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Potencijalno maligni oralni poremećaji sva su stanja koja mogu prethoditi nastanku karcinoma usne šupljine. Tradicionalna podjela prema iz 1978. godine na premaligne lezije i premaligna stanja napuštena je 2005. godine kada Svjetska zdravstvena organizacija (SZO) predlaže korištenje termina „potencijalno maligni oralni poremećaji“ (PMOP). Upotreba naziva „prekanceroza”, „epitelne prekursorske lezije”, „premaligno”, „prekancerozno” i „intraepitelne lezije” ne preporuča se u znanstvenoj literaturi. Na konsenzusnoj radionici SZO-a 2020. godine dorađena je definicija PMOP-a koja ih sada određuje kao „bilo koju abnormalnu promjenu sluznice u usnoj šupljini povezanu sa statistički povećanim rizikom od razvoja raka usne šupljine“. U PMOP-e ubrajamo leukoplakiju, proliferativnu verukoznu leukoplakiju, eritroplakiju, oralnu submukoznu fibrozu, oralni lihen planus, oralne lihenoidne lezije, aktinički heilitis (aktiničnu keratozu), nepčane lezije kod obrnutih pušača, diskoidni eritematozni lupus, oralnu reakciju presatka protiv primatelja te nasljedne poremećaje i imunodeficijencije. Najčešći PMOP su leukoplakija i eritroplakija. Najčešći etiološki faktori su konzumacija alkohola i duhanskih proizvoda te njihov sinergistički učinak. Dijagnostika PMOP-a često predstavlja poseban izazov, a temelji se na uzimanju detaljne stomatološke i medicinske anamneze, kliničkom nalazu, biopsiji te pomoćnim dijagnostičkim metodama. Biopsija je metoda izbora u dijagnostici PMOP-a. Liječenje obuhvaća konzervativni i kirurški pristup, a sama prognoza ovisi o ranoj dijagnostici. Konzervativni pristup podrazumijeva praćenje bolesti i najčešće medikamentozno liječenje koje može biti topikalno i sustavno, dok se kirurški pristup sastoji od uobičajene kirurške ekscizije, krioterapije, elektrokoagulacije i laserske ablacije, najčešće CO2 laserom. Od iznimne važnosti je redovno praćenje pacijenta nakon terapije. Potentially malignant oral disorders are all conditions that can precede the development of oral cancer. The traditional World Health Organization 1978 division into premalignant lesions and premalignant conditions was abandoned in 2005 when the WHO proposed the use of the term potentially malignant oral disorders (PMOD). The use of the terminology like "precancer", "epithelial precursor lesions", "premalignant", "precancerous" and "intraepithelial lesions" is not recommended in the scientific literature. The definition of oral disorders was updated in 2020 at the WHO consensus workshop to "any abnormal change in the mucosa in the oral cavity associated with a statistically increased risk of developing oral cancer". PMOD includes leukoplakia, proliferative verrucous leukoplakia, erythroplakia, oral submucosal fibrosis, oral lichen planus, oral lichenoid lesions, actinic cheilitis (actinic keratosis), palatal lesions in reverse smokers, discoid lupus erythematosus, oral graft-versus-recipient reaction, and hereditary disorders and immunodeficiencies. The most common PMOD are leukoplakia and erythroplakia. The most common etiological factors are the consumption of alcohol and tobacco products and their synergistic effect. The diagnosis of PMOD is often a special challenge, and is based on taking a detailed dental and medical history, on clinical findings, biopsy and auxiliary diagnostic methods. Biopsy is the method of choice in the diagnosis of PMOD. The treatment includes a conservative and surgical approach, and the prognosis itself depends on early diagnosis. A conservative approach implies monitoring the disease and, most often, prescription medication treatment, which can be topical and systemic, while the surgical approach consists of the usual surgical excision, cryotherapy, electrocoagulation and laser ablation, most often with a CO2 laser. Regular monitoring of the patient after therapy is extremely important.

Background: The purpose of this study was to investigate the expression of nuclear EGFR (nEGFR) and the stem cell marker ABCG2 in oral leukoplakia (OL) and oral erythroplakia (OE) and to assess their significance as prognostic biomarkers for malignant transformation. Methods: In this study we included 50 patients with oral potentially malignant disorders (OPMD), 31 with OL and 19 with OE, in whom we examined the expression of nEGFR and ABCG2 by immunohistochemical methods. Results: Twenty-one (42%) of 50 patients with OL and OE developed oral squamous cell carcinoma (OSCC). The malignant transformation was increased 12, 84-fold (95% CI, 2.15-76.44, p = 0.005) in OPMD expressing both ABCG2 and nEGFR. Expression of nEGFR is a strong indicator of malignant transformation, unlike ABCG2 expression, respectively. Conclusions: Determining the co-expression of the biomarkers nEGFR and ABCG2 in OPMD may serve us to determine the risk of malignant transformation in OSCC.

This study evaluated and compared the expression of secreted protein acidic and rich in cysteine (SPARC) in epithelial cells and fibroblasts of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) using normal oral mucosa as a control.The expression of SPARC was determined in samples of normal oral mucosa (n = 12), OL without dysplasia (n = 31), OL with dysplasia (n = 54), and OSCC (n = 69) using immunohistochemistry. The percentage of positive cells in epithelial cells and fibroblasts was independently evaluated.Epithelial SPARC was found in 33.3%, 35.5%, 25.9%, and 66.7% of normal oral mucosa, OL without dysplasia, OL with dysplasia, and OSCC, respectively. Fibroblast SPARC was found in 50.0%, 29.0%, 46.3%, and 84.1% of normal oral mucosa, OL without dysplasia, OL with dysplasia, and OSCC, respectively. OSCC had higher epithelial and fibroblast SPARC expression than normal oral mucosa, OL without dysplasia, and OL with dysplasia (P.05). No significant differences were observed in epithelial and fibroblast SPARC among normal oral mucosa or OL with and without dysplasia.Overexpression of epithelial and fibroblast SPARC was observed in OSCC but not in OL, suggesting that SPARC is involved in the late stage of oral carcinogenesis.

Type VII collagen (Col7) is a major component of anchoring fibrils. Col7 plays a role in tumor development and aggressiveness of cutaneous squamous cell carcinoma of recessive dystrophic epidermolysis bullosa. However, the role of Col7 in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL) remains largely unknown. Objective To elucidate the role of Col7 and its diagnostic potential during oral carcinogenesis. Methodology Col7 expression was immunohistochemically studied in 254 samples, including normal oral mucosa (NM), OL without dysplasia, OL with dysplasia, and OSCC. The correlation between Col7 expression and clinicopathologic parameters of OSCC was also determined. Results Col7 was present as a linear deposit at the basement membrane of NM, OL without dysplasia and OL with dysplasia, and at the tumor-stromal junction around tumor islands in OSCC. Discontinuity of expression was frequently observed in OL with dysplasia and OSCC. OSCC had the significantly lowest Col7 expression (p

Oral squamous cell carcinoma (OSCC) is often preceded by a white patch on a surface of the mouth, called oral leukoplakia (OL). As accelerated telomere length (TL) shortening in dividing epithelial cells may lead to oncogenic transformation, telomere length measurement could serve as a predictive biomarker in OL. However, due to high variability and lack of a universal reference, there has been a limited translational application. Here, we describe an approach of evaluating TL using paired peripheral blood mononuclear cells (PBMC) as an internal reference and demonstrate its translational relevance. Oral brush biopsy and paired venous blood were collected from 50 male OL patients and 44 male healthy controls (HC). Relative TL was measured by quantitative PCR. TL of each OL or healthy sample was normalized to the paired PBMC sample (TL ratio). In OL patients, the mean TL ratio was significantly smaller not only in the patch but also in distal normal oral tissue, relative to healthy controls without a high-risk oral habit. Dysplasia was frequently associated with a subgroup that showed a normal TL ratio at the patch but significantly smaller TL ratio at a paired normal distal site. Our data suggest that evaluation of TL attrition using a paired PBMC sample eliminates the requirement of external reference DNA, makes data universally comparable and provides a useful marker to define high-risk OL groups for follow-up programs. Larger studies will further validate the approach and its broader application in other premalignant conditions.

