

To investigate the expression of Ki-67, Cyclin D1, P53, and P16 in patients with oral leukoplakia (OLK) and OLK cancerization who have aspicy diet in Chengdu. Thirtypatients with OLK andspicy diet and 15 patients with OLK without spicy diet in Chengdu were divided into three groups: hyperplastic OLK (OLK-), OLK with mild to moderate dysplasia (OLK+), and severe dysplastic OLK or oral squamous cell carcinoma (OSCC) transforming from OLK (OLK++/OSCC). The expression of Ki-67, Cyclin D1, P53, and P16 were detected by immunohistochemistry and statistically analyzed. The expression of Ki-67 and P53 in patients with or without spicy diet in the OLK+and OLK++/OSCC groups were stronger than that of the OLK- group (P<0.05). The OLK++/OSCC group showed a higher expression of Cyclin D1 and lower expression of P16 than the OLK- group (P<0.05). The expression of Ki-67, Cyclin D1, P53, and P16 in patients with spicy diet and without spicy diet had no substantial difference. The expression of Ki-67 and Cyclin D1 showed a positive correlation (r=0.439, P=0.015). Spicy diet did not have an influence on the expression of Ki-67, Cyclin D1, P53, and P16 in patients with OLK and OSCC. The expression of Ki-67, Cyclin D1, and P53 increased with the development of OLK, whereas P16 showed opposite expression trend.

Assessment of Betel Quid Habits and Risk of Precancerous Oral Lesions Among Paniya Tribes of Wayanad, India - A Cross-Sectional Study

Background: Betel quid habits in India is widely prevalent and responsible for increased incidence of head and neck cancer in the country. Head and neck cancer is a major public health problem among Paniya tribes, a marginalized tribal group in Kerala state, India. Previous studies among Paniya tribals in Wayanad have documented a high prevalence of betel quid habit. Oral leukoplakia (OL) and oral submucous fibrosis (OSF) are the most common oral mucosal diseases that have a very high malignant transformation rate. Aim: Aim of this study was to evaluate the risks imposed by betel quid habits in the development of oral leukoplakia and oral submucous fibrosis among Paniya tribes of Wayanad. Methods: A cross-sectional study was carried out in 300 residents between September 01, 2009 and March 31, 2017 using a structured questionnaire containing details of betel quid habits and socio-demographic details. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. Results: In the 300 subjects, the mean age was 32.4 ±SD 11.4 years, gender distribution (57.5% males vs. 42.5% females). 32.5% out of the study population were betel quid chewers (46.5% of males and 14.6% of females). The prevalence of OL and OSF was 12.9% and 13.02%, respectively among betel quid chewers. Conclusion: Awareness of head and neck cancer by betel quid habits varied with socioeconomic status among Paniya tribes of Wayanad. Despite their awareness of tobacco chewing as a risk factor for head and neck cancer, most of them still continue to chew. There is an urgent need to develop and implement culturally appropriate awareness-raising activities to target betel quid habit.

Role of Tobacco in the Development of Oral Leukoplakia and Oral Cancer

Tobacco smoking is associated with the development of many diseases, including oral cancer and leukoplakia. This fact is described in the 2014 annual report of the US Office of the Surgeon General The results of smoking on health, 50 years of progress. Despite the fact that different forms of tobacco(cigarettes, cigars, pipes, dipping and chewing tobacco or inhaled) are used in order to reduce pulmonary and cardiac complications, tobacco has a negative influence on human health. Tobacco smoking increases the death rate of smokers by 30-80%. Based on the mentioned we can determine the causal relationship between smoking and the development of oral cancer, leukoplakia and chronic impact on oral organs, i.e. lips during constant tobacco use.

Carcinogenic potential of sanguinarine, a phytochemical used in 'therapeutic' black salve and mouthwash.

