Transformation Of Oral Submucous Fibrosis Research Articles

The interplay of EMT and stemness driving malignant transformation of Oral Submucous Fibrosis

BackgroundOral submucous fibrosis (OSF) is a persistent oral mucosal condition that carries an elevated risk of undergoing malignant transformation. Our objective was to elucidate the involvement of epithelial-to-mesenchymal transition (EMT) in OSF and its progression to malignancy by studying a panel of EMT markers, thereby understanding the molecular mechanisms. MethodsAn immunohistochemical analysis was done to detect the presence of E-cadherin, N-cadherin, pan-cytokeratin (PanCK), vimentin, α-SMA (alpha-smooth muscle actin), and CD44 in a total of 100 tissue samples. These samples comprised 40 cases of OSF, 20 cases of oral squamous cell carcinoma associated with OSF (OSFSCC), and 40 cases of oral squamous cell carcinoma (OSCC). A whole transcriptomic analysis was performed on a group of seven matched samples encompassing NOM, OSF, OSFSCC, and OSCC. ResultsWe observed significantly decreased expression of E-cadherin and PanCK, while N-cadherin, vimentin, α-SMA, and CD44 showed significantly higher expression in OSFSCC and OSCC as compared to OSF, both at protein and RNA levels. CD44 expression was noticeably higher in OSFSCC (p < 0.001) than in OSCC. ConclusionDownregulation of epithelial markers with concomitant upregulation of mesenchymal and stem cell markers suggests the potential role of EMT and stemness in accelerating the pathogenesis and malignant transformation of OSF. The high levels of CD44 expression seen in OSFSCC indicate a high propensity for aggressiveness and acquisition of stem-like characteristics by the cells undergoing EMT.

IRF4 as a novel target involved in malignant transformation of oral submucous fibrosis into oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) in the context of oral submucous fibrosis (OSF) has a high incidence owing to undefined pathogenesis. Identifying key genes and exploring the underlying molecular mechanisms involved in the conversion of OSF into OSCC are in urgent need. Differentially expressed genes (DEGs) between OSCC and OSF were dug from GEO databases and a total of 170 DEGs were acquired. Functional association of DEGs were analyzed by GO and KEGG. Protein–protein interactions (PPIs) analysis was carried out and candidate biomarkers were identified by Gene co-expression analysis and Cox analyses. Hub genes were confirmed by qRT-PCR in tissues and cell lines, of which we found that IRF4 mRNA was successively up-regulated from Normal to OSF and then to OSCC and associated with immune infiltrating levels. In addition, Immunohistochemical (IHC) and Immunofluorescence (IF) assays were conducted to validate the consistent upregulation of IRF4 and the oncogene role of IRF4 in OSF and OSCC at translation level. IRF4 may be indicative biomarker in transformation of OSF into OSCC. High IRF4 expression contribute to increased immune infiltration of OSCC and may provide a novel diagnostic marker for OSCC patients translated from OSF.

Malignant transformation rate of oral submucous fibrosis: A systematic review and meta‐analysis

AbstractAimTo review and summarize all the available data from the literature regarding the malignant transformation of oral submucous fibrosis and derive a mean malignant transformation rate (MTR).Materials and MethodsThe electronic search was conducted using PubMed and google scholar. Only full‐text English language articles published from the earliest possible date to 30 April 2019 were included in the study. Abstracts, reviews, letters to editors and editorials were excluded. The study protocol was registered in PROSPERO(CRD42019124563). Data were extracted by 2 reviewers. The random effects model was used to perform the meta‐analysis.ResultA total of 10 articles were included in the review after screening 1177 records. The majority of studies available were from India and Taiwan. Out of 5428 oral submucous fibrosis cases, 298 cases transformed to oral squamous cell carcinoma. Males showed a greater predilection for transformation. The MTR rates varied from 1.9% to 12%. The overall mean MTR obtained based on the available data was 5.5%, and the MTR of India and Taiwan obtained were 5.0% and 5.5%, respectively.ConclusionThe systematic review and meta‐analysis based on the available literature have concluded that patients with OSF have a mean risk of 5.5% for malignant transformation into OSCC.