Background MiRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level and have been associated with malignant transformation of oral epithelial precursor lesions such as oral leukoplakia. The aim was to perform a scoping review of the contemporary literature about the different roles of miRNAs during the malignant transformation of oral leukoplakia. Material and Methods We conducted a systematic search with the following MeSH terms: ‘oral leukoplakia’, ‘carcinoma in situ’, ‘microRNAs’, ‘mouth neoplasms’ and ‘epithelial–mesenchymal transition’ in PubMed/MEDLINE, EMBASE and SpringerLink. Results Fifteen articles were included for analysis, among which in vivo and in vitro articles were included. A total of 21 different miRNAs were found to be involved in the malignant transformation process of oral leukoplakia. Regarding their possible effects, 6 miRNAs were classified as oncogenic, 5 as tumour suppressors and 10 were related to epithelial–mesenchymal transition, invasion and migration. Conclusions Based on the current review, we concluded that miRNAs-21, 345, 181-b and 31* seem to be potential markers of malignant transformation of oral leukoplakia. However, further clinical prospective studies are needed in order to validate their utility as prognostic biomarkers. Key words:miRNAs, oral leukoplakia, oral squamous cell carcinoma, biomarkers, malignant transformation.

Human papillomavirus (HPV) infection is mainly a problem of the female reproductive tract. It can occur in the oral cavity as well. Commonly HPV infections are subclinical, without any visible symptoms, and last no longer than 2 years. Usually the clinical manifestation of HPV infection is benign, but in some cases it can also promote malignant transformation. In the paper we have tried to estimate the prevalence of HPV detected in samples of oral leukoplakia (OLK), the most common premalignant lesions of the oral mucosa.To review the current literature to estimate the prevalence of HPV (HPV DNA) detected in samples of oral leukoplakia.We searched PubMed/Medline, Scopus, and Cochrane Library databases for studies that examined the prevalence of HPV in leukoplakia with HPV DNA detection by polymerase chain reaction.HPV positive cases in OLK ranged from 0% to 100% in studies. The overall HPV prevalence in leukoplakia was 6.66%. The prevalence of HPV 16 positive cases was 2.95%. The high-risk HPV prevalence was 5.16%, when the low-risk HPV prevalence was 3.32%. When dysplasia is mentioned, HPV was detected in 19.56% of lesions with dysplasia, compared to 38.16% among non-dysplastic lesions.Further studies should be extended also to include low-risk HPV and compare its prevalence with presence of dysplasia in leukoplakia. Besides, leukoplakia and other premalignant lesions can no longer be treated as one lesion.

Introduction Oral squamous cell carcinomas (OSCCs) frequently develop from oral potentially malignantdisorders (OPMDs). Oral leukoplakia (OL) is a white lesion in the oral mucosa and the mostprevalent OPMD. Malignant transformation rates for OL to OSCC has recently been reportedto 9.8%. Tobacco and alcohol abuse are risk factors. Brush biopsies of OL is a valid noninvasivemethod with high diagnostic accuracy and an alternative to scalpel biopsies. It’s hardto estimate which OL malignifies. An important question is if there are biomarkers obtainedfrom the cells from brush biopsies which can predict the malignant transformation of OL. Aim To elucidate available biomarkers in oral keratinocytes collected from brush biopsies, toidentify OL at risk of malignant transformation and early-stage oral squamous cell carcinoma. Methods Systematic literature search in PubMed and Cochrane was made to find relevant studies. Asystem of “PICOS” was made for inclusion which focused on OL and OSCC, brush biopsiesand biomarkers. Results Initial search resulted in 817 studies, after assessment of titles, abstracts and full texts tenarticles were included. Included articles had a total of 795 brush biopsy samples andinvestigated 39 different biomarkers. Conclusion We found a heterogeneity and lack of standardized reporting of data among the studiesincluded. Examination of the studies published so far indicated that biomarkers that couldpredict the risk of malignant transformation in patients with OL are still in a discovery phaseand biomarkers with high sensitivity and specificity are still not recognized.

Background Beta-thalassemia major is an inherited disorder that can cause bone deformity and loss of bone mineral density. The objective of this study is to evaluate the cortical and trabecular mandibular bone morphology of children and adolescents who have beta-thalassemia major (ß-TM) using a fractal dimension (FD) analysis and different panoramic radiomorphometric indices with digital panoramic radiographic images (DPRIs). Material and Methods The study included 80 patients (with 40 patients each of ß-TM and control). The mandibular cortical width (MCW), panoramic mandibular index (PMI), mandibular cortical index (MCI), and simple visual estimation (SVE) were evaluated, and an FD analysis of five regions of interest (ROIs) (ROI 1: in basal cortical bone; ROI 2: in premolar region; ROI 3: in molar region; ROI 4: in angulus mandible and ROI 5: in condyle region) was obtained in all DPRIs. Quantitative variables were analyzed using the student’s t-test , Kruskal–Wallis and Mann-Whitney U tests. Results When the ß-TM groups were compared with controls, there were no statistically significant differences found in the mean FD values, the ROIs of the trabecular bone, or the SVE. There was a significant correlation in the mean MCW, PMI, ROI of cortical bone (ROI 1), and MCI between ß-TM and control groups (p < 0.001, p < 0.001, p = 0.047, and p = 0.046, respectively). The mean MCW values correlated with the SVE in both the ß-TM and control groups (p = 0.031 and p < 0.001, respectively). While the mean MCW values correlated with the MCI (p = 0.04) in the control group, the mean MCW values were not correlated with the MCI (p = 0.493) in ß-TM group. Conclusions The current study revealed lower MCW and PMI values in the ß-TM group. While the mean FD values of trabecular bone is similar to the control groups, the mean FD value is lower in cortical bone in the ß-TM group. MCW, PMI, FD of cortical bone and MCI may be key indicators in individuals with beta-thalassemia major. Key words:Beta-thalassemia major, fractals, panoramic radiography.

By using a meta-analytical approach, this study aimed to analyse the diagnostic capacity of protein-based biomarkers in saliva for the differential diagnosis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) from healthy individuals as control group (HCG). Articles on protein-based biomarkers in saliva, which provided quantitative expression in individuals with clinical and histopathological diagnosis of OPMD or oral leukoplakia (OL) were considered eligible. Searches were conducted in eight electronic databases. The methodological quality was assessed using the Quality Assessment of Diagnostic Studies tool (QUADAS-2). Functional analysis was also performed. Meta-analyses were performed using the OpenMeta tool (Analyst). Meta-analysis was possible for 4 of the 11 biomarkers studied. Only the carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA21) were significant for the OSCC/OPMD subgroup, both with a very low heterogeneity. CEA had an OE = 25.854 (CI95%: 13.215–38.492, p< 0.001, I2 = 0) and CYFRA21 had an OE = 9.317 (CI95%: 9.014–9.619, p< 0.001, I2 = 0). For the OPMD/HCG subgroup, only CYFRA21 was significant, with an OE = 3.679 (CI95%: 0.663–6.696, p= 0.017) although with high heterogeneity (I2 = 91.24). The CEA and CYFRA21 markers proved very useful when differentiating OSCC from OPMD. The CYFRA21 was the only protein that was capable of distinguishing between OPMD and healthy controls.

Background/purpose Our previous study found significantly lower serum hematinic levels and higher serum homocysteine level as well as higher frequencies of serum hematinic deficiencies and hyperhomocysteinemia in oral leukoplakia (OL) patients than in healthy control subjects. This study evaluated whether carcinoembryonic antigen (CEA)-positive or squamous cell carcinoma-antigen (SCC–Ag)-positive OL patients had significantly lower serum hematinic levels and higher serum homocysteine level as well as significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients or healthy control subjects. Methods The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 184 OL patients including 85 CEA-positive, 99 CEA-negative, 25 SCC-Ag-positive, and 159 SCC-Ag-negative OL patients and in 184 age- and sex-matched healthy control subjects were measured and compared. Results We found that the 85 CEA-positive or 25 SCC-Ag-positive OL patients had a significantly lower mean serum folic acid level and a significantly higher mean serum homocysteine level as well as significantly higher frequencies of serum folic acid deficiency and hyperhomocysteinemia than 184 healthy control subjects. Moreover, the 25 SCC-Ag-positive OL patients had a significantly higher mean serum homocysteine level than the 159 SCC-Ag-negative OL patients. The 85 CEA-positive OL patients had a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than 99 CEA-negative OL patients (marginally significant, P = 0.060). Conclusion CEA-positive or SCC-Ag-positive OL patients tend to have a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients, respectively.

