Ductal carcinoma in situ develops within clonal fields of mutant cells in morphologically normal ducts.

Mutations are abundantly present in tissues of healthy individuals, including the breast epithelium. Yet it remains unknown whether mutant cells directly induce lesion formation or first spread, leading to a field of mutant cells that is predisposed towards lesion formation. To study the clonal and spatial relationships between morphologically normal breast epithelium adjacent to pre-cancerous lesions, we developed a three-dimensional (3D) imaging pipeline combined with spatially resolved genomics on archival, formalin-fixed breast tissue with the non-obligate breast cancer precursor ductal carcinoma in situ (DCIS). Using this 3D image-guided characterization method, we built high-resolution spatial maps of DNA copy number aberration (CNA) profiles within the DCIS lesion and the surrounding normal mammary ducts. We show that the local heterogeneity within a DCIS lesion is limited. However, by mapping the CNA profiles back onto the 3D reconstructed ductal subtree, we find that in eight out of 16 cases the healthy epithelium adjacent to the DCIS lesions has overlapping structural variations with the CNA profile of the DCIS. Together, our study indicates that pre-malignant breast transformations frequently develop within mutant clonal fields of morphologically normal-looking ducts. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer.

Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and the most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco- and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ~ 65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome toward PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage.

Expecting the unexpected: incidental findings at a level 1 trauma center.

INTRODUCTION: Incidental findings on comprehensive imaging in the adult trauma population occur at rates as high as 54.8%. We sought to determine the incidence of potentially malignant or pre-malignant incidental findings in a high-volume level 1 trauma center and to evaluate follow-up recommendations. METHODS: This was a retrospective review of all patients with incidental findings on imaging who were admitted to the trauma service at our level 1 trauma center between January 1st, 2014, and October 1st, 2019. A multi-disciplinary team characterized findings as potentially malignant or pre-malignant. RESULTS: The study included 495 patients who had incidental findings, 410 of whom had potentially malignant or pre-malignant findings on imaging, resulting in a cumulative incidence of 6.6%. The mean age was 65 and 217 (52.9%) patients were male. The majority of "incidentalomas" were discovered on CT imaging (n=665, 98.1%); over half were solid (n=349, 51.5%), while 27.4% were cystic (n=186) in nature. The lungs (n=199, 29.4%), kidneys (n=154, 22.8%), liver (n=74, 10.9%), thyroid gland (n=58, 8.6%), and adrenal glands (n=53, 7.8%) harbored the most incidentalomas. Less than half of patients with incidental findings received specific follow-up recommendations on the radiologist's report (n=150, 39%). Sixty-one percent of patients (n=250) had their incidentalomas detailed in the discharge paperwork. CONCLUSION: The results of our study suggest that potentially malignant or pre-malignant incidental findings are common among trauma patients. Specific follow-up recommendations were not presented in 61% of the radiology reports, highlighting the need to standardize medical record capture of an incidentaloma to ensure adequate and appropriate follow-up.

Rigid Tissue Increases Cytoplasmic pYAP Expression in Pre-Malignant Stage of Lung Squamous Cell Carcinoma (SCC) In Vivo.

Increased tissue rigidity is able to activate the Hippo signaling pathway, leading to YAP inactivation by phosphorylation and translocation into the cytoplasm. Accumulating evidence suggests that cytoplasmic pYAP serves as a tumor suppressor and could be a prognostic biomarker for several solid cancers. However, the relationship between tissue rigidity and cytoplasmic pYAP expression in the early stage of lung squamous cell carcinoma (SCC) remains elusive; this was determined in this study by using a mouse model. Female BALB/c mice were assigned into two groups (n = 6; the vehicle (VC) and the pre-malignant (PM) group, which received 70% acetone and 0.04 M N-nitroso-tris-chloroethylurea (NTCU) for 15 weeks, respectively. In this study, the formation of hyperplasia and metaplasia lesions was found in the PM group, indicating the pre-malignant stage of lung SCC. The pre-malignant tissue appeared to be more rigid as characterized by significantly higher (p < 0.05) epithelium thickness, proliferative activity, and collagen content than the VC group. The PM group also had a significantly higher (p < 0.05) cytoplasmic pYAP protein expression than the VC group. In conclusion, increased tissue rigidity may contribute to the upregulation of cytoplasmic pYAP expression, which may act as a tumor suppressor in the early stage of lung SCC.

