Oral Precancerous Lesions Research Articles

Knowledge, Attitude, and Practice regarding Management of Oral Cancer and Oral Precancerous Lesions among Oral Surgeons in Chhattisgarh State, India

Knowledge, Attitude, and Practice regarding Management of Oral Cancer and Oral Precancerous Lesions among Oral Surgeons in Chhattisgarh State, India

Alteration in serum lipid profile pattern in oral cancer and oral submucous fibrosis patients

Introduction: Oral cancer is the sixth most common cancer worldwide. Oral submucous fibrosis (OSMF) is one of the commonest potentially malignant disorders in India. Hypolipidemia can be considered as one of the biochemical marker in early detection of cancer. Context: This study is undertaken to evaluate the role of serum lipids as tumor markers in the diagnosis of oral precancerous lesions and oral cancer. Aim: To determine the significance of total cholesterol (TC), high-density lipid cholesterol (HDLC) triglycerides as tumor markers in the diagnosis of OSMF. Materials and Methods: Study was conducted in outpatient Department of Oral medicine and Radiology. Thirty cases each of clinically diagnosed and histopathologically confirmed oral squamous cell carcinoma (OSCC), OSMF, and 30 controls were selected and serum lipid analysis was done. Statistical Analysis Used: Unpaired t-test (student t-test) was used for statistical analysis in this study. Results: The serum lipid level was statistically significantly lowered in patients with oral cancer and OSMF when compared with normal control group. There is an inverse relationship between serum lipid profile pattern in oral cancer as well as in OSMF. Conclusions: The serum lipid level was statistically significantly lowered in patients with oral cancer and OSMF when compared with normal control group. The lower serum lipid status may be considered as a useful biochemical marker for early detection of cancer.

Immunohistochemically Detection of Angiogenesis in Oral Pre-Cancerous Lesions Compared with Oral Invasive Carcinomas

BackgroundAngiogenic activity is an important event in oral carcinogenesis. During transition of normal oral mucosa to different grades of dysplasia and to invasive carcinoma, significant increase of vascularity occurs. Angiogenesis can be determined by immunohistochemical assessment of several endothelial cell markers like Endogelin (CD 105), expressed in activated endothelial cells and associated with neovasculature, and the vascular endothelial growth factor (VEGF). This study was conducted to evaluate angiogenic activity in oral precancerous lesions compared with oral invasive carcinomas by immunohistochemical staining of VEGF and CD 105 proteins.MethodsIn the present cross-sectional study, 20 normal, 20 pre-cancerous mucosa and 20 oral invasive carcinoma samples were immunohistochemically stained. Positive cells were counted in each section and micro vessel density (MVD) was determined. The data were statistically analyzed by Mann-Whitney and Kruskal-Wallis tests, with a P-value ≤0.05 considered significant.ResultsThe mean expression value for VEGF was 24.6 in oral invasive carcinoma, 16.4 in precancerous mucosa and 15.5 in normal mucosa, with no significant differences between the latter two. Endoglin was negative in all normal mucosa samples, but had scores of 7.58 for precancerous mucosa and 19.4 in oral invasive carcinoma specimens. MVD was significantly higher in SCC than in dysplastic mucosa.ConclusionOral invasive carcinoma has more angiogenic activity in comparison with pre-cancerous lesions and normal mucosa. Given the high expression of CD105 positive vessels in malignant lesions, we can argue that determination of mean vessel density (MVD) by application of the CD105 marker could be a useful parameter to differentiate cancerous from pre-cancerous lesions.

Interaction between transcriptional factor E26 transformation specific 1 and peroxiredoxin 1 in nicotine-induced oral precancerous lesion cells

