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Caregivers providing care for their family members with oral cancer usually endure the caregiving burden in silence, which affects their quality of life and necessitates the need for supportive care. The aim of this study is to determine the relationship between the quality of life (QOL) of oral cancer caregivers and their supportive care needs (SCN) in Malaysia. The Malaysian versions of the Caregiver Oncology Quality of Life Questionnaire (M-CarGOQoL) and the Comprehensive Needs Assessment Tool for Cancer Caregivers (M-CNAT-C) were self-administered by 56 family caregivers of oral cancer patients from five tertiary hospitals throughout Peninsular Malaysia and Sarawak between October and December 2021. Correlation and multiple regression analyses were employed, and the significance level was set at p < 0.05. The mean score for the QOL of caregivers was 76.16 ± 16.01, with the lowest scores in the psychological well-being (64.87 ± 30.12) and self-esteem (68.64 ± 28.29) domains. The mean score for SCN of caregivers was 36.42 ± 24.16, with the highest scores in the healthcare staff (58.44 ± 33.80) and information (55.35 ± 29.98) domains. The correlation between QOL and SCN was moderately inversed, (r(54) = 0.58, p < 0.01). There was a significant effect of caregiving duration (<3 h/day versus >3 h/day) on the combined dependent variables (QOL and SCN), F(2, 53) = 5.006, p < 0.01, partial η2 = 0.16. QOL and caregiving duration accounted for a significant 43% of SCN, R2 = 0.43, adjusted R2 = 0.41, F(2, 53) = 20.32, p < 0.01. In conclusion, oral cancer caregivers with poorer QOL have higher SCN. It is recommended that oral cancer caregivers be recognized by healthcare providers in order to deliver holistic patient care. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this meta‐analysis was to compare implant survival in irradiated and non‐irradiated bone and to investigate potential risk factors for implant therapy in oral cancer patients. Material and methods: An extensive search in the electronic databases of the National Library of Medicine was performed. Systematic review and meta‐analysis were conducted according to PRISMA statement. The meta‐analysis was performed for studies with a mean follow‐up of at least three and five years, respectively. Results: The systematic review resulted in a mean overall implant survival of 87.8% (34%–100%). The meta‐analysis revealed a significantly higher rate of implant failure in irradiated bone compared to non‐irradiated bone (p <.00001, OR 1.97, CI [1.63, 2.37]). The studies also showed that implants placed into irradiated grafted bone were more likely to fail than those in irradiated native bone (p <.0001, OR 2.26, CI [1.50, 3.40]). Conclusion: Even though overall implant survival was high, radiotherapy proves to be a significant risk factor for implant loss. Augmentation procedures may also increase the risk of an adverse outcome, especially in combination with radiotherapy. Clinical relevance: The treatment of patients receiving radiotherapy of any form requires precise individual planning and a close aftercare. Implants should be placed in local bone rather than in bone grafts, if possible. [ABSTRACT FROM AUTHOR]

Objective: Oral squamous cell carcinoma (OSCC) is the most common cancer in oral and maxillofacial tissue. This study aimed to investigate the expression of SLC3A2 in human OSCC tissues and its regulatory roles in OSCC. Methods: The expression of SLC3A2 in human OSCC tissues was assessed using immunohistochemistry. The proliferation, migration, and invasion of oral squamous cells were evaluated after knockdown of SLC3A2. Results: The expression of SLC3A2 in OSCC was higher than that in normal oral epithelial cells. SLC3A2 had higher expression levels in OSCC tissues than that in adjacent normal tissues. Upregulation of SLC3A2 was associated with advanced stages and poor survival of OSCC patients. In vitro experiments showed that knocking down of SLC3A2 was associated with reduced migration, invasion, and proliferation, but increased apoptosis of OSCC cells. Conclusion: SLC3A2 exerted a harmful effect on OSCC patients by increasing migration, invasion and proliferation, and decreasing apoptosis. [ABSTRACT FROM AUTHOR]

It has been recognized that systemic inflammatory markers (SIMs) are associated with patient survival in various types of cancer. This study aimed to determine the optimal cut-off values, and to evaluate the prognostic performance of SIMs for oral squamous cell carcinoma (OSCC) within the framework of the American Joint Committee of Cancer (AJCC) cancer staging manual, 8th edition. Records were collected for a total 291 patients who had had a peripheral blood test within 1 week prior to surgery and had undergone the surgical resection of OSCC in a single institution between 2005 and 2018. The cut-off values of SIMs were obtained, and the survival analyses for overall survival (OS) and disease-free survival (DFS) were performed. Multivariate analyses incorporating other clinicopathologic factors were performed to verify the independent risk factors for survival. The cut-off values of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were 2.23, 135.14 for OS and 2.16, 131.07 for DFS, respectively, demonstrating a significant association for OS and DFS in OSCC. AJCC pathologic regional lymph node category (pN) (P < 0.001), perineural invasion (PNI) (P < 0.001) and NLR (P < 0.001) were independent predictors for OS. Meanwhile, for DFS, AJCC pN (P = 0.018) and NLR (P = 0.015) were shown to be independent predictors. Before the curative surgery, NLR and PLR could be auxiliary parameters for OS and DFS in OSCC. And based on the 8th edition of AJCC staging system, elevated NLR will be a potential indicator of the worse OS or DFS along with pN or PNI in OSCC. [ABSTRACT FROM AUTHOR]

Oral cancer is one of the 6th most common cancers in the world and globally more than 50% of the head and neck cancers occur in Asia, remarkably in India. In India, according to the current epidemiology statistics (2018), the age standardized ratio of incidence of lip, oral cavity cancers is 9.1. Long standing irritations or Chronic mucosal trauma have been postulated as the risk factor for developing oral cancer. Chronic irritation of the oral mucosa may result due to the poor oral hygiene, poor dentition, missing teeth or sharp teeth. Even in the absence of clinical changes of the oral mucosa, the cytopathic and nuclear changes can be detected through the exfoliative cytology. This study aims at assessing the cytopathic and nuclear changes of oral mucosa in patients with non habit oral cancer at the contralateral site of malignancy. A pilot study was conducted among the patients with non habit oral cancer with concurrent irritation of oral mucosa in 2018. The study group included 25 patients, the cases of oral cancer which included squamous cell carcinoma, verrucous carcinoma and others which were confirmed histopathologically. They were questioned on their dietary habits, occupation, stress, medical and dental history, ulceration history and so on. The patients were also enquired about their negligence towards any lesion because of the chronic mucosal trauma. The data were collected and tabulated. The results were statistically analysed using SPSS and Pearson’s chi-square test was performed. A total of 115 oral cancer patients were recorded in the hospital during the period of January to December 2018. Among these 25 patients did not have any habits. Out of these 25 patients, 9 (36%) were females and 16 (64%) were males. The mean age group was 53 years. The study group revealed that 90% of the patients were unemployed. Their dietary habits were normal. The study group showed that the following oral cancers were found which were just noted as Oral carcinoma (20%), squamous cell carcinoma (64%), verrucous carcinoma [8%] and verrucous carcinoma turning into squamous cell carcinoma (8%). Regarding the location, tongue (48%), buccal mucosa (24%), mucosa adjacent to the tooth region (28%), tonsillar papillae (4%) were involved. Chronic irritation of the oral mucosa acts as a cofactor in oral malignancies. Proper treatment of the mechanical injuring factors could reduce the risk of oral cancer. Thus more epidemiological and clinical studies that concentrate on chronic irritation of oral mucosa and onset of oral cancers are needed. [ABSTRACT FROM AUTHOR]

Background: This study aimed to elucidate the correlation between gene amplification, protein expression of receptor tyrosine kinase, and prognosis of patients with oral squamous cell carcinoma (OSCC) using immunohistochemistry (IHC) and next-generation sequencing data.Methods: We evaluated data pertaining to 208 patients with OSCC using IHC for epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET).Results: High expressions of EGFR and MET were detected in 60 and 41 patients, respectively. We evaluated the association of clinicopathological variables with high expressions of EGFR and/or MET. Distant metastasis was found in 9 of 41 patients (22.0%) and 6 of 15 patients (40.0%) with high expression of MET and high co-expressions of EGFR and MET, respectively; statistically significant differences were detected in both high expression of MET (P = .003) and high co-expressions of EGFR and MET (P = 3.41 × 10-5 ). The cumulative 5-year survival rate of patients with high and low expressions of EGFR or MET was approximately 65% and 85%, respectively. Conversely, among cases with high expressions of EGFR or MET, there was no additional decrease in the survival rate of patients harboring TP53 mutations. Moreover, the survival rate of patients with high co-expression of both EGFR and MET was very poor (22.0%) (P < 1.0 × 10-9 ).Conclusion: Our findings suggest that evaluation of protein expressions of EGFR and MET may facilitate prognostic assessment of patients with OSCC; in addition, patients with OSCC should be screened for enrollment in clinical trials of combination therapy with EGFR and MET inhibitors. [ABSTRACT FROM AUTHOR]