DNA methylation markers as triage test for the early identification of cervical lesions in a Chinese population.

Objective strategies are required in cervical cancer screening. We have identified several DNA methylation markers with high sensitivity and specificity to detect cervical intraepithelial neoplasia 2 or worse (CIN2+) in Dutch women. Our study aims to analyze the diagnostic characteristics of these markers in a Chinese cohort. A total of 246 liquid-based cytology samples were included, of which 205 women underwent colposcopy due to an abnormal cytology result (atypical squamous cells of undetermined significance [ASCUS] or worse), while 227 were tested high-risk human papillomavirus (hrHPV) positive. All six individual markers (ANKRD18CP, C13ORF18, EPB41L3, JAM3, SOX1 and ZSCAN1) showed enhanced methylation levels and frequency with increasing severity of the underlying lesion (P ≤ .001). In cytological abnormal women, sensitivity to detect CIN2+ was 79%, 76% and 72% for the three panels (C13ORF18/EBP41L3/JAM3, C13ORF18/ANKRD18CP/JAM3 and ZSCAN1/SOX1, respectively), with a specificity of 57%, 65% and 68%. For the first two panels, these diagnostic characteristics were similar to the Dutch cohort, while for ZSCAN1/SOX1 the sensitivity was higher in the Chinese cohort, but with a lower specificity (both P < .05). In hrHPV-positive samples, similar sensitivity and specificity for the detection of CIN2+ were found as for the abnormal cytology cohort, which were now all similar between both cohorts and non-inferior to HPV16/18 genotyping. Our analysis reveals that the diagnostic performances are highly comparable for C13ORF18/EBP41L3/JAM3 and C13ORF18/ANKRD18CP/JAM3 methylation marker panels in both Chinese and Dutch cohorts. In conclusion, methylation panels identified in a Dutch population are also applicable for triage testing in cervical cancer screening in China.

Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma.

The current model for breast cancer progression proposes independent 'low grade (LG)-like' and 'high grade (HG)-like' pathways but lacks a known precursor to HG cancer. We applied low-coverage whole-genome sequencing to atypical ductal hyperplasia (ADH) with and without carcinoma to shed light on breast cancer progression. Fourteen out of twenty isolated ADH cases harboured at least one copy number alteration (CNA), but had fewer aberrations than LG or HG ductal carcinoma in situ (DCIS). ADH carried more HG-like CNA than LG DCIS (e.g. 8q gain). Correspondingly, 64% (7/11) of ADH cases with synchronous HG carcinoma were clonally related, similar to LG carcinoma (67%, 6/9). This study represents a significant shift in our understanding of breast cancer progression, with ADH as a common precursor lesion to the independent 'low grade-like' and 'high grade-like' pathways. These data suggest that ADH can be a precursor of HG breast cancer and that LG and HG carcinomas can evolve from a similar ancestor lesion. We propose that although LG DCIS may be committed to a LG molecular pathway, ADH may remain multipotent, progressing to either LG or HG carcinoma. This multipotent nature suggests that some ADH cases could be more clinically significant than LG DCIS, requiring biomarkers for personalising management. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Atypical endometrial polyps and the incidence of endometrial cancer: a retrospective cohort study.

