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Cancer Research Communications Oct 2021Oral leukoplakia is common and may, in some cases, progress to carcinoma. Proliferative leukoplakia is a progressive, often multifocal subtype with a high rate of...
UNLABELLED
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 = 58 patients (proliferative leukoplakia, = 29; localized leukoplakia, = 29), only the clinical diagnosis of proliferative leukoplakia was associated with significantly decreased CFS (HR, 11.25; < 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 ( < 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 (log fold change, 1.93; < 0.001). Programmed death ligand 1 (PD-L1) was comparatively overexpressed among proliferative leukoplakia samples, with higher (>5) PD-L1 scores predicting worse CFS ( < 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.
Topics: Humans; CD8-Positive T-Lymphocytes; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Leukoplakia, Oral; Gene Expression Profiling; Tumor Microenvironment
PubMed: 36860910
DOI: 10.1158/2767-9764.CRC-21-0060 -
Indian Journal of Dental Research :... 2021An individual's risk towards development of cancer depends not only on environmental factors or extrinsic exposure to carcinogens but also on individual's genetic...
BACKGROUND
An individual's risk towards development of cancer depends not only on environmental factors or extrinsic exposure to carcinogens but also on individual's genetic susceptibility.
AIM
To determine two genetically established parameters such as prevalence of GSTM1 null polymorphism and analysis of Palmar dermatoglypics (PD) in patients with Oral Leukoplakia (OL) and Controls.
MATERIALS AND METHODS
Group I (cases) 30 patients with established histopathological diagnosis of OL and Group II (controls) 30 patients without any habits of tobacco, alcohol usage and without OL were selected. After informed consent, the palm prints were recorded using a Canon PIXMA MP250 scanner and 2 ml of blood was collected and transported under cold cycle and taken for evaluation of GSTM1 null polymorphism using Multiplex PCR.
RESULTS
There exists a highly significant difference in GSTM1 null polymorphism (p-0.002), Finger ridge patterns (arches- p-0.027, loops p-0.001, whorls p-0.001), hypothenar pattern (p-0.015), ATD angle (p-0.001), AB count (p-0.007) between cases and controls. Similarly, when analysing the GSTM1 null polymorphism with PD among cases, there exists a significant association between loops (p-0.001), AB count (p-0.058) and hypothenar pattern (p-0.076), respectively 43% of OL cases had alteration in both which implies that those patients are at a higher risk of developing cancer.
CONCLUSION
Not all patients who smoke or chew tobacco develop cancer. This could probably be due to the individual's genetic susceptibility. Environment gene interactions, in the form of GSTM1 polymorphism, and carcinogenesis, share links that can help in the prediction of risk for oral cancer development, and use of such markers can aid in prediction of oral cancer susceptibility in exposed individuals. Palm prints once formed do not change throughout life and are not influenced by environment. It can also serve as genetic markers to predict the risk of occurrence of oral cancer.
Topics: Case-Control Studies; Genetic Predisposition to Disease; Glutathione Transferase; Humans; Leukoplakia, Oral; Mouth Neoplasms; Polymorphism, Genetic; Risk Factors; Smoking; Tobacco, Smokeless
PubMed: 34269240
DOI: 10.4103/ijdr.IJDR_18_18 -
International Journal of Molecular... Sep 2020Oral potentially malignant disorders (OPMDs) comprise a range of clinical-pathological alterations frequently characterized by an architectural and cytological... (Review)
Review
Oral potentially malignant disorders (OPMDs) comprise a range of clinical-pathological alterations frequently characterized by an architectural and cytological derangements upon histological analysis. Among them, oral leukoplakia is the most common type of these disorders. This work aims to analyze the possible use of drugs such as immunochemopreventive agents for OPMDs. Chemoprevention is the use of synthetic or natural compounds for the reversal, suppression, or prevention of a premalignant lesion conversion to malignant form. Experimental and in vivo data offer us the promise of molecular prevention through immunomodulation; however, currently, there is no evidence for the efficacy of these drugs in the chemoprevention action. Alternative ways to deliver drugs, combined use of molecules with complementary antitumor activities, diet influence, and better definition of individual risk factors must also be considered to reduce toxicity, improve compliance to the protocol treatment and offer a better individualized prevention. In addition, we must carefully reconsider the mode of action of many traditional cancer chemoprevention agents on the immune system, such as enhancing immunosurveillance and reversing the immune evasion. Several studies emphasize the concept of green chemoprevention as an alternative approach to accent healthy lifestyle changes in order to decrease the incidence of HNSCC.