Role of immunohistochemical markers in evaluating malignant transformation of oral submucous fibrosis

Objective(s): We present a systematically to identify, evaluate and assess the role of Immunohistochemical markers in Malignant Transformation of Oral Submucous Fibrosis (OSF). Materials and Methods: Extensive literature search was done to identify eligible through “MEDLINE”/ “PubMed”, “Scopus” and “Cochrane library” were searched for relative studies until December 2021. The included studies were published in English language were mainly retrospective original research\.These studies mainly evaluated the role of Immunohistochemical markers in Malignant Transformation of Oral Submucous Fibrosis. Results: Thirteen studies were included in the present study which had total of 549 cases. Most of the studies suggested use of combined biomarker model or panel of antibodies to minimize the risk of bias. Almost all the studies used ANOVA and chi-square test while kappa test analysis for interobserver variability test. Conclusions: The significance of immunohistochemical markers has been shown in study which can significantly contribute in diagnosing early event in process of malignant transformation of suspicious OSF cases so that better treatment plan could be formulated for better prognosis. More efforts should be emphasized on combination of \antibodies and its importance in target drug therapy.

Oral Submucous Fibrosis Patients Expressed Hypoxia Inducible Factor-1α (HIF-1α) in Saliva: A Biomarker for Detection of Malignant Transformation

Objective: Aim of this current study was to determine the malignant transformation associated with hypoxia inducible factor-1α among patients of oral submucous fibrosis (OSF). Study Design: This Retrospective study was carried from 1st January, 2021 to 31st December, 2021 at the Department of Dental Materials, Sardar Begum Dental College, Gandhara University, Peshawar Methods: There were forty five diagnosed patients of oral submucous fibrosis with ages 18-50 years were included in the current study. After taking informed consent for baseline details were recorded which includes age, gender, causes and symptoms of OSF. Inter Incisal Opening (IIO) of mouth among all the patients were measured. Hypoxia inducible factor-1α was observed among all the cases. Staining intensity of fibroblast and correlation of different grades of staining intensity with blood vessels were assessed in terms of mild, moderate and severe. SPSS 26.0 version was used to analyze complete data. Results: There were 32 (71.1%) males and 13 (28.9%) females in this study. 22.13±5.29 kg/m2 was the mean body mass index of patients with mean age 31.02±3.45 years. Most common cause was tobacco found in 20 (44.4%) cases, followed by smoking in 15 (33.3%) patients and areca nut found in 10 (22.2%) cases. Most common symptom was burning sensation, pain, ulceration and dry mouth. Twenty four (53.3%) patients had IIO level &lt;27mm and &gt;27mm level was in 21 (46.7%) patients. Mean blood vessels were 11.1±2.34 with majority of the cases had mild staining intensity in 23 (51.1%) cases. Mean fibroblasts were 42.23±5.64 and had mild staining intensity in majority cases 21 (46.7%). Conclusion: According to our study HIF-1α was an effective factor in the malignant transformation of oral submucous fibrosis. Aside from that, our findings revealed that OSF malignancy can be detected by the use of HIF-1 as a biomarker. Keywords: OSF, Hypoxia Inducible Factor-1α, Fibroblast, Staining Intensity, Blood Vessels

Immunohistochemical Analysis of Myofibroblasts Using α- SMA in Oral Submucous Fibrosis Turning into Malignancy- A Case Report and Review

Oral submucous fibrosis is a premalignant condition, characterized by fibrosis in oral mucosa causing stiffness of mucosa and leading to reduced mouth opening. The malignant transformation of oral submucous fibrosis is very high among the rest of the premalignant conditions. Chronic chewing of arecanut causes production of myofibroblasts. These myofibroblasts plays an important role in neoangiogenesis as well as disintegration of the basement membrane at the tumor invasive front leading to carcinoma. Here, we are doing an Immunohistochemical study using alpha SMA for proper microscopic visulizations of myofibroblastic activity in an OSF patient, encompassing the pathogenesis and malignant potentiality of the disease.