Objective: To investigate the interaction between nuclear transcriptional factor E26 transformation specific 1 (Ets1) and peroxiredoxin 1 (Prx1) in nicotine-induced oral precancerous lesion cells. Methods: Human oral precancerous lesion dysplastic oral keratinocyte (DOK) cells were cultured and divided into nicotine group, control group, knockdown group and knockdown control group. The nicotine group, knockdown group and knockdown control group were treated with 1 μmol/L nicotine for 7 days while the control group was untreated. Western blotting, co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) were performed to detect Prx1 and Ets1 protein expression, Prx1 and Ets1 protein interaction, combined activity of Ets1 with PRDX1 gene promoter region in nicotine group and control group DOK cells. In nicotine group, DOK cells were transfected with siRNA or lentivirus to knockdown Ets1 and Prx1 expression. Prx1 and Ets1 protein expression was examined by Western blotting. Results: Nicotine increased the expression of Prx1 and Ets1 protein in DOK cells. The relative expression of Prx1 and Ets1 was 0.71±0.02, 0.12±0.01 in nicotine group and 0.53±0.06, 0.01±0.01 in control group (P=0.009, P=0.000). Co-IP showed that Prx1 could form protein complex with Ets1. The expression of Prx1 and Ets1 complex protein was increased in nicotine group. ChIP revealed that nicotine upregulated the combination of transcriptional factor Ets1 with PRDX1 gene promoter region, and the enrichment fold was 80.9±19.7 in nicotine group and 13.8±1.2 in control group (P=0.004). Ets1 and Prx1 protein expression was knocked down. The relative expression of Ets1 and Prx1 was 0.60±0.06, 0.48±0.03 in knockdown group and 0.83±0.08, 0.80±0.06 in knockdown control group (P=0.016, P=0.002). Ets1 knockdown suppressed the expression of Prx1 (P=0.002). Conversely, Prx1 knockdown also inhibited the expression of Ets1 significantly (P=0.000). Conclusions: In oral precancerous lesion cells, Ets1 directly regulates Prx1 expression and nicotine might promote the development of oral precancerous lesion by magnifying the positive feedback signal pathway between Ets1 and Prx1.

356P - Betel nut chewing habits and risk of precancerous oral lesions among Paniya tribes of Wayanad, India: A cross sectional study

356P - Betel nut chewing habits and risk of precancerous oral lesions among Paniya tribes of Wayanad, India: A cross sectional study

P3.06-001 Tobacco Use, Awareness and Oral Health among Kanchipuram Silk Weavers, Tamil Nadu, India

India is one of the world’s largest producers of textile and garments. Kanchipuram is a city in Indian state of Tamil Nadu known for saree, which is traditionally made by weavers from Kanchipuram popularly known as kanjivaram sari. The silk weavers are considered as the master weaver of Gods. The silk is also known for its quality and craftsmanship, which has helped earn its name globally. The people living around Kanchipuram take weaving as their main profession. Weaving being a sedentary work, tobacco has been used by this community as an entertainment factor to ward off boredom. Till date, there are no studies that have been conducted on the oral health status of silk weavers. Hence this study was contemplated with an aim to assess the tobacco use and its awareness among silk weavers. A cross-sectional descriptive study was conducted to assess the tobacco use, its awareness and oral examination among 400 silk weavers at Kanchipuram, India. Silk weavers aged 18 to 75 years who were involved in this occupation for more than 5years were included. Data was collected using a survey ProForma which comprised of a questionnaire and WHO Oral Health Surveys – Basic Methods ProForma(1997). .Results showed that among 400 study populations, 57% had no formal education. Of those who had tobacco habit - 26% smoked beedi, 10.9% smoked cigarette, 65% chewed raw tobacco, 18% chewed Hans and 28% had a combination of smoking and smokeless tobacco usage. 34% of oral precancerous lesions were observed. The reason for practicing these habits were as a measure to combat boredom, relieving stress and body pain after work, and the lack of awareness of the hazards of the materials used. From the results of this study it may be concluded that the silk weavers were characterized by a lack of awareness about oral health, high prevalence of tobacco use and limited access to health services. Prevalence of oral mucosal lesions in the study population was due to tobacco usage and alcohol consumption and lack of awareness regarding the deleterious effects of the products used.