Oral leukoplakia is common and may, in some cases, progress to carcinoma. Proliferative leukoplakia is a progressive, often multifocal subtype with a high rate of malignant transformation compared with the more common localized leukoplakia. We hypothesized that the immune microenvironment and gene expression patterns would be distinct for proliferative leukoplakia compared with localized leukoplakia. We summarize key clinicopathologic features among proliferative leukoplakia and localized leukoplakia and compare cancer-free survival (CFS) between subgroups. We analyze immunologic gene expression profiling in proliferative leukoplakia and localized leukoplakia tissue samples (NanoString PanCancer Immune Oncology Profiling). We integrate immune cell activation and spatial distribution patterns in tissue samples using multiplexed immunofluorescence and digital image capture to further define proliferative leukoplakia and localized leukoplakia. Among N = 58 patients (proliferative leukoplakia, n = 29; localized leukoplakia, n = 29), only the clinical diagnosis of proliferative leukoplakia was associated with significantly decreased CFS (HR, 11.25; P < 0.01; 5-year CFS 46.8% and 83.6% among patients with proliferative leukoplakia and localized leukoplakia, respectively). CD8+ T cells and T regulatory (Treg) were more abundant among proliferative leukoplakia samples (P < 0.01) regardless of degree of epithelial dysplasia, and often colocalized to the dysplasia–stromal interface. Gene set analysis identified granzyme M as the most differentially expressed gene favoring the proliferative leukoplakia subgroup (log2 fold change, 1.93; Padj < 0.001). Programmed death ligand 1 (PD-L1) was comparatively overexpressed among proliferative leukoplakia samples, with higher (>5) PD-L1 scores predicting worse CFS (Padj < 0.01). Proliferative leukoplakia predicts a high rate of malignant transformation within 5 years of diagnosis. A prominent CD8+ T-cell and Treg signature along with relative PD-L1 overexpression compared with localized leukoplakia provides strong rationale for PD-1/PD-L1 axis blockade using preventative immunotherapy. Significance: This is the first in-depth profiling effort to immunologically characterize high-risk proliferative leukoplakia as compared with the more common localized leukoplakia. We observed a notable cytotoxic T-cell and Treg signature with relative overexpression of PD-L1 in high-risk proliferative leukoplakia providing a strong preclinical rationale for investigating PD-1/PD-L1 axis blockade in this disease as preventative immunotherapy.

Early detection of Oral Cancer (OC) with non-invasive tools and screening of high-risk populations remains to be an unmet need. Metabolic reprogramming is an important hallmark of cancer. This review discusses the role of Salivary metabolomics (SM) in the diagnosis of OC and precancer. An electronic search was carried out in various databases with keywords "Salivary Metabolomics" “Oral Cancer” “Oral leukoplakia” and “Oral Lichen planus” from 2005 to July 2020. A total number of 48 studies were included out of which 38 were excluded. Several characteristic salivary metabolites were significantly altered in OC and precancer patients. SM techniques can be used to explore the metabolic signatures in OC and precancer, unravel its pathogenesis and develop targeted therapies.

Oralna leukoplakija (OL) je potencijalno zloćudna lezija sluznice usne šupljine kod koje postoji povećan rizik za zloćudnu transformaciju u odnosu na zdravu sluznicu. Razumijevanje procesa karcinogeneze i razvoj molekularne biologije doveo je do otkrivanja novih molekularnih biomarkera poput Ki67 i CD44 koji bi mogli pomoći u ranom otkivanju tumora te njihovom liječenju. Cilj ovog retrospektivnog presječnog istraživanja je imunohistokemijski utvrditi izraženost CD44 i Ki67 u OL te usporediti dobivene podatke s izraženosti CD44 i Ki67 u oralnom planocelularnom karcinomu (OPK) i zdravoj oralnoj sluznici, kako bi se iz obrazaca njihovih pojavnosti pretpostavila uključenost u patološke događaje, a što bi moguće indiciralo potrebu za prospektivnim studijama koje uključuju i ishode. Analizirano je 30 uzoraka sluznice usne šupljine s dijagnozom OL, 30 uzoraka sluznice usne šupljine s dijagnozom OPK i 20 uzoraka sluznice usne šupljine bez patohistoloških promjena. Imunohistokemijska analiza za protutijela vodila se LSAB metodom kao vizualizacijskim sistemom na Dako TechMate TM Horizon (Dako, Copenhagen, Danska) automatiziranom stroju za imunohistokemijsko bojenje. Zabilježena je značajna razlika između ispitivanih skupina u odnosu na izraženost CD44 u epitelu kao i u odnosu na izraženost Ki67 u epitelu. Statistički značajna razlika zabilježena je između ispitivanih skupina u odnosu na imunohistokemijsku izraženost CD44 u upalnom infiltratu, dok je značajna razlika s obzirom na izraženost Ki67 u upalnom infiltratu zabilježena između skupine OPK i OL te OPK i zdrave sluznice, ali ne i između OL i zdrave sluznice. Pozitivna korelacija zabilježena je između upale detektirane na hematoksilin eozinskom preparatu (HE) i Ki67 u upalnom infiltratu u skupini OL. Značajne i pozitivne korelacije zabilježene su i s CD44 i u epitelu i u upalnom infiltratu iste skupine. Nije zabilježena značajna korelacija između upale HE i ispitivanih molekularnih biljega u skupini OPK. Značajna pozitivna korelacija zabilježena je između CD44 u upalnom infiltratu s CD44 i Ki67 u epitelu, ali samo u skupini OL, dok za OPK nije bilo značajne povezanosti. Povećana imunohistokemijska izraženost biljega CD44 i Ki67 u OL upućuje na potrebu provođenja novih opsežnijih studija koje bi omogućile kliničarima dodatne mogućnosti praćenja i predviđanja ponašanja pojedinih lezija. INTRODUCTION: Oral leukoplakia (OL) is a potentially malignant lesion of the oral mucosa in which there is an increased risk of malignant transformation compared to healthy mucosa. Today, many clinical, histopathological, and molecular factors are used as potential predictors of malignant transformation. Overall, conventional histopathological assessment remains the golden standard to determine malignancy in such cases. However, the assessment of dysplasia is subjective and for an accurate histopathological assessment experience is necessary. Understanding the process of carcinogenesis and the development of molecular biology has led to the discovery of new molecular biomarkers such as Ki67 and CD44 that could help in the early detection of tumors and their treatment. AIM OF THE RESEARCH: The aim of the research to immunohistochemically determine the presence of CD44 and Ki67 in OL and to compare the obtained data with the presence of CD44 and Ki67 in the oral squamous cell carcinoma (OSCC) and healthy oral mucosa. METHODS: 30 samples of oral mucosa diagnosed with OL, 30 samples of oral mucosa diagnosed with OSCC and 20 samples of oral mucosa without pathohistological changes analyzed. Sections of paraffin blocks and primary monoclonal antibodies to Ki67 (MO A-HU Ki67, clone MIB-1, 1: 150, DAKO) and to CD44 (MO A-HU CD44, clone DF 1485, 1:50, DAKO) used for immunohistochemical analysis. Immunohistochemical analysis for antibodies performed using the LSAB method as a visualization system on a Dako TechMateTM Horizon (Dako, Copenhagen, Denmark) automated machine for immunohistochemical staining. RESULTS: In the group diagnosed with OSCC, significantly more men compared to the OL groups and healthy oral mucosa were detected. The OSCC group was the oldest with a median age of 66.5 (IQR 52.2–72.0) years. A significant difference was noticed considering the presence of inflammation between the OL and OSCC group in regard to healthy mucosa, while no difference between the OL and OSCC group were observed. The inflammatory infiltrate described on hemalaun eosin (HE) in the stroma correlated with the presence of Ki67 in the inflammatory infiltrate in the stroma. Significant difference between the examined groups in relation to the presence of CD44 in the epithelium as well as in relation to the presence of Ki67 in the epithelium were observed. A statistically significant difference between the examined groups in relation to the CD44 in inflammatory infiltrate was observed, while a significant difference in terms of Ki67 in inflammatory infiltrate between OSCC and OL and OSCC and healthy mucosa, but not between OL and healthy mucosa were detected. A positive correlation between HE and Ki67 in the inflammatory infiltrate in the OL group were observed. Significant and positive correlations between HE inflammatory infiltrate and CD44 both in the epithelium and in the inflammatory infiltrate of the same group were observed. No significant correlation between HE inflammation and the examined molecular markers in the OSCC group was observed. A significant positive correlation between CD44 in inflammatory infiltrate with CD44 and Ki67 in the epithelium was observed, but only in the OL group, whereas no significant connection for OSCC was observed. CONCLUSION: An increased immunohistochemical presence of CD44 and Ki67 markers in OL suggests the need for new more extensive studies that would provide clinicians additional options for monitoring and predicting the behavior of individual lesions.

