The fibroblast population in oral submucous fibrosis

The purpose of the investigation was to compare the morphology of fibroblasts cultured from healthy oral mucosa and mucosa of patients with oral submucous fibrosis (OSF) and to collate the occurrence of cell types of similar morphology. Cells cultured from biopsy specimens from the buccal mucosa of six subjects who did not chew the areca nut and six patients with OSF who chewed areca nut were grown according to standard techniques. Ninety cells per cell line were recorded daily for 8 days, classified into types F1, F2 and F3 according to their morphology, and the results statistically analyzed. We found that there was a relative increase of F3 cells in relation to Fl cells in OSF resulting in the ratio of F3 to F1 cells being significantly larger in OSF than the ratio in the controls. As it has been reported that F3 cells m rat connective tissues produce significantly more collagen types I and III than F1 cells, we concluded that a change of fibroblast population has occurred in OSF and that this relative increase of F3 cells in humans, which could be committed to the production of large quantities of collagen, can be an explanation for the excessive collagen formation in OSF.     

HLA-antigens in oral submucous fibrosis

HLA–typing was carried out on 122 areca nut chewers who attended hospitals for complaints unrelated to the habit. The subjects were South Africans of Indian extraction. The study did not include haplotypes. Palpable fibrous bands in the mouth indicated oral submucous fibrosis. The subjects were divided into 4 groups based on specific oral symptoms and signs. Groups A and B were without fibrous bands. Group A (47 subjects) included those with one or no symptoms while group B (28 subjects) suffered from 2 to 7 oral symptoms. Group C (17 subjects) had oral symptoms and represented early or mild oral submucous fibrosis and exhibited at least one discrete palpable fibrous hand. Group D (30 subjects) were classic oral submucous fibrosis cases with multiple bands. The high occurrence of oral submucous fibrosis in this study group (39%) is similar to the occurrence in comparable age groups reported earlier–n South Africa and is conceivably due to the higher age range of the subjects and their relatively long exposure to the area nut. We were unable to demonstrate a specific pattern of HLA–antigen frequencies in chewers with or without the disease. Furthermore, there were no differences between the study population and the controls. It is concluded that there is not necessarily a HLA–associated susceptibility in oral submucous fibrosis.     

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口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种慢性、隐匿性且具有癌变倾向的疾病,主要发生于印度、巴基斯坦等东南亚国家以及我国湖南、台湾两省。OSF病因不明,咀嚼槟榔是其最主要的致病因素,且咀嚼槟榔的频率越高、年限越长,越易患OSF。所有OSF患者都有咀嚼槟榔史,咀嚼槟榔还与口腔白斑、口腔癌发病高度相关。此外,OSF的发生还与遗传因素、免疫反应、胶原相关性基因,营养缺乏等有关。本文就OSF致病因素做一简单介绍。     

Growth of oral and skin fibroblasts from patients with oral submucous fibrosis

The purpose of the investigation was to evaluate and compare the proliferation (growth) of mouth fibroblasts and skin fibroblasts from patients with oral submucous fibrosis (OSF). Material comprised fibroblasts from fibrous bands situated in the buccal mucosa and from the inner aspect of the forearm of 8 patients with classic features of OSF as well as fibroblasts from 6 buccal mucosa and 8 skin biopsy specimens from healthy non-areca nut chewing individuals. Cells were cultured for 8 days according to standard techniques. Their growth was monitored daily, under optimal conditions as well as exposure to concentrations of arecoline. The data were analyzed using regression analysis, analysis of variance and the Kruskal-Wallis test. We found no statistically significant differences between the proliferation patterns of oral and skin fibroblasts from patients or between those from patients and controls. The reaction of the cells exposed to concentrations of arecoline was similar; at low concentrations (0.1–10 μg/ml) normal growth was maintained, while 100 μg/ml inhibited growth. It is concluded that fibroblasts from mouths affected by OSF have proliferation patterns which fall within normal parameters, that the excessive collagen formation in established OSF is not due to increased fibroblast proliferation and that arecoline does not stimulate fibroblast proliferation.     