Objective: To investigate possible associations between disease-specific survival (DSS) of oral cancer and single nucleotide polymorphisms (SNPs) in transforming growth factor beta receptor 1 (TGFBR1).Methods: Using iPLEX Sequenom MassARRAY platform, three SNPs in TGFBR1 gene were genotyped in 356 newly diagnosed patients with histologically confirmed primary oral cancer. Demographic and clinical information of all cases were obtained from face-to-face interviews and electronic medical records, and telephone interviews were carried out every 6 months to timely gain follow-up data. Univariate and multivariate Cox proportional hazards model were used to assess the association between the polymorphisms of tagging loci and DSS of oral cancer.Results: TGFBR1 rs33438 polymorphism was protective against death of oral cancer in codominant (AG vs AA: HR = 0.55, 95% CI = 0.35-0.88) and dominant (GG + AG vs AA: HR = 0.57, 95% CI = 0.38-0.87) models. Moreover, better DSS was particularly significant in radiotherapy patients who carrying GG + AG genotype. There also existed a positive multiplicative interaction on DSS between the polymorphism of TGFBR1 rs334348 and radiotherapy (P = .001). Not any associations between TGFBR1 rs334354 or rs3739798 polymorphism and DSS were observed.Conclusions: This preliminary prospective study suggests that polymorphism of TGFBR1 rs334348 may act as a potentially independent factor and novel genetic biomarker to predict oral cancer DSS especially for patients with radiotherapy. A much more extensive investigation will need to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: MLL2 (mixed-lineage leukemia 2) is recognized as an essential role in regulating histone 3 lysine 4 tri-methylation (H3K4me3) in mammalian cells. It is frequently mutated to promote developmental diseases and tumor initiation. However, the expression pattern of MLL2 and its clinical significance for patients with early-stage oral squamous cell carcinoma (OSCC) remain totally unknown.Methods: Eighty-five samples of primary early-stage OSCC were enrolled in this retrospective study, and immunohistochemistry (IHC) was performed to detect the spatial pattern of MLL2. The diagnostic and prognostic value of MLL2 were assessed.Results: MLL2 was widely expressed in tumor cells (TCs), fibroblast-like cells (FLCs), and tumor-infiltrating lymphocytes (TILs), both in tumor center and invasive tumor front, and showed no distributive heterogeneity. Moreover, regardless of cell types and microlocalization, patients with high expressed MLL2 had increased depth invasion of tumor (DOI). Besides, upregulation of MLL2TC and MLL2TIL in tumor center were both associated with poor differentiation, but showed no correlation with tumor growth with comparable Ki-67 levels. Prognostic analysis indicated that early-stage OSCC patients with enhanced MLL2TIL in invasive tumor front were susceptible to occur postoperative metastasis and recurrence. Indeed, patients with higher expressed MLL2TIL showed shorter overall survival (OS) and disease-free survival (DFS), and MLL2TIL in invasive tumor front was an independent risk factor of DFS.Conclusion: TIL-derived MLL2 in invasive tumor front was an independent prognostic factor of DFS for early-stage OSCC patients. [ABSTRACT FROM AUTHOR]

Oral cancer is found to be the sixth most common cancer around the globe. The most common reasons for the occurrence of oral cancer was found to be tobacco smoking and alcohol consumption but there have been reports where a well established relationship was found with the dietary habits and oral cancer. The aim of the study was to understand and compare various factors other than the established etiological factors in the occurrence of oral cancer in the non habit population. A total of 43 cases were proposed to be recruited which was reported within a time period of 2018 to 2020. Questionnaires regarding the demographic details and food habits were formulated and a telephonic interview was held by trained experienced interviewers. During the course of the interview a total of 36 profiles of oral cancer patients and 36 controls were examined. Even though the parameters that we compared were found to be statistically not significant it has major variations between the cases and controls. [ABSTRACT FROM AUTHOR]

Oral cancer is the 6th most common cancer in the world. Oral cancer mostly involves the tongue floor of the mouth. The main cause's oral cancers are smoking, alcohol, and human papillomavirus. The more importantly specific hallmarks and features preferably include tongue, mouth, gums. Smoking and chewing tobacco with or without alcohol consumption, and human papillomavirus infections are considered as important etiological factors associated with oral cancer. The major complications in oral cancer patients due to chemo/radiotherapy include dry mouth, cavities, oral communications with sinuses, and difficulty in speaking, eating and drinking. Chemotherapy and radiation treatment moderate or stop the development of new cells. The most common oral complications related to chemo/radiotherapy are bisphosphonate osteonecrosis, dysgeusia, oral fungal and viral infections, osteoradionecrosis, trismus, oral pain, salivary gland and taste dysfunction, rampant dental caries and xerostomia in oral cancer patients. In severe oral toxicities cases, dose reduction or treatment schedule modifications if necessary, treatment should be discontinued. Assessment of oral status, pre-treatment interventions and timely management of lesions, patient education, and identification of high-risk populations before and after chemo/radiotherapy are necessary for the management of above oral complications. [ABSTRACT FROM AUTHOR]

PURPOSE: Patient-reported outcome measures (PROMs) for symptom monitoring during cancer therapy have been shown to have a positive impact on outcomes. These findings have primarily been shown for patients receiving intravenous chemotherapy. In addition, there is known discordance between physician reporting of symptoms and patient self-report. This initiative sought to describe patient-reported symptom burden and medication adherence and to indicate the degree of PROM results being discussed with the provider as indicated by documentation in the medical record for patients taking oral oncolytic therapy. METHODS: The Michigan Oncology Quality Consortium (MOQC) PROM, which included symptom ratings, medication adherence, and patient confidence in self-management, was completed during outpatient visits and compared with corresponding data documented in the electronic medical record (EMR). RESULTS: There were 82 completed PROMs. Approximately half included at least one symptom rated as severe (46%). Sixty-five percent of reported severe symptoms were documented in the EMR. Patient-reported moderate-to-severe pain was most likely to be documented in the EMR (100%), whereas patient-reported moderate-to-severe depression and anxiety were least likely to be documented (21%). Of the total symptoms documented, grading of symptom severity matched that of the patients' own report for 11% of severe symptoms. Adherence to oral oncolytics was excellent for 63% of patients, and patient adherence was documented in 7% of provider notes. CONCLUSION: Patients frequently reported moderate-to-severe symptoms, and approximately 40% of patients reported nonadherence. Clinician report (documented in the EMR) of the patient symptom burden, symptom severity, and adherence to oral oncolytic therapy was not consistent with the patients' self-report. Use of a PROM for patients taking oral oncolytics has the opportunity to improve symptom management and medication adherence. [ABSTRACT FROM AUTHOR]

Abstract Cetuximab, an inhibitor of the epidermal growth factor receptor that is used widely to treat human cancers including oral squamous cell carcinoma (OSCC), has characteristic side effects of skin rash and hypomagnesemia. However, the mechanisms of and therapeutic agents for skin rashes and hypomagnesemia are still poorly understood. Our gene expression profiling analyses showed that cetuximab activates the p38 MAPK pathways in human skin cells (human keratinocyte cell line [HaCaT]) and inhibits c-Fos-related signals in human embryonic kidney cells (HEK293). We found that while the p38 inhibitor SB203580 inhibited the expression of p38 MAPK targets in HaCaT cells, flavagline reactivated c-Fos-related factors in HEK293 cells. It is noteworthy that, in addition to not interfering with the effect of cetuximab by both compounds, flavagline has additive effect for OSCC growth inhibition in vivo. Collectively, our results indicate that combination of cetuximab and these potential therapeutic agents for cetuximab-related toxicities could be a promising therapeutic strategy for patients with OSCC. Highlights • Cetuximab activates the p38 MAPK pathways in human skin cells. • Cetuximab inhibits c-Fos-related signals in human embryonic kidney cells. • SB203580 inhibited the expression of p38 MAPK targets and tumor growth in vivo. • Flavagline reactivated c-Fos-related factors and tumor growth in vivo. [ABSTRACT FROM AUTHOR]

