Exploring the microbiome of oral epithelial dysplasia as a predictor of malignant progression.

A growing body of research associates the oral microbiome and oral cancer. Well-characterized clinical samples with outcome data are required to establish relevant associations between the microbiota and disease. The objective of this study was to characterize the community variations and the functional implications of the microbiome in low-grade oral epithelial dysplasia (OED) using 16S rRNA gene sequencing from annotated archival swabs in progressing (P) and non-progressing (NP) OED. We characterised the microbial community in 90 OED samples - 30 swabs from low-grade OED that progressed to cancer (cases) and 60 swabs from low-grade OED that did not progress after a minimum of 5 years of follow up (matched control subjects). There were small but significant differences between P and NP samples in terms of alpha diversity as well as beta diversity in conjunction with other clinical factors such as age and smoking status for both taxa and functional predictions. Across all samples, the most abundant genus was Streptococcus, followed by Haemophilus, Rothia, and Neisseria. Taxa and predicted functions were identified that were significantly differentially abundant with progression status (all Ps and NPs), when samples were grouped broadly by the number of years between sampling and progression or in specific time to progression for Ps only. However, these differentially abundant features were typically present only at low abundances. For example, Campylobacter was present in slightly higher abundance in Ps (1.72%) than NPs (1.41%) and this difference was significant when Ps were grouped by time to progression. Furthermore, several of the significantly differentially abundant functions were linked to the Campylobacteraceae family in Ps and may justify further investigation. Larger cohort studies to further explore the microbiome as a potential biomarker of risk in OED are warranted.

Ultrasensitive rapid cytokine sensors based on asymmetric geometry two-dimensional MoS2 diodes.

The elevation of cytokine levels in body fluids has been associated with numerous health conditions. The detection of these cytokine biomarkers at low concentrations may help clinicians diagnose diseases at an early stage. Here, we report an asymmetric geometry MoS2 diode-based biosensor for rapid, label-free, highly sensitive, and specific detection of tumor necrosis factor-α (TNF-α), a proinflammatory cytokine. This sensor is functionalized with TNF-α binding aptamers to detect TNF-α at concentrations as low as 10 fM, well below the typical concentrations found in healthy blood. Interactions between aptamers and TNF-α at the sensor surface induce a change in surface energy that alters the current-voltage rectification behavior of the MoS2 diode, which can be read out using a two-electrode configuration. The key advantages of this diode sensor are the simple fabrication process and electrical readout, and therefore, the potential to be applied in a rapid and easy-to-use, point-of-care, diagnostic tool.

Predicting Progression of Low-Grade Oral Dysplasia Using Brushing-Based DNA Ploidy and Chromatin Organization Analysis.

Most oral cancers arise from oral potentially malignant lesions, which show varying grades of dysplasia. Risk of progression increases with increasing grade of dysplasia; however, risk prediction among oral low-grade dysplasia (LGD), that is, mild and moderate dysplasia can be challenging as only 5%-15% transform. Moreover, grading of dysplasia is subjective and varies with the area of the lesion being biopsied. To date, no biomarkers or tools are used clinically to triage oral LGDs. This study uses a combination of DNA ploidy and chromatin organization (CO) scores from cells obtained from lesion brushings to identify oral LGDs at high-risk of progression. A total of 130 lesion brushings from patients with oral LGDs were selected of which 16 (12.3%) lesions progressed to severe dysplasia or cancer. DNA ploidy and CO scores were analyzed from nuclear features measured by our in-house DNA image cytometry (DNA-ICM) system and used to classify brushings into low-risk and high-risk. A total of 57 samples were classified as high-risk of which 13 were progressors. High-risk DNA brushing was significant for progression (P = 0.001) and grade of dysplasia (P = 0.004). Multivariate analysis showed high-risk DNA brushing showed 5.1- to 8-fold increased risk of progression, a stronger predictor than dysplasia grading and lesion clinical features. DNA-ICM can serve as a non-invasive, high-throughput tool to identify high-risk lesions several years before transformation. This will help clinicians focus on such lesions whereas low-risk lesions may be spared from unnecessary biopsies.Prevention Relevance: DNA ploidy and chromatin organization of cells collected from oral potentially malignant lesions (OPMLs) can identify lesions at high-risk of progression several years prior. This non-invasive test would enable clinicians to triage high-risk (OPMLs) for closer follow-up while low-risk lesions can undergo less frequent biopsies reducing burden on healthcare resources.

Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions.

BACKGROUNDThe aberrant activation of the PI3K/mTOR signaling circuitry is one of the most frequently dysregulated signaling events in head and neck squamous cell carcinoma (HNSCC). Here, we conducted a single-arm, open-label phase IIa clinical trial in individuals with oral premalignant lesions (OPLs) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention.METHODSIndividuals with OPLs, but who were otherwise healthy and without diabetes, underwent pretreatment and posttreatment clinical exam and biopsy. Participants received metformin for 12 weeks (week 1, 500 mg; week 2, 1000 mg; weeks 3-12, 2000 mg daily). Pretreatment and posttreatment biopsies, saliva, and blood were obtained for biomarker analysis, including IHC assessment of mTOR signaling and exome sequencing.RESULTSTwenty-three participants were evaluable for response. The clinical response rate (defined as a ≥50% reduction in lesion size) was 17%. Although lower than the proposed threshold for favorable clinical response, the histological response rate (improvement in histological grade) was 60%, including 17% complete responses and 43% partial responses. Logistic regression analysis revealed that when compared with never smokers, current and former smokers had statistically significantly increased histological responses (P = 0.016). Remarkably, a significant correlation existed between decreased mTOR activity (pS6 IHC staining) in the basal epithelial layers of OPLs and the histological (P = 0.04) and clinical (P = 0.01) responses.CONCLUSIONTo our knowledge this is the first phase II trial of metformin in individuals with OPLs, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.TRIAL REGISTRATIONNCT02581137FUNDINGNIH contract HHSN261201200031I, grants R01DE026644 and R01DE026870.

Basement membrane degeneration is common in lichenoid mucositis with dysplasia.

Background: Two subtypes of lichenoid mucositis (LM) with oral epithelial dysplasia have been proposed, with differing risks of malignant transformation. However, no research has been done to authenticate this hypothesis. The study objective was to determine whether there are 2 subcategories within this entity, one with primary lichenoid and secondary dysplastic features (L1D2), and the other with primary dysplastic and secondary lichenoid features (D1L2), and to compare the proportion of malignant progression in these groups. Methods: Patients with a diagnosis of lichenoid mucositis with low-grade (mild/moderate) oral epithelial dysplasia, no history of head and neck cancer, and who had at least 5 years of follow-up were eligible to participate in this nested case-control study. Cases (n = 10) were defined as lesions that progressed to severe dysplasia, carcinoma in situ or squamous cell carcinoma; controls (n = 32) were defined as those that did not progress. Immunohistochemistry was performed to assess for basement membrane (BM) degeneration using collagen IV-an integral BM protein. Results: Lesions that progressed to cancer exhibited a similar proportion of BM degeneration at baseline (70%) compared to non-progressors (78%), with no statistically significant difference between groups (p = 0.69). Conclusion: BM degeneration is frequently seen in LM with dysplasia and alone does not appear to be a predictor of malignant progression in lesions with both lichenoid and low-grade dysplastic features. Dysplasia should not be discounted in the presence of LM. Lesions that display any degree of dysplasia warrant clinical follow-up and continued monitoring.