Skewed Th17/Treg balance during progression and malignant transformation of oral submucous fibrosis

The aim of our study was to determine the impact of Th17/Treg imbalance on the progression and malignant transformation of oral submucosal fibrosis (OSF). To assess Th17 and Treg expression, overall 52 peripheral blood samples from OSF, oral squamous cell carcinoma (OSCC) patients, and healthy donors were analyzed by flow cytometry. Thirty normal oral mucosa, 72 OSF, and 90 OSCC samples were analyzed by immunohistochemistry. In peripheral blood samples, in OSCC with OSF, Th17 and Treg expression were significantly higher than those in OSF and OSCC without OSF as confirmed by immunohistochemistry. During OSF progression, Th17 and Th17/Treg ratio showed an increasing trend, while Treg expression showed a decreasing trend. Treg expression was significantly higher in OSCC with OSF than in OSF and OSCC without OSF, whereas the Th17/Treg ratio was significantly lower in OSCC with OSF. Treg expression was significantly correlated with smoking and clinical stage. Th17/Treg ratio was significantly associated with tumor size, lymph node metastasis, and clinical stage. A low Th17/Treg ratio was significantly associated with poor prognosis. Th17/Treg ratio is a potential diagnostic indicator for OSF occurrence and malignant transformation and was an independent prognostic factor for OSCC.

Malignant transformation of Oral submucous fibrosis to Oral Squamous cell carcinoma : A case report

Oral submucous fibrosis (OSMF) is a potentially malignant disorder with high rate of malignant transformation. Oral epithelium being thin and atrophic becomes more vulnerable to attack of carcinogens. Malignant transformation in OSMF usually occurs gradually over a long period of time. Here, we report a case of oral submucous fibrosis turning into malignancy in a 27-year-old male patient.

Biomarkers in saliva as diagnostic tool in early diagnosis of oral submucous fibrosis

The potentially malignant lesions of oral cavity pose a sensitive challenge to the public health status. The risk is considerably high of malignant transformation of oral submucous fibrosis (OSMF) into oral cancer. The more rapidly they get diagnosed early, the better it is for public oral health. The need of the hour is to put into general practice the minimally invasive and noninvasive procedures of diagnostics for these lesions. Salivary biomarkers are recently advanced diagnostic tools fit for the requirement. With more researches and developments in technology, they are becoming a fast and with ease both patient and clinician-friendly choice and also medically appropriate. High expectations are that salivary biomarkers become sole noninvasive and exact method of diagnosing premalignant disorders such as OSMF.

Expression and methylation of Dickkopf-1 in the pathogenesis and malignant transformation of oral submucous fibrosis.

Dickkopf-1 is an inhibitor of the Wnt/β-catenin pathway, but the role of Dickkopf-1 in oral submucous fibrosis remains unclear. We evaluated the protein expression and gene methylation levels of dickkopf-1 to determine the mechanism underlying abnormal Wnt/β-catenin pathway activation. Healthy mucosa, oral submucous fibrosis, oral squamous cell carcinoma, and cancer-adjacent tissues were collected. The expression and promoter methylation levels of dickkopf-1 were analyzed. The expression levels of dickkopf-1 in oral submucous fibrosis and oral squamous cell carcinoma tissues were lower than those in healthy and cancer-adjacent tissues. The methylation levels of the dickkopf-1 gene in oral submucous fibrosis and oral squamous cell carcinoma tissues were higher than those in healthy and cancer-adjacent tissues. Dickkopf-1 expression was negatively correlated with dickkopf-1 gene methylation. High dickkopf-1 methylation levels in oral submucous fibrosis and oral squamous cell carcinoma tissues may decrease dickkopf-1 expression, which may induce an abnormal activation of the Wnt/β-catenin pathway and oral submucous fibrosis pathogenesis.

Comparative Evaluation of role of Lysyl oxidase gene (LOXG473A) expression in pathogenesis and malignant transformation of Oral Submucous Fibrosis.

BackgroundIdentification and comparison of gene expression of Lysyl oxidase (LOX) in oral submucous fibrosis and controls and to determine its role in Pathogenesis of Oral submucous fibrosis.Material and MethodsOf total sample size (n=127), the whole blood sample were collected from case and control group in citrate vial. It is centrifused and stored at -800C. We collected and isolated RNA from blood of case group (n=127) and age and sex matched control group (n=127) recruited on the basis of inclusion criteria. The cDNA was prepared for 127 samples which were processed for gene expression of Lysyl oxidase (LOX) in relation to housekeeping genes (Beta actin and 18srRNA) and its role in pathogenesis of Oral submucous fibrosis.ResultsIn relative expression (Normalized ratio),relatively 11 cases shown down-regulation of lysyl oxidase gene while 27 cases shows up-regulation of lysyl oxidase gene while in 89 cases there were no regulation i.e expression of lysyl oxidase gene in case group was of same degree of control. In non-relative expression results (Non-normalized ratio), the 38 cases shown down regulation of LOX gene while in 53 cases, it was up-regulated however in remaining 36 cases there was neither up-regulation nor down-regulation of Lysyl oxidase gene i.e the expression of LOX gene is null.ConclusionsIn oral submucous fibrosis, the expression of Lysyl oxidase gene is mixed type i.e either it will down regulate/upregulate or there will be no expression at all comparatively. However in majority of cases the upregulation of lysyl oxidase is relatively more common than down-regulation or non expression of Lysyl oxidase gene. Key words:Oral submucous fibrosis, lysyl oxidase, betel nut, premalignant disorders.