OBJECTIVE: The aim of this study was to evaluate the incidence of endometrial carcinoma, proven after hysterectomy, in patients diagnosed with atypical endometrial hyperplasia confined to a polyp. A secondary aim was to establish factors associated with (pre-)malignant alterations in a polyp. DESIGN: A retrospective cohort study. SETTING: Maastricht University Medical Centre (MUMC+) and Máxima Medical Centre in Eindhoven/Veldhoven (Máxima MC). POPULATION: Women who underwent a hysteroscopic polyp resection between 2008 and 2016. METHODS: Patient characteristics and histopathology results of the polyp and, in the case of a hysterectomy, uterus were collected from patients' charts. RESULTS: A total of 1445 complete hysteroscopic polyp resections were included. Of those, 1390 polyps showed benign histopathology results, 39 polyps contained atypical hyperplasia and 16 polyps contained endometrial carcinoma. A hysterectomy was performed in 35 women who were diagnosed with atypical hyperplasia confined to a polyp after hysteroscopic polyp resection. Histopathological assessment showed no additional (pre-)malignant changes of the endometrium in 12 women (30.8%), atypical hyperplasia in 11 women (28.2%) and endometrial carcinoma in 12 women (30.8%). None of the prognostic factors under consideration were significantly associated with (pre-)malignant changes in a polyp. CONCLUSION: The incidence of endometrial carcinoma in the surrounding endometrium after complete resection of a polyp with atypical hyperplasia is 30.8% in this study. This supports the current advice to perform a hysterectomy and bilateral salpingo-oophorectomy. No prognostic factor for (pre-)malignant changes in a polyp was established. TWEETABLE ABSTRACT: The incidence of endometrial carcinoma after complete resection of a polyp with atypical hyperplasia is high.

Oral Submucous Fibrosis: A Review on Biomarkers, Pathogenic Mechanisms, and Treatments.

Oral submucous fibrosis (OSF) is a collagen deposition disorder that affects a patient's oral function and quality of life. It may also potentially transform into malignancy. This review summarizes the risk factors, pathogenic mechanisms, and treatments of OSF based on clinical and bio-molecular evidence. Betel nut chewing is a major risk factor that causes OSF in Asia. However, no direct evidence of arecoline-induced carcinogenesis has been found in animal models. Despite identification of numerous biomarkers of OSF lesions and conducting trials with different drug combinations, clinicians still adopt conservative treatments that primarily focus on relieving the symptoms of OSF. Treatments focus on reducing inflammation and improving mouth opening to improve a patient's quality of life. In conclusion, high-quality clinical studies are needed to aid clinicians in developing and applying molecular biomarkers as well as standard treatment guidelines.

DNA methylation markers as a triage test for identification of cervical lesions in a high risk human papillomavirus positive screening cohort.

Objective triage strategies are required to prevent unnecessary referrals for colposcopy in population-based screening programs using primary high-risk human papillomavirus (hrHPV) testing. We have identified several DNA methylation markers with high sensitivity and specificity for detection of high-grade cervical intraepithelial neoplasia or worse (CIN2+) in women referred for colposcopy. Our study assessed diagnostic potential of these methylation markers in a hrHPV-positive screening cohort. All six markers (JAM3, EPB41L3, C13orf18, ANKRD18CP, ZSCAN1 and SOX1) showed similar association across histology in the hrHPV-positive cohort when compared to the Dutch cohort (each p > 0.15). Sensitivity for CIN2+ was higher using methylation panel C13orf18/EPB41L3/JAM3 compared to the other 2 panels (80% vs. 60% (ANKRD18CP/C13orf18/JAM3) and 63% (SOX1/ZSCAN1), p = 0.01). For CIN3+ all three methylation panels showed comparable sensitivity ranging from 68% (13/19) to 95% (18/19). Specificity of SOX1/ZSCAN1 panel (84%, 167/200) was considerably higher compared to ANKRD18CP/C13orf18/JAM3 (68%, 136/200, p = 2 × 10-5 ) and C13orf18/EPB41L3/JAM3 (66%, 132/200, p = 2 × 10-7 ). High negative predictive value (NPV) (91-95% and 96-99%) was observed for CIN2+ and CIN3+, for all three methylation panels, while positive predictive value (PPV) varied from 25 to 40% for CIN2+ and 15-27% for CIN3+. Interestingly, 118/235 samples were negative for all six markers (including 106 controls (89.8%), 6 CIN1 (5.1%), 5 CIN2 (4.2%) and 1 CIN3 (0.8%)). Methylation results from both independent cohorts were comparable as well as high sensitivity for detection of cervical cancer and its high-grade precursors in hrHPV-positive population. Our study therefore validates these methylation marker panels as triage test either in hrHPV-based or abnormal cytology-based screening programs.