Contexte: Deux sous-types de mucosites lichénoïdes (ML) avec dysplasie épithéliale buccale ont été proposés, avec des risques différents de transformation maligne. Cependant, aucune recherche n'a été faite pour valider cette hypothèse. L'objectif de l'étude était de déterminer s'il y a 2 sous-catégories au sein de cette entité, la première avec des caractéristiques lichénoïdes primaires et dysplasiques secondaires (L1D2), et l'autre avec des caractéristiques dysplasiques primaires et lichénoïdes secondaires (D1L2), et de comparer la proportion de progression maligne dans ces groupes. Méthodologie: Les patients ayant reçu un diagnostic de mucosite lichénoïde avec une dysplasie épithéliale buccale de faible intensité (faible/modérée), qui n'avaient aucun antécédent de cancer de la tête et du cou, et qui avaient eu au moins 5 ans de suivi, étaient admissible à participer à cette étude de cas-témoins emboîtés. Les cas (n = 10) étaient définis comme des lésions qui ont progressé à la dysplasie sévère, un carcinome in situ ou un carcinome squameux; les contrôles (n = 32) étaient définis comme ceux qui n'ont pas progressé. L'immunohistochimie a été effectuée pour évaluer s'il y avait eu une dégénérescence de la membrane basale (MB) en utilisant du collagène IV, une protéine MB intrinsèque. Résultats: Les lésions qui ont évolué en cancer ont présenté une proportion semblable de dégénérescence de MB au début (70 %) par rapport aux non-progresseurs (78 %), et aucune différence statistiquement significative entre les groupes (p = 0,69). Conclusion: La dégénérescence des MB est fréquemment constatée dans les ML avec dysplasie et seule, ne paraît pas être une variable explicative de l'évolution maligne dans les lésions à caractéristiques à la fois lichénoïdes et dysplasiques de faible intensité. Il ne faut pas sous-estimer la dysplasie en présence de ML. Les lésions qui présentent de la dysplasie, peu importe son étendue, exigent un suivi clinique et une surveillance continue.

Intraoral Photography Recommendations for Remote Risk Assessment and Monitoring of Oral Mucosal Lesions.

Oral cancer is a global health issue with substantial morbidity and a high mortality rate mainly because of late-stage diagnosis. Cancerous lesions are often preceded by potentially malignant lesions that may be detected during routine dental examinations. Not only is the oral cavity easily accessible for screening, but the clinical risk factors of the disease are also known. However, patients may not always be able to access screening services or receive follow-up for diagnosed lesions. In these circumstances, intraoral photos are crucial for timely triage, risk assessment, and monitoring of oral lesions. Further, photos form an integral part of a patient's records, facilitate patient education and communication between health care providers, and provide important information during the referral process. To ensure that intraoral photos are of good quality and standardised there is a need to establish recommendations regarding intraoral photography in oral mucosal screening. This article recommends methods to help health professionals and patients obtain interpretable intraoral photographs. Suggestions to achieve ideal lighting, mirror placement, camera angle, and retraction have been discussed. These recommendations are adaptable to easily available smartphone or point-and-shoot cameras and may be further used to develop future teledentistry platforms.

Visual Analytics: A Method to Explore Natural Histories of Oral Epithelial Dysplasia.

Risk assessment and follow-up of oral potentially malignant disorders in patients with mild or moderate oral epithelial dysplasia is an ongoing challenge for improved oral cancer prevention. Part of the challenge is a lack of understanding of how observable features of such dysplasia, gathered as data by clinicians during follow-up, relate to underlying biological processes driving progression. Current research is at an exploratory phase where the precise questions to ask are not known. While traditional statistical and the newer machine learning and artificial intelligence methods are effective in well-defined problem spaces with large datasets, these are not the circumstances we face currently. We argue that the field is in need of exploratory methods that can better integrate clinical and scientific knowledge into analysis to iteratively generate viable hypotheses. In this perspective, we propose that visual analytics presents a set of methods well-suited to these needs. We illustrate how visual analytics excels at generating viable research hypotheses by describing our experiences using visual analytics to explore temporal shifts in the clinical presentation of epithelial dysplasia. Visual analytics complements existing methods and fulfills a critical and at-present neglected need in the formative stages of inquiry we are facing.

