Oral Premalignant Conditions Research Articles

MiRNAs as non-invasive biomarkers in the serum of Oral Squamous Cell Carcinoma (OSCC) and Oral Potentially Malignant Disorder (OPMD) patients

ObjectiveCell-free microRNAs have shown differential levels in the serum of individuals under disease conditions suggesting its potential to act as biomarkers. A population specific miRNA signature in oral cancer is reported in different studies. We aim to identify a set of serum specific miRNAs that may differentiate oral cancer, oral pre-malignant conditions from the healthy individuals. DesignWe investigated the levels of 24 miRNAs in the serum of 47 Oral squamous cell carcinoma (OSCC) patients, 20 patients with Oral potentially malignant disorders (OPMD) and 42 healthy controls from Eastern India. Small RNAs were isolated from serum samples followed by cDNA synthesis. Levels of miRNAs were determined using qRT-PCR. The sources of serum specific miRNAs were evaluated using GTEx-RNAseq and TCGA-HNSCC database. ResultsFive miRNAs, miR-483–5p, miR-31–5p, Let-7b-5p, miR-486–5p and miR-30e-5p showed significant elevation in OSCC patients. An Elastic-Net model with 4 miRNAs classified OSCC from healthy controls with 80 % sensitivity, 64.3 % specificity, and 72.4 % accuracy. Mir-483–5p and miR-31–5p was significantly overexpressed in OSCC tissues as well as significantly higher in the serum of Leukoplakia and Verrucous carcinoma patients suggesting their potential as early disease markers. MiR-483–5p showed a consistent elevated level in the serum/plasma of oral cancer patients across different population and was found to be tumour specific while, the rest of the miRNAs showed variable results across different studies. ConclusionsOur study suggested that the serum miRNAs in oral cancer and pre-malignant disorder conditions can be used as a non-invasive marker for screening of these oral conditions.

Insulin-like growth factor-I signaling plays a pivotal role in the development of oral premalignant lesions in patients with diabetes mellitus

<p>Diabetes mellitus is a disorder of the metabolic system that is diagnosed by hyperglycemia and glucose intolerance. Diabetic patients are frequently prone to developing oral health complications, such as being at a higher risk for developing oral precancerous conditions like lichen planus, leukoplakia, and erythroplakia. Insulin-like growth factor-I (IGF-I) is a peptide hormone with a structure similar to insulin and belongs to the family of growth factors that play a vital role in the development of embryonic, postembryonic, and normal physiological functions of the human body. IGF-I, through autophosphorylation of its receptor, activates the mitogen-activated protein kinases pathway that leads to the expression of IGF-I hormone. In oral premalignant conditions, like lichen planus, submucous fibrosis, leukoplakia, and erythroplakia, the levels of the IGF-I hormone are increased. Subsequently, IGF-I can be used as a marker for early detection of malignancy in oral premalignant lesions.</p>

A Comparative Study to Evaluate the Efficacy of Curcumin Lozenges (TurmNova®) and Intralesional Corticosteroids with Hyaluronidase in Management of Oral Submucous Fibrosis

This study aims to compare the efficacy of TurmNova® lozenges and its active ingredient "curcumin" as a low-cost, safe, and noninvasive chemopreventive agent with intralesional corticosteroids (with hyaluronidase) in the management of oral submucous fibrosis (OSMF). A total of 80 patients with group III OSMF (Khanna JN and Andrade NN classification) visiting the dental outpatient clinic of the Department of Oral Medicine and Radiology Rama Dental College Hospital and Research Center, Kanpur, were selected for the study. A total of 80 patients were randomly divided into two groups (40 participants each): group A to whom TurmNova® lozenges containing turmeric extract 100 mg along with clove oil 10 mg three times daily for 3 months were given and group B to whom intralesional infiltration of 2 mL dexamethasone (4 mg/mL) + hyaluronidase 1500 IU dissolved in 0.5 mL of 2% lignocaine twice a week for 3 months was given. Data were analyzed using the IBM SPSS Statistics, version 21 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, version 21.0. Armonk, New York: IBM Corp.) Results: Statistical analysis revealed that there was significant clinical improvement in mouth opening and subjective symptoms, like burning sensation/pain associated with the lesion and tongue protrusion in the group A as compared to group B. Curcumin (100 mg) in an innovative delivery system of lozenge results in a higher level of plasma curcumin level. The aforementioned dosages prevent its biotransformation and inactivation by the liver enzymes. Because of these properties, curcumin lozenges are safer, low-cost, and effective alternative treatment in contrast to the present traditional treatment. Further long-term, prospective, large-scale studies need to be done. Curcumin has a role in the treatment of oral premalignant conditions and acts as a very effective chemopreventive agent in the prevention of cancer.