Endorsing cellular competitiveness in aberrant epithelium of oral submucous fibrosis progression: neighbourhood analysis of immunohistochemical attributes.

Epithelial abnormality during the transformation of oral submucous fibrosis (OSF) into oral squamous cell carcinoma has been well studied and documented. However, the differential contribution of atrophy and hyperplasia for malignant potentiality of OSF is yet to be resolved. Existing diagnostic conjectures lack precise diagnostic attributes which may be effectively resolved by substantiation of specific molecular pathology signatures. Present study elucidates existence of cellular competitiveness in OSF conditions using computer-assisted neighbourhood analysis in quantitative immunohistochemistry (IHC) framework. The concept of field cancerization was contributory in finding correspondence among neighbouring cells of epithelial layers with reference to differential expression of cardinal cancer-related genes [c-Myc (oncogene), p53 (tumour suppressor), and HIF-1α (hypoxia regulator)] which are known to be important sensors in recognizing cellular competitive interface. Our analyses indicate that different states of OSF condition may be associated with different forms of competitiveness within epithelial neighbouring cells which might be responsible to shape the present and future of the pre-malignant condition. Analytical findings indicated association of atrophic epithelium with stress-driven competitive environment having low c-Myc, high-p53, and stable HIF-1α (the looser cells) which undergo apoptosis. Whereas, the cells with high c-Myc+ (winner cells) give rise to hyperplastic epithelium via possible mutation in p53. The epithelial dysplasia plausibly occurs due to clonal expansion of c-Myc and p53 positive supercompetitor cells. Present study proposes quantitative IHC along with neighbourhood analysis which might help us to dig deeper on to the interaction among epithelial cell population to provide a better understanding of field cancerization and malignant transformation of pre-malignancy.

Malignant transformation of oral submucous fibrosis in Taiwan: A nationwide population-based retrospective cohort study.

Oral submucous fibrosis (OSF) is one of the well-recognized oral potentially malignant disorders. In this study, we investigated the malignant transformation of OSF in a Taiwanese population. A retrospective cohort study was analyzed from Taiwan's National Health Insurance Research Database. A comparison cohort was randomly frequency-matched with the OSF cohort according to age, sex, and index year. Oral leukoplakia (OL) was further stratified to evaluate for the possible synergistic effects of OSF-associated malignant transformation. In this cohort, 71 (9.13%) of 778 cases of OSF were observed to transform into oral cancer. The malignant transformation rate was 29.26-fold in the OSF cohort than in the comparison cohort after adjustment (95% confidence intervals 20.55-41.67). To further stratify with OL, OSF with OL (52.46%; 95% confidence intervals 34.88-78.91) had higher risk of malignant transformation rate than OSF alone (29.84%; 95% confidence intervals 20.99-42.42). The Kaplan-Meier plot revealed the rate free of malignant transformation was significant over the 13-year follow-up period (log-rank test, P<.001). The mean duration of malignant transformation was 5.1, 2.7, and 2.2years for non-OSF, OSF alone, and OSF with OL, respectively. Oral submucous fibrosis patients exhibited a significantly higher risk of malignant transformation than those without OSF. OL could enhance malignant transformation in patients with OSF.