Overexpression of immunomodulatory mediators in oral precancerous lesions

Human leukocyte antigen (HLA) G and E, programmed cell death 1 ligand 1 (PD-L1), IL-10 and TGF-β are proteins involved in failure of the antitumor immune response. We investigated the expression of these immunomodulatory mediators in oral precancerous lesions (oral leukoplakia-OL; n=80) and whether these molecules were related to the risk of malignant transformation. Samples of normal mucosa (n=20) and oral squamous cells carcinoma (OSCC, n=20) were included as controls. Tissue and saliva samples were analyzed by immunohistochemistry and ELISA respectively. Fifteen OL samples showed severe dysplasia (18.7%) and 40 samples (50%) presented combined high Ki-67/p53. Irrespective of the degree of epithelial dysplasia and the proliferation/apoptosis index of OL, the expression of HLA-G, -E, PD-L1, IL-10, TGF-β2 and -β3 was higher to control (P<0.05) and similar to OSCC (P>0.05). The number of granzyme B+ cells in OL was similar to control (P=0.28) and lower compared to OSCC (P<0.01). Salivary concentrations of sHLA-G, IL-10 and TGF-β did not allow for a distinction between OL and healthy individuals. Overexpression of immunosuppressive mediators in the OL reflects the immune evasion potential of this lesion, which is apparently independent of at cytological and proliferation/apoptosis status.

Nicotine suppresses apoptosis by regulating α7nAChR/Prx1 axis in oral precancerous lesions.

Nicotine, a tumor promoter in tobacco, can increase Peroxiredoxin (Prx1) and nicotinic acetylcholine receptors (nAChRs) in oral squamous cell carcinoma (OSCC). In the present study, we investigate the effects of nicotine in oral precancerous lesions focusing on apoptosis and nAChR/Prx1 signaling. We detected expression of Prx1, α3nAChR, α7nAChR, phosphorylation of mitogen-activated protein kinases (MAPK) and apoptosis in dysplastic oral keratinocyte (DOK) cells as well as in 4-nitroquinoline 1-oxide (4NQO) or 4NQO + nicotine – induced oral precancerous lesions in Prx1 wild-type (Prx1+/+) and Prx1 knockdown (Prx1+/-) mice. In DOK cells, Prx1 knockdown and blocking α7nAChR activated apoptosis, and nicotine increased the expression of Prx1, α3nAChR and α7nAChR, and inhibited MAPK activation. Moreover, nicotine suppressed apoptosis depending on Prx1 and α7nAChR in DOK cells. In animal bioassay, nicotine and Prx1 promoted growth of 4NQO-induced precancerous lesions in mouse tongue. 4NQO plus nicotine suppressed MAPK activation in Prx1 wild-type mice but not in Prx1 knockdown mice. Our data demonstrate that nicotine inhibits cell apoptosis and promotes the growth of oral precancerous lesions via regulating α7nAChR/Prx1 during carcinogenesis of OSCC.

口腔前癌病変および扁平上皮癌における増殖細胞核抗原 （PCNA）と p53 蛋白の発現に関する免疫組織化学的研究

口腔前癌病変および扁平上皮癌における増殖細胞核抗原 （PCNA）と p53 蛋白の発現に関する免疫組織化学的研究

Expression of immunoregulatory molecules PD-L1 and PD-1 in oral cancer and precancerous lesions: A cohort study of Japanese patients

ObjectiveAn association of the programmed cell death-1 (PD-1) and its ligand PD-L1 with various types of malignant tumors has been established. This study aimed to investigate the role of the PD-L1/PD-1 pathway in oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPL). Materials and methodsWe examined 106 OSCC and 79 OEPL specimens for PD-L1 and PD-1 expression by immunohistochemistry. The results were compared with clinicopathological features of OSCC patients. ResultsIn OSCC and OEPL specimens, PD-L1 expression was detected predominantly in epithelial or carcinoma cells, whereas PD-1 expression was found mainly in infiltrating or stromal lymphocytes. Seventy-two OSCC (67.9%) and 21 OEPL (26.6%) specimens were positive for PD-L1, and 73 OSCC (68.9%) and 23 OEPL (29.2%) specimens were positive for PD-1. PD-L1 and PD-1 expression levels were significantly different between OEPL and OSCC specimens (P < 0.001). There were significant positive correlations between PD-L1 and PD-1 expression in OEPL and OSCC specimens (P < 0.001). PD-L1 and PD-1 immunoreactivity was significantly associated with tumor size (P < 0.05). PD-L1 and PD-1 immunoreactivity in cases with advanced TNM staging was significantly higher than that in low staging cases (P < 0.01). There were significant correlations between PD-L1 and PD-1 expression in OSCC specimens and pathological variables such as stromal lymphocytic reaction (P < 0.05) and invasion depth (P < 0.01). ConclusionPD-L1 and PD-1 immunohistochemical status may be related to carcinogenesis, tumor progression, and prognosis in oral epithelial lesions. Agents targeting PD-1 and PD-L1 might be useful for OSCC treatment.