Background: ADAR1 is an enzymatic protein, which catalyzes a RNA editing reaction by converting Adenosine to Inosine, and its expression has been found to be dysregulated in many cancer types. The aim of this study was to analyze the expression of ADAR1 in oral squamous cells carcinoma.Methods: In order to analyze the ADAR1 mRNA expression, data from The Cancer Genome Atlas (TCGA) database were downloaded and analyzed. In addition, immunohistochemistry analysis was performed on an institutional database including 46 samples of oral squamous cell carcinoma in a tissue microarray (TMA).Results: No statistically significant correlation linked the mRNA ADAR1 expression to any clinic-pathological variables in the TCGA database. Immunohistochemistry analysis of ADAR1 showed different expressions between normal mucosa and tumor tissue. Focusing on the subcellular localization, the nuclear expression of ADAR1 correlated with higher grading of differentiation (ρ = 0.442; P-value = 0.002); the general expression of ADAR1 either in cytoplasm or in nuclei, correlated with the Gender of patients (Cytoplasm expression: ρ = -0.295; P-value = 0.049; while for nuclear expression: ρ = +0.374; P = 0.011); cytosol expression resulted to be an independent protective prognostic factor (HR = 0.047; C.I. 95% 0.007-0.321; P-value = 0.002).Conclusion: Higher expression of ADAR1 into the cytoplasm resulted to be an independent prognostic factor. In order to understand ADAR1 role in cancer, further studies should be performed, in bigger cohort and under a bio-molecular point of view. [ABSTRACT FROM AUTHOR]

Purpose: Patients with p16/human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma have a favorable outcome after treatment. In this group of patients who could have a long life expectancy, the optimal surveillance strategy and modality is not well established. We aim to determine the ability of a negative postradiation positron emission tomography (PET)/computed tomography scan to predict the risk of subsequent relapse in these patients.Materials and Methods: A retrospective analysis of patients with p16/HPV-associated oropharyngeal squamous cell carcinoma who completed definitive (chemo)radiation therapy and had a posttreatment PET/computed tomography scan from 2006 to 2013 was performed. Patient, tumor, and treatment characteristics and clinical outcomes were recorded. Tumors were considered HPV/p16 positive if either HPV (by in situ hybridization) or p16 (by immunohistochemistry) was positive. Disease-free survival and overall survival rates were estimated using the Kaplan-Meier method.Results: In our study, 327 patients were evaluated. The median age was 57 years. The most common primary sites were base of tongue (50%) and tonsil (48%). Of the patients evaluated, 291 (89%) had a negative posttreatment PET scan. For these 291 patients who had a complete metabolic response after treatment, the 5-year disease-free survival and overall survival rates were 91% and 89%, respectively. The median time to development of recurrence was 16 months. Of the 291 patients, 24 patients (8%) had disease recurrence; 13 recurrences were locoregional, and 13 were distant. Eleven (4%) patients with recurrence had further surgery or radiation, and 8 patients (3%) were without disease as of the last follow-up.Conclusions: Patients who achieve a complete metabolic response on posttreatment PET imaging have an excellent prognosis, and the risk of developing a recurrence in the future is very low. Therefore, a more cost effective surveillance program should be considered for this subgroup of patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether a response assessment using mid-treatment computed tomography (CT) scans during definitive radiation therapy (RT) for oropharyngeal head and neck cancer can predict for locoregional recurrence (LRR).Methods and Materials: Head and neck cancer patients who receive RT at our institution undergo CT repeat scans at the 15th fraction, with treatment replanning in the case of an inadequate dose to gross disease or an increased dose to organs at risk. A retrospective cohort analysis was performed of 96 consecutive patients with oropharyngeal cancer treated from 2007 to 2015 with mid-treatment repeat CT scans available. The primary disease volume and involved lymph node volume were delineated on the pre- and mid-treatment CT scans. Univariable and multivariable Cox proportional hazards regression analyses were used to evaluate the efficacy of the mid-treatment reduction in tumor volume as a predictor of LRR. Risk stratification was performed by dichotomizing the patients into high- and low-risk groups according to the mid-treatment response and p16 status and smoking history.Results: With a median follow-up of 34 months, 14 patients experienced LRR. The median reduction in the total tumor volume was 18.7% (interquartile range 8.4%-30.9%). A reduction in total tumor volume greater than the median was an independent predictor of LRR (hazard ratio 0.22, 95% confidence interval 0.05-0.89; P = .020). The reduction in primary tumor volume was an even stronger predictor of LRR (hazard ratio 0.11, 95% confidence interval 0.02-0.57; P = .002). Stratifying patients into a high-risk group for those with a reduction in the total tumor volume at mid-treatment at or less than the median, p16 negative status, and smoking status of >10 pack-years and a low-risk group for those without these factors, we found a clear separation in Kaplan-Meier curves, with actuarial 3-year locoregional control, progression-free survival, and overall survival rates for the high-risk patients of 45.7%, 38.2%, and 71.8% compared with 90.7%, 70.6%, and 89.8% for low-risk patients, respectively (P ≤ .021 for all).Conclusions: Our results have shown that the treatment response from an early assessment using mid-treatment CT scans is an independent predictor of LRR and can be used to effectively distinguish high- and low-risk patients, allowing for risk-adaptive treatment stratification at the midway point. [ABSTRACT FROM AUTHOR]

Purpose Distant metastasis (DM) is the main cause of death for patients with human papillomavirus (HPV)–related oropharyngeal cancers (OPCs); yet, there are few reliable predictors of DM in this disease. The role of quantitative imaging (ie, radiomic) analysis was examined to determine whether there are primary tumor features discernible on imaging studies that are associated with a higher risk of DM developing. Methods and Materials Radiation therapy planning computed tomography scans were retrieved for all nonmetastatic p16-positive OPC patients treated with radiation therapy or chemoradiation therapy at a single institution between 2005 and 2010. Radiomic biomarkers were derived from each gross tumor volume. The biomarkers included 4 representative radiomic features from tumor first-order statistics, shape, texture, and wavelet groups, as well as a combined 4-feature signature. Univariable Cox proportional hazards models for DM risk were identified. The discriminative performance of prognostic univariable and multivariable models was compared using the concordance index (C-index). Subgroup analyses were performed. Results There were 300 HPV-related OPC patients who were eligible for the analysis. A total of 36 DM events occurred within a median follow-up period of 5 years. On univariable analysis, top results included the 4 representative radiomic features (C-index, 0.670-0.686; P <.001), the radiomic signature (C-index, 0.670; P <.001), tumor stage (C-index, 0.633; P <.001), tumor diameter (C-index, 0.653; P <.001), and tumor volume (C-index, 0.674; P <.001), which demonstrated moderate discrimination of DM risk. Combined clinical-radiomic models yielded significantly improved performance (C-index, 0.701-0.714; P <.05). In subgroup analyses, the radiomic biomarkers consistently stratified patients for DM risk, particularly for those cohorts with greater risks (C-index, 0.663-0.796), such as patients with stage III disease. Conclusions Radiomic biomarkers appear to classify DM risk for patients with nonmetastatic HPV-related OPC. Radiomic biomarkers could be used either alone or with other clinical characteristics in the assignment of DM risk in future HPV-related OPC clinical trials. [ABSTRACT FROM AUTHOR]

Objective: Greater time that patients take to present symptoms to health care providers (HCPs) increases the likelihood of later stage cancer, which increases mortality and morbidity in symptomatic cancers. The common-sense model (CSM) is used to understand time to first consultation with a healthcare provider, but inconsistencies exisy between its current use and important empirical findings.Method: To resolve inconsistencies, we conducted a qualitative examination to determine how the CSM could be revised to better account for these findings. We conducted in-depth interviews of a consecutive sample of 38 recently diagnosed patients who described events from first noticing symptoms to first consultation. Framework analysis was used to develop a theoretical model of processes leading to presentation or non-presentation.Results: Patients reported median presentation times of 3-4 weeks. Early presentation was facilitated by pre-symptomatic perceptions of vulnerability to serious illnesses and beliefs that early intervention could mitigate illness. These patients rarely tried to identify symptoms. They responded inductively, seeking help because symptoms were unusual. Where patients did not describe pre-symptom perceptions of vulnerability, many deductively tried to identify symptoms but misattributed them to minor conditions. Pre-symptomatic perceptions of vulnerability could also prolong presentation. When vulnerability was characterized by intense fears of cancer and cancer treatment, patients tended to avoid thinking about symptoms which extended presentation time.Conclusion: Risk perception theories explain how participants' pre-symptomatic perceptions of vulnerability and potential treatment outcomes influence presentation time. Incorporating risk perception perspectives into the CSM can improve its ability explain responses to ambiguous symptoms. [ABSTRACT FROM AUTHOR]