Aim: The aim of this study is to assess the efficacy of CO2 laser treatment in oral leukoplakia and to analyse the recurrence rate of oral leukoplakia lesions at 18-month follow-up. Materials and methods: A prospective clinical study regarding CO2 laser treatment for oral leukoplakia was conducted, in which 39 patients with a total of 53 oral leukoplakias were included. Follow-up was performed at 18 months post-surgery and the following variables were studied: sex, age, associated risk factors, clinical classification, size, location and presence of epithelial dysplasia, recurrence, and rate of malignant transformation after resection. Results: In the analysis of the final results 18 months after baseline, a treatment success rate of 43.75% was observed. Oral leukoplakia recurred in 54.17% of cases, and 2.08% of leukoplakias progressed to cancer. Among all the studied variables (age, tobacco use, size, location, clinical type or histology), no significant differences were found with regard to recurrence. Conclusion: The use of CO2 laser therapy to treat leukoplakia lesions is sufficient to remove such lesions. However, parameters that can assess recurrence need to be sought.

The aim of the study is to identify key genes during the progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC) and predict effective diagnoses. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were performed to identify seven genes associated with the progression from OL to OSCC. Twelve machine learning algorithms including k-nearest neighbor (KNN), neural network (NNet), and extreme gradient boosting (XGBoost) were used to construct multi-gene models, which revealed that each model had good diagnostic efficacy. The functional mechanism or the pathways associated with these genes were evaluated using enrichment analysis, subtype clustering, and immune infiltration analysis. The enrichment analysis revealed that the genes enriched were associated with the cell cycle, cell division, and intracellular energy metabolism. The immunoassay results revealed that the genes primarily affected the infiltration of proliferating T cells and macrophage polarization. Finally, a nomogram and Kaplan–Meier survival analysis were used to predict the prognostic efficacy of key genes in OSCC patients. The results showed that genes could predict the prognosis of the patients, and patients in the high-risk group had a poor prognosis. Our study identified that the seven key genes, including DHX9, BCL2L12, RAD51, MELK, CDC6, ANLN, and KIF4A, were associated with the progression from OL to OSCC. These genes had good diagnostic efficacy and could be used as potential biomarkers for the prognosis of OSCC patients.

Objective We desired to establish an active surveillance clinic for head and neck cancer. In this review we examined. Methods We examined the natural history of human oral carcinogenesis, the types of preneoplastic lesions, and efforts at oral chemoprevention over the past decades for presentation here. Results We established a clinic and program for patients with oral premalignant lesions approximately over 15 years ago based on an unmetneed for this service. We have completed over 4000 outpatient visits for this cohort and have a place for referrals of difficult oral lesions. We have leveraged this population for multiple federally funded trials on oral cancer prevention as well as specimen banking. Conclusion There is need for routine active surveillance for oral preneoplastic conditions in patients at high risk for conversion to cancer. There are no effective durable treatment or preventions for these individuals and we have attempted to fill this unmet need with our program., Oral preneoplasia presents an opportunity for earlier diagnosis and treatment of head and neck squamous cell carcinoma. In this review we present the most recent literature in diagnosis and treatment in oral leukoplakia, as well as our program of Active Surveillance for head and neck squamous cell carcinoma.

Objective The objective of this study was to develop the first edition of a Chinese evidence-based position paper on the management of oral leukoplakia (OLK). Study Design The consultant group for drafting the position paper consisted of 31 oral medicine specialists and 2 evidence-based medicine specialists. English studies (searched in PubMed, EMBASE, and the Cochrane Library) and Chinese studies (searched in China National Knowledge Infrastructure and WanFang) published before January 2018 were used. The quality of the study was assessed using the Grading of Recommendations Assessment, Development, and Evaluation grid, and the strength of the recommendations was determined based on the results of 3 rounds of voting among the consultant group members using the Delphi method. Results Twenty-two evidence-based guidelines for clinical management and monitoring of OLK were established in this position paper. A clinical path diagram for oral health practitioners was constructed based on the recommendations. Conclusion Current evidence suggests that management and monitoring of patients with OLK should be performed by experienced clinicians to control the lesion and for early detection of malignant transformation. However, all recommendations are based on evidence of low or extremely low quality and may require further modification as new evidence is produced.

Objective: The objective of this study was to investigate the levels of salivary SIRT-1 and CD44 in patients suffering from oral squamous cell carcinoma (OSCC), dysplastic and non-dysplastic oral leukoplakia to assess their potential role as early diagnostic biomarkers for patients with oral leukoplakia and OSCC. Subjects and Methods: sixty patients were recruited from the outpatient clinic of the Department of Oral Medicine and Periodontology, Faculty of Dentistry, Cairo University. Participants were divided into four groups:15 healthy individuals, 15 patients with non-dysplastic leukoplakia, 15 patients with dysplastic leukoplakia, and 15 patients with oral squamous cell carcinoma. Whole unstimulated saliva (WUS) was collected from all participants. Soluble CD44 (solCD44) and SIRT1 were measured using ELISA. Results: CD44 was expressed in all the four study groups with different levels. OSCC showed a statistically significant highest CD44 level. While the control group showed the lowest CD44 level. There was no statistically significant difference between dysplastic leukoplakia and non-dysplastic leukoplakia groups. Similarly, there was no statistically significant difference between non-dysplastic leukoplakia and control groups. OSCC showed the statistically significantly highest SIRT-1 level. There was no statistically significant difference between dysplastic leukoplakia, non-dysplastic leukoplakia, and control groups; all showed statistically significantly lower SIRT-1 levels than the OSCC group. Conclusion: salivary SIRT-1 and CD44 could be used as a screening tool to improve early detection and diagnostic precision of oral leukoplakia and OSCC.

Oral leukoplakia (OL) has the potential for malignant transformation; unfortunately, there are no strategies to prevent this possible outcome. Surgical intervention has been reported to be effective in reducing but not eliminating the risk of malignant transformation. Meta-analyses have reported that patients who underwent excision of OL lesions had a significantly lower chance of malignant transformation than those whose lesions were not excised. The present study aimed to report a case of successful management of extensive OL using a high-power laser. The patient has been under periodic monitoring, and we aim to continue the follow-up as long as possible. Recurrence or signs of malignancy were not observed at the 2-year follow-up.