Topics: Anticarcinogenic Agents; Humans; Leukoplakia, Oral; Mouth Neoplasms
PubMed: 32961682
DOI: 10.3390/ijms21186874 -
Cancer Medicine Jul 2023The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high-risk individuals and lesions... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high-risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation.
METHODS
PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method.
RESULTS
A total of seven saliva biomarkers were analyzed in this paper, including interleukin-1alpha, interleukin-6 (IL-6), interleukin-6-8, tumor necrosis factor alpha (TNF-α), copper, zinc, and lactate dehydrogenase. IL-6 and TNF-α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL-6, TNF-α, C-reactive protein, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, albumin, protein, β2-microglobulin, fucose, lipid-bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC.
CONCLUSION
IL-6 and TNF-α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration.
Topics: Humans; Interleukin-6; Tumor Necrosis Factor-alpha; N-Acetylneuraminic Acid; Leukoplakia, Oral; Biomarkers; Mouth Neoplasms; Cell Transformation, Neoplastic
PubMed: 37199052
DOI: 10.1002/cam4.6095 -
International Dental Journal Dec 2019To analyse the clinical and histopathological features of oral leukoplakia (OL) in the Sudan, and to identify the risk factors associated with dysplastic and malignant...
OBJECTIVES
To analyse the clinical and histopathological features of oral leukoplakia (OL) in the Sudan, and to identify the risk factors associated with dysplastic and malignant changes.
METHODS
Records of 117 cases with the diagnosis of OL at the Department of Oral Pathology in the period from 2010 to 2017 were reviewed.
RESULTS
Of the 117 cases included in this study, 30 cases (25.6%) showed carcinoma in the initial diagnostic biopsy. The mean age at diagnosis was 59.8 years with a male/female ratio of 3.3:1. The lip (48.7%) and the gingiva (31.6%) were the predominantly affected sites. Multivariate regression analysis revealed that females were associated with 3.36-fold [95% confidence interval (CI), 1.36-10.76; P = 0.012] higher risk of malignant transformation compared with males. Verrucous leukoplakia was associated with 3.38-fold (95% CI, 1.12-10.19; P = 0.031) higher risk of malignant transformation compared with homogeneous leukoplakia. Exclusive Toombak dipping was the significant risk factor for the presence of dysplasia in OL (odds ratio, 9.35; 95% CI, 1.28-67.99; P = 0.027).
CONCLUSIONS
Clinical and histopathological features of OL were analysed and correlated. Toombak dipping was the significant risk factor for dysplastic changes, while female gender and verrucous leukoplakia were the factors associated with malignant transformation.
Topics: Cell Transformation, Neoplastic; Female; Humans; Leukoplakia, Oral; Male; Middle Aged; Odds Ratio; Risk Factors; Sudan
PubMed: 31407319
DOI: 10.1111/idj.12509 -
The Journal of Evidence-based Dental... Dec 2020To estimate the association of human papillomavirus (HPV) infection with oral lichen planus (OLP) and oral leukoplakia (OLK), and determine risk cofactors. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To estimate the association of human papillomavirus (HPV) infection with oral lichen planus (OLP) and oral leukoplakia (OLK), and determine risk cofactors.
STUDY DESIGN
Seven databases were searched for case-control or cross-sectional studies of OLP and OLK with healthy controls, published between 1976 and 2020. The Meta package of R software was applied to calculate the pooled odds ratios (OR) and 95% confidence interval (CI).