Introduction: The introduction of universal health insurance coverage aims to provide equal accessibility and affordability of health care, but whether such a policy eliminates health inequalities has not been conclusively determined. This research aims to examine the healthcare outcomes of oral cancer and determine whether the universal coverage system in Taiwan has reduced health inequality. Methods: Linking the databases of the National Cancer Registry with the National Mortality Registry in Taiwan, we stratified patients with oral squamous cell carcinoma by gender and income to estimate the incidence rate, cumulative incidence rate aged from 20 to 79 (CIR20-79), life expectancy, and expected years of life lost (EYLL). The difficulties with asymmetries and short follow-up periods were resolved through applying survival analysis extrapolation methods. Results: While all people showed a general improvement in life expectancy after the introduction of the NHI, the estimated change in EYLL’s of the high-, middle-, and low-income female patients were found to have +0.3, -0.5 and -7 years of EYLL, respectively, indicating a reduction in health inequality. Improvements for the male patients were unremarkable. There was no drop in the CIR20-79 of oral cancer in disadvantaged groups as in those with higher incomes. Conclusions: Universal coverage alone may not reduce health inequality across different income groups for oral cancer unless effective preventive measures are implemented for economically disadvantaged regions. [ABSTRACT FROM AUTHOR]

Objective: To assess the usefulness of modified esophagogastroduodenoscopy (EGD) for the detection of second primary malignancies of the esophagus or hypopharynx in patients with oral squamous cell carcinoma and determine the association between the oral lesion subsite and esophageal or hypopharyngeal lesion occurrence. Study Design: Retrospective review. Methods: In total, 166 patients with oral squamous cell carcinoma without any established symptoms of esophageal or hypopharyngeal squamous cell carcinoma underwent modified EGD based on the Valsalva maneuver and U‐turn method, image‐enhanced endoscopy, and chromoendoscopy using Lugol's iodine for diagnosis. All suspected lesions were biopsied to determine the clinical stages and duplication rates. Odds ratios for the occurrence of duplicate lesions according to the oral lesion subsite were determined. Results: In total, 37 esophageal and 16 hypopharyngeal lesions were detected. According to the Union for International Cancer Control/American Joint Committee on Cancer classification (2009), 75.7% and 5.4% esophageal lesions were classified as stage IA and IB, respectively, and 50% and 18.8% hypopharyngeal lesions as stage II and stage I, respectively. Approximately 59.1% and 50% esophageal and hypopharyngeal lesions, respectively, were successfully treated by endoscopic resection. Oral lesions involving the floor of the mouth were more frequently accompanied by second primary malignancies of the esophagus or hypopharynx. Conclusions: Modified EGD is an effective noninvasive technique for early diagnosis and treatment of second primary malignancies of the esophagus and hypopharynx in patients with oral squamous cell carcinoma. In particular, patients with floor of the mouth lesions need close monitoring for hypopharyngeal and esophageal lesions. Level of Evidence: 3b. [ABSTRACT FROM AUTHOR]

Background: Availability of reliable methods distinguishing high-risk recurrent tumours from regressive tumours prior to surgery could help in better management of the disease. This study was aimed to estimate pre-surgical serum CD44 concentration and assess the possibility of using it as a non-invasive prognostic tool in oral cancer.Methods: ELISA was performed on pre-surgical serum samples from 64 primary oral cancer patients and 16 healthy individuals to estimate soluble CD44 levels. Immunohistochemistry was performed on parallel 64 solid tumours and 10 recurrent tumours. All patients clinically followed up for median period of 19.2 months and obtained prognostic information correlated with CD44 concentration in serum as well as in tumours.Results: Serum CD44 concentration was found significantly high in patients as compared to healthy individuals (P < .001) and also in patients whose disease locally recurred as compared to those did not recur (P = 0026). High serum CD44 concentration inversely affected on patients survival (P = .032). CD44v6 staining intensity was detected significantly high in recurrent tumours as compared to primary tumours (P < .001), and it also correlated with poor survival (P < .001). Furthermore, in combination, patients with increased CD44 concentration in serum and CD44v6 expression in tumours significantly correlated with local recurrence (P < .001) and poor survival (P < .001).Conclusion: Our data suggest that the ELISA-based estimation of pre-surgical serum CD44 concentration could be a non-invasive reliable method distinguishing high-risk recurrent tumours which can further assist in post-surgery treatment planning. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is a cancer of the oral cavity that is a major health problem in India. There is an urgent need to identify biomarkers that have prognostic significance. We studied HIF-1α levels as well as single-nucleotide polymorphism of HIF-1α gene in cancer and healthy controls.Methods: Fifty newly diagnosed OSCC patients and 50 age and sex-matched healthy control were included in the study. Serum concentrations of HIF-1α were measured by sandwich ELISA; whereas HIF-1α gene polymorphism study was performed using restriction enzyme digestion by HpH I.Results: The major genotype observed was CC genotype in both control (84%) and patients (86%) followed by CT genotype (control 16%, cases 14%). CT genotype led to more aggressive tumors. On subgroup analysis based on prognosis, the median overall survival of patients who were treatment responders was 488 days (16.2 months) and that of the patients with progressive disease was 365 days (12.1 months). The patients who expired during the study observation period had median survival of 330 days (11 months).Conclusion: Our study showed that CT genotype for C1772T polymorphism of HIF-1α predisposes to aggressive tumor phenotype in patients with OSCC. Moreover, patients with CT genotype had poor survival rate as compared to CC genotype. A cut-off value of 460 pg/mL of HIF-1α can help to segregate patients with OSCC from healthy controls. [ABSTRACT FROM AUTHOR]

The psychoactive effects of using areca nut and its potential for dependence have been observed. However, the factors that create barriers to or promote chewing cessation are not well understood. This study aims to explore the behavioral changes of betel quid chewers who have been diagnosed with oral cancer within a transtheoretical model framework. Thirty oral cancer patients with betel quid chewing history were chosen for in-depth interviews. Qualitative content analysis was used to analyze the data and identify themes that described the behavioral changes of betel quid cessation. Our research showed that betel quid chewers with oral cancer typically experience four significant stages of behavior: pre-contemplation, contemplation, action, and maintenance. Each stage change was marked by specific characteristics. At first, chewers showed positive attitudes toward the psychoactive or social effects of betel quid. They then realized the negative effects of betel quid, such as dental or other physical problems. Some also realized that they were addicted to betel quid. When they decided to quit, most chewers reported going “cold turkey.” Some chewers successfully quit betel quid and attributed it to willpower. Those quitting because of the loss of oral functions were unable to chew anymore, though some chewers had experienced a relapse. In the maintenance stage, ex-chewers reported overcoming their addiction; however, relapse was possible. In this study, those who quit betel quid because of oral cancer usually quit tobacco and alcohol as well, with a lesser chance of recurrence. As the maintenance of chewing betel quid is multifactorial, this study provides information for betel quid cessation and oral cancer prevention. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the demographics, clinical features, survival outcomes, and prognostic indicators of patients with acinic cell carcinoma (ACC) of the parotid gland with emphasis on the roles of grade, tumor size, and nodal status in survival.Materials and Methods: A retrospective analysis of cases diagnosed between 2004 and 2012 from the National Cancer Database was performed. Multivariable logistic regression was used to determine factors associated with survival.Results: 2362 cases were identified. Most patients were females (61.3%) and Caucasian (85.4%) with a median age of 54 years (range, 18-90 years). Most tumors were <3 cm in size (75.8%). Regional metastases and high-grade histology were rare (8.2%, 5.1%). All patients received surgery as primary treatment with 42.7% of patients receiving adjuvant radiation therapy or chemoradiotherapy. 5 year overall survival was 88.6%. On multivariable analysis, age >70 years (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 5.64-17.91), high-grade (HR: 5.30, 95% CI: 3.39-8.29), tumor size of 3 to 6 cm (HR: 1.53, 95% CI: 1.10-2.12), tumor size >6 cm (HR: 2.98, 95% CI: 1.681-5.289), pN2+ (HR: 3.14, 95% CI: 2.10-4.69), T4 (HR: 2.89, 95% CI: 1.74-4.80) were significant prognosticators.Conclusion: Although patients with ACC generally are considered to have a favorable prognosis, an aggressive subgroup with poor outcomes was identified. This group is characterized by high-grade, advanced T classification, tumors larger than 3 cm, with regional metastases and age greater than 70 years. Histologic grade is a substantially stronger predictor of survival than T and N classifications. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the commonest subtype of oral cancer, mainly affecting older patients. It used to be a rare disease among individuals younger than 40 years, but recently increased incidences in this age group are being reported worldwide. The pathogenesis of OSCC affecting young patients remains controversial, and the well-known etiological factors for oral cancer, tobacco, and alcohol use are believed to play a minor role in the carcinogenesis of the neoplasm, suggesting that the etiology and the molecular basis of OSCC may differ between younger and older patients. Although several molecular markers and chromosomal abnormalities have been demonstrated to differ between both groups, most of the studies have failed to find significant differences. Moreover, divergent results have also been obtained regarding the presence of high-risk human papillomavirus infection in OSCC of young patients. Given these contradictory results and the limited methodological approaches of the majority of the studies, the exact difference between both age groups remains to be fully established. In this review, we evaluate the available data to establish the current evidence that might support the hypothesis that the molecular basis of OSCC in young patients (especially those under 40 years) differ from the older patients. [ABSTRACT FROM AUTHOR]