Effect of Fluorescence Visualization-Guided Surgery on Local Recurrence of Oral Squamous Cell Carcinoma: A Randomized Clinical Trial.

Importance: High local recurrence rates with aggressive disease remain the main concern in oral cancer survival. Use of a translational device using fluorescence visualization (FV) approved by the US Food and Drug Administration and Health Canada, has shown a marked reduction in the 3-year local recurrence rate of high-grade oral lesions in a single-center observational study. Objective: To determine whether FV- guided surgery can improve local control rates in the treatment of in situ or T1 to T2 category oral squamous cell carcinoma (OSCC). Design, Setting, and Participants: A multicenter randomized clinical trial was conducted in a surgical setting. A total of 457 patients were enrolled between January 18, 2010, and April 30, 2015. Data analysis of the intention-to-treat population was performed from April 3, 2019, to March 20, 2020. Patients with histologically confirmed high-grade dysplasia/carcinoma in situ or T1 to T2 category OSCC were randomized to receive traditional peroral surgery or FV-guided surgery. Intervention: Fluorescence visualization during surgery. Main Outcomes and Measures: The primary outcome was local recurrence of OSCC. Secondary outcomes were failure of the first-pass margin, defined as a histologically confirmed positive margin for severe dysplasia or greater histologic change of the main specimen (ie, not the margins taken from the resection bed), regional or distant metastasis, and death due to disease. Results: Of the 457 patients enrolled in the study, 443 patients (264 [59.6%] men; mean [SD] age, 61.5 [13.3] years) completed the randomized treatment: 227 FV-guided and 216 non-FV guided surgery. The median follow-up was 52 (range, 0.29-90.8) months. In total, 45 patients (10.2%) experienced local recurrence. The 3-year local recurrence rate was 9.4% in the FV-guided group and 7.2% in the non-FV group (difference, 2.2%; 95% CI, -3.2% to 7.4%). Other similarities between the FV vs non-FV groups included failure of first-pass margin (68/227 [30.0%]) vs 65/216 [30.1%]), regional failure (39/227 [17.2%] vs 37/216 [17.1%]), disease-specific survival (23/227 [10.1%] vs 19/26 [8.8%]), and overall survival (41/227 [18.1%] vs 38/216 [17.6%]) were also similar between groups. No adverse events were judged to be related to the intervention. Conclusions and Relevance: In this randomized clinical trial, FV-guided surgery did not improve local control rates in the treatment of patients with in situ or T1 to T2 category oral cancer. Under a controlled environment, FV-guided surgery did not have an evident effect in reduction of local recurrence for localized OSCC. This result suggests that attention be directed to strategies other than improving definitions of nonapparent disease at clinical margins to identify the sources of local recurrence. Trial Registration: ClinicalTrial.gov Identifier: NCT01039298.

Exploring Knowledge and Perspectives of South Asian Children and Their Parents Regarding Healthy Cardiovascular Behaviors: A Qualitative Analysis.

South Asian children and parents have been shown to have a higher risk for cardiovascular disease (CVD) relative to white individuals. To design interventions aimed at addressing the comparatively higher burden in South Asians, a better understanding of attitudes and perspectives regarding CVD-associated behaviors is needed. As a result, we sought to understand knowledge about CVD risk in both children and parents, and attitudes toward physical activity and diet in both the children and parents, including potential cultural influences. In-depth interviews were conducted with 13 South Asian child-and-parent dyads representing a range of child body mass index (BMI) levels, ages, and with both sexes. South Asian children and parents demonstrated good knowledge about CVD prevention; however, knowledge did not always translate into behavior. The influence of social and cultural dynamics on behavior was also highlighted. To ensure that interventions aimed at this population are effective, an understanding of the unique social dynamics that influence diet and physical activity-related behaviors is needed.

Multifactorial correlates of blood pressure in South Asian children in Canada: a cross-sectional study.