Interrelationship of Autophagy and Oxidative Stress in Malignant Transformation of Oral Submucous Fibrosis

ABSTRACT Oral submucous fibrosis (OSMF) is a potentially malignant disorder. Malignant transformation is a major concern related with OSMF. Despite array of studies discussed, pathogenic factors responsible for carcinogenesis in OSMF is still a field of research. Autophagy is a degradation of unwanted cytoplasmic material to maintain cellular biosynthesis when cell is under metabolic stress. Tissue microenvironment consists of diverse mechanisms. It is found that the autophagy has a major impact on these mechanisms to maintain homeostasis. However, dysregulated autophagy has been involved in disruption of the homeostasis and leads to formation of various diseases including cancer. Altered autophagy enhances oxidative stress in the cell which is a critical cause of genetic instability and oncogenesis. Plethora of studies supports that autophagy is implicated in carcinogenesis process and are interlinked with each other. In OSMF, areca nut causes increase in production of reactive oxygen species and formation of oxidative stress which is being wielded by autophagy. Furthermore, modulated autophagy has an impact on senescence and immunity which can lead to cancer. There is an explicit cause and effect relationship present between autophagy and oncogenesis in OSMF. It is our sincere efforts to elucidate this relationship in OSMF so that it can be incorporated in therapeutic purpose at an early stage. How to cite this article Ganjre AP. Interrelationship of Autophagy and Oxidative Stress in Malignant Transformation of Oral Submucous Fibrosis. World J Dent 2017;8(2):139-144.

Oral submucous fibrosis: A quantitative assessment of serum malondialdehyde, superoxide dismutase and correlation with clinical staging.

Background:Oral submucous fibrosis (OSMF) is a progressive disorder affecting the oral mucosa. OSMF predominantly seen in South-east Asian countries. There are some biochemicals parameters which are modify in oral submucous fibrosis; this alteration can be used as a tool for diseases progress and avert malignant transformation.Aims and Objectives:The aim of this study is to evaluate the serum malondialdehyde (malondialdehyde [MDA]), and Superoxide dismutase (SOD) in oral sub mucous fibrosis cases and compare clinical stages.Materials and Methods:Thirty cases of clinical and histopathological established oral submucous fibrosis and thirty cases of nonsymptomatic features of oral submucous fibrosis preferred as controls. Venous blood was collected and separation of serum for estimation of MDA and SOD levels was done using an ultraviolet spectrophotometer.Statistical Analysis:Data were analyzed using SPSS software using Student's t-test and Kruskal–Wallis ANOVA test.Results:Serum MDA levels were elevated when clinical staging increases, where as SOD levels were decreased when clinical stage increases when compared with control cases and it showed stastically significant.Conclusion:Estimation of serum MDA and SOD in patients with OSMF, we can assess the degree of oxidative damage of the disease. This can be used as an early diagnostic tool for preventing malignant transformation of oral submucous fibrosis.

Pathogenesis in the malignant transformation of oral submucous fibrosis: a review

Oral submucous fibrosis (OSMF) is a disease of the oral mucous membrane predominant in South Asia. With the increased availability and popularity of areca nut, the incidence of the disease has increased. The manufacturers have managed to make the tiny sachets more appealing and attractive for all age groups. OSMF draws attention because the disease has no known cure and the number of areca nut chewers is increasing without any check, despite of the bans setup by the governments curbing the sale of such products. There are millions of people suffering from the disease. Besides arecanut, autoimmunity is also a causal factor. OSMF has a known malignant potential, with its transformation to oral squamous cell carcinoma (OSCC) documented. The article reviews the mechanism behind malignant transformation of OSMF and henceforth the newer treatment options that are being studied.

An analysis of rate and factors affecting malignant transformation of oral submucous fibrosis in patients attending the Oral Medicine Clinic, Dental Hospital Peradeniya, Sri Lanka - A retrospective study

Background: Oral submucous fibrosis (OSF) is a chronic, progressive, scarring and potentially malignant disease of the oral mucosa seen primarily in the Indian subcontinent and in South East Asia. OSF is a premalignant condition with a malignant transformation rate varying from 7-12%. Even though OSF and oral cancer are common in Sri Lanka, malignant transformation potential and rate have not been studied in our population. Objectives: To identify the relationship of malignant transformation with age, gender, habits, amount of mouth opening, duration of follow up, presence of other oral potentially malignant disorders and dysplasia in a group of patients with OSF attending the Oral Medicine clinic, University Dental Hospital Peradeniya. Methods: All the clinical files of patients with OSF attending the Oral Medicine clinic, University Dental Hospital Peradeniya were selected. Cases with OSF where histopathological diagnosis was not available, patients who had developed oral cancer before the diagnosis of OSF and patients who were diagnosed with OSF and received prior surgical therapy were excluded. Data were analysed to identify any relationship of malignant transformation with other variables. Results: There were 135 patients with a follow up period ranging from 6 months to 23 years and average follow up period was 5.26 years. 75.6% of them were males. 42.2% of them presented with burning sensation as the main complaint. 96.3% of them chewed betel with all ingredients whereas the rest chewed only arecanut. Eight patients developed malignancy during the follow up period giving a malignant transformation rate of 5.9% after a mean follow up period of 6.5 years. Conclusions: Malignant transformation in patients with OSF is significantly associated with presence of dysplasia on the initial biopsy, presence of any other potentially malignant disorder and the duration of betel chewing.