Role of lycopene in the prevention of oral precancerous lesions. A review

Objective. To systematically review the methodology and results of clinical trials conducted on oral precancer patients using lycopene. Methods. An internet search using google search engine including key words -''lycopene, oral submucous fibrosis oral leukoplakia and oral cancer''- was done Full text articles in English language of all the clinical trials that were published in journals from the year 2004 to 2016 were obtained and evaluated. Results. The data available from the clinical trials were analyzed and presented under broad headings of sample size, duration of study, dosage and results and presented in tabular form. Conclusions. Lycopene is a promising candidate in reducing cancer and oral diseases in human beings. This review discusses the benefits of lycopene in prevention of different oral diseases.

Programmed death ligand 1 (PD-L1) expression and tumor microenvironment: Implications for patients with oral precancerous lesions

ObjectivesCancer immunoediting represents a relatively novel concept attempting to explain the process of tumor escape from the host immune system response. Here, we attempted to elucidate the role of programmed death ligand 1 (PD-L1), the tumor microenvironment, and tumor escape mechanisms that allow malignant transformation of oral precancerous lesions. Materials and methodsPatients with oral precancerous lesions managed at the Nara Medical University Hospital, Japan, (n=120) were enrolled in this study. Epithelial dysplasias were graded by experienced pathologists, and subepithelial PD-L1-, CD163-, and CD8-positive cells were counted in the superficial lamina propria of oral mucosa. Epithelial PD-L1 expression was evaluated according to the staining intensity. The association of clinicopathological factors with epithelial dysplasia, malignant-free survival time, and significance of risk factors for malignant transformation were determined. ResultsMultivariate analysis showed that the subepithelial CD163-positive cell count was the only significant risk factor for high-grade epithelial dysplasia (P<0.001), while subepithelial CD163- and PD-L1-positive cell counts, and epithelial PD-L1 positivity were significantly associated with malignant-free survival (P=0.004, 0.04, and <0.001, respectively). Subepithelial PD-L1-positive cell count and epithelial PD-L1 positivity were significantly associated with malignant transformation (P=0.01 and 0.04, respectively). ConclusionOur results indicate that PD-L1-expressing dysplastic epithelial and recruited subepithelial cells in oral precancerous legions may evade the host immune system, and that the inhibition of PD-1/PD-L1 pathway may potentially prevent malignant transformation of oral precancerous legions as well as can treat advanced cancers.

Novel quantitative analysis of autofluorescence images for oral cancer screening

ObjectivesVELscope® was developed to inspect oral mucosa autofluorescence. However, its accuracy is heavily dependent on the examining physician’s experience. This study was aimed toward the development of a novel quantitative analysis of autofluorescence images for oral cancer screening. Materials and methodsPatients with either oral cancer or precancerous lesions and a control group with normal oral mucosa were enrolled in this study. White light images and VELscope® autofluorescence images of the lesions were taken with a digital camera. The lesion in the image was chosen as the region of interest (ROI). The average intensity and heterogeneity of the ROI were calculated. A quadratic discriminant analysis (QDA) was utilized to compute boundaries based on sensitivity and specificity. Results47 oral cancer lesions, 54 precancerous lesions, and 39 normal oral mucosae controls were analyzed. A boundary of specificity of 0.923 and a sensitivity of 0.979 between the oral cancer lesions and normal oral mucosae were validated. The oral cancer and precancerous lesions could also be differentiated from normal oral mucosae with a specificity of 0.923 and a sensitivity of 0.970. ConclusionThe novel quantitative analysis of the intensity and heterogeneity of VELscope® autofluorescence images used in this study in combination with a QDA classifier can be used to differentiate oral cancer and precancerous lesions from normal oral mucosae.

Detection of genome mutations in high risk oral pre-cancer lesions

Detection of genome mutations in high risk oral pre-cancer lesions

Determinants of Tobacco Use and Prevalence of Oral Precancerous Lesions in Cab Drivers in Bengaluru City, India.