OBJECTIVE: We sought to explore various correlates of blood pressure (BP) and hypertension, and to identify the most important aggregate combination of correlates for BP in South Asian children. DESIGN: Cross-sectional study SETTING: Community-based recruitment in two Canadian cities PARTICIPANTS: South Asian children (n=762) provided a range of physiological, lifestyle and social variables. BP was assessed using an automated device. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and BP were transformed to z-scores using published standards. OUTCOME MEASURES: Linear and logistic regression analyses were used to explore associations between the range of variables with BP z-scores and hypertension while stepwise regression was used to identify aggregate factors that provided explanatory capacity for systolic BP (SBP) and diastolic BP (DBP) z-scores. RESULTS: A range of variables were associated with BP z-score and hypertension in unadjusted analysis. On adjustment for confounders, the association between age (ß=-0.054, 95% CI=-0.078 to 0.029), female sex (ß=-0.208, 95% CI=-0.350 to -0.067), height (ß=0.022, 95% CI=0.011 to 0.033), weight (ß=0.047, 95% CI=0.040 to 0.055), BMI z-score (ß=0.292, 95% CI=0.249 to 0.336), WC z-score (ß=0.273, 95% CI=0.219 to 0.326), WHtR z-score (ß=0.289, 95% CI=0.236 to 0.342), heart rate (ß=0.016, 95% CI=0.010 to 0.022), child's perception of body image (ß=0.183, 95% CI=0.128 to 0.239) and grip strength (ß=0.025, 95% CI=0.007 to 0.043) with SBP z-score remained. In stepwise regression, age, sex, BMI z-score, heart rate and weight accounted for 30% of the variance of SBP z-score, while age, BMI z-score, heart rate and daily fast food intake accounted for 23% of the DBP z-score variance. CONCLUSION: Our findings suggest that variables, such as age, sex, height, adiposity and heart rate, provide stronger explanatory capacity to BP variance and hypertension risk than other variables in South Asian children.

Adiposity measures and their validity in estimating risk of hypertension in South Asian children: a cross-sectional study.

OBJECTIVE: Given the South Asian phenotype of higher body fat at similar body mass index (BMI) relative to Caucasians, we sought to explore the association between prominent adiposity indicators with blood pressure (BP) and hypertension, to compare the accuracy of these indicators in estimating hypertension, and to provide cut-off values associated with adverse hypertension risk in South Asian children. DESIGN: Cross-sectional study. SETTING: Community-based recruitment in two Canadian cities (Hamilton and Surrey). PARTICIPANTS: South Asian children (n=762) were recruited from two Canadian cities. Waist circumference, waist to height ratio and BMI were determined. Body fat percentage was assessed by bioelectrical impedance analysis and BP was assessed using an automated device. All variables (except body fat percentage) were transformed to z-scores using published standards. OUTCOME MEASURES: Linear and Poisson regression was used to explore associations between the adiposity indicators with BP z-score and hypertension. Receiver operating curve (ROC) analysis was used to explore the strength of the adiposity indicators in estimating hypertension risk and sex-stratified optimal adiposity cut-off values associated with hypertension risk. RESULTS: Significant associations were detected in adjusted and unadjusted models between the adiposity indicators with BP z-score and hypertension (p<0.01 for all). The area under the curve (AUC) values for the adiposity indicators for boys and girls ranged from 0.74 to 0.80, suggesting that the adiposity indicators are fair measures of estimating hypertension risk. Sex-stratified cut-off associated with adverse risk of hypertension for girls and boys, respectively, were at the 92nd and 82nd percentile for BMI z-scores, 65th and 80th percentile for WC z-score, 63rd and 67th percentile for WHtR z-score and at 29.8% and 23.5% for body fat. CONCLUSION: Our results show associations between adiposity indicators with BP and hypertension and suggests that South Asian children might be at adverse risk of hypertension at levels of adiposity considered normal.