RESULTS
Thirty-six articles were finally included. OLP and OLK cases had a higher association with HPV infection than controls (OLP: OR: 4.91, 95% CI: 2.76-8.72; OLK: OR: 2.51, 95% CI: 1.55-4.07). In subgroup analyses, the OR of HPV infection was higher with erosive lesions than with nonerosive lesions (OLP: OR: 5.36 and 3.47, respectively; OLK: OR: 3.34 and 3.21, respectively). Oral lesions were more strongly associated with HPV16/18 than with HPV6/11 (OLP: OR: 7.84 and 1.42, respectively; OLK: OR: 6.05 and 1.87, respectively) and varied by geographic region (OLP: OR: 4.01-7.02; OLK: OR: 1.46-27.13).
CONCLUSIONS
Oral HPV infection, particularly infection with HPV 16/18, was strongly associated with OLP and OLK. Risk cofactors included erosive lesions and geographic region.
Topics: Alphapapillomavirus; Cross-Sectional Studies; Human papillomavirus 16; Human papillomavirus 18; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Papillomaviridae
PubMed: 33303094
DOI: 10.1016/j.jebdp.2020.101485 -
Journal of Zhejiang University.... May 2023Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma, which indicates a high potential of malignancy. The malignant transformation of oral... (Review)
Review
Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma, which indicates a high potential of malignancy. The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life; however, it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management. As a major problem in the field of head and neck pathologies, it is imperative to identify biomarkers of malignant transformation in oral leukoplakia. In this review, we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside. Although no single biomarker has yet been applied in the clinical setting, profiling for genomic instability might be a promising adjunct.
Topics: Humans; Mouth Neoplasms; Carcinoma, Squamous Cell; Quality of Life; Leukoplakia, Oral; Biomarkers; Head and Neck Neoplasms
PubMed: 37752089
DOI: 10.1631/jzus.B2200589 -
Oral Diseases Nov 2023The management of oral potentially malignant disorders (OPMD) including oral leukoplakia (OL) is not currently structured according to agreed guidelines. The current...
The management of oral potentially malignant disorders (OPMD) including oral leukoplakia (OL) is not currently structured according to agreed guidelines. The current report presents survey data gathered from Oral Medicine Practitioners (OMPs) in Europe and Australia and is aimed to investigate attitudes and practice in the diagnosis, risk stratification and treatment of OL. In the presence of a clinical provisional diagnosis of OL, respondents reported always undertaking biopsy in 83% of cases, with most OMPs also relying on diagnostic adjuncts. The potential for malignant transformation is almost invariably assessed through epithelial dysplasia status, with other biomarkers described in the literature used less often. Active treatment of OL was considered mandatory by 20% of OMPs, while others reserve treatment for selected cases only. OMPs are mostly driven to active treatment by lesion-related features which are frequently jointly considered including lesion site, clinical appearance and dysplasia status. Inconsistent assessment was observed regarding mild dysplasia, lesion size, presence of unavoidable trauma, exposure to tobacco and patient age. Frequently observed geographical variations were seldom statistically significant. In agreement with previous surveys, a lack of consensus around the management of OL was observed, supporting claims from learned academies and societies for treatment guidelines aiming to reduce inter-practitioner variability.
Topics: Humans; Leukoplakia, Oral; Precancerous Conditions; Hyperplasia; Australia; Europe; Cell Transformation, Neoplastic
PubMed: 35792047
DOI: 10.1111/odi.14301 -
Modern Pathology : An Official Journal... Jul 2019Leukoplakia is a potential precursor of oral as well as laryngeal squamous cell carcinoma. Risk assessment of malignant transformation based on the grade of dysplasia of...