Background/Purpose: Several previous studies have reported higher serum tumor marker levels in patients with oral or head and neck squamous cell carcinomas. This study evaluated whether 232 patients with oral precancerous lesions (oral precancer patients) had significantly higher serum carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and ferritin levels than healthy control subjects. Methods: The serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients and 187 healthy control subjects were measured and compared. Patients with serum CEA level ≥3 ng/mL, SCC-Ag level ≥2 ng/mL, and ferritin level ≥250 ng/mL were scored as serum positive for CEA, SCC-Ag, and ferritin, respectively. Results: We found significantly higher mean serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients than in 187 healthy control subjects (all P-values

Oral leukoplakia, which presents as white lesions in the oral cavity, including on the tongue, is precancerous in nature. Conservative treatment is preferable, since surgical removal can markedly reduce the patient’s quality of life. In the present study, we focused on the flavonoid apigenin as a potential compound for preventing carcinogenesis, and an apigenin-loaded mucoadhesive oral film was prepared using a three-dimensional (3D) bioprinter (semi-solid extrusion-type 3D printer). Apigenin-loaded printer inks are composed of pharmaceutical excipients (HPMC, CARBOPOL, and Poloxamer), water, and ethanol to dissolve apigenin, and the appropriate viscosity of printer ink after adjusting the ratios allowed for the successful 3D printing of the film. After drying the 3D-printed object, the resulting film was characterized. The chemopreventive effect of the apigenin-loaded film was evaluated using an experimental rat model that had been exposed to 4-nitroquinoline 1-oxide (4NQO) to induce oral carcinogenesis. Treatment with the apigenin-loaded film showed a remarkable chemopreventive effect based on an analysis of the specimen by immunohistostaining. These results suggest that the apigenin-loaded mucoadhesive film may help prevent carcinogenesis. This successful preparation of apigenin-loaded films by a 3D printer provides useful information for automatically fabricating other tailored films (with individual doses and shapes) for patients with oral leukoplakia in a future clinical setting.

Traballo Fin de Grao en Odontoloxía. Curso 2021-2022 Antecedentes: La leucoplasia oral (LO) es un trastorno oral potencialmente maligno (TOPM) que se asocia con un riesgo incrementado de desarrollar cáncer. Actualmente, el gold standard para la valoración de los TOPMs es la biopsia, que se emplea principalmente para detectar la presencia de displasia. El análisis de la dimensión fractal (DF) se presenta como una herramienta no invasiva para el estudio de lesiones leucoplásicas cuyo valor podría relacionarse con factores indicadores de la progresión de la lesión. Objetivos y métodos: Se han utilizado 89 fotografías de LO y leucoplasia verrucosa proliferativa (LVP) de pacientes tratados en la Unidad de Medicina Oral de la Universidad de Santiago de Compostela entre los años 2008 y 2021. Luego se emplearon los programas Qupath e ImageJ para calcular la DF y estudiar si puede convertirse en una herramienta objetiva para pronosticar la malignización de dichas lesiones. Resultados: Los resultados obtenidos muestran diferencias estadísticamente significativas entre lesiones con y sin displasia (p=0’016). La media de DF fue superior en lesiones sin displasia que en aquellas que sí la presentaban (1’870 ± 0’058 y 1’832 ± 0’084, respectivamente). La DF se presenta en este estudio como una herramienta de escasa capacidad diagnóstica (37’9% de sensibilidad y 25% de especificidad). Conclusión: La DF podría llegar a ser una valiosa herramienta para el diagnóstico precoz. Aunque no sustituya a la biopsia, puede constituir una prueba complementaria económica, versátil e inocua para el paciente Antecedentes: A leucoplasia oral (LO) é un trastorno oral potencialmente maligno (TOPM) que se asocia cun risco incrementado de desenvolver un cancro. Actualmente, o gold standard para a valoración dos TOPMs é a biopsia, que se emprega principalmente para detectar a presenza de displasia. A análise da dimensión fractal (DF) preséntase como unha ferramenta non invasiva para o estudo de lesións leucoplásicas cuxo valor podería relacionarse con factores indicadores da progresión da lesión. Obxectivos e métodos: Utilizáronse 89 fotografías de LO e leucoplasia verrucosa proliferativa (LVP) de pacientes tratados na Unidade de Medicina Oral da Universidade de Santiago de Compostela entre os anos 2008 e 2021. Despois empregáronse os programas Qupath e ImageJ para calcular a DF e estudar se pode converterse nunha ferramenta obxectiva para prognosticar a malignización de ditas lesións. Resultados: Os resultados obtidos mostran diferenzas estatisticamente significativas entre lesións con e sen displasia (p=0’016). A media da DF foi superior en lesións sen displasia que en aquelas que si a presentaban (1’870 ± 0’058 e 1’832 ± 0’084, respectivamente). A DF preséntase neste estudo como unha ferramenta de escasa capacidade diagnóstica (37’9% de sensibilidade e 25% de especificidade). Conclusión: A DF podería chegar a ser una valiosa ferramenta para o diagnóstico precoz. Aínda que non substitúa á biopsia, pode constituír unha proba complementaria económica, versátil e inocua para o paciente Background: Oral leukoplakia (OL) is an oral potentially malignant disorder (OPMD) associated with an increased risk of developing cancer. Currently, the gold standard for the assessment of OPMDs is biopsy, which is mainly used to detect the presence of dysplasia. The analysis of fractal dimension (FD) is presented as a non-invasive tool for the study of leukoplastic lesions whose value could be related to indicators of the progression of the lesion. Aims and methods: 89 photographs of OL and proliferative verrucous leukoplakia (PVL) of patients treated at the Oral Medicine Unit of the University of Santiago de Compostela between 2008 and 2021 were used. Qupath and Image J softwares were afterwards used to calculate the FD and to study whether it could become an objective tool for predicting the malignancy of these lesions. Results: The results obtained show statistically significant differences between lesions with and without dysplasia (p=0.016). The mean FD value was higher in lesions without dysplasia than in those with dysplasia (1.870 ± 0.058 and 1.832 ± 0.084, respectively). The DF is presented in this study as a tool with a low diagnostic capacity (37.9% sensitivity and 25% specificity). Conclusion: The FD might become a valuable tool for early diagnosis. Although it does not replace biopsy, it can be an inexpensive, versatile and harmless complementary test for the patient

Objective. To assess the clinical-pathological factors related to the malignant transformation of oral leukoplakia. Materials and Methods. A search for articles on malignant transformation factors related to oral leukoplakia was conducted in the following electronic databases: PubMed (MEDLINE, Cochrane Library), Web of Science (WoS) and Google Scholar. Thirty-seven articles with a low-moderate risk of bias according to the Newcastle-Ottawa methodological quality scale were included in this meta-analysis. The data were analyzed using the statistical programs RevMan 5.4 (The Cochrane Collaboration, Oxford, UK) and MedCalc Statistical Software version 16.4.3 (MedCalc Software Ltd. Ostend, Belgium) programs. The estimated prevalence was calculated according to DerSimonian and Laird random method. For dichotomous outcomes, the estimates of effects of an intervention were expressed as odds ratios (OR) using the Mantel-Haenszel (M-H) method with 95% confidence intervals. Results. The estimated global prevalence of malignant transformation of oral leukoplakia was 9.15%. The factors with the highest malignant transformation risk of oral leukoplakia were: non-homogeneous clinical types (OR: 5.41; p0.05).Conclusions. Non-homogenous oral leukoplakias and with moderate-severe dysplasia are those with the highest probability of malignant transformation.

The authors detected some minor errors in the published manuscript (Rubert A, Bagan L, Bagan JV. Oral leukoplakia, a clinical-histopathological study in 412 patients. J Clin Exp Dent. 2020 Jun 1;12(6):e540-e546. doi: 10.4317/jced.57091. PMID: 32665812; PMCID: PMC7335600.) and have requested that the entire article be republished with these errors already rectified. Background A retrospective clinical-histopathological study was made of the evolution of oral leukoplakia over time, staging the disease according to the classification of van der Waal. Material and methods A study was made of 412 patients with oral leukoplakia, analyzing the corresponding clinical factors and histopathological findings; assessing associations between the different clinical presentations and epithelial dysplasia; and evaluating the factors influencing malignant transformation of the lesions. Results Clinically, homogeneous presentations were seen to predominate (n = 336, 81.6%), while histologically most of the lesions exhibited no dysplastic changes (n = 271; 65.7%). Stage 1 of the van der Waal classification was the most common presentation (n = 214; 51.9%). The lesion malignization rate was 8.5%, and the factors associated to a significantly increased malignization risk were non-homogeneous OL lesions (p=0.00), lesion location in the tongue (p=0.00), and the presence of epithelial dysplasia (p=0.00). Conclusions In our series of patients with oral leukoplakia, malignization was associated to the less common clinical presentations of the disease, i.e., non-homogeneous lesions, and the latter tended to exhibit high grade epithelial dysplasia. Key words:Oral leukoplakia, potentially malignant disorders, malignant transformation.