Black salves are escharotic skin cancer therapies in clinical use since the mid 19th century. Sanguinaria canadensis, a major ingredient of black salve formulations, contains a number of bioactive phytochemicals including the alkaloid sanguinarine. Despite its prolonged history of clinical use, conflicting experimental results have prevented the carcinogenic potential of sanguinarine from being definitively determined. Sanguinarine has a molecular structure similar to known polyaromatic hydrocarbon carcinogens and is a DNA intercalator. Sanguinarine also generates oxidative and endoplasmic reticulum stress resulting in the unfolded protein response and the formation of 8-hydroxyguanine genetic lesions. Sanguinarine has been the subject of contradictory in vitro and in vivo genotoxicity and murine carcinogenesis test results that have delayed its carcinogenic classification. Despite this, epidemiological studies have linked mouthwash that contains sanguinarine with the development of oral leukoplakia. Sanguinarine is also proposed as an aetiological agent in gallbladder carcinoma. This literature review investigates the carcinogenic potential of sanguinarine. Reasons for contradictory genotoxicity and carcinogenesis results are explored, knowledge gaps identified and a strategy for determining the carcinogenic potential of sanguinarine especialy relating to black salve are discussed. As patients continue to apply black salve, especially to skin regions suffering from field cancerization and skin malignancies, an understanding of the genotoxic and carcinogenic potential of sanguinarine is of urgent clinical relevance.

Abstract 2280: Role of apoptosis signal-regulating kinase 1 in the cell apoptosis in oral leukoplakia

Abstract Oral leukoplakia is a common precancerous lesion. The mechanism is not clear. The aim is to investigate the roles of apoptosis signal-regulating kinase 1(ASK1) in the cell apoptosis in oral leukoplakia. Archival tissue sections of 10 oral leukoplakia,23 oral leukoplakia with mild to moderate dysplasia, 7 normal oral mucosa were detected by real time PCR and immunohistochemical staining of markers of ASK1 and p-ASK1.The cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nucleotide shift enzyme(TdT) mediated d-UTP end labeling(TUNEL). The results showed The mRNA and protein expression of ASK1 in oral leukoplakia with mild to moderate dysplasia was higher than the normal mucosa(p&amp;lt;0.05).From oral normal mucosa to oral leukoplakia to mild to moderate dysplasia, the expression of p-ASK1 was increased with the increasing grade( p&amp;lt;0.05).The apoptosis in oral leukoplakia and mild to moderate dysplasia increased more than normal mucose(p&amp;lt;0.05). It suggests that ASK1 and p-ASK1 are positive correlation with the increased apoptosis in the development of oral leukoplakia, its related signal pathways and cascade may play an important role in the cell apoptosis in oral leukoplakia. Citation Format: Xiaofei Tang, Jian-Fei Zhang, Wen-wen Niu, Min Zhang. Role of apoptosis signal-regulating kinase 1 in the cell apoptosis in oral leukoplakia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2280. doi:10.1158/1538-7445.AM2014-2280

Role of CYP2E1 genetic polymorphism in the development of oral leukoplakia among tobacco users in North Indian population.

The aim of the study to find out role of CYP2E1 genetic polymorphism in development of oral leukoplakia among tobacco users in North Indian population, this study was carried out at Department of Oral and Maxillofacial Pathology, King George's Medical University, Lucknow, UP. Study include a total of 105 leukoplakia patients were genotyped for CYP2E1 polymorphism (93 males and 12 females; mean age ± SD: 47.5 ± 10.6) and 96 unrelated healthy controls (85 males and 11 females; mean age ± SD: 49 ± 11.1). All the patients had either reported for treatment of leukoplakia or were diagnosed with leukoplakia during routine oral examination. A total of 105 leukoplakia patients and 96 controls were included in the study. The mean age of leukoplakia patients and control were 47 ± 10 and 51 ± 10 years respectively. The exclusive smokers comprised 62 (59%) leukoplakia patients and 53 (53%) controls. The exclusive smokeless tobacco users were 16 (15%) in leukoplakia patients and 27 (28%) in controls groups, while 27 (26%) leukoplakia patients and 16 (17%) controls have both types (smoking as well as smoke less) of tobacco habits simultaneously. Range of life time smoking exposure in leukoplakia and controls were (5-80 PY in both groups) but the mean smoking exposure in both groups were (leukoplakia: 28 ± 21.8 PY, control: 27: ±17 PY). But the mean smokeless tobacco dose in two groups were (leukoplakia: 150 ± 175 CY, controls: 137 ± 110 CY). All the results demonstrate an association between CYP2E1 genetic polymorphism and leukoplakia risk, premalignant lesion. It indicates that the CYP2E1 polymorphism, singly showed a protection towards the oral leukoplakia. Independent confirmation of this finding is required, and additional examination of the joint effect of CYP2E1genotype and other non-tobacco-related exposures is needed before more conclusive interpretation of our results can be made. This study demonstrates the importance of genetic variations in CYP2E1genes in susceptibility towards oral leukoplakia and it is conceivable that these variants will interact with environmental carcinogens and possibly some combinations of these genotypes will be at a high risk to oral leukoplakia.