Prevalence of oral submucous fibrosis among areca nut chewers: A systematic review and meta-analysis

Background: Worldwide millions peoples consume AN who are at risk of OSMF. Prevalence of OSMF is reported between 0.03% and 30% irrespective of AN habit. Further, these estimates are based on sample population comprised of OSMF patients or general population rather AN chewers (ANC). Therefore, available evidence does not reflect the true prevalence of OSMF among ANC. Method: The studies providing the prevalence of OSMF in ANC were identified in PubMed, Scopus, and Web of Science. Pooled prevalence and quality assessment using New-Ottawa Scale were performed. Results: Fifteen studies reported the prevalence of OSMF (929) in ANC (53,213). Most studies were from China (six studies) and India (four studies) correlating with regions having high ANC. The pooled prevalence of OSMF in ANC was 5% (0.05 [95% CI, 0.03, 0.08]). All studies' quality was satisfactory; however, the OSMF diagnosis method, age, gender, and habits need further scrutiny. Conclusion: Available evidence suggested a low prevalence of OSMF in ANC, although further large-scale studies are recommended to validate this finding. Understanding the prevalence and distribution patterns of OSMF might aid intervention healthcare programs and contribute to the reduction of the oral cancer burden related to OSMF.     

Development of an in vivo mouse model to study oral submucous fibrosis

BACKGROUND: Epidemiological data have shown an association of areca nut chewing with oral submucous fibrosis (OSF). Experimental evidence to confirm this has been limited. Fibrosis-promoting activity of areca nut was tested in an animal model. METHOD: Buccal mucosa of a group of 20 female BALB/c strain mice, 10-12 weeks of age, was treated twice daily 6 days per week with topical application of aqueous areca nut extracts for 300-600 days. A control group (n = 20) was treated with 50 mM NaCl. The influence of areca nut on the oral epithelium and connective tissue was recorded semiquantitatively by light microscopy. RESULTS: The areca nut-treated oral epithelium showed progressive changes in epithelial thickness leading to atrophy, increased cellularity of fibroblasts, fibrosis of connective tissue, focal infiltration of inflammatory cells and muscle atrophy. On killing after 600 days of treatment, the scores on cellularity, inflammation and muscle atrophy were significantly different to the control group (P = 0.03). CONCLUSION: The study provides further evidence that areca nut contributes to the development of OSF in treated animals. The model has the potential to test synergism of areca nut with other carcinogens and any therapeutic interventions.     

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口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种慢性、隐匿性、具有癌变倾向的口腔黏膜病。本文对OSF的病名来由、病因、发病机制和病变的性质进行了系统的描述。     

Predictors of the severity of oral submucous fibrosis among gutka consumers: a regression analysis

Oral submucous fibrosis (OSMF) is an insidious chronic disease of the oral mucosa that is characterised by severely limited mouth opening, blanching of the oral mucosa, and a burning sensation in the oral cavity. Consumption of betel nut and/or gutka are the known risk factors. We undertook this study to correlate the frequency and duration of gutka intake with the severity of OSMF and to determine the predictors of severe OSMF (mouth opening <20mm). A cross sectional study was conducted on 300 participants (who were known gutka chewers) selected at the Baqai Dental College and Fatima Hospital, Karachi, Pakistan. Participants’ medical and dental histories were recorded. Informed consent was obtained, and clinical oral examination was done. Information regarding the extent of mouth opening, chewing habits, frequency and duration of gutka intake, the site of placing gutka, duration of chewing, and whether they swallowed or spat out the gutka were collected. A standardised questionnaire was used to document the findings. Binary logistic regression was applied using the severity of OSMF (mouth opening <20mm) as an outcome variable. Out of 300 participants, 172 (57.3%) were males; mean (SD) age of the sample was 38.2 (12.3) years. A total of 156 (52%) participants had the habit of chewing gutka, of which 213 (71%) had clinical stage I OSMF, 75 (25%) had stage II, and 12 (4%) had stage III. As per functional staging, 18 (6%) subjects had mouth opening <20mm. Nearly 144 (48%) participants were consuming other forms of tobacco in addition to the gutka. Patients with palpable bands = 232 (77.3%), ulcerative lesions = 212 (70.7%), altered taste sensation = 210 (70%) and altered hunger = 252 (85.7%) were common findings. The duration of gutka intake was found to be positively correlated with the severity of OSMF; however; its frequency was not. Among intraoral findings, the presence of red and white lesions inside the mouth was the most significant predictor of the severity of OSMF.     