Dietary intake from birth through adolescence in relation to risk of benign breast disease in young women.

PURPOSE: Nutritional factors during different periods in life impact breast cancer risk. Because benign breast disease (BBD) is a well-established risk factor for breast cancer, we investigated childhood nutrition from birth through age 14 year and subsequent BBD. METHODS: A prospective cohort study of 9031 females, 9-15 year at baseline, completed questionnaires (including heights, weights) annually from 1996 to 2001, in 2003, 2005, 2007, 2010, 2013 and 2014. In 1996, mothers reported infant feeding practices during their daughters first year of life. Beginning in 1996, participants completed annual food frequency questionnaires. In 2005, participants (18 year +) began reporting whether they had ever been diagnosed with biopsy-confirmed BBD (N = 173 cases). Multivariable logistic regression models estimated associations between childhood nutrition and BBD, adjusted for maternal breast disease and childhood body size factors. RESULTS: Although no infant nutrition factors were associated with biopsy-confirmed BBD, certain adolescent dietary factors were. A multivariable model simultaneously included the most important diet and body size factors from different age periods: higher BBD risk was associated with greater age 10 year consumption of animal (non-dairy, energy-adjusted) fat (OR 2.27, p < .02, top vs. bottom quartiles) and with lower 14 year consumption of nuts/peanut butter (OR 0.60, p = .033, top vs. bottom quartiles). CONCLUSION: Greater intake of animal (non-dairy) fat at 10 year and lower intake of nuts/peanut butter at 14 year were independently associated with higher BBD risk. These dietary factors appeared to operate on BBD risk independent of childhood growth (gestational weight gain, childhood BMI and height, adolescent height growth velocity), young adult height and BMI, and family history.

Local inflammatory reaction to benign, pre-malignant and malignant glottic lesions: A matched case-control study.

OBJECTIVES: To study the inflammatory infiltrates associated with the different stages of laryngeal carcinogenesis. DESIGN: Observational, matched case-control study of histopathologic specimens. SETTING: An academic referral centre. PARTICIPANTS: A total of 45 patients who underwent removal of glottic lesions between 2008 and 2015. Patients were enrolled and categorised into three matched groups according to lesions' histopathologic diagnoses, 15 patients in each group: benign, pre-malignant and squamous cell carcinoma (SCC). Matching was based on age, gender and pack-years. MAIN OUTCOME MEASURES: Immunohistochemistry staining using monoclonal antibodies against CD4, CD8, CD68, CD20 and S100 representing T-helper cells, cytotoxic T cells, macrophages, B cells and dendritic cells, respectively. Cell counts and distributions were measured and compared between groups. Correlations between the different cells were examined. RESULTS: The predominant cell type was CD8+, followed by CD68+ and CD4+. All inflammatory cells increased significantly in number in SCC (P-value < 0.001), with no significant difference between benign and pre-malignant groups. Strong correlations between the different cells were demonstrated only in the malignant group. S100+ cells correlated with both T-cell subsets, CD4+ (rho = 0.769, P-value = 0.001) and CD8+ (rho = 0.697, P-value = 0.0004). Infiltrates exhibited more extensive distribution in SCC compared to pre-malignant and benign; CD8+ and CD68+ cells were demonstrated in both intraepithelial and stromal regions in 93% of SCC lesions (P-value = 0.0001). CONCLUSIONS: Laryngeal carcinoma demonstrates a unique pattern of inflammatory infiltrates, with significant changes in cell counts and distribution. Leucocyte infiltrates increased significantly in the transition from laryngeal pre-malignant lesion to malignancy while no significant differences were seen between benign and pre-malignant lesions.

