Quantification of CD44, Epidermal Growth Factor Receptor, E-cadherin, and Vimentin in Oral Squamous Cell Carcinoma as an Indicator for Disease Progression and Survival.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is commonly associated with early recurrence due to loco-regional spread. Changes at the cellular levels can be studied and are often an early indicator of disease progression, much before clinical symptoms become visible. Identifying parameters indicating an impending recurrence could help the clinician plan for early treatment and thus improve survival. Hence, this study aimed to determine if quantifiable parameters could be established for CD44, epidermal growth factor receptor (EGFR), E-cadherin, and vimentin and if these values could be used as indicators of disease progression on follow-up. METHOD: A total of 150 cases of OSCC were included in the study and followed up linearly for 36 months. Paraffin-embedded tissues of these cases were subjected to immunohistochemical analysis for reactivity to CD44, EGFR, E-cadherin, and vimentin. The immunohistochemical staining correlated with the tumor's clinical and histological grade. Statistical analysis was done using SPSS Statistics version 17 (IBM Corp., Armonk, NY, USA). The receiver operating characteristics (ROC) were deployed for determining the correlation of recurrence with the immunohistochemistry (IHC) markers, while the Kaplan-Meier curve was employed for survival analysis. RESULTS: A recurrence rate of 70.0% and a survival rate of 66.6% were noted after a follow-up period of three years. It was found that both CD44 and E-cadherin decreased with the grade of tumor, while EGFR and vimentin increased with tumor de-differentiation. The E-cadherin was found to be the best predictor of recurrence and survival among all the four markers. CONCLUSION: The cut-off values could be identified for all four biomarkers, which on follow-up proved to be a valuable tool with a high sensitivity and specificity for predicting recurrence and three-year survival in patients with OSCC.

A prospective study of circulating estrogen in oral leukoplakia and oral squamous cell carcinoma.

BACKGROUND: Reports suggested that hormone replacement therapy decreased the incidence of squamous cell carcinoma (SCC) of the oral cavity. AIM: The aim of this study was to analyze and quantify the serum 17ß-estradiol (E2) level by chemiluminescence immunoassay in four groups, Group I (control group with no habit of tobacco and areca), Group II (control group with a habit of tobacco and areca), Group III (potentially malignant disorder-leukoplakia), and Group IV (oral squamous cell carcinoma (OSCC)). It was the first study to evaluate E2 in four study groups with and without the habit of tobacco. METHOD: The serum analysis was carried out in Cobas e411 analyzer by electrochemiluminescence immunoassay analysis. RESULTS: As per the Kruskal--Wallis test, statistically significant rise in estradiol levels in Group IV as in comparison to Group III as compared with Groups II and I. CONCLUSION: This study proved that irrespective of the gender bias, the female sex hormone, estradiol levels were significantly raised in OSCC patients. This study suggests that E2 may play a vital role in determining the patient prognosis in OSCC with tobacco habit. The confounding results of this preliminary study opened up new advents emphasizing the role of E2 in OSCC. The role of E2 in estrogen receptor regulation can also be a subject of study for targeted therapies in improving the patient's prognosis.

Malignant transformation in oral submucous fibrosis: Tertiary level evidence: An umbrella review.

OBJECTIVES: An umbrella review is a systematic review of systematic reviews, which provides a tertiary level of evidence. This umbrella review of systematic reviews and meta-analysis (SR-MA) aimed to determine the proportion of oral cancer (OC) development in oral submucous fibrosis (OSF) patients. MATERIALS AND METHODS: We searched electronic databases including PubMed, Scopus, Web of Science, Cochrane and grey literature. Two reviewers independently screened abstracts and assessed for eligible papers. The methodological quality of SR-MA was evaluated using AMSTAR2, and we also checked the quality of evidence of the included papers. RESULTS: Out of 454 papers identified in the primary search, 105 underwent eligibility screening. Inclusion criteria were met by four SR-MA. OC ratios ranged between 4.2% and 6% for OSF. Substantial heterogeneity was observed for this outcome in all four MA (I2 = 71.31% to 86.37%). None of the SRs assessed the quality of evidence, and half of them were judged to be of critically low methodological quality. CONCLUSION: There is lack of quality of evidences and critically low methodological quality among SRs and MA leading to substantial heterogeneity. However, due to potentially malignant nature, OSF patients should be monitored carefully for early detection of OC.

Heterogeneity of outcome measures in the clinical trials of treatment for oral submucous fibrosis-Systematic review.