Epidemiological survey of oral submucous fibrosis and leukoplakia in aborigines of Taiwan

A population-based survey was designed to investigate the prevalence of areca/betel quid chewing, oral submucous fibrosis and leukoplakia in a typical aboriginal community of southern Taiwan. Three hundred and twelve people 20 years of age or older were collected in the study. The prevalence of chewing areca/betel quid was 69.5%, with an average of 17.3 portions a day for an average 24.4 years. More women (78.7%) than men (60.6%) chewed areca/betel quid. The prevalences of oral submucous fibrosis and leukoplakia were 17.6% and 24.4%, respectively. It was found that the odds ratio for chewing areca/betel quid and having at least one of the above oral mucosal lesions was 8.21. Any additional smoking or drinking habits were not significant for having oral mucosal lesions. Although the areca/betel quid in Taiwan does not contain any tobacco, a significant association was still identified between areca/betel quid chewing and oral mucosal lesions.     

Depigmentation of oral mucosa as the earliest possible manifestation of oral submucous fibrosis in Sri Lankan preschool children

This article reports the presentation of oral submucous fibrosis in five Sri Lankan preschool children, aged 2–3 years, with loss of pigmentation of the lips as the sole clinical feature. Oral submucous fibrosis has not been reported in this age group of children. The five 2–3 year olds did not display any classical features of oral submucous fibrosis, due to the disease having been detected at a very early stage. The present study attempts to establish that depigmentation of the lips and oral mucosa is perhaps the earliest feature to develop in the natural history of oral submucous fibrosis. The differential diagnosis of oral mucosal depigmentation relevant to these cases is also discussed. Previously‐reported cases of oral submucous fibrosis in children are reviewed.     

Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing

Oral submucous fibrosis (OSF) is a high risk precancerous condition, predominantly affecting Indians. Consumption of chilli was hypothesized as an etiologic factor on the basis of ecological observations and a solitary animal experimental study. Subsequent epidemiologic studies that included case-series reports, large cross-sectional surveys, case-control studies, cohort and intervention studies have identified areca nut as the major etiologic agent. Tissue-culture studies involving human fibroblasts, areca nut extracts and areca nut alkaloids supported this etiologic hypothesis by showing fibroblastic proliferation and increased collagen formation. Currently, the role of genetic susceptibility and that of autoimmunity are receiving attention. The influence of nutritional factors, if any, remains unclear.     

Cytokeratin expression in oral submucous fibrosis – an immunohistochemical study

BACKGROUND: Oral submucous fibrosis (OSF) is a pre-malignant condition caused by habitual use of areca nut, affecting the oro-pharynx and characterized by progressive fibrosis. Alteration of cytokeratin (CK) expression has been documented in leukoplakia and oral cancer (OC). However, very little is known of CK alterations in OSF. The present study was carried out to characterize the CK profile in OSF and ascertain if this could be used as a surrogate marker for malignant transformation. METHODS: Paraffin-embedded tissues of OSF (n = 50), normal (n = 10) and OC (n = 10) were stained with pancytokeratin (PanCK), high molecular weight cytokeratin (HMWCK), CKs 18, 14, 8, 5, 4 and 1 by immunohistochemistry. RESULTS: Significant difference in the CK staining pattern was seen between normal, OSF and cancer. Significant changes in OSF included increased intensity of staining for PanCK and HMWCK, aberrant expression of CK8 and decreased expression of CKs 5 and 14. CONCLUSION: Cytokeratin profile of OSF was significantly different from normals for PanCK, HMWCK, CK8, 5 and 14 suggesting their potential to be used as surrogate markers of malignant transformation. Further studies will help in better defining the nature and clinical implications of these alterations.     

湖南地区口腔黏膜下纤维性变流行趋势变化(附278例回顾性研究)

目的 :观察湖南地区口腔黏膜下纤维性变 (OSF)流行趋势。方法 :对 2 78例OSF患者的年龄、性别、职业、地区来源、咀嚼槟榔时间、频率、主要症状、病变部位、张口度等临床资料进行分析。结果 :OSF患者平均年龄3 4.5岁 ,男女性别比为 94.6∶5 .4,OSF发病以司机、公务员、商人、警察等职业为多 ,湖南各地区都发现OSF患者。OSF患者典型临床表现为黏膜刺激痛、黏膜苍白、张口受限、纤维条索。其它症状有舌功能障碍 ,黏膜水疱、溃疡、烧灼痛等 ,病变部位以口腔后份为主 ,病变部位越靠前 ,范围越广 ,张口度越小 ,病变程度越严重 ( p <0 .0 0 5 ) .结论 :湖南地区OSF流行趋于年轻化 ,以男性为主 ,OSF发病覆盖全省各地区 ,OSF在某些职业中发病率较高 ,OSF患者到医院就诊大多为中晚期 ,临床症状、体征明显 ,病变部位与疾病严重程度 (即张口度 )有明显关系     