Gene expression of oncogenes, antimicrobial peptides, and cytokines in the development of oral leukoplakia

The aim of this study was to investigate the expression pattern of oncogenes, antimicrobial peptides, and genes involved in inflammation in leukoplakia of the oral cavity compared with healthy gingiva. Biopsies of healthy gingiva (n=20) and leukoplakia (n=20), were obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of alpha-defensin (DEFA) 1/3, DEFA-4, S100-A7, deleted-in-oral-cancer (Doc) 1, interleukin (IL) 1beta, IL-6, IL-8, IL-10, tumor necrosis factor (TNF) alpha, cyclooxygenase (Cox) 2, epidermal growth factor (EGF), keratinocyte growth factor (KGF), transforming growth factor (TGF) beta1, TGF-alpha, collagen-IA1 (Col-1), and tenascin-c were analyzed by real-time reverse-transcription polymerase chain reaction. The proteins encoded by the different genes were visualized by immunostaining. Compared with healthy gingiva (set as 1), there was an increased gene expression of DEFA-4 (179.2-fold), S100-A7 (25.4-fold), EGF (24.8-fold), TGF-beta1 (25.2-fold), and tenascin-c (34.3-fold) in oral leukoplakia. The expression of IL-1beta and Doc-1 was decreased (0.01-fold and 0.2-fold, respectively). The combination of an increased expression of the antimicrobial peptide DEFA-4, the oncogene S100-A7, EGF, and tenascin-c, and a decreased Doc-1 expression in oral leukoplakia might characterize its potency of malignant transformation. Chronic inflammation seems not to be involved in the development of this lesion.

Polymorphisms in the apoptosis-associated genes FAS and FASL and risk of oral cancer and malignant potential of oral premalignant lesions in a Taiwanese population

Our aim was to measure the relationship of FAS (-1377G>A and -670A>G), FASL (-844C>T) gene variants and risk of oral cancer. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to determine the FAS and FASL polymorphisms in 294 oral squamous cell carcinoma (OSCC), 53 oral submucous fibrosis (OSF), and 84 oral leukoplakia (OL) patients, as well as in 333 healthy controls. A standardized questionnaire was applied to collect demographic data, and potential confounding factors. JMP statistical software was used to analyze the association. FAS and FASL polymorphisms were not correlated with OSCC development or the malignant potential of OL by simple and multivariate logistic regression. However, a two- to fourfold difference in the risks of betel quid chewing, alcohol consumption, and smoking on OSCC development were observed between participants with different FAS polymorphisms. FAS polymorphisms were significantly correlated with the malignant potential of OSF. Multivariate logistic regression analysis indicated that FAS A(-1377)-G(-670) vs. G(-1377)-A(-670) haplotype (OR = 2.26, 95% CI = 1.16-4.41) was correlated with the malignant potential of OSF. We suggest that FAS and FASL polymorphisms are not significantly correlated with OSCC development or malignant potential of OL. The impact of substance usage on OSCC development could be differentiated by FAS polymorphisms. FAS A(-1377)-G(-670) haplotype may play a role in the malignant potential of OSF.