OBJECTIVE: This systematic review was performed to evaluate the range of outcome measures used in interventional trials for oral submucous fibrosis (OSF). MATERIALS AND METHODS: PubMed, Scopus, and Cochrane databases were searched to identify randomized controlled trials (RCTs) published from 2004 to 2018 about OSF treatment. All the outcome measures and measurement methods mentioned in the trials were extracted and analyzed. RESULTS: Out of 120 published papers, 12 RCTs that met the inclusion criteria were included. A total of 38 single outcome measures and 29 composite outcome measures were considered under four different outcome domains, of which clinical symptoms and clinical response were the most commonly used. The linear measurement of mouth opening (11 trials; 91.66%) and Visual Analogue Scale (10 trials, 83.33%) were the predominant measurement methods. CONCLUSIONS: This systematic review highlights the high heterogeneity in outcome measures in therapeutic RCTs of OSF. This lack of widely agreed standard outcome measures in OSF is a great concern as it prevents the comparison of studies and meta-analyses to gather evidence. There is a dire need of establishing a core outcome set for reporting in the future clinical trials that may help facilitate treatment choice for OSF to improve life quality of patients.

Ki-67, CD105, and α-smooth muscle actin expression in oral squamous cell carcinoma corresponds with different forms of tobacco consumption habits.

Background: Association with variety of etiological agents is one of the characteristic features of oral squamous cell carcinoma (OSCC). We hypothesized the existence of tobacco consumption habit-based heterogeneity in the immunohistochemical expression of carcinogenesis relevant molecular markers in OSCC. Hence, the present study was conducted to investigate the carcinogenesis relevant three commonly expressed markers (Ki-67, CD105, and α-smooth muscle acting [SMA]) in various forms of tobacco consumption habits in OSCC patients. Materials and Methods: A total of 217 patients of OSCC were included in the study, and based on the habit, they were broadly categorized into tobacco lime (TL), TL and areca nut (TLAN), and areca nut (AN). Further, categorization was done on the basis of absence or presence of additional habit of smoking. Immunohistochemistry (IHC) was performed using Ki-67, CD105, and α-SMA markers on formalin-fixed paraffin-embedded tissues. Results: TLAN (62.21%) was the most common habit noted in OSCC patient followed by TL (20.73%) and AN (15.20%). The additional habit of smoking was observed in 31.11% and 25.92% of TL and TLAN habits of OSCC patients, respectively. All the three markers (Ki-67, CD105, and α-SMA) showed statistically significant differences in the habit group such as TL, TLAN, and AN (P < 0.001). Although the expression of all the three markers was increased in TL as compared with TLAN, differences were not statistically significant. When these markers were compared in with and without smoking category, only TLAN with smoking and TLAN without smoking showed statistically significant differences in the expression of all three markers. Conclusions: Ki-67 CD105 and α-SMA immunohistochemical expression in OSCC corresponds with different forms of tobacco consumption habits. Habit-related unique carcinogenesis events are reflected at IHC level thus providing proof of concept for future studies.

Significance of HIF-1α and CD105 in establishing oral squamous cell carcinoma associated with oral submucous fibrosis a distinct clinicopathological entity.

Context: Oral squamous cell carcinoma associated with oral submucous fibrosis (OSCC with OSMF) is clinicopathologically a distinct entity. However, scientific proof in view of assessment of biomarkers of hypoxia and neoangiogenesis to differentiate them are lacking. The expression of hypoxia-inducible factor 1-α (HIF-1α) and CD105 in OSCC with and without OSMF possibly will be explicated along these lines. Aim: This study aims to evaluate the molecular basis of hypoxia and neoangiogenesis in terms of immunohistochemical expression of HIF-1α and CD105 in OSCC with and without OSMF cases. Settings and Design: A retrospective cohort. Subjects and Methods: The study comprise of 203 histopathologically diagnosed surgically operated cases of OSCC retrieved from the departmental archives. The OSCC cases were subgrouped into two, OSCC with OSMF (Group I) and OSCC without OSMF (Group II). The evaluation of hypoxia and angiogenesis was carried out by immunohistochemical markers, HIF-1α and CD105. MVD is the parameter of angiogenesis expressed by CD105. Statistical Analysis Used: Differences in CD105, and HIF-1α immunoreactivity between study groups were done using descriptive statistics using "Kruskal-Wallis test," "Mann-Whitney test." Statistical significance was set at P < 0.05. Results: On comparison of MVD in Group I and II, statistically significant difference was found in MVD (8.88 ± 3.41, 16.13 ± 5.86, P = 0.0001). The HIF1-α expression was less in Group I (6.85 ± 2.62) as compare to Group II (7.22 ± 3.08) but the difference was statistically nonsignificant (P = 0.35). Conclusions: The OSCC with OSMF is not only clinicopathologically distinct entity of OSCC but also diverse in its molecular pathogenesis as explicited by distinct expression of HIF-1 α and CD105.