A 42-year-old man with a history of surgery for tongue cancer was referred to our hospital due to an abnormal chest shadow. High-resolution computed tomography showed lower lobe reticulation. A physical examination revealed nail dystrophy, oral leukoplakia, and reticulated hypopigmentation. Lung biopsy revealed subpleural and perilobular fibrosis, suggestive of usual interstitial pneumonia. However, multiple pathological findings, including homogenous fibrosis and cell infiltration in the centrilobular region, which were compatible with nonspecific interstitial pneumonia, and bronchiolitis were also seen. Genetic testing showed a hemizygous missense mutation in the DKC1 gene, and the patient was diagnosed with dyskeratosis congenita. Although anti-fibrotic therapy was initiated, the patient's respiratory function has continued to decrease.

To study the association of Candida and antifungal therapy with pro-inflammatory cytokines (PIC) in oral leukoplakia (OL). A prospective observational study where immunocompetent adult subjects with OL (30 homogenous (HL), 30 non-homogenous (NHL)) and 30 age and sex-matched healthy controls (C) with no predisposing factors for oral Candida infection were recruited. Sterile cotton swabs and ophthalmic sponges were used to sample the lesion surface in OL and buccal mucosa in C, for direct microscopy and culture for Candida and to determine levels of PIC (IL-6, IL-8. IL-17, TNF-α) by ELISA, respectively. Sampling for PIC was repeated at same sites in OL, 2 weeks after antifungal therapy. Candida was associated with 55.3% of NHL, 23.3% of HL and 13.3% of C. The oral secretary levels of PIC were raised in NHL as compared to HL and C. The levels of IL-6, IL-8, TNF-α (p

It is essential to identify markers that could indicate the presence of early molecular changes in premalignant tissues like oral leukoplakia (OL). CD44 adhesion molecule is not only a stem cell marker, but also determines cell proliferation and migration in malignant processes. The aim of our study was to assess the amount and pattern of CD44 antigen expression by epithelial and mononuclear cells in the lamina propria under OL and their role in premalignant lesions. The current study included 102 cases of OL and ten biopsies from healthy oral mucosa. Immunohistochemical CD44 antigen expression was determined in 34 cases by a standard EnVision imaging system in three points of OL: both edges and centre. Statistical analysis was done using GraphPad Prism software version 8.4.0. In OL, statistically significant overexpression of membranous CD44 was demonstrated compared to healthy mucosa (p < 0.0001). The intra-cytoplasmatic CD44 expression of epithelium together with characteristic nuclear changes may be used as a predictive factor for potential malignant transformation of non-homogenous leukoplakia. CD44 expression in mononuclear cells under the basal membrane in OL (p < 0.05) possibly influences the process of premalignant lesion transformation into intraepithelial cancer. Further study of CD44 antigen expression in intra-cytoplasmatic structures is required for better explanation of the role of this glycoprotein.

OBJECTIVE Oral leukoplakia (OL) is the most frequently encountered oral potentially malignant disorder. The aims of this systematic review are to estimate the overall malignant transformation of OL and to assess the risk factors associated with malignant transformation of OL published in the last 5 years (2015-2020). MATERIALS AND METHODS We performed a bibliographic search in PubMed, Scopus, Web of Science, Embase, and Cochrane databases with keywords "oral leukoplakia", "oral cancer", "oral carcinoma" and "oral squamous cell carcinoma". Meta-analysis was conducted using a random-effects model. RESULTS Twenty-four studies were selected, that reported a total of 16,604 patients. Malignant transformation proportion varied between 1.1% and 40.8%. Female gender, non-homogeneous clinical type, and presence of epithelial dysplasia were significantly related to MT. Other risk factors previously suggested did not show significant results. CONCLUSIONS The pooled proportion of malignant transformation MT was 9.8% (95% CI: 7.9-11.7). It is necessary to continue to conduct well-designed prospective clinicopathological studies on OL, using a uniform definition for OL to reduce the risk of bias for evaluating various factors associated with the MT.

To evaluate the application of medical magnifying loupes in diagnosis of oral mucosal diseases. Twenty-four patients with plaque-type oral lichen planus or homogeneous oral leukoplakia were inspected by naked eyes or assistance with magnifying loupes. Histopathological results were used as the gold standard to evaluate the sensitivity, specificity and accuracy of the two methods in clinical diagnosis. Questionnaires were used to evaluate the subjective effect of magnifying loupes on the diagnosis efficiency of oral mucosal diseases and to explore the most suitable parameters for application. The sensitivity, specificity and accuracy of medical magnifying loupes for the identification of plaque-type oral lichen planus and homogeneous oral leukoplakia were 94.74%, 100.00% and 95.83%, respectively, which were significantly higher than those of naked eye inspection (89.47%, 80.00% and 87.50%). The effective rate of magnifying loupes assisted diagnosis was 91.76% according to physicians' subjective evaluation. The most suitable parameters were 3.5 times magnification and working distance. The medical magnifying loupes can effectively improve the efficiency of the inspection and diagnosis of oral mucosal diseases, and have the characteristics of convenience and real-time. The recommended clinical parameters are 3.5 times magnification and working distance.

Made available in DSpace on 2022-05-01T09:30:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 Background: DNA damage is accumulated in the cells over time as the result of both exogenous and endogenous factors. The objective of this study was to analyze the immunohistochemical expression of the repair proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). Materials and Methods: Paraffin blocks were selected from the archives of the Laboratory of Hospital Clinico Universitario de Santiago de Compostela, Spain. The sample was composed of 16 cases of OL without dysplasia, 14 cases of OL with dysplasia, and 15 cases of OSCC. The patients' clinical data were collected and immunohistochemical analysis was performed for MLH1, MSH2, MRE11, and XRCC1. The data were submitted to the χ2and the Kruskal-Wallis (P≤0.05) tests. Results: MSH2 was overexpressed in OSCC (P=0.020) and was positive in 100% of patients with OL with dysplasia or OSCC (P=0.019). Positivity for MLH1 was significantly associated with comorbidity (P=0.040), especially in patients who presented with 2 or more pathologies (P=0.028). XRCC1 positivity was also associated with comorbidity (P=0.039). No significant associations were found for the MRE11A expression. Although the simultaneous positivity for the 4 markers was observed in presence of comorbidities (P=0.006). Conclusions: This study supports the effect of the overexpression of MSH2 protein in samples of OL with dysplasia and OSCC, most notably in patients who present with comorbidities and negativity for OL without dysplasia. Oral Medicine Unit Technology Research Center (NPT) Mogi das Cruzes University Mogi das Cruzes, 200 Dr. C ndido Xavier de Almeida Souza Avenue Department of Pathology Clinical Hospital Santiago de Compostela Department of Forensic Sciences and Pathology University of Santiago de Compostela Translational Oncology Laboratory Idichus Foundation Santiago de Compostela School of Medicine Anhembi Morumbi University Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP) Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP)

Background The best treatment approach for wide oral leukoplakia (OL) remains to be determined. Aims To evaluate the outcomes of using an allograft dermal matrix (ADM) for reconstructing large oral epithelial defects following resection of OLs. Patients and methods A total of 27 OLs in 26 patients were excised, and residual large lingual and buccal epithelial defects were reconstructed using an ADM, which ranged in size from 3.0 × 5.0 to 6.0 × 6.0 cm. The patients were classified into mild (n = 1), moderate (n = 13), and severe dysplasia (n = 12) groups; 57.7% of the patients were tobacco smokers, 46.2% were alcoholics, 47.2% were both smokers and alcoholics, and 11.5% were both smoking and betel quid chewers. Patients who underwent surgery were advised to quit smoking, drink alcohol in moderation, or quit betel quid chewing. Results Two patients developed slight hematomas that resolved spontaneously within 2 weeks. A total of 76.9% of the smokers followed the advice to quit smoking, 83.3% of the alcoholics followed the advice to drink in moderation, and all three betel quid chewers followed the advice to quit chewing betel quid. The mean follow-up was 26.7 months. No MT occurred and recurrence was seen in two patients. Conclusions Large epithelial defect reconstruction using an ADM following resection of wide lingual and buccal OLs was safe and reliable for preventing MT of OL. The recurrence of OL may be related to patient habits such as tobacco smoking or/and drinking alcohol.