Background: In this study scales and items for the Oral Cancer Quality-of-life Questionnaire (QOL-OC) were designed and the instrument was evaluated.Methods: The QOL-OC was developed and modified using the international definition of quality of life (QOL) promulgated by the European Organization for Research and Treatment of Cancer (EORTC) and analysis of the precedent measuring instruments. The contents of each item were determined in the context of the specific characteristics of oral cancer. Two hundred thirteen oral cancer patients were asked to complete both the EORTC core quality of life questionnaire (EORTC QLC-C30) and the QOL-OC. Data collected was used to conduct factor analysis, test-retest reliability, internal consistency, and construct validity.Results: Questionnaire compliance was relatively high. Fourteen of the 213 subjects accepted the same tests after 24 to 48 h demonstrating a high test-retest reliability for all five scales. Overall internal consistency surpasses 0.8. The outcome of the factor analysis coincides substantially with our theoretical conception. Each item shows a higher correlation coefficient within its own scale than the others which indicates high construct validity.Conclusions: QOL-OC demonstrates fairly good statistical reliability, validity, and feasibility. However, further tests and modification are needed to ensure its applicability to the quality-of-life assessment of Chinese oral cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: To develop a core information set for informed consent to surgery for oral/oropharyngeal surgery. A core information set is baseline information rated important by patients and surgeons and is intended to improve patients' understanding of the intended procedure. Design: A mixed‐methods study. Systematic reviews of scientific and written healthcare literature, qualitative interviews and observations, Delphi surveys, and group consensus meetings identified information domains of importance for consent. Setting: A regional head and neck clinic in the United Kingdom. Questionnaire participants were recruited from around the UK. Participants: Patients about to undergo, or who had previously undergone, surgery for oral/oropharyngeal cancer. Healthcare professionals involved in the management of head and neck cancer. Main outcome measures: The main outcome was a core information set. Results: Systematic reviews, interviews and consultation observations yielded 887 pieces of information that were categorised into 87 information domains. Survey response rates were 67% (n = 50) and 71% (n = 52) for patient and healthcare professional groups in round one. More than 90% responded in each group in the second round. Healthcare professionals were more likely to rate information about short‐term or peri‐operative events as important while patients rated longer term issues about survival and quality of life. The consensus‐building process resulted in an agreed core information set of 13 domains plus two procedure‐specific domains about tracheostomy and free‐flap surgery. Conclusion: This study produced a core information set for surgeons and patients to discuss before surgery for oral/oropharyngeal cancer. Future work will optimise ways to integrate core information into routine consultations. [ABSTRACT FROM AUTHOR]

Objectives: Late-stage diagnosis is one of the major confounders for poor prognosis of patients with oral cancer owing to lack of a biomarker to diagnose this disease at an early stage. Moreover, till date, invasive biopsies are the only option to assess disease occurrence and progression in this malignancy. Thus, this study aims to identify and assess potential salivary markers in OSCC patients in order to open newer avenues in the field of non-invasive biopsies.Methodology: Bioinformatic-based analysis was performed to identify potential biomarkers that could be assessed in OSCC patients. The expression patterns of CD44v and its genetic and epigenetic modulators were assessed in saliva of OSCC patients, leukoplakia, and controls using real-time and methylation-specific PCR. Statistical analysis was conducted to understand the significance of these markers in terms of their clinical relevance.Results: CD44v/SYNE1/miR34a axis was identified using bioinformatic analysis, and the expression profile of these markers was assessed in saliva of OSCC patients. CD44v6 and CD44v10 demonstrated a significantly increased expression, whereas SYNE1 and miR34a depicted a significantly decreased expression in OSCC patients. Statistical analysis suggested a probable role of CD44v6, SYNE1, and miR34a in early stages of the malignancy, whereas a strong association was observed between CD44v6, CD44v10, and miR34a expression with locoregional aggressiveness and histopathological conditions.Conclusion: Collectively, these findings suggested a plausible role of CD44v/SYNE1/miR34a axis as non-invasive salivary biomarkers to diagnose this disease at an early stage and predict the early onset of metastasis. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to explore the prognostic value of cancer stem cell markers, namely CD133, NANOG, and NOTCH1, in early stage oral squamous cell carcinoma (OSCC).Materials and methods: One hundred forty-four patients with early stage (cT1T2N0) OSCC were identified from a pre-existing database of patients with oral cancer. We examined the impact of the immunohistochemical expression of CD133, NANOG, and NOTCH1 in OSCC. Overall survival (OS) curves were calculated using the Kaplan-Meier method. Predictors of outcome were identified using multivariate analysis.Results: We found that CD133, NANOG, and NOTCH1 were significantly associated with lymph node metastasis, and NOTCH1 was also significantly associated with depth of invasion and locoregional recurrence.Conclusions: NOTCH1 was identified as an independent prognostic factor for OS.Clinical relevance: NOTCH1 might prove to be a useful indicator for high-risk patients with occult metastases from early stage OSCC. [ABSTRACT FROM AUTHOR]

Background Aberrations in Wnt signaling pathway are related to the pathogenesis of head and neck carcinomas and their activation frequently results from epigenetic alterations. This study aimed to assess the frequency of the methylation of DAB2, which acts as a negative regulator of Wnt signaling, and correlate it with clinicopathological features in a group of oral cancer patients. Material and methods Forty nine patients with primary oral squamous cell carcinoma were enrolled in the study. DNA samples were isolated from surgical sections using phenol-chloroform extraction. Methylation-specific PCR was used to detect gene promoter methylation. Results The analysis of the occurrence of DAB2 promoter methylation in primary oral carcinomas indicated that the gene is methylated in 70% of cases. However, no correlation was found between its methylation and TNM staging or overall survival. Conclusions Our findings corroborate that DAB2 is a frequent target of epigenetic silencing in oral carcinomas and may be potentially used for tumor detection. [ABSTRACT FROM AUTHOR]