Polymorphisms of COX-2 -765G > C and p53 codon 72 and risks of oral squamous cell carcinoma in a Taiwan population

The association between polymorphisms of COX-2 -765G>C and p53 codon 72, and oral squamous cell carcinoma (OSCC) remains unclear. We investigated the associations between COX-2 and p53 polymorphisms, oral precancerous lesions (OPL), and OSCC. Demographic data and substance use (smoking, drinking, and betel quid chewing) data were collected from 297 patients with OSCC, 70 with oral leukoplakia (OL), 39 with oral submucosal fibrosis (OSF), and 280 healthy controls. COX-2 and p53 polymorphisms were determined by PCR-RFLP methods. A significantly higher proportion of OSCC and OPL patients were male, and frequent habitual users of the three substances. No association was found between p53 and COX-2 polymorphisms, ethnicity, and gender. Polymorphisms of p53 were not associated with OSCC development and malignant potential of OPL, OSF, and OL. The frequency of COX-2 -765G/G genotype was significantly higher in healthy controls (chi(2)=93.83, p<0.0001). After adjusting for possible confounding factors, COX-2 -765C allele vs. -765G/G genotype (OR=0.22, 95%CI=0.12-0.39) was a protective factor against OSCC development, but was a risk factor for malignant potential of OSF (OR=3.20, 95%CI=1.32-8.94) and OL (OR=6.73, 95%CI=2.84-19.87). We suggest that COX-2 -765G>C polymorphisms play a different role in OSCC development than in malignant potential of OSF and OL. However, p53 codon 72 polymorphisms show no such correlation.

Prevalence of oral cancer and pre‐cancer and associated risk factors among tea estate workers in the central Sri Lanka

To screen for oral cancer or not is being debated, but for high-risk populations with minimal access to regular dental care systematic oral examinations could provide some benefit. We undertook oral mucosal examinations of labourers employed in tea estate plantations in Sri Lanka. In a two-stage screening procedure, first by estate medical officers and then by visiting specialists, we examined 12 716 persons at their workplaces achieving a coverage of one-sixth of the total workforce. Fourteen oral cancers and 848 subjects with oral pre-cancer (6.7%) were detected giving population prevalences of 46.1 per 1000 for leukoplakia and 16.4 per 1000 for oral submucous fibrosis. Among subjects with any oral mucosal disorder (n = 1159) proportions of current users of betel quid, smokers and alcohol use was recorded at 92%, 31% and 61% respectively. The synergistic effect of these three risk habits on the development of oral leukoplakia was evident in mixed habit groups. The prevalence of oral pre-cancer in tea estate labourers was higher than estimates reported in previous studies. In the absence of state-sponsored preventive activities, it is necessary to improve the capacity of individual health practitioners and small medical centres to participate in oral health promotion and oral cancer/pre-cancer screening.

Oral hygiene practices and risk of oral leukoplakia

To determine the influence of oral hygiene habits and practices on the risk of developing oral leukoplakia. Case control study. Githongo sublocation in Meru District. Eighty five cases and 141 controls identified in a house-to-house screening. The relative risk (RR) of oral leukoplakia increased gradually across the various brushing frequencies from the reference RR of 1.0 in those who brushed three times a day, to 7.6 in the "don't brush" group. The trend of increase was statistically significant (X2 for Trend : p = 0.001). The use of chewing stick as compared to conventional tooth brush had no significant influence on RR of oral leukoplakia. Non-users of toothpastes had a significantly higher risk of oral leukoplakia than users (RR = 1.8; 95% confidence levels (CI) = 1.4-2.5). Among tobacco smokers, the RR increased from 4.6 in those who brushed to 7.3 in those who did not brush. Among non-smokers, the RR of oral leukoplakia in those who did not brush (1.8) compared to those who brushed was also statistically significant (95% CL = 1.6-3.8). Failure to brush teeth and none use of toothpastes are significantly associated with the development of oral leukoplakia, while the choice of brushing tools between conventional toothbrush and chewing stick is not. In addition, failure to brush teeth appeared to potentiate the effect of smoking tobacco in the development of oral leukoplakia. Oral health education, instruction and motivation for the improvement of oral hygiene habits and practices; and therefore oral hygiene status, should be among the strategies used in oral leukoplakia preventive and control programmes.