Prevalence of Trismus and Its Impact on Oral Health-Related Quality of Life in Patients Treated for Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma, one of the most common malignancies, has a poor prognosis due to impairment in oral functions secondary to treatment. Trismus one of the major causes of impairment of oral function. The present study investigated the prevalence of trismus and its impact on oral health-related quality of life (OHRQoL) in patients treated for oral squamous cell carcinoma (OSCC). The maximum inter-incisal mouth opening of hundred OSCC patients was recorded at post-treatment and 3 months post-treatment. OHRQoL questionnaire (OHIP-14) was intervened to assess the OHRQoL of patients post-treatment and 3 months follow-up, with emphasis on correlation with grades of trismus. The prevalence of trismus was 16% pre-treatment, 72% post-treatment, and 62% at 3 months after treatment. The overall OHIP-14 scores indicated that patients with trismus reported greater impairment of OHRQoL than those without trismus at the end of treatment and 3 months follow-up. At the end of treatment, patients with severe trismus demonstrated a higher mean OHIP-14 score (23.47 ±3.34) than those with moderate (17.72 ±2.83) and mild trismus (12.66 ±3.84) with statistically significant differences (p <0.001). Equivalent results were obtained at 3 months follow-up period. Patients with trismus suffer greater impairment of OHRQoL. The findings demand the need of identifying risk factors for developing trismus and early institution of newer/modified treatment approaches for better OHRQoL in OSCC survivors.
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Why do Only Certain Cases of Oral Submucous Fibrosis Undergo Malignant Transformation?

Oral submucous fibrosis (OSMF) causes desmoplasia and rigidity of submucosa of the oral cavity, resulting in reduced mouth opening, and in advanced stage causes difficulty in swallowing. OSMF has poor morbidity in terms of oral function as well as general health due to loss of oral function, such as eating. In severe conditions, it can cause dysphagia and hearing loss. Various clinicians have tried the different treatment modalities to reverse the disease process, but with limited success and that too in alleviating the associated symptoms.

Impact of Oral Lichen Planus on Oral Health-Related Quality of Life: A Systematic Review and Meta-Analysis.

Oral health-related quality of life (OR-QoL) measurement in patients with oral lichen planus (OLP) can provide valuable information for the optimal management of their clinical conditions. The main objective of the present study was to assess the OR-QoL of patients with OLP as measured by the short-form Oral Health Impact profile-14 (OHIP-14) questionnaire. PubMed/MEDLINE, ISI/Web of Science, clinical trial registry, Embase, Scopus, and grey literature (via Google Scholar and Scilit) were searched. Reviewers independently screened titles/abstracts, assessed full-text articles, extracted data, and appraised their quality. Random effect analysis along with subgroup analysis for age, gender, and clinical type was performed. Seventeen studies were included. Mean overall OH-QoL was 15.20, [95% CI 12.176, 18.231]; a higher OHIP-14 score was seen in OLP patients, resulting in poor OH-QoL. The impact of OLP on OH-QoL life was moderate as compared to healthy subjects. However, medical treatment of the disease improved the OH-QoL and thus reduced the impact of OLP on it. OH-QoL among patients with OLP is generally poor. Clinicians and physicians should consider the OH-QoL of these patients as part of patients' evaluation and modulate the administered treatment based on the OH-QoL response.

Exploring the role of immunotherapeutic drugs in autoimmune diseases: A comprehensive review.

Autoimmune diseases are group of disorders where an immune response is mounted against the self. The prevalence and burden of this well established and recognised entity is on the rise. Irrespective of being a systemic or organ specific autoimmune disorder, the common underlying mechanism of action, is the imbalance in immune system resulting in loss of tolerance to self-antigens. The oral cavity is no alien to these disorders or to their influences. Pemphigus group of lesions, systemic lupus erythematosus, psoriasis and even Sjogren's syndrome are some of the established autoimmune disorders with prominent oral manifestations. Though these diseases are well documented and enumerated, however addressing them is where the dilemma lies. Science, research and discoveries are a crucial part of medical discipline which help in looking beyond the horizon. With the introduction of selective targeted immunotherapies for autoimmune diseases as a treatment modality either in solitary or in combination with the conventional immunosuppressive treatments, are emerging as a promising elixir for patients enduring them. However, being unique, exploration of these biologics from its inception, to its mechanism of action, recognition of its application and evaluation of its safety norms are equally vital. Therefore, this review aims to provide a comprehensive particular on the novel biologics, the immunotherapies in autoimmune disorders targeting the different cells, their receptors or cytokines of the immune system.