Purpose: Human papilloma virus (HPV) is the main source of cervical cancer. Many recent studies have revealed the prevalence and prognosis of HPV associated with oropharyngeal squamous cell carcinoma, but fewer reports have evaluated HPV in oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the prevalence and prognosis of HPV associated with OSCC according to HPV and tumor types.Materials and methods: We used a DNA chip kit (MY-HPV chip kit ®, Mygene Co., Korea) to detect high-risk HPV subtypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 54, 56, 58) and low-risk subtypes (6, 11, 34, 40, 42, 43, 44) among 187 patients. The prevalence was determined by Chi-square and Fisher’s exact tests, and the prognosis was calculated by the Kaplan–Meier method and the log-rank test.Results: The overall prevalence of HPV in OSCC was 7.0% for all HPV positives and 4.3% for high-risk HPV positives. The prevalence of HPV was significantly higher in individuals under 65 years old and in those with tumors in the tongue and gum regions. The prognosis did not differ between the HPV-positive and -negative groups. Although the prevalence of HPV-positive cases in OSCC was low (7.0, 4.3%) and the prognosis did not depend on HPV positivity, HPV-associated OSCC should be considered in the evaluation and treatment of oral cancer patients. In addition, separating high- and low-risk groups based on the HPV status of other body parts might not be appropriate. Discussion: The DNA microarray method can accurately detect known HPV subtypes simultaneously, but has limitations in detecting new subtypes. Vaccines can also be used to prevent HPV-associated OSCC in patients, so further studies on the prognosis and efficacy of vaccines should be undertaken. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We present a rare case of intraoral nerve sheath myxoma. Clinically, the neoplasm mimics many other oral mucosal pathosis, underscoring the importance of histopathology in ensuring accurate diagnosis of oral mucosal lesions. Reports of intraoral nerve sheath myxomas are essential to enhance our understanding of this rare intraoral entity. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the total costs of treating head and neck cancers, specifically oropharyngeal, laryngeal and oral cavity cancer, in secondary care facilities in England during the period 2006/2007 to 2010/2011. Design: Patient records were extracted from an English hospital database to estimate the number of patients treated for oropharyngeal, laryngeal and oral cavity cancer in England. Identified resource use was linked to published United Kingdom cost estimates to quantify the reimbursement of treatment through the Payment by Results system. Setting: Retrospective hospital data analysis. Participants: From the hospital data, patient records of patients treated for oropharyngeal, laryngeal and oral cavity cancer were selected. Main outcome measures: Annual total costs of treatment, stratified by inpatient and outpatient setting and by male and female patients. Results: From 2006/2007 to 2010/2011, total costs of treatment across the three head and neck cancer sites were estimated to be approximately £309 million, with 90% attributable to inpatient care (bundled costs). Oropharyngeal cancer accounted for 37% of total costs. Costs and patient numbers increased over time, largely due to a rise in oropharyngeal cancer, where total costs increased from £17.21 million to £30.32 million, with over 1400 (52%) more inpatients treated in 2010/11 compared to 2006/07. Conclusions: In 4 years, the number of patients with oropharyngeal cancer receiving some form of inpatient care increased by more than half, and associated costs increased by three quarters. This reinforces the case for prevention and early detection strategies to help contain this epidemiological and economic burden. [ABSTRACT FROM AUTHOR]

Objectives: To examine the relative length of the patient and primary care intervals in symptomatic oral cancer. Design: Quantitative systematic review. Search strategy: Oral cancer OR oral squamous cell carcinoma OR oropharyngeal cancer AND time interval OR diagnostic delay. Setting: Primary and secondary care. Participants: Oral and oropharyngeal cancer patients. Main outcome measures: We computed five measures (patient, primary care, diagnosis, total diagnosis and total treatment intervals). Most studies did not provide any dispersion measure. We then used the sample size of each study to compute a weighted average of the mean intervals. When the median was provided, we assumed normality of the distribution of the means and used the median as a proxy of the mean. Results: A total of 1089 articles were identified, and 22 met the inclusion criteria, reporting on 2710 patients from Europe, USA, India, Australia, Japan, Argentina and Iran. The weighted average of patient interval was 80.3 days. Primary care interval was five times shorter: 15.8 days. The diagnostic interval was appreciably shorter (47.9 days) when compared with the patient interval during symptomatic period. Conclusions: Patient interval represents the major component of waiting times since the detection of the first signs/symptoms to the definitive diagnosis of oral cancer. Thus, strategies focused on high‐risk patients should be prioritised. Interventions aimed at optimising the health systems should be implemented by monitoring and facilitating diagnostic and treatment pathways of patients with oral cancer. [ABSTRACT FROM AUTHOR]

Background: Our previous study showed that overexpression of cyclin D1 protein is associated with poor prognosis in oral squamous cell carcinoma (OSCC) patients. Regarding the alteration in the transactivating pathway regulating cyclin D1 expression is still unclear in OSCC from our population. Objectives: The major objective of this study is to understand the alteration associated with the transactivation pathway regulating the cyclin D1 overexpression in OSCC patients from our population. Materials and Methods: Alteration in the transactivation pathway regulating cyclin D1 expression was evaluated in tumor sample from OSCC patients. The findings were further validated using in vitro knockdown model in OSCC cell line. Results: Results from the patients' samples showed that the Phospho-STAT3 has a significant association with cyclin D1 overexpression in OSCC tumor samples. Further knockdown in vitro studies using SCC66 showed a significant correlation between STAT3 and cyclin D1 in OSCC. Conclusion: The results from this study showed that in our population the cyclin D1 overexpression is associated with hyperactivation of STAT3 pathway. Our previous result has shown that the cyclin D1 protein overexpression is associated with poor prognosis in OSCC patients. Hence, STAT3 pathway will be better target for the patients with increased cyclin D1 in OSCC patients from our population. [ABSTRACT FROM AUTHOR]

Oral cavity and oropharyngeal carcinomas (oral cancer) represents a significant cause of morbidity and mortality. Despite efforts in improving early diagnosis and treatment, the 5-year survival rate of advanced stage of the disease is less than 63%. The field of nanomedicine has offered promising diagnostic and therapeutic advances in cancer. Indeed, several platforms have been clinically approved for cancer therapy, while other promising systems are undergoing exploration in clinical trials. With its ability to deliver drugs, nucleic acids, and MRI contrast agents with high efficiency, nanomedicine platforms offer the potential to improve drug efficacy and tolerability. The aim of the present mini-review is to summarize the current preclinical status of nanotechnology systems for oral cancer therapy. The nanoplatforms for delivery of chemopreventive agents presented herein resulted in significantly higher anti-tumor activity than free forms of the drug, even against a chemo-resistant cell line. Impressive results have also been obtained using nanoparticles to deliver chemotherapeutics, resulting in reduced toxicity both in vitro and in vivo. Nanoparticles have also led to improvements in efficacy of photodynamic therapies through the development of targeted magnetic nanoparticles. Finally, gene therapy using nanoparticles demonstrated promising results specifically with regards to inhibition of gene expression. Of the few in vivo studies that have been reported, many of these used animal models with several limitations, which will be discussed herein. Lastly, we will discuss several future perspectives in oral cancer nanoparticle-based therapy and the development of appropriate animal models, distinguishing between oral cavity and oropharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to verify that RACK1 is an organ-specific prognostic predictor in patients with oral squamous cell carcinoma (OSCC).Experimental Design: The RACK1 expression level was assessed by immunohistochemistry (IHC) in a total of 342 OSCC patients from 3 independent cohorts. The multivariate hazard ratios for Overall Survival (OS) was determined by Cox proportional hazards regression model. OS was analyzed in 460 Head Neck Squamous Cell Carcinoma (HNSCC) patients from TCGA data set. The expression level of RACK1 was analyzed in 60 cases multiple organ tissue microarrays representing both normal and cancer tissues by IHC, and in TCGA database of mRNA abundance in cancers and paired normal tissues.Results: The median follow-up times of patients in the study was 74, 52, and 78 months. High expression of RACK1 was identified in tumors from 103 of 151 patients (68.2%), 51 of 83 patients (61.4%), and 59 of 108 patients (54.6%). Compared with low expression, high expression of RACK1 was strongly associated with worse OS, with HR of 0.5995 (95% CI, 0.3929 to 0.9147; P=0.0176), 0.4402 (95% CI, 0.2321 to 0.8348; P=0.0120), and 0.5010 (95% CI, 0.2886 to 0.8699; P=0.0141). This finding is consistent with TCGA HNSCC data (P=0.0276). Tissue microarrays analyses showed different protein expression level of RACK1 in multiple human carcinomas and this finding is consistent with the TCGA database analysis of RACK1 mRNA abundance.Conclusion: Our findings demonstrated that RACK1 is a good independent organ-specific predictor of the risk of death in OSCC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oral cancers are one of the most common cancers in India. Surgery is the main modality of treatment for oral cancer patients. It is important to understand the postoperative morbidity and mortality as it influences patient outcomes. AIM: The aim of this study was to determine oral cancer patients' characteristics, treatment details, 30-day morbidity and mortality, and survival outcomes. SETTINGS AND DESIGN: This was a retrospective analysis of prospectively collected data in a tertiary cancer center. MATERIALS AND METHODS: This study included 850 surgically treated oral cancer cases between January and December 2012. STATISTICAL ANALYSIS: We performed univariate survival analysis by log-rank test, and all significant (P < 0.05) variables underwent multivariate analysis using Cox regression. RESULTS: The median age was 52 years and the male-to-female ratio was 3.4:1. Nearly one-third of the patients received some form of prior treatment. Buccal mucosa (BM) was the most common subsite (64.94%). BM cancers (81.1%) were more likely to present in advanced stage compared to tongue cancers (52%) (P = 0.000). The incidence of postoperative morbidity and mortality was 36.4% and 0.9%, respectively. Complications were higher in cT3-4 (P = 0.000), cN positive (P = 0.000), and those requiring microvascular reconstruction (P = 0.004). The 5-year overall survival of the entire study group was 70.4%. The survival of early and locally advanced stages was 75.1% and 68.4%, respectively. The factors influencing survival were age (>50 years), advanced cT stage, nodal metastasis, overall stage, and presence of orocutaneous fistula. CONCLUSION: The morbidity, mortality, and long-term outcomes of surgically treated oral cancer patients at our center are comparable to those treated in the developed world. Aggressive management of postoperative complications is crucial for early recovery and timely initiation of adjuvant treatment. [ABSTRACT FROM AUTHOR]