Background:Tobacco is a most important risk factor for various types of cancer as well as some noncommunicable disease. Around 34.6% of Indian population consume tobacco. The tobacco consumption is higher in some vulnerable population such as drivers, daily wage laborers, and policemen. Tobacco consumption is known to cause oral cancers, and screening for oral cancer in these individuals is known to reduce mortality from cancer. The study was designed to assess the determinants of tobacco use and the prevalence of oral precancerous lesions in cab drivers.Methods:This is a cross-sectional study among cab drivers at prepaid taxi counters in Bengaluru city. A total of 450 cab drivers were enrolled in the study, of which 225 cab drivers were interviewed during morning hours and remaining half at night time using a semi-structured questionnaire. All were screened for oral cancer/precancerous lesions.Results:Nearly 70.88% of cab drivers were consuming tobacco in any form. Long working hours, working at night, and family members consuming tobacco were significant risk factors for tobacco use among cab drivers. Forty-eight drivers were detected to have oral precancerous lesions.Conclusions:It was very evident that long hours of driving and infrequent shifts played a greater role in acquiring the habit. Behavioral counseling and new laws need to be formed to limit the working hours in drivers to have an effective tobacco control.

Evolution of oral neoplasm in an andalusian population (Spain).

BackgroundHead and neck cancer are one of the most common neoplasm pathologies in humans. The aim of this study was to analyze the type, characteristics, treatment and evolution of oral neoplasm or precancerous lesion in a sample of Andalusian population (Spain) derived from the Oncology Rehabilitation Hospital Unit during a period of 20 years.Material and MethodsA retrospective descriptive study was carried out during the years 1991 and 2011 analyzing the type, characteristics, treatment and follow-up of oral neoplasm in the Oral and Maxillofacial Surgery Unit of the Universitary Hospital “Virgen del Rocío”. The inclusion criteria were patients whose underlying pathology was any type of benign or malignant neoplasm or presence of precancerous lesion that, after treatment, had been referred to the Prosthetic Rehabilitation Unit.ResultsOf the initial analyzed sample of 60 patients, only 45 patients met the inclusion criteria. Of the final sample analyzed, 31 subjects were men (68.9%) and 14 women (31.1%) (p = 0.0169). The mean age of the sample was 57 years ± 13.83, been more frequently in older people with more than 50 years (73.3%) (p = 0.0169). The most common type of neoplasm was epidermoid carcinoma (64.4%). The site most frequently found in squamous cell carcinoma was the floor of the mouth (31%). The most frequent treatment modality was surgery with postoperative radiotherapy (42.2%). All patients had a minimum follow-up of 5 years, and a recurrence in this period was identified in 11.1% of the sample. Multivariate logistic regression showed a statistically significant association for the variables age (p = 0.0063) and smoking (p = 0.0434).ConclusionsEpidermoid carcinoma is the most frequent tumor in the oral cavity, where increase age and smoking are confirmed as associated risk factors. Key words:Head and neck neoplasm, Squamous cell carcinoma, epidermoide carcinoma, epidemiology, risk factors.

Individualized five-year risk assessment for oral premalignant lesion progression to cancer

The standard of care for premalignant lesion risk assessment is dysplasia grading by histopathology. With significant overlap between dysplasia grades and high inter- and intraobserver variations, histopathology dysplasia grading alone is not a useful prognostic tool. Our aim is to investigate whether a method for quantitatively assessing S100A7, a prognostic biomarker, using image analysis can better predict clinical outcome in cases with oral dysplasia. Using the Visiopharm image analysis system, we analyzed a cohort of 150 oral biopsy samples to build and test Straticyte, a model for individualized assessment of the 5-year risk of progression of oral precancerous lesions to invasive squamous cell carcinomas. Straticyte classified lesions more accurately than histopathological dysplasia grading for risk to progression to cancer over the following 5years. The sensitivity of low-risk versus intermediate- and high-risk Straticyte groups was 95% compared to 75% for mild versus moderate and severe dysplasia. Furthermore, the negative predictive value for low-risk versus intermediate- and high-risk Straticyte groups was 78% compared to 59% for mild versus moderate and severe dysplasia. By quantitatively assessing S100A7, Straticyte better defines the risk for developing oral squamous cell carcinoma than histopathological dysplasia grading alone.