Oral submucous fibrosis: a case-control study in Chennai, South India

BACKGROUND: Oral submucous fibrosis (OSF) is a pre-cancerous condition caused by the use of areca nut in various forms. There are very few published reports on areca nut use and OSF from Chennai, South India. METHODS: A hospital-based case-control study on habits and OSF was performed in Chennai over a 3-year period. A total of 185 consecutive patients with OSF were matched with age- and sex-matched controls. History was recorded in a pre-determined format by qualified dental surgeons. RESULTS: The male to female ratio of OSF cases was 9.9 : 1. All areca nut products were associated with OSF, with the risk being greatest for pan masala. The duration of the habit was more significant than the frequency of the chewing habit. CONCLUSION: The present study confirms the strong association between areca nut use and OSF and the increasing use of pan masala.     

Collagen in submucous fibrosis: an electron-microscopic study

A comparison of the electron-microscopic features of 11 examples of submucous fibrosis in its moderately advanced and advanced stages with 15 control specimens revealed no obvious abnormality of the collagen fibrils. The notable feature of the collagen in this disease is the densely packed bundles in the lamina propria, reaching close to the epithelial-connective tissue junction, to blood vessel walls, salivary glands and muscle fibers. The width and the periodicity of fibrils vary in both groups of specimens, noticeably so, next to the junction and close to blood vessels, salivary glands and muscles. This is due to the presence of the thinner Type III collagen fibrils in these sites and the natural variation of Type I fibrils. Immunofluorescent microscopy and special staining with sirius red and polarization microscopy demonstrate both types, confirming that Type I collagen forms the bulk of the collagen and that Type III is localized in the sites mentioned above. It is concluded that although there is an excessive increase of collagen, especially Type I, in submucous fibrosis, the fibrils are still morphologically normal.     

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口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种慢性、隐匿性、具有癌变倾向的炎性疾病.患者进食刺激性食物时口内疼痛,口腔黏膜苍白僵硬,触摸有条索感,舌运动、张口受限,以致咀嚼、吞咽困难,有的甚至发生癌变,严重影响患者的生存质量和身心健康.复杂的发病机制导致该病至今尚无满意的治疗方法.本文介绍了目前主要的治疗方法,包括药物治疗、物理治疗和手术治疗等,主张根据病变发展的阶段,采用多种方法联合治疗.     

Psychiatric morbidity among patients with oral sub‐mucous fibrosis: a preliminary study

J Oral Pathol Med (2010) 39 : 761–764 Background: Oral submucous fibrosis (OSF) is a chronic oral mucosal condition with pre‐malignant potential. The association between psychiatric morbidity and OSF has been sparsely studied. Methods: This cross‐sectional study included 33 consecutive subjects clinically diagnosed with OSF who attended an academic tertiary care dental centre. General Health Questionnaire‐28 was administered to assess the psychological morbidity. Dependence to areca products was assessed using the ICD‐10 criteria. Patient group was compared with an age and gender matched control group (n = 33) from the same hospital that comprised patients who had dental diseases other than OSF and had no areca/tobacco habit. Results: Total mean scores (SD) of GHQ‐28 for study group and control group respectively were 48.2 (18.1) vs. 24.2 (6.5) (P < 0.001). Among the patient group, the mean total GHQ scores were significantly higher in those with functional stage C (those with worst functional staging) of OSF 63.4 (15.2) when compared with those with stage B 54 (14.2) and stage A 38.7 (17) (d.f. = 2; P = 0.005). 22 (66.7%) of patients met ICD‐10 criteria for dependence to areca products. Conclusions: OSF may be associated with considerable psychological morbidity. This morbidity may be significantly more in patients with worst functional staging. It is difficult to determine whether this is the cause or effect of the disease. Further systematic studies are urgently needed to address this issue.