Salivary detection of human Papilloma virus 16 & 18 in pre-malignant and malignant lesions of oral cavity: Is it feasible in Pakistani context of Socio-Cultural Taboos?

OBJECTIVE: To evaluate salivary detection of HPV-16 & 18 would be feasible and informative biomarker for oral pre-malignant and malignant lesion in our population. METHODS: This non-interventional, case control study was carried out at department of E.N.T, Head and Neck Surgery, Dow University of Health Sciences, Dow Medical College and Civil Hospital Karachi, Pakistan between July 2011 to December 2012. Total of 105 cases were recruited. These were divided in three groups 'A', 'B' & 'C' having 35 subjects each. Group'A' constitutes patients having strong clinical evidence of oral pre-malignant lesions (PML). Group 'B' includes histologically proven oral squamous cell carcinoma (OSCC) and Group 'C' comprised disease free subjects as controls. After taking informed consent, relevant clinical history was recorded on institutional approved performa. Saliva from all subjects was procured by standard 'drooling method'. Samples were stored at +4°C and later transferred to Laboratory to store at-20°C before further process. Samples were centrifuged at 4500 rpm for 15 minutes at 4°C. Cell pellets sediments were used for identification of HPV-16 & 18 by real-time PCR method. Data was entered and analysed using SPSS version 16. P-value of 0.05 was taken as standard. RESULTS: In group 'A', HPV-16 was detected in 3 (8.6%) cases while HPV-18 was not detected in any of the subject. In group 'B', HPV-16 was detected in 07 (20%) while HPV-18 was found in 06 (17.1%) cases. Mixed HPV-16 and HPV-18 were found in 02 (5.7%) cases. In group 'C', HPV-16 was detected in 03(8.6%) while HPV-18 was not detected in any of the subjects. Significant relationship was observed between the groups for HPV-18 detection (P= 0.002) while for HPV-16, no significant association was found (P= 0.245). CONCLUSION: HPV infection for the causation of oral cancer cannot be fully established possibly due to small sample size. More over differences in genetic makeup, environment, indulgence in peculiar risk factor habits, sexual practices and difficult evaluation of the acquisition of viral load due to socio-cultural and religious restrictions could be the reason.

Pediatric Type of Early Pilomatricoma of the Auricle: A Case Report.

Pilomatricoma is a benign adnexal neoplasm that has been associated with malignancy transformation. Yet, it is not considered as pre-malignant lesion. It is divided into pediatrics type and adult type on the age of occurrence and based on stage of presentation it can described as early and late. We hereby report a 16-year-old female patient with Early-Stage Pediatric Type Pilomatricoma of the Auricle. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04584-0.

Antifibrotic Effect of Baicalin on Arecoline Induced Human Oral Fibroblast: An In-Vitro Study.

BACKGROUND: Baicalin is a flavonoid obtained from the Chinese herb Scutellaria baicalensis, which has a wide varieties of health benefits and scope to be studied for its therapeutic potential in oral fibrosis. AIM: The aim of the study was to investigate the antifibrotic effect of a Baicalin in arecoline induced human oral fibroblast in vitro setting. MATERIAL AND METHODS: Arecoline and ethanolic extracts of Baicalin were commercially purchased from Sigma-Aldrich. Human oral fibroblasts were cultured and characterized with specific fibroblast markers, and cells were stimulated with arecoline. An MTT assay (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) was executed to determine the half-maximal inhibitory concentration of arecoline and Baicalin. Arecoline-induced cells (25µg/ml) were treated with a non-toxic dose of Baicalin (proliferative dose of 25µg/ml). Cytokine (CCL2, CXCL-8, IL17, IL-beta, and IL-6) and fibrotic marker genes were studied by reverse transcription-polymerase chain reaction (RT-PCR). The inhibitory effect of Baicalin was studied to prove its antifibrotic properties. RESULTS: Arecoline significantly upregulated all inflammatory and fibrotic markers. On treatment with 25µg/ml of Baicalin, all inflammatory and fibrotic markers were inhibited. Arecoline affects fibroblast morphology, supporting the fact that arecoline is cytotoxic to cells. CONCLUSION: Baicalin can be used as an antifibrotic herb to treat OSMF.