Cause and Effect Relationship between Candida Spp. and Oral Premalignant Conditions: A Review

Cause and Effect Relationship between Candida Spp. and Oral Premalignant Conditions: A Review

In vivo Raman spectroscopic characteristics of different sites of the oral mucosa in healthy volunteers.

Investigate the biochemistry of in vivo healthy oral tissues through Raman spectroscopy. We aimed to characterize the biochemical features of healthy condition in oral subsites (buccal mucosa, lip, tongue, and gingiva) of healthy subjects. More specifically, we investigated Raman spectral characteristics and biochemical content of in vivo healthy tissues on Brazilian population. This characterization can be used to better define normal tissue and improve the detection of oral premalignant conditions in future studies. For spectroscopic analysis a Raman spectrometer (Kaiser Optical Systems imaging spectrograph Holospec, f / 1.8i-NIR) coupled with a laser 785nm, 60mW was used. Raman measurements were obtained by means of an optical fiber (EMVision fiber optic probe) coupled between the laser and the spectrometer. Three spectra per site were acquired from the lip, buccal mucosa, tongue, and gingiva of ten healthy volunteers. This resulted in 30 spectra per oral sub-site and in total 120 spectra. We report detailed biochemical information on these subsites and their relative composition based on deconvolution studies of their spectra. Finally, we also report classification efficiency of 61, 83, 41, and 93% for buccal, gingiva, lip, and tongue respectively after applying multivariate statistical tools. We quantitated the contribution of various biochemicals in terms of percentage, and this will enable comparison not only across anatomical sites but also across studies. Raman spectroscopy can rapidly probe tissue biochemistry of healthy oral regions. Moreover, the study suggests the possibility of using Raman spectroscopy combined with signal processing and multivariate analysis methods to differentiate the oral sites in healthy conditions and compare with pathological conditions in future studies. The spectral characterization of the healthy condition of oral tissues by a noninvasive, label-free, and real-time analytical techniques is important to create a spectral reference for future diagnosis of pathological conditions.

Raman exfoliative cytology for oral precancer diagnosis.

Oral premalignant lesions (OPLs) such as leukoplakia, erythroplakia, and oral submucous fibrosis, often precede oral cancer. Screening and management of these premalignant conditions can improve prognosis. Raman spectroscopy has previously demonstrated potential in the diagnosis of oral premalignant conditions (in vivo), detected viral infection, and identified cancer in both oral and cervical exfoliated cells (ex vivo). The potential of Raman exfoliative cytology (REC) in identifying premalignant conditions was investigated. Oral exfoliated samples were collected from healthy volunteers (n=20), healthy volunteers with tobacco habits (n=20), and oral premalignant conditions (n=27, OPL) using Cytobrush. Spectra were acquired using Raman microprobe. Spectral acquisition parameters were: λex: 785nm, laser power: 40mW, acquisition time: 15s, and average: 3. Postspectral acquisition, cell pellet was subjected to Pap staining. Multivariate analysis was carried out using principal component analysis and principal component-linear discriminant analysis using both spectra- and patient-wise approaches in three- and two-group models. OPLs could be identified with ∼77% (spectra-wise) and ∼70% (patient-wise) sensitivity in the three-group model while with 86% (spectra-wise) and 83% (patient-wise) in the two-group model. Use of histopathologically confirmed premalignant cases and better sampling devices may help in development of improved standard models and also enhance the sensitivity of the method. Future longitudinal studies can help validate potential of REC in screening and monitoring high-risk populations and prognosis prediction of premalignant lesions.

Alterations of serum lipid profile in oral submucous fibrosis

<p class="abstract"><strong>Background:</strong> Oral cancer is one of the most common form of malignancies in India. In many cases it develops at the site of premalignant lesion. Of all oral premalignant conditions, oral submucous fibrosis (OSMF) is of greater concern because of its disabling nature and relative greater chances of malignant transformation. This study is aimed to evaluate the serum lipid profile in OSMF patients as the change in lipid levels may have a diagnostic and prognostic role in the potentially malignant lesions. The present study aimed to evaluate the alteration in serum lipid profile in OSMF and to compare them with healthy controls and to correlate the relationship between pathogenesis of OSMF and lipid profile.</p><p class="abstract"><strong>Methods:</strong> It is a case control study. The study included 50 diagnosed cases of OSMF and 50 matched healthy controls. Fasting venous blood of 3 ml was collected in both cases and controls and serum was separate. Fasting serum lipid profile including total cholesterol (TC), very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL) and triglycerides (TG) were measured using automatic analyser. Statistical analysis was done using student 't' test .Pearson's correlation was performed to establish the relationship between study variables. </p><p class="abstract"><strong>Results:</strong> It was observed that there was statistically significant decrease in serum total cholesterol, TG, LDL, VLDL and HDL observed in patients with OSMF as compared to the control group (p<0.005).</p><p><strong>Conclusions:</strong> The low lipid levels associated with OSMF indicates that there is inverse relationship between oral cancer and serum lipid profile. Decrease in the lipid levels may be considered as a valuable biochemical marker in the early diagnosis and prognosis of oral malignancy. </p>