Leukoplakia is a potential precursor of oral as well as laryngeal squamous cell carcinoma. Risk assessment of malignant transformation based on the grade of dysplasia of leukoplakia often does not lead to reliable results. However, oral squamous cell carcinoma, laryngeal squamous cell carcinoma, and leukoplakia express single or multiple members of the melanoma-associated antigens A (MAGE-A) family, while MAGE-A are absent in healthy mucosal tissue. The present study aimed at determining if there is an association between the expression of MAGE-A in leukoplakia and malignant transformation to oral or laryngeal squamous cell carcinoma. Paraffin-embedded tissues of 205 oral and laryngeal leukoplakia, 90 corresponding tumors, and 40 healthy oral mucosal samples were included in the study. The grade of dysplasia of the leukoplakia samples was determined histopathologically. The leukoplakia samples were divided into lesions that transformed to oral and laryngeal squamous cell carcinoma (n = 91) and lesions that did not (n = 114) during a 5 years follow-up. The expression of MAGE-A3/6 and MAGE-A4 was analyzed by real-time RT-PCR. The expression of MAGE-A 1-4, 6, and 12 was determined by immunohistochemistry. A total of 59.3% of the transforming leukoplakia expressed at least one of the examined antigens as opposed to an expression rate of 3.5% of all non-transforming leukoplakia. There was no MAGE-A expression in healthy oral mucosa. The risk of malignant transformation was statistically significantly associated with MAGE-A expression in immunohistochemistry (p < 0.001) and real-time RT-PCR (MAGE-A3/6, p = 0.001; MAGE-A4, p = 0.002) analyses. There was no significant association between MAGE-A expression and the grade of dysplasia ("low-grade", D0/D1; "high-grade", D2/D3) in immunohistochemistry (p = 0.412) and real-time RT-PCR (MAGE-A3/6, p = 0.667; MAGE-A4, p = 0.756). It seems that the analysis of the MAGE-A expression profile may support the identification of leukoplakia at risk for malignant transformation. Therefore, efforts should be made to establish this analysis as a routine procedure in addition to conventional histopathology.
Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Case-Control Studies; Cell Transformation, Neoplastic; Female; Humans; Laryngeal Neoplasms; Leukoplakia, Oral; Male; Middle Aged; Neoplasm Grading; Neoplasm Proteins; Risk Assessment; Risk Factors; Squamous Cell Carcinoma of Head and Neck; Time Factors
PubMed: 30936424
DOI: 10.1038/s41379-019-0253-5 -
Journal of Cancer Research and... 2017Metabolomics is a core discipline of system biology focusing on the study of low molecular weight compounds in biological system. Analysis of human metabolome, which is...
CONTEXT
Metabolomics is a core discipline of system biology focusing on the study of low molecular weight compounds in biological system. Analysis of human metabolome, which is composed of diverse group of metabolites, can aid in diagnosis and prognosis of oral squamous cell carcinoma (OSCC).
AIM
The aim of the present study is to analyze and identify serum metabolites in oral leukoplakia and OSCC as a potential diagnostic biomarker and a predictor for malignant transformation of oral leukoplakia.
SUBJECTS AND METHODS
Serum metabolomic profile of patients diagnosed with oral leukoplakia (n = 21) and OSCC (n = 22) was compared with normal controls (n = 18) using quadrupole time of flight-liquid chromatography-mass spectrometry. MassHunter profile software was used for metabolite identification, and statistical analysis to assess the variation of the metabolites was performed using Mass Profiler Professional software. Statistical significance between the three groups was expressed using ANOVA (P < 0.05), and intergroup comparison was done using Student's t-test (P < 0.05).
RESULTS
Significant upregulation of estradiol-17-beta-3-sulfate, L-carnitine, 5-methylthioadenosine (MTA), 8-hydroxyadenine, 2-methylcitric acid, putrescine, and estrone-3-sulfate was seen in oral leukoplakia and OSCC than in normal controls. Furthermore, significant upregulation of 5,6-dihydrouridine, 4-hydroxypenbutolol glucuronide, 8-hydroxyadenine, and putrescine was evident in OSCC group than in oral leukoplakia.
CONCLUSION
Upregulation of L-carnitine, lysine, 2-methylcitric acid, putrescine; 8-hydroxyadenine; 17-estradiol; 5,6-dihydrouridine; and MTA suggests their diagnostic potential in oral leukoplakia and OSCC. Further, a significant upregulation of putrescine, 8-hydroxyadenine, and 5,6-dihydrouridine in OSCC than in oral leukoplakia indicates their potential role in predicting the malignant transformation of oral leukoplakia.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Female; Humans; Leukoplakia, Oral; Male; Metabolomics; Mouth Neoplasms; Prognosis
PubMed: 28862226
DOI: 10.4103/jcrt.JCRT_1233_16