Aim: To compare the clinical and histopathological presentation of oral leukoplakia among different forms of tobacco users. Material and Methods: This study was carried out among 300 patients with oral leukoplakia, analyzing the corresponding clinical factors and histopathological findings, different forms of tobacco usage and assessing associations between the different clinical presentations and epithelial dysplasia. Results: Out of a total of 300 subjects, most (87.33%) of the subjects were males, among 138 tobacco chewers, maximum (60.87%) were having homogenous leukoplakia, among 85 tobacco smokers, maximum (61.18%) were seen with homogenous leukoplakia and among 77 subjects having mixed habit, maximum of 51.95% were diagnosed as having homogenous leukoplakia. The association between clinical type of leukoplakia and habit type was statistically not significant (Chi-square= 5.0806, p=0.5336). Majority of the cases which were diagnosed clinically diagnosed as leukoplakias presented a histological diagnosis of hyperkeratosis (45%) and mild epithelial dysplasia (33.33%). The association between histopathological type of leukoplakia and habit type was found to be statistically significant (Chi-square= 23.2166, p=0.0007). Conclusion: Most of the patients were having homogenous leukoplakia and majority of the cases which were diagnosed clinically diagnosed as leukoplakias presented a histological diagnosis of hyperkeratosis, mild epithelial dysplasia.

Background Two-dimensional (2D) radiographic techniques are commonly used for assessing lesion prognosis after endodontic surgery. The present retrospective cohort study analyzes the sensitivity and ability of different radiographic techniques in obtaining area and volume measurements of periapical lesions. Material and Methods Preoperative and follow-up (6-48 months) periapical and panoramic radiographs (index test) and cone-beam computed tomography (CBCT) images (reference standard) were selected from an endodontic microsurgery database. Sensitivity was analyzed independently by two examiners. The areas of the 2D radiographic images and CBCT volumes were studied using Itk-Snap software and Romexis viewer. Results The sample comprised 105 patients and 105 teeth, with a mean follow-up of 21 months (range 6-48). Preoperatively, CBCT detected all the periapical areas, periapical radiography detected 67, and panoramic radiography detected 60. Postoperatively, of the 52 cases in which CBCT detected remains of the periapical area, periapical radiography detected 22, and panoramic radiography detected 17. The measurements of the areas obtained by the 2D methods, and the volumes obtained by CBCT, had to be transformed into linear measures for comparison purposes. The measurements were found to be significantly different in both the preoperative and the follow-up images. Conclusions Periapical radiography showed greater sensitivity than panoramic radiography, both preoperatively and at follow-up. The lesions measured with CBCT were larger, with significant differences than as evidenced by the periapical and panoramic radiographs. Key words:Periapical radiography, panoramic radiography, CBCT, sensitivity, treatment outcome, size of periapical radiolucency, area, volume.

Yunping Lu, Lingyu Li, Hui Chen, Xinying Jing, Min Wang, Lihua Ge, Jing Yang, Min Zhang, Xiaofei Tang Beijing Institute of Dental Research, Beijing Key Laboratory, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Beijing 100050, People’s Republic of ChinaCorrespondence: Xiaofei Tang; Min ZhangDivision of Oral Pathology, Beijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, No. 4 Tiantan Xili, Dongcheng District, Beijing 100050, People’s Republic of ChinaTel +86-10-57099311; +86-10-57099313Fax +86-10-57099313Email xftang10@ccmu.edu.cn; 13691135741@163.comPurpose: Cellular senescence is a physiological phenomenon by which cells irreversibly lose their proliferative potential. It is not clear whether senescent cells are related to malignant transformation in oral precancerous lesions. The role of peroxiredoxin1 (Prx1)-induced cell senescence in OLK malignant transformation has not been reported. The aim of this study is to investigate the role and mechanism of cell senescence in oral carcinogenesis.Methods: In this study, 4-nitro-quinoline-1-oxide (4NQO) induced tongue carcinogenesis model in Prx1+/+ and Prx1+/- mice and dysplastic oral keratinocyte (DOK) were used. Prx1 knockdown DOK cells were harvested with shRNA injection, and cell senescence was detected via the senescence-associated β-galactosidase (SA β-gal) assay. The senescence and mitophagy-related proteins were observed by immunohistochemistry (IHC), Western blot and qRT-PCR. The binding of Prx1 with prohibitin 2 (PHB2) and light chain 3 (LC3) was predicted via ZDOCK and measured in mice by Duolink analysis.Results: Histologically, 4NQO treatment induced epithelial hyperplasia, dysplasia (mild, moderate and severe), carcinomas in situ and oral squamous cell carcinoma (OSCC) in mouse tongue mucosa. The malignant transformation rate in Prx1+/- mice (37.5%) was significantly lower compared with Prx1+/+ mice (57.1%). In Prx1+/+ mice, a higher number of senescent cells and greater expression of p53 and p21 were observed in hyperplastic and dysplastic tongue tissues when compared with those in OSCC tissues. Prx1 knockdown induced a greater number of senescent cells in hyperplastic tissues, and DOK cells accompanied cell cycle arrest at the G1 phase and PHB2/LC3II downregulation. Prx1 was predicted to dock with PHB2 and LC3 via ZDOCK, and the interactions were confirmed by in situ Duolink analysis.Conclusion: Prx1 silencing inhibits the oral carcinogenesis by inducing cell senescence dependent on mitophagy.Keywords: peroxiredoxin1, oral leukoplakia, oral squamous cell carcinoma, cell senescence, mitophagy

Aims: Evaluation of total serum creatine phosphokinase and serum lactate dehydrogenase levels as a biochemical parameter in the diagnosis of oral cancer, oral leukoplakia by the case-control method. Settings and Design: A hospital-based, case-control study was conducted at the Department of Oral Medicine, Diagnosis, and Radiology. Materials and Methods: The study included clinically and histopathologically diagnosed oral leukoplakia and oral cancers with 20 patients in each group. The control group consisted of 20 healthy patients without lesions or tobacco-related habits or any systemic diseases. The blood samples were collected from the study and control groups, centrifuged, and serum was analyzed for serum creatine phosphokinase and serum lactate dehydrogenase (CK and LDH) levels using an autoanalyzer. Statistical Analysis: Comparison of three groups with respect to each biochemical parameter was done by one-way ANOVA. Comparison between the groups was done by Tukey's multiple post hoc test. Results: It was found that total serum CK levels were statistically significantly decreased in both oral leukoplakia and oral cancer when compared with that of the control group. Total serum LDH levels were statistically significantly increased in both oral leukoplakia and oral cancer when compared with that of the control group. Conclusion: Although the results of the present study showed increased levels of LDH in both oral leukoplakia and oral cancer, and CK levels statistically decreased but they were within normal limits. Further. studies with a greater number of samples, different grades of epithelial dysplasias, and assessment of individual isoenzymes has to be carried out to evaluate the exact role of CK and LDH in the etiopathogenesis of oral cancer.

Oral potentially malignant disorders (OPMDs) refer to all epithelial lesions and conditions with an increased risk for malignant transformation, including oral leukoplakia, oral submucous fibrosis, oral lichen planus, erythroplakia, etc. Additionaly, oral infection of Candida albicans is considered to be closely related to the development of OPMDs. It was demonstrated in previous studies that the detection rate of Candida albicans was higher in the oral mucosa with OPMDs; in addition, Candida albicans showed high virulence by adhering to and destroying the epithelium. Moreover, Candida albicans was able to induce the immune response and cause chronic inflammation in the epithelium, producing carcinogenic products such as acetaldehyde. The factors mentioned above play a key role in the occurrence and development of OPMDs. Furthermore, the oral mucosa is highly susceptible to Candida albicans. The present review provides an introduction to the relationship between Candida albicans and OPMDs.