Level of serum lactate dehydrogenase in oral submucous fibrosis

<p class="abstract"><strong>Background:</strong> Oral cancer is one of the most common form of malignancies in India. In many cases it develops at the site of premalignant lesion. Of all oral premalignant conditions, oral submucous fibrosis (OSMF) is of greater concern because of its disabling nature and relative greater chances of malignant transformation. Transformation of normal tissue to premalignant lesion and further to oral cancer results in alteration in glycolytic pathway and hence the lactate dehydrogenase (LDH) levels. The aim of this study was to estimate the LDH levels in serum of subjects with OSMF and to compare them with healthy controls and to correlate the relationship between pathogenesis of OSMF and the LDH enzyme.</p><p class="abstract"><strong>Methods:</strong> It is a case control study. The study included 40 diagnosed cases of OSMF and 40 matched healthy controls. Venous blood of 3 ml was collected in both cases and controls. Serum was separated by centrifugation and LDH was estimated by using standard kits. Statistical analysis was done using student ‘t’ test. Pearson's correlation was performed to establish the relationship between study variables. </p><p class="abstract"><strong>Results:</strong> It was observed that serum LDH levels were significantly increased in cases of OSMF as compared to controls (p <0.005).</p><p><strong>Conclusions:</strong> Serum LDH was significantly increased in OSMF and can be used as a valuable biochemical marker in prognosis of OSMF.</p>

Serum lipid profile as a prognostic marker in oral submucous fibrosis

Introduction: Oral submucous fibrosis (OSMF) is the most prevalent precancerous condition in India, with high prevalence rates found in North Gujarat. In spite of the high prevalence and its potential to undergo malignant transformation, this condition has not been widely investigated with respect to the serum lipid levels. The changes in lipid profile have long been associated with cancer as lipids play a key role in the maintenance of cell integrity. Aim: To investigate the alterations and clinical significance of serum lipid profiles in OSMF patients. Materials and Methods: A total of 50 subjects were included in the study and divided into two groups. Group I consisted of 40 clinically diagnosed OSMF subjects and group II consisted of 10 healthy subjects. After taking a thorough history, clinical examination, and informed consent, all the patients were sent for lipid profile estimation, which consisted of (i) serum total cholesterol (TC), (ii) low density lipoprotein (LDL) cholesterol, (iii) high density lipoprotein (HDL) cholesterol, (iv) very low density lipoprotein (VLDL) cholesterol, and (v) serum triglycerides (TG). Results: The serum lipid levels were significantly lower in patients with OSMF than in the controls, which was most evident in stage IV OSMF. From the present results, it is evident that the level of serum lipids decreases with the progression of the disease. Conclusion: This study suggests that decrease in lipid levels may be considered as a useful marker in the early diagnosis of oral premalignant conditions like OSMF.

Comparative evaluation of genotoxicity by micronucleus assay in the buccal mucosa over comet assay in peripheral blood in oral precancer and cancer patients

Early detection and quantification of DNA damage in oral premalignancy or malignancy may help in management of the disease and improve survival rates. The comet assay has been successfully utilised to detect DNA damage in oral premalignant or malignancy. However, due to the invasive nature of collecting blood, it may be painful for many unwilling patients. This study compares the micronucleus (MN) assay in oral buccal mucosa cells with the comet assay in peripheral blood cells in a subset of oral habit-induced precancer and cancer patients. For this, MN assay of exfoliated epithelial cells was compared with comet assay of peripheral blood leucocytes among 260 participants, including those with oral lichen planus (OLP; n = 52), leukoplakia (LPK; n = 51), oral submucous fibrosis (OSF; n = 51), oral squamous cell carcinoma (OSCC; n = 54) and normal volunteers (n = 52). Among the precancer groups, LPK patients showed significantly higher levels of DNA damage as reflected by both comet tail length (P < 0.0001) and micronuclei (MNi) frequency (P = 0.0009). The DNA damage pattern in precancer and cancer patients was OLP < OSF < LPK < OSCC, and with respective oral habits, it was multiple habits > cigarette + khaini > cigarette smokers > areca + khaini > areca. There was no significant difference in the comet length and MNi frequency between males and females who had oral chewing habits. An overall significant correlation was observed between MNi frequency and comet tail length with r = 0.844 and P < 0.0001. Thus, the extent of DNA damage evaluation by the comet assay in peripheral blood cells is perfectly reflected by the MN assay on oral exfoliated epithelial cells, and MNi frequency can be used with the same effectiveness and greater efficiency in early detection of oral premalignant conditions.