Papillary Neoplasms of the Gallbladder and Extrahepatic Bile Ducts: A Report of Two Cases With Associated Invasive Carcinoma.

Intracholecystic papillary neoplasm (ICPN) of the gallbladder is a macroscopically visible premalignant lesion protruding into the gallbladder lumen, with infrequent association with invasive adenocarcinoma. Intraductal papillary neoplasm of the bile ducts (IPNB) is a non-invasive lesion characterized by intraductal papillary or villous architecture. Both ICPN and IPNB are rare findings in the gallbladder and biliary tract pathology. Diagnosis relies on clinical manifestations, imaging techniques, and comprehensive histological examination. Here, we present two cases: a 63-year-old male with mild abdominal pain found to have a gallbladder mass, diagnosed histologically as ICPN with associated invasive carcinoma; and a 65-year-old female with chronic jaundice and a large tumor mass in the common bile duct, histologically diagnosed as IPNB with associated invasive carcinoma. These cases highlight the importance of a careful and thorough microscopic examination to rule out differential diagnoses and to reveal any potential invasive carcinoma associated with these uncommon lesions.

Does Portal Hypertension Increase the Risk of Helicobacter pylori Infection and Pre-Malignant Gastric Lesions?

Background and Aims: The presence of portal hypertension in cirrhotic patients is a major prognostic factor associated with the development of severe complications and increased mortality. The gold standard for diagnosing portal hypertension is the hepatic venous pressure gradient. More recently, spleen stiffness has emerged as a new and non-invasive diagnostic tool, and has already been included in the last Baveno VII guidelines. The exact prevalence of Helicobacter pylori infection, pre-malignant lesions and their relation to portal hypertension have never been described. The aim of our study was to evaluate the relationship between the presence of portal hypertension assessed via liver and spleen elastography and Helicobacter pylori infection and pre-malignant gastric lesions. Methods: An observational study was conducted, including consecutive patients admitted from December 2020 to December 2022. All patients underwent upper endoscopy and were also subjected to liver and spleen elastography (using the new probe of 100 Hz) by the same blinded operator in a tertiary center. Results: We included 155 cirrhotic patients, with a mean age of 64.1 years (±8.8), and 81.3% were male. The most common etiology was alcoholic liver disease (72.9%). The median value of liver stiffness measurement was 24.4 kPa [3.1-75.0], and the spleen stiffness measurement was 49.1 kPa [12.8-100.0]. Akin to endoscopic findings, 50.3% presented esophageal varices, 5.2% gastric atrophy, 11.6% gastric metaplasia, and 32.9% portal hypertension gastropathy. Regarding histologic findings, we found that 34.8% presented H. pylori infection, 35.5% gastric atrophy (OLGA 1-58.2%) and 38.7% gastric metaplasia (OLGIM 1-63.3%). Liver stiffness and spleen stiffness measurements were associated with the presence of portal hypertensive gastropathy (p < 0.01), but not with H. pylori infection or pre-malignant gastric lesions. Conclusions: Although present in almost one third of cirrhotic patients, H. pylori infection and pre-malignant gastric lesions are not associated with liver stiffness and spleen stiffness measurements. On the other hand, we found an association between liver stiffness and spleen stiffness measurements and portal hypertensive gastropathy.

Association Between Oral Microbiota and Oral Leukoplakia: A Systematic Review.