Urine metabolic profiling for the pathogenesis research of erosive oral lichen planus

ObjectiveOral lichen planus (OLP) is a relatively common chronic immune-pathological and inflammatory disease and potentially oral precancerous lesion. Erosive OLP patients show the higher rate of malignant transformation than patients with non-erosive OLP. Identifying the potential biomarkers related to erosive OLP may help to understand the pathogenesis of the diseases. MethodsMetabolic profiles were compared in control and patient subjects with erosive OLP by using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods An integrative analysis was used to identify the perturbed metabolic pathways and pathological processes that may be associated with the disease. ResultsIn total, 12 modulated metabolites were identified and considered as the potential biomarkers of erosive OLP. Multiple metabolic pathways and pathological processes were involved in erosive OLP. ConclusionThe dysregulations of these metabolites could be used to explain the pathogenesis of the disease, which could also be the potential therapeutic targets for the disease.

1391P - Oral health disparities among privileged and underprivileged tribes of South India - a study on precancerous oral lesions prevalence

The tribal populations throughout India have remained socially and culturally alienated from mainstream Indian society until developmental and conservation activities in tribal areas forced interactions between them. Precancerous oral lesion is a major public health problem among South Indian tribes in Kerala state. The aim of this study was to explore oral health disparities among the underprivileged Paniya and the privileged Kurichiya tribes of Wayanad, South India from the Precancerous oral lesions perspective. A cross sectional survey was done among 600 Kurichiya and 400 Paniya tribal populations of Wayanad District, India from January 2013 to June 2013 after approval from the Institutional ethical committee. A pretested structured questionnaire was used to collect data regarding study variables. Oral health survey form was used to record the oromucosal status of the study population after obtaining informed consent. In this study Precancerous oral lesions was found to be far more prevalent among the underprivileged Paniyas than among the privileged Kurichiyas (P < 0.0001). The prevalence of leukoplakia was found to be 42% amongst the Paniyas. This was much higher than the 2% found among the Kurichiyas.Among the Paniyas a statistically significant relationship was observed between Precancerous oral lesions and poor access to oral health care (P< 0.001). Oral cancer and precancerous oral lesions were at a very high among underprivileged Paniya community.Prevalence of precancerous oral lesions in the study population was due to tobacco usage and alcohol consumption and lack of awareness regarding the deleterious effects of the products used. Regular oral examination by dental professionals, dental health education and motivation to maintain oral hygiene should be insisted to improve the oral health status of this community.

Inter-laboratory consistency and variability in the buccal micronucleus cytome assay depends on biomarker scored and laboratory experience: results from the HUMNxl international inter-laboratory scoring exercise.

The buccal micronucleus cytome (BMNcyt) assay in uncultured exfoliated epithelial cells from oral mucosa is widely applied in biomonitoring human exposures to genotoxic agents and is also proposed as a suitable test for prescreening and follow-up of precancerous oral lesions. The main limitation of the assay is the large variability observed in the baseline values of micronuclei (MNi) and other nuclear anomalies mainly related to different scoring criteria. The aim of this international collaborative study, involving laboratories with different level of experience, was to evaluate the inter- and intra-laboratory variations in the BMNcyt parameters, using recently implemented guidelines, in scoring cells from the same pooled samples obtained from healthy subjects (control group) and from cancer patients undergoing radiotherapy (treated group). The results indicate that all laboratories correctly discriminated samples from the two groups by a significant increase of micronucleus (MN) and nuclear bud (NBUD) frequencies and differentiated binucleated (BN) cells, associated with the exposure to ionizing radiation. The experience of the laboratories was shown to play an important role in the identification of the different cell types and nuclear anomalies. MN frequency in differentiated mononucleated (MONO) and BN cells showed the greatest consistency among the laboratories and low variability was also detected in the frequencies of MONO and BN cells. A larger variability was observed in classifying the different cell types, indicating the subjectivity in the interpretation of some of the scoring criteria while reproducibility of the results between scoring sessions was very good. An inter-laboratory calibration exercise is strongly recommended before starting studies with BMNcyt assay involving multiple research centers.