Carcinoma-associated fibroblasts (CAFs) are dominant components of the tumor microenvironment (TME) that promote the development, progression and metastasis of cancer. c-Met is a receptor of the hepatocyte growth factor (HGF), which is involved in lymphangiogenesis. Currently, the roles of CAFs during lymphangiogenesis are unknown. It has been hypothesized that CAFs contribute to lymphangiogenesis of oral squamous cell carcinoma (OSCC) via a HGF/c-Met complex. The expression of HGF in OSCC was determined using CAFs derived from OSCC tissue and it was demonstrated that HGF is overexpressed in OSCC-derived CAFs. It was also revealed that c-Met was highly expressed in human lymphatic endothelial cells (HLECs) when co-cultured with CAFs. Furthermore, it was demonstrated that recombinant human HGF significantly enhanced the proliferation, migration, invasion and tube formation of HLECs. By contrast, the inhibition of c-Met expression suppressed the aforementioned biological activities and also downregulated the expression of c-Met, phosphoinositide 3-kinase and phosphorylated protein kinase B. Taken together, these data demonstrate that c-Met is associated with the regulation of lymphangiogenesis. Thus, the results of the present study indicate that c-Met may be a promising novel therapeutic target to treat patients with OSCC. [ABSTRACT FROM AUTHOR]

Objectives: To improve margin revision, this study characterizes the number, fragmentation, and orientation of tumor bed margins (TBM) in patients with pT1-2 pN0 squamous cell carcinoma (SCC) of the oral tongue.Materials and Methods: Pathology reports (n=346) were reviewed. TBM parameters were indexed. In Group 1 patients all margins were obtained from the glossectomy specimen and there were no TBM. In Revision Group/Group 2 (n=103), tumor bed was sampled to revise suboptimal margins identified by examination of the glossectomy specimen. In Group 3 (n=124), TBM were obtained before examination of the glossectomy specimen.Results and Conclusions: Fewer TBMs were obtained per patient in Group 2 compared to Group 3 (57/103, 55% of patients with <3 vs. 117/124, 94%, ≥3 TBMs, respectively). The new margin surface was more frequently indicated in Group 2 compared to Group 3 (59/103, 57%, vs. 19/124, 15%, p<.001). If glossectomy specimen margins are accepted as the reference standard, then the TBM was 15% sensitive in Group 2 (95% confidence interval [CI], 7-29) and 32% sensitive in Group 3 (95% CI, 15-55). TBM fragmentation (23/103, 22% vs. 42/124, 34%) and frozen vs. permanent discrepancies (8/103, 3% vs. 3/124, 2%) were similar between Groups 2 and 3. The new margin surface was not indicated in 6 of 11 cases with discrepant frozen vs. permanent pathology findings, precluding judgment on final margin status. To facilitate the assessment of final margins, TBM should be represented by one tissue fragment with a marked new margin surface. [ABSTRACT FROM AUTHOR]

Objective: TORS-based therapy including chemotherapy or RTx was administered to patients with stage III-IV OPSCC. We analyzed the oncological and functional outcomes of stage III-IV OPSCC patients who underwent TORS-based therapy.Materials and Methods: Between May 2008 and May 2016, 80 patients participated in this clinical trial.Results: A negative margin was identified in 66 patients (82.5%) and a positive margin in 14 (17.5%). TNM stages were III in 13 patients (16.3%) and IV in 67 patients (83.8%). Of the patients, 13 received surgery alone, 28 had adjuvant RTx and 39 had adjuvant CCRTx. At last follow-up, 67 patients had no evidence of disease, seven were alive with disease, and six had died. Local recurrence developed in 2 patients and regional recurrence in 10. Five-year overall survival was 88.8%, disease-specific survival was 89.9%, and recurrence-free survival was 78.3%. The 5-year disease-specific survival of OPSCC patients with p16+ disease was 93.2%, which was higher than 89.0% of patients with p16- disease, but the difference was not statically significant. On multivariate analysis, only extranodal extension showed a significant relationship with recurrence-free survival on Cox regression analysis.Conclusion: TORS-based therapy showed excellent oncological and functional outcomes for treatment of stage III-IV OPSCC. For advanced T stage OPSCC, clear margins were obtained using TORS-based therapy and patients with clear margins showed good local control. Risk stratification of patients based on pathological information obtained after surgery and decision about additional treatment based on the information helped improve OS and DSS of OPSCC patients. [ABSTRACT FROM AUTHOR]

Oral leukoplakia and erythroleukoplakia are common oral potentially malignant disorders diagnosed in the oral cavity. The specific outcome of these lesions remains to be elucidated, as their malignant transformation rate exhibits great variation. The ability to predict which of those potentially malignant lesions are likely to progress to cancer would be vital to guide their future clinical management. The present study reported two patients with tongue squamous cell carcinoma: Case study 1 was diagnosed with a simultaneous leukoplakia and case study 2 developed an erythroleukoplakia following the primary tumor treatment. Whole genome copy number alterations were analyzed using array comparative genomic hybridization. The present study determined more genomic imbalances in the tissues from leukoplakia and erythroleukoplakia compared with their respective tumors. The present study also identified in tumor and potentially malignant lesions common alterations of chromosomal regions and genes, including FBXL5, UGT2B15, UGT2B28, KANSL1, GSTT1 and DUSP22, being some of these typical aberrations described in oral cancer and others are linked to chemoradioresistance. Several putative genes associated with hallmarks of malignancy that may have an important role in predicting the progression of leukoplakia and erythroleukoplakia to squamous cell carcinoma, namely gains in BNIPL, MCL1, STAG2, CSPP1 and ZNRF3 genes were also identified. [ABSTRACT FROM AUTHOR]

Purpose: Oral agents for cancer treatment are increasingly prescribed due to their benefits. However, oral cancer medications are difficult to handle and have a considerable potential for side effects. This type of therapy requires a high level of self-management competence by the patient. A standardized patient education program provided by physicians and oncology nurses may positively influence the handling of oral agents. The aim of the study was to evaluate the impact of a standardized patient education program provided by specially trained oncology nurses on therapy management regarding side effects and unplanned therapy interruptions.Methods: One hundred sixty-five patients from 28 office-based oncology practices from all over Germany participated in this cluster-randomized controlled study. Patients of both intervention (n = 111) and standard care groups (n = 54) received the usual oncologist counseling; in addition, the patients from the intervention group (k = 17 practices) received an education from specially trained oncology nurses. The time of observation was 3 months per patient.Results: The patients of the intervention group reported fewer side effects (skin rash, pain, fatigue, nausea, vomiting). Patients in the standard care group interrupted the therapy more frequently without informing their oncologist, compared to the intervention group.Conclusions: Patients benefit from a standardized patient education program provided by specially trained oncology nurses. They tend to handle side effects and critical situations better. [ABSTRACT FROM AUTHOR]