Literature evidence suggests a significant gap in research exploring the association between the oral microbiota and leukoplakia. So, this review aimed to thoroughly assess the body of research and look at the connection between leukoplakia and the oral microbiome. Databases such as Pubmed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase (Excerpta Medica Database), Web of Science, Scopus, CINAHL (Cumulated Index to Nursing and Allied Health Literature), and Cochrane Library were searched using MeSH keywords using a standard data extraction protocol that was designed to ensure comprehensive extraction of relevant information from the selected studies, adhering to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Seven studies were selected that were relevant to this review's objectives. The findings indicate that patients with leukoplakia had a diverse oral microbiota compared to healthy controls. The connection between the oral microbiomes of leukoplakia patients and oral cancer cases was also found, indicating possible microbial profile similarities. By shedding light on particular microbial species and variations in the oral microbial flora of leukoplakia, the studies that were included in this review reveal possible biomarkers and provide a deeper knowledge of the disease mechanism. The considerable overlap between oral microbiomes in leukoplakia cases highlights the need for more research into common microbial indicators and the implications for diagnosis and prognosis.

Oral Potentially Malignant Disorders and Oral Cancer in Saudi Arabia: An Epidemiological Review of the Literature.

Background: Oral potentially malignant disorders (OPMDs) are a group of chronic oral mucosal diseases associated with an increased risk of malignant transformation. Multiple studies have investigated the prevalence of these conditions in multiple regions; however, there are limited data about the prevalence of OPMDs in the Kingdom of Saudi Arabia (KSA). This paper aims to review the prevalence of OPMDs in the KSA, to ensure better understanding of the population risk and propose a more standardised approach to the diagnosis and management of this group across the KSA. In addition, this review will discuss the prevalence of oral cancer in the KSA, considering independent risk factors for oral cancer development. Methods: Electronic databases including PubMed, Medline, Medscape, ScienceDirect, StatPearls, BMC Oral Health and the Cochrane Library were searched with the keywords "Oral Potentially Malignant Disorders"; "Saudi Arabia"; and "Oral Cancer". Identified articles were reviewed independently by 2 reviewers against defined inclusion and exclusion criteria. Results: 16 studies were included in this review. The prevalence of OPMDs in KSA varies significantly depending on age, gender, social habits, background disease and dental status. Conclusions: This review highlights the need for up-to-date data on the prevalence, distribution, and characteristics of OPMDs in KSA. The diverse prevalence rates and distinct characteristics of various OPMDs emphasise the necessity for targeted preventive measures. As the data on OPMDs in KSA remains limited, future research efforts should prioritise the establishment of comprehensive epidemiological studies to inform effective public health interventions in this region.

Practice patterns for initial management of oral leukoplakia amongst otolaryngologists and oral and maxillofacial surgeons.

OBJECTIVE: Oral leukoplakia is encountered frequently by otolaryngologists and oral and maxillofacial surgeons (OMFS). There are no consensus practice management guidelines for oral leukoplakia, resulting in heterogeneity in practice patterns. Characterization of practice patterns of providers who treat oral leukoplakia will be valuable to establish standards of care and future practice guidelines. MATERIAL AND METHODS: A survey was designed by the American Head and Neck Society Cancer Prevention Service collecting demographic and practice management data for treating oral leukoplakia. The survey was approved and distributed to members of the American Academy of Otolaryngology-Head and Neck Surgery and American Association of Oral and Maxillofacial Surgeons. Data analysis was performed using chi square and t-test where appropriate. RESULTS: 396 responses were collected: 83 OMFS, 81 head and neck fellowship-trained providers, and 232 otolaryngologists (non-head and neck fellowship-trained). Providers saw a wide volume of oral leukoplakia (23.0% >30 cases/year, 35.1% 11-30 cases/year, 41.2% 10 or less cases/year), with OMFS seeing more cases of oral leukoplakia. Factors most associated with consideration of initial biopsy included physical exam findings (94.4%), erythroplakia (82.3%), and smoking status (81.6%). The majority of respondents saw patients in follow-up within 1 month (24.8%) or within 1-3 months (46.5%). CONCLUSION: This survey identifies a range of practice patterns in initial management of oral leukoplakia, including indications for biopsy, and time for follow-up. This data provide insight into practice patterns amongst different groups of providers and can potentially lead to consensus guidelines for initial management of oral leukoplakia.