Oral leukoplakia is the most prevalent potentially malignant disorder of the oral mucosa globally and its management remains a challenge. Photodynamic therapy is a minimally invasive alternative method in the treatment of premalignant lesions; and the use of the topical 5-ALA photosensitizer plus irradiation with light emitting diode (LED) or laser light has been one of the most recommended approaches for the treatments of oral leukoplakia by photodynamic therapy. The present study was carried out to determine its clinical efficacy as a chemoprevention alternative in the different clinical forms of oral leukoplakia. An exhaustive search of scientific articles published in the last 30 years in English was carried out, using keywords with the MeSH guideline, about the use of topical 5-ALA-mediated photodynamic therapy as a photosensitizer and under low intensity laser radiation or light LED as a source of illumination, in different digital bases. The systematic review under PRISMA guidance recognized an efficacy of 88.6% for this mode of phototherapy in the management of oral leukoplakia, with a greater effect size in the homogeneous clinical forms with dysplastic changes, regardless of the type of light source. However, the evidence used in this analysis was moderate. Based on the results of the present study, we can conclude that topical 5-ALA-mediated photodynamic therapy appears to be a high-performance alternative in the oncopreventive management of oral leukoplakia lesions. However, we recommend running controlled and randomized clinical trials with homogeneous methodologies that allow us to generate a met analysis with a high level of evidence.

Background: Oral leukoplakia (OL) is considered one of the most common potentially malignant oral disorders (OPMD), with a verified increased risk of developing oral cancer. The identification of the dysplasia grade (low–high) is the only consolidated factor used to evaluate this risk. The objective of this study was to verify the role of the fractal dimension (FD) in assessing this dysplasia. Methods: To begin, 29 OL and 10 normal oral mucosa (NOM) biopsies were retrieved for FD analysis of the epithelial (dime) and the connective (dimc) tissue. Results: In the OL group, the median value of dime is higher (1.67, IQR = 0.12) than for the NOM group (1.56, IQR = 0.08), with statistically significant differences (Wilcoxon test, p = 0.0031). There were no differences in relation to dimc. Significant differences were observed between the non-dysplasia vs. high-grade (p = 0.0156) and low-grade vs. high-grade (p = 0.0049) groups. No significant differences were identified in relation to dimc for the different degrees of dysplasia. For a cut-off point of 1.44 of dime, a specificity of 96.6% was obtained, a sensitivity of 100%, and an AUC = 0.819 (p = 0.003). Conclusions: FD at the level of the epithelium may be used as a diagnostic tool in OL This research was funded by Santiago de Compostela University SI

Our aim was to evaluate the expression of biomarkers, CD44v6, CD147, EGFR, p53, p63, p73, p16, and podoplanin in oral leukoplakias (OL) and to assess their potential for prediction of malignant transformation (MT). We analyzed the expression of CD44v6, CD147, EGFR, p53, p63, p73, p16, and podoplanin by immunohistochemistry in 52 OL, comprised of 41 low-grade (LG) dysplasia and 11 high-grade (HG) cases. Twelve healthy normal tissues (NT) were also included. Univariate and multivariate analysis were performed to evaluate any association with MT. Variable expression among the studied markers was observed, with a significant increase of high expression from NT to LG and HG cases in CD44v6 (p = 0.002), P53 (p = 0.002), P73 (p = 0.043), and podoplanin (p < 0.001). In multivariate analysis, cases with high podoplanin score showed a significant increased risk of MT (HR of 10.148 (95% CI of 1.503–68.532; p = 0.017). Furthermore, podoplanin combined with binary dysplasia grade obtained a HR of 10.238 (95% CI of 2.06–50.889; p = 0.004). To conclude, CD44v6, p53, p73, and podoplanin showed an increasing expression along the natural history of oral carcinogenesis. Podoplanin expression independently or combined with dysplasia grade could be useful predictive markers of MT in OL.

Tobacco is a common name for the plants belonging to the genus Nicotiana and nightshade family. It contains a highly addictive stimulant which is used in cigarettes and other smokeless forms of tobacco. The product has a lot of carcinogens and other harmful mixtures which lead to the causation of oral submucous fibrosis, leukoplakia and erythroplakia. In this study, we would be seeing how common it is to have a history of tobacco usage in the patients diagnosed with Leukoplakia between march 2019 and march 2020 in Saveetha dental college. Materials and methods: This study was done in Saveetha dental college, Chennai, Tamilnadu, India. The study data were taken between March 2019 to March 2020. We took patients reporting with oral leukoplakia and checked their history for Smoking or smokeless tobacco usage. These data are recorded by the dental students in saveetha dental college. A total of 100 patient's record was taken and among the patients with smoking, history was identified. The number of patients with and without smoking/smokeless tobacco usage record was deduced. Results: There were a total of 100 participants, in which 95 were males and 5 were females who reported to the clinic with oral leukoplakia. In this sample, a total of 76 patients had a homogenous variant of leukoplakia while 24 patients had a non-homogenous variant. Eighty-four patients had the habit of smoking, while 16 patients had the habit of smokeless tobacco usage. Conclusion: There were 100 participants and with the result deduced from the data obtained from the participants, it is clear that smoking is one of the major etiology of Oral leukoplakia.

The authors consider the possibilities of pain management during photodynamic therapy (PDT) of visible tumors based on the observation of 102 patients. Of the total number of patients, 62 had verified basal cell skin cancer, 10 people - squamous cell skin cancer, another 10 - oral and oropharynx mucosa cancer, 8 - oral leukoplakia and dysplasia, in 6 - lower lip cancer, in 4 - breast cancer, in 2 - other localizations of neoplasms. In 15 patients, nonsteroidal anti-inflammatory drugs (NSAID) were used as pain management, in 69 - a combination of NSAID with tramadol, in 14 - nerve block anesthesia, in 4 - PDT was performed under general anesthesia. The intensity of pain syndrome during laser irradiation of the tumor was assessed on the verbal rating scale (VRS). The absence of pain was recorded in 9% of cases. Mild pain was noted by 58% of patients, moderate pain - 20%, severe pain - 10%, very severe pain was noted by 3% of patients.The degree of expression of pain syndrome during PDT depends on the incidence of a lesion, histological form of tumor, and method of anesthesia. NSAID alone, or in combination with an opioid analgesic, allows effective control of pain syndrome in PDT of basal cell skin cancer in 89%, in PDT of squamous cell skin cancer in 66% of observations. Nerve block anesthesia allows stoping pain syndrome during PDT of oropharyngeal tumors.

Zhongjing Lv,1,2,* Rong Cong,1,* Jiafeng Li,1,2 Kun Cao,1,2 Qiang Bao,1,2 Linlin Li,1,3 Feng Yang,1,2 Jian Yuan1,2 1School of Stomatology, Xuzhou Medical University, Xuzhou City, Jiangsu Province, Mainland China; 2Department of Stomatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, Mainland China; 3Department of Pathology, Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, Mainland China*These authors contributed equally to this workCorrespondence: Jian Yuan; Feng YangDepartment of Stomatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province 221000, Mainland ChinaEmail yuanjian2009_2010@163.com ; yangfeng0909@126.comBackground: Oral leukoplakia is the most common oral mucosal disease. A proportion of such cases can progress to oral squamous cell carcinoma (OSCC). The mechanism of oral leukoplakia malignant transformation is still unclear. In this study, we analyzed the expression of parathyroid hormone-like hormone (PTHLH) in oral leukoplakia and the effect on prognosis, so as to find reliable molecular markers that can predict oral leukoplakia malignant transformation.Methods: We measured PTHrP which is coded by PTHLH in oral leukoplakia tissues of 79 cases (30 cases progressed to OSCC and 49 did not) and analyzed the clinical outcomes. Then, PTHLH expression was reduced using lentivirus-mediated small hairpin RNA (shRNA) interference to determine the biological role of PTHLH in DOK cells.Results: PTHrP was found to be highly expressed in 38% of tissues of oral leukoplakia. There was weak or no PTHrP expression in 25 patients, moderate expression in 24 patients, and strong in 30 patients with oral leukoplakia. The expression level was associated with the degree of atypical hyperplasia and poor prognosis. The cell proliferation, invasion, migration, cell cloning, and cell cycle were affected after reducing PTHLH expression.Conclusion: Our data suggest that either PTHLH or PTHrP plays a key role in the malignant transformation of oral leukoplakia and might be a reliable biomarker for predicting the carcinogenesis of oral leukoplakia.Keywords: PTHLH, oral leukoplakia, malignant transformation