Although platelet to lymphocyte ratio (PLR) and red cell distribution width (RDW) have been reported as good predictors for survival outcomes in various cancers, there is limited data supporting these as reliable predictors in oral cancer. This study thus aimed to assess the prognostic value of PLR and RDW markers in predicting survival and recurrence rates in patients with oral cancer. The records of 374 oral cancer patients treated with curative intent over a 7-year period (2009-2015) were reviewed. Survival and recurrence outcomes were compared between those with low and high PLR (≤135 vs. >135) and those with low and high RDW (≤14.05 vs. >14.05) using hazard ratios (HR). The 5-year disease-specific survival was significantly higher and recurrence rate significantly lower among the low PLR group compared to the high PLR group (65.7 vs. 37.6%; p < 0.001 and 34.4 and 57.5%; p < 0.001), respectively. There were no significant differences between the low and high RDW groups for disease-specific survival (53.6 vs. 54.7%, p = 0.408) and recurrence (40.0% vs. 53.8%, p = 0.079). Multivariate analysis showed that PLR was associated with disease-specific survival (HR = 2.05, p < 0.001) and recurrence (HR = 1.69, p < 0.005) after adjusting for other factors, but not RDW. High PLR shows promise as a prognostic predictor for poor survival and recurrence in patients with oral cancer, but further studies are required. RDW has no prognostic value on any outcome. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to compare costs and clinical outcomes of two protocols for implant placement in edentulous oral cancer patients: implant placement during ablative surgery and postponed implant placement. Material and methods All edentulous patients who underwent curative tumor surgery between 2007 and 2009 at the Radboud university medical center (Radboudumc) and UMC Utrecht, both in the Netherlands, were included retrospectively. At the Radboudumc, 79 of 98 patients received implants during ablative surgery. At the UMC Utrecht, 18 of 95 patients received implants after a disease-free period of at least 6 months, because satisfying conventional dentures could not be made. Costs, implant details and clinical outcomes were recorded retrospectively up to 5 years after tumor surgery. Results Individual costs of implant placement were lower in the during-ablative-surgery protocol (€2235 vs. €4152), while implant failure and loading were comparable to the postponed-placement protocol. In the during-ablative-surgery protocol, more patients received implant-retained overdentures (62% vs. 17%) and more patients had functioning dentures (65% vs. 47%), which were placed at an earlier stage (291 vs. 389 days after surgery). Overall costs of the during-ablative-surgery protocol were higher, as more patients received implants and functioning implant-retained dentures, which were more expensive than conventional dentures. Conclusions Placing implants during ablative surgery lowered the individual costs of implant placement and led to more patients with functioning dentures, while implant failure and loading were comparable to postponed placement. [ABSTRACT FROM AUTHOR]

Raman spectroscopy (RS) is a sensitive vibrational spectroscopic method that can detect even subtle biochemical changes during the onset of disease. Consequently, RS has been extensively investigated for disease diagnosis, including cancers. Oral cancers are known to suffer from dismal survival rates, which have not improved for several decades. As delayed diagnosis contributes to the low disease-free survival rate observed in oral cancers, RS has also been explored for the early diagnosis of oral cancers. This review summarizes the major developments in the field, including diagnosis, surgical margin assessment and prediction of treatment response, and in the overall management of oral cancers. The article comprises an overview of epidemiology, diagnosis, treatment, and recently introduced diagnostic adjuncts for oral cancers, the basic principle, instrumentation of RS, multivariate analysis that impart objectivity to the approach, and finally a discussion on the recent applications in oral cancers. PubMed and Google Scholar database have been used to compile information available online till December 2015. [ABSTRACT FROM AUTHOR]

Cell-derived microparticles (MPs), which are biogenic nanosized membrane vesicles that convey bioactive molecules between cells, have exhibited great potential to serve as therapeutic platforms. However, so far, all the MPs used as theranostic vectors in previous studies have been produced in vitro from cell culture supernatants, which is still associated with several concerns regarding practical applications. In this study, circulating MPs (CMPs), which are freshly purified from the peripheral blood of oral squamous cell carcinoma (OSCC) patients, are directly and efficiently embedded with ultrasmall near-infrared-fluorescent magnetic quantum dots (Ag2Se@Mn QDs) via electroporation. By virtue of the superior photostability, favorable biocompatibility, and dual-mode traceability of Ag2Se@Mn QD-labeled CMPs in vivo, the tissue distribution and natural tumor-targeting behavior of CMPs from OSCC patients are directly visualized in living mice for the first time. Moreover, by simultaneously embedding antitumor siRNA and Ag2Se@Mn QDs into CMPs derived from OSCC patients, a dual-modally traceable and actively tumor-targeted nanoplatform for cancer theranostics is developed. This study reports the first reliable conjugation-free labeling strategy for in vivo dual-mode tracking of CMPs harvested from the human body, and, more importantly, reports the development of traceable tumor-targeted theranostic vectors based on naturally occurring CMPs from cancer patients. [ABSTRACT FROM AUTHOR]

Background: Oral cancers are one of the most common cancers in India. Surgery is the main modality of treatment for oral cancer patients. It is important to understand the postoperative morbidity and mortality as it influences patient outcomes.Aim: The aim of this study was to determine oral cancer patients' characteristics, treatment details, 30-day morbidity and mortality, and survival outcomes.Settings and Design: This was a retrospective analysis of prospectively collected data in a tertiary cancer center.Materials and Methods: This study included 850 surgically treated oral cancer cases between January and December 2012.Statistical Analysis: We performed univariate survival analysis by log-rank test, and all significant (P < 0.05) variables underwent multivariate analysis using Cox regression.Results: The median age was 52 years and the male-to-female ratio was 3.4:1. Nearly one-third of the patients received some form of prior treatment. Buccal mucosa (BM) was the most common subsite (64.94%). BM cancers (81.1%) were more likely to present in advanced stage compared to tongue cancers (52%) (P = 0.000). The incidence of postoperative morbidity and mortality was 36.4% and 0.9%, respectively. Complications were higher in cT3-4 (P = 0.000), cN positive (P = 0.000), and those requiring microvascular reconstruction (P = 0.004). The 5-year overall survival of the entire study group was 70.4%. The survival of early and locally advanced stages was 75.1% and 68.4%, respectively. The factors influencing survival were age (>50 years), advanced cT stage, nodal metastasis, overall stage, and presence of orocutaneous fistula.Conclusion: The morbidity, mortality, and long-term outcomes of surgically treated oral cancer patients at our center are comparable to those treated in the developed world. Aggressive management of postoperative complications is crucial for early recovery and timely initiation of adjuvant treatment. [ABSTRACT FROM AUTHOR]

Objective: Is the use of harmonic scalpel for neck dissection useful? Literature search did not show a single, prospective, randomised control trial. We intended to study the role of harmonic scalpel in neck dissection and compare it with conventional electrocautery technique for oral cavity carcinoma.Methods: 40 patients undergoing selective neck dissection for primary oral cavity malignancy were enrolled in this study. The harmonic scalpel (HS) group consisted of 20 patients, and the electrocautery technique (ET) group comprised of 20 patients. The following variables were examined: intraoperative blood loss, operative time, number of ligatures used, postoperative drain, and postoperative hospital stay.Results: Intraoperative blood loss was found to be significantly reduced in harmonic scalpel group as compared to electrocautery group. However, we found no difference in other parameters like operative time, postop drain, postoperative hospital stay and number of ligatures used between both groups.Conclusion: Harmonic scalpel for neck dissection is associated with significantly lesser intraoperative blood loss as compared to electrocautery. There is no effect on operative time and postoperative hospital stay in both groups. [ABSTRACT FROM AUTHOR]

Background: The aim was to explore the immunophenotype of neutrophils and lymphocytes and the inflammatory mediators in patients with oral squamous cell carcinoma, comparing with controls; and to associate with clinicopathological data.Methods: Blood was collected from 13 patients and 13 controls. The immunophenotype of neutrophils (CD66b, CD16, CD11a, arginase-1), T lymphocytes (CD4, CD8) and the intracellular cytokine production (IL-10, TNF, IFN-γ) was evaluated by flow cytometry. Plasma concentration of sVCAM-1, sTNF-RI, sTNF-RII, and IL-1β was measured by ELISA. MPO, Lipocalin-2/NGAL, sICAM-1, and p-selectin were quantified by Luminex assay. The excised tumors were submitted to immunohistochemistry for neutrophils (CD66b) and lymphocytes (CD3, CD4, CD8). Association with clinical data was explored. P values <.05 were considered significant.Results: Patients presented higher percentage of neutrophils and lower lymphocytes, resulting a higher neutrophil/lymphocyte ratio than controls. They also presented higher percentage of neutrophils expressing CD66b+ , CD66b+ Arginase-1+ , CD66b+ IL10+ , CD66b+ TNF+ , CD66b+ Arginase-1+ IL-10+ , and lower CD66b+ CD16+ CD11a+ and CD66b+ Arginase-1+ TNF+ . CD66b+ neutrophils were detected in all tumors, with a CD66b+ /CD3+ ratio of 0.40. Patients showed higher concentration of plasmatic sVCAM-1 and lower Lipocalin-2/NGAL. Patients with good outcome presented lower percentage of neutrophils, higher percentage of lymphocytes, and lower NLR than patients who died.Conclusion: The amount and immunophenotype of neutrophils and lymphocytes differ between patients and healthy individuals, with a pro-tumorigenic profile of neutrophils. As these cells also get within tumor microenvironment, they possibly exert systemic and local functions in cancer pathogenesis. The association of neutrophil count with outcome corroborates recent studies and this merits further investigation for applicability as a prognosticator. [ABSTRACT FROM AUTHOR]