High-performance liquid chromatographic determination of arecoline in human saliva

Arecoline (methyl-1,2,5,6-tetrahydro-1-methyl nicotinate) is an alkaloid found in the areca catechu nut which is a major component of the ‘betel quid’ chewed by a large proporation of the population in India, South Asia and the South Pacific islands. It is commonly associated with the development of oral leukoplakia, oral submucous fibrosis and oral cancer. We have developed a new ion-pairing reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of arecoline in saliva, using arecaidine (1,2,5,6-tetrahydro-1-methylnicotinic acid) as an internal standard. The optimal wavelength was established using UV absorbance scans. It was showed that 215 nm is the optimal wavelength to maximise the signal in detecting arecoline in the mobile phase. Arecoline was extracted from saliva with hexane–isoamyl alcohol (1%) and reconstituted with mobile phase for HPLC analysis. The developed method is an easy and reliable method of determining arecoline concentrations in saliva. Sensitivity, specificity, precision, accuracy and reproducibility of the method were demonstrated to be satisfactory for measuring the arecoline level.

The precancer risk of betel quid chewing, tobacco use and alcohol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan.

In areas where the practise of betel quid chewing is widespread and the chewers also often smoke and drink alcohol, the relation between oral precancerous lesion and condition to the three habits is probably complex. To explore such association and their attributable effect on oral leukoplakia (OL) and oral submucous fibrosis (OSF), a gender–age-matched case–control study was conducted at Kaohsiung, southern Taiwan. This study included 219 patients with newly diagnosed and histologically confirmed OL or OSF, and 876 randomly selected community controls. All information was collected by a structured questionnaire through in-person interviews. A preponderance of younger patients had OSF, while a predominance of older patients had OL. Betel quid chewing was strongly associated with both these oral diseases, the attributable fraction of OL being 73.2% and of OSF 85.4%. While the heterogeneity in risk for areca nut chewing across the two diseases was not apparent, betel quid chewing patients with OSF experienced a higher risk at each exposure level of chewing duration, quantity and cumulative measure than those who had OL. Alcohol intake did not appear to be a risk factor. However, cigarette smoking had a significant contribution to the risk of OL, and modified the effect of chewing based on an additive interaction model. For the two oral premalignant diseases combined, 86.5% was attributable to chewing and smoking. Our results suggested that, although betel quid chewing was a major cause for both OL and OSF, its effect might be difference between the two diseases. Cigarette smoking has a modifying effect in the development of oral leukoplakia.

Prevalence of oral leukoplakia

This paper reviews epidemiologic studies on prevalence of oral leukoplakia. Special emphasis is placed on population selection, diagnostic criteria, type and training of examiners and risk factor assessment. Prevalence of leukoplakia in these studies has ranged from 0.6% to 4.6%. Variations in prevalence among the studies could depend on methodology, especially studied populations and diagnostic criteria. Most investigations have investigated the entire available adult population in a geographic region or a random sample. Others have comprised selected populations, such as hospital or clinic patients. Our study has shown that prevalence of oral leukoplakia was 2.2% in a relatively small and highly selected population. The onset of leukoplakia usually takes place after the age of 30 years. Our study showed that oral leukoplakia occurred in men over 40 years of age and in women over 50 years of age. These results are supported most previous findings. Gender distribution varies in most studies, ranging from a strong male predominance (4:1), to almost 1:1 in the Netherlands. Tobacco smoking is the most important known etiological factor in development of oral leukoplakia. Smokers have a six-fold increase in the risk of developing leukoplakia of the oral mucosa in regard to non-smokers. Six European studies, including our study, found a prevalence of smoking between 56 and 97 percent in leukoplakia patients. Our study also showed that the majority of smokers with leukoplakia (74.0%) smoked more than 20 cigarettes per day compared to 34.5% of those without leukoplakia. Smoking and alcohol consumption are often coexistent factors making it difficult to assess the effects of these factors individually. In our study the highest prevalence of leukoplakia (33.3%) was established in subjects who smoked cigarettes and consumed alcohol, compared to those who smoke tobacco only (18.2%).

In situ staining with DNA-binding fluorescent dye, Hoechst 33258, to detect microorganisms in the epithelial cells of oral leukoplakia.