A review of Indian literature for association of smokeless tobacco with malignant and premalignant diseases of head and neck region.

In India, about 60% of tobacco users use smokeless tobacco (ST) alone. Head and neck squamous cell carcinoma is one of the most common cancers in India. International Agency for Research on Cancer (IARC) monograph (Vol 89) found a significant association between ST use and oral cancer. However, only a few articles from India were included in this monograph. To overcome this lacuna, we have reviewed the articles published from India investigating the association between ST use and malignant and premalignant diseases of head and neck region. Data collection has been performed by computer-aided search of the MedLine and PubMed databases using different combinations of the key words. For malignant lesions, only cohort and case control studies were considered for review. For premalignant lesions and dental diseases other than case control studies, some cross-sectional studies have also been reviewed. Studies found a significant association between ST use and cancer of the oral cavity. The association was stronger for the buccal mucosa compared to tongue and for females compared to males. Significant association noted between cancer of the hypopharynx and oropharynx with ST use but no definitive association noted for cancer of the larynx and nasopharynx. Some dental disease and oral premalignant conditions were also associated with ST use. Indian studies suggest ST use is strongly associated with cancer of the oral cavity, oropharynx and hypopharynx.

Thalidomide: features and potential significance in oral precancerous conditions and oral cancer

Thalidomide was originally marked as a sedative and anti-emetic, but was withdrawn after severe teratogenic effects had been discovered. More recently it has been claimed to alleviate a wide range of inflammatory disorders and malignancies. Studies showed that thalidomide might play a role in the management of some oral premalignant conditions and its potential to be an adjunct in the prevention of oral cancer. The aim of this study is to summarize the characteristics and feasibility of thalidomide in the development and prevention of oral precancerosis, and to draw attentions of researchers to its therapeutic potential in oral cancer. Databases were searched on the basis of PubMed and EMbase. Thalidomide associated with the oral lichen planus, chronic discoid lupus erythematosus (CDLE) and oral cancer were assessed. We have summed up the structure and pharmacokinetics of thalidomide, possible role of thalidomide in cancer prevention, as well as the recent data concerning its effects in prevention of oral premalignant conditions and potential for the treatment of oral cancer. Therapeutic effects of thalidomide in oral lichen planus and CDLE have been discussed by clinical trials. And increasing evidences from in vitro and in vivo experiments show that thalidomide is a promising anticancerous agent for oral cancer, which should be paid attention to. It is necessary to perform more studies and clinical trials of large sample size to clarify underlying mechanisms and demonstrate the potential roles of thalidomide in clinical routine management of oral diseases.

Self‐awareness of premalignant oral lesions among veterans attending six U.S. Veterans Affairs Medical Centers

Early identification is key to reducing the morbidity and mortality of oropharyngeal cancer. This study identified factors associated with self-awareness among patients newly diagnosed with a premalignant oral lesion. Data describing sociodemographics, medical/dental histories, tobacco/alcohol use and oral health were obtained by questionnaire and clinical examination of 73 veterans at six U.S. Veterans Affairs Medical Centers. Lesion types included homogenous and non-homogenous leukoplakia, smokeless tobacco lesion (STL), papilloma, lichen planus and erythroplakia. Prior to diagnosis, 29 subjects (39.7%) were unaware of their lesion. In bivariate analyses, lesion self-awareness was associated with anatomic location, multifocal/generalized appearance, pain, oral sores, and cigar use (p<0.05). Awareness varied with lesion diagnosis and was more likely with STL and less likely with homogenous leukoplakia (p<0.05). In multivariate analyses, awareness was predicted by the presence of a lesion on easily visible mucosa (adjusted odds ratio, OR=11.2) and a history of mouth sores (OR= 11.2). These findings identified marked variations in patient self-awareness of oral premalignant conditions.

Rapid progression from oral leukoplakia to carcinoma in an immunosuppressed liver transplant recipient

Immunosuppression used to avoid graft rejection in solid organ transplantation recipients leads to a variety of side-effects, and an increased rate of infections and de novo malignancies. Oral conditions usually associated with immunosuppressive drugs include fungal and viral infection, and lip lesions, but intra-oral carcinoma has not been reported as having a high incidence. This report deals with a male liver transplant recipient receiving FK506 (5 mg/day) and prednisone (20 mg/day) who was diagnosed with a homogeneous leukoplakia on the floor of the mouth 4 months after transplantation, and 4 months later with a squamous cell carcinoma growth at the site of this lesion. The rapid transformation of the lesion suggests that in patients who display oral premalignant conditions, immunosuppression must be considered as an important risk factor for oral cancer.