Connecting cyto-nano-architectural attributes and epithelial molecular expression in oral submucous fibrosis progression to cancer

ObjectiveProblems in pre-cancer diagnosis complicate cancer theragnosis as well as life expectancy. There is uncertainty regarding malignant transformation of oral submucous fibrosis (OSF), an oral pre-cancer with dysplastic (OSFWD) and...

Synergistic effects of betel quid chewing, tobacco use (in the form of cigarette smoking), and alcohol consumption on the risk of malignant transformation of oral submucous fibrosis (OSF): a case-control study in Hunan Province, China

Oral submucous fibrosis (OSF) is a potentially malignant disorder, wherein 7% to 13% of patients with OSF develop oral squamous cell carcinoma (OSCC) at clinically coincident sites established to have OSF. We aimed at investigating the lifestyle-related risk factors for malignant transformation of OSF. A case-control study was conducted among 80 cases with OSF-associated OSCC and 80 controls with OSF but without clinically or histopathologically evident OSCC, recruited from January 2012 to October 2014 in the Xiangya Hospital, Hunan Province, Mainland China. The odds ratios (OR) for OSCC were 13.3 (95% confidence interval [95% CI]: 3.1-56.4) and 45.1 (95% CI: 9.6-212.9) at the highest exposure of betel quid (BQ) chewing, by duration and frequency, respectively. Higher risks were also found to be associated with the consumption of cigarette (OR = 5.0, 95% CI: 1.7-14.8) and alcohol (OR = 3.1, 95% CI: 1.1-8.6). Adjusted ORs increased substantially among patients who consumed BQ and cigarette or alcohol simultaneously, which were 26.1 (95% CI: 4.0-172.6) and 55.-(95% CI: 1.8-1742.8) at the longest duration, and 160.3 (95% CI: 18.7-11371.2) and 58.1 (95% CI: 2.4-1434.9) at the highest dose, respectively. The use of BQ, cigarette, and alcohol were identified as risk factors for malignant transformation of OSF in the Hunan province, Mainland China. Synergistic effects between BQ chewing and cigarette or alcohol consumption were revealed.

Expression of p16 in Oral Squamous Cell Carcinoma, Potentially Malignant Disorders and Normal Mucosa

BACKGROUND: It has been hypothesized that inactivation of p16 plays a vital role in evolution of potentially malignant disorders [Epithelial Dysplasia, Oral SubmucousFibrosis (OSF)] and in Oral Squamous Cell Carcinoma (OSCC). We wanted to ascertain the role of p16 in OSF, epithelial dysplasia and OSCC as an early marker for malignant transformation and its liability in OSCC. AIM: To study the expression of p16 in normal mucosa (Group I), OSF (Group II), epithelial dysplasia (Group III) and OSCC (Group IV). MATERIALS AND METHODS: A total sample size of 70 which includes 10 controls of Group I, 20 cases of Group II, 20 cases of Group III, 20 cases of Group IV were studied for p16 expression by immunohistochemistry. We have employed p16 monoclonal antibody of clone G175-405 in our study. The positive control sample of our study is squamous cell carcinoma of uterine cervix. RESULTS: Out of 70 samples 16 cases (22.9%) of cases were p16 positive which includes five in group I, seven in group II, one in group III, three in group IV. Out of sixteen p16 positive samples four cases showed cytoplasmic staining (12,1 in Group I,II,IV respectively) , eleven cases showed nuclear and cytoplasmic staining (3,5,1,2 in Group I,II,III,IV respectively) and one showed cytoplasmic and membrane staining. CONCLUSION: In this study we addressed the association particularly between p16 and OSF, epithelial dysplasia and OSCC. The results of this study with respect to OSF data, highlights that p16 could play a role in malignant transformation of OSF and we hypothesize that it could be associated with HPV.Further studies should ascertain the HPV status of the cases to be included, with a larger sample size to establish and understand if p16 expression could have a role in oral potentially malignant lesions and OSCC.