This study was performed to investigate the presence of microorganisms in the epithelial cells of leukoplakia. Frozen sections of 20 specimens of leukoplakia were stained with DNA-binding bisbenzimide Hoechst 33258. As a control, 20 specimens of normal oral mucosa and five specimens of normal skin were used. In all preparations of leukoplakia, small granular fluorescing structures were observed within the cytoplasm of the epithelial cells, predominantly within the cytoplasm of prickle cells, although the amount of the granular structures varied between specimens, layers of the epithelium and even areas of the epithelium within a single section. Less granular structures were observed, or none at all, in the cytoplasm of the epithelial cells of normal mucosa. No structures were observed in the cytoplasm of the epithelium of skin. The results in this study strongly suggest that microorganisms are present in the epithelial cells of oral mucosa, and that they are closely associated with the development of oral leukoplakia. It is postulated that the microorganisms in the epithelial cells could be bacteria, particularly mycoplasmas.

Tobacco usage in relation to the anatomical site of oral leukoplakia

Tobacco usage is the most important known aetiological factor in the development of oral leukoplakia. The purpose of this study was to investigate the possible relation of tobacco usage to the anatomical site of the leukoplakia. Clinical data regarding tobacco usage and localisation of leukoplakia obtained from 166 patients with oral leukoplakia. Leukoplakias in the floor of mouth appeared to be statistically significantly more often present in smokers than in non-smokers, compared to all other oral sites (P < 0.001; OR = 8.47 and 18.13 for men and women, respectively). On the contrary, leukoplakias on the borders of the tongue were statistically significantly more common among non-smokers, than smokers, compared to all other oral sites (P < 0.001; OR = 0.22 and 0.12 for men and women, respectively). The present study suggests that the influence of tobacco on the development of leukoplakia varies by anatomical site.

Tobacco usage in relation to the anatomical site of oral leukoplakia

OBJECTIVE: Tobacco usage is the most important known aetiological factor in the development of oral leukoplakia. The purpose of this study was to investigate the possible relation of tobacco usage to the anatomical site of the leukoplakia. SUBJECTS AND METHODS: Clinical data regarding tobacco usage and localisation of leukoplakia obtained from 166 patients with oral leukoplakia. RESULTS: Leukoplakias in the floor of mouth appeared to be statistically significantly more often present in smokers than in non-smokers, compared to all other oral sites (P < 0.001; OR = 8.47 and 18.13 for men and women, respectively). On the contrary, leukoplakias on the borders of the tongue were statistically significantly more common among non-smokers, than smokers, compared to all other oral sites (P < 0.001; OR = 0.22 and 0.12 for men and women, respectively). CONCLUSION: The present study suggests that the influence of tobacco on the development of leukoplakia varies by anatomical site.

Viadent usage and oral leukoplakia: a spurious association.

Oral rinse and toothpaste products (Viadent) containing Sanguinaria extract have been shown through extensive clinical trials to be effective against plaque build-up and gingivitis. To establish safety, a comprehensive research program was conducted, including a series of clinical studies and a number of animal studies to evaluate acute, subchronic, and chronic toxicity, and the potential for irritation of mucosal tissues. In 1990 and 1993, an Expert Panel reported on reviews of these data and concluded that Viadent products are safe for their intended use. Despite the large database of information to support the safety of Viadent products, Damm et al. (1999) recently raised the possibility that their usage may be causally associated with development of oral leukoplakia. However, a critique of this recent report shows that it does not fulfil criteria for establishing causation. In particular, the study does not show that exposure to Viadent preceded the onset of leukoplakia, it does not demonstrate dose-response or biological plausibility, and it suffers from selection and information bias and from potential confounding. Furthermore, upon critical evaluation, the Damm et al. (1999) report on a case-series is inconsistent with the weight of available clinical evidence showing that Sanguinaria extract-containing oral health care products cause no cytotoxic or significant irritant effects in the oral mucosa in human studies of up to 6 months duration. The animal data similarly do not support a causal association between Viadent usage and oral leukoplakia in humans. These data demonstrate that Sanguinaria extract and whole Viadent formulations are without significant irritation potential and have no effects on the oral mucosa, even in studies with life-long dietary exposure to Sanguinaria extract. The mutagenicity and genotoxicity data do not indicate that Sanguinaria extract or its components are genotoxic in vivo. The results of 2 GLP-compliant rat oncogenicity studies provide no evidence of any carcinogenic effect of Sanguinaria extract. In conclusion, the available clinical and animal data provide no support for and in fact argue strongly against the hypothesis that the use of Viadent toothpaste and/or oral rinse products may be causally associated with the development of leukoplakia in humans.