Using quantitative tissue phenotype to assess the margins of surgical samples from a pan-Canadian surgery study.

BACKGROUND: The purpose of this study was to use quantitative tissue phenotype (QTP) to assess the surgical margins to examine if a fluorescence visualization-guided surgical approach produces a shift in the surgical field by sparing normal tissue while catching high-risk tissue. METHODS: Using our QTP to calculate the degree of nuclear chromatin abnormalities, Nuclear Phenotypic Score (NPS), we analyzed 1290 biopsy specimens taken from surgical samples of 248 patients enrolled in the Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer (COOLS) trial. Multiple margin specimens were collected from each surgical specimen according to the presence of fluorescence visualization alterations and the distance to the surgical margins. RESULTS: The NPS in fluorescence visualization-altered (fluorescence visualization-positive) samples was significantly higher than that in fluorescence visualization-retained (fluorescence visualization-negative) samples. There was a constant trend of decreasing NPS of margin samples from non-adjacent-fluorescence visualization margins to adjacent-fluorescence visualization margins. CONCLUSION: Our results suggested that using fluorescence visualization to guide surgery has the potential to spare more normal tissue at surgical margins.

Effect of age on chronic inflammation and responsiveness to bacterial and viral challenges.

To identify reliable biomarkers of age-related changes in chronic inflammation and responsiveness to bacterial and viral challenges, we evaluated endogenous and ex vivo stimulated levels of 18 inflammatory markers, using whole blood collected in EDTA and sodium heparin tubes from 41 healthy volunteers, i.e., 11 men + 10 women aged 20-35 and 10 men + 10 women aged 50-77. These studies revealed significant differences in the levels of inflammatory markers when blood was collected in EDTA versus sodium heparin and age related differences in these biomarkers were confirmed with blood collected in EDTA from 120 healthy volunteers in 3 age categories, ie, 20 men + 20 women, aged 20-35, 36-49 and 50-77. Studies with unstimulated blood samples, to measure levels of chronic inflammation, revealed a significant increase with age in IL-12p70, CRP and PGE2, consistent with the concept of "inflammaging", and a decrease in G-CSF in both men and women. Interestingly, in response to E. coli stimulation, PGE2 levels were markedly reduced in the 50-77 year old cohort while they were increased following Herpes Simplex virus-1 (HSV-1) stimulation, along with IL-8. In addition, unlike E. coli, HSV-1 potently stimulated IFNα production, but levels were dramatically reduced in the older cohort, consistent with a reduced ability to generate an anti-viral response. We also found platelets and CD8+ T cells were reduced with age while CD4+ T cells were significantly increased, resulting in a substantially higher CD4/CD8 ratio in the older cohort. Surprisingly, however, we found that the older cohort exhibited more T cell proliferation and IFNγ production in response to anti-CD3+anti-CD28 stimulation. Importantly, there was considerable person-to-person variation in these inflammatory markers in all age groups, making possible comparisons between a person's "inflammage" and chronological age. These assays should help to identify individuals at high risk of autoimmune disorders and cancer.

Socioeconomic disparities in head and neck cancer patients' access to cancer treatment centers.

INTRODUCTION: Both socioeconomic status and travel time to cancer treatment have been associated with treatment choice and patient outcomes. An improved understanding of the relationship between these two dimensions of access may enable cancer control experts to better target patients with poor access, particularly in isolated suburban and rural communities. METHODS: Using geographical information systems, head and neck cancer patients across British Columbia, Canada from 1981 to 2009, were mapped and their travel times to the nearest treatment center at their time of diagnosis were modelled. Patients' travel times were analysed by urban, suburban, and rural neighborhood types and an index of multiple socioeconomic deprivation was used to assess the role of socioeconomic status in patients' spatial access. RESULTS: Significant associations between socioeconomic deprivation and spatial access to treatment were identified, with the most deprived quintiles of patients experiencing nearly twice the travel time as the least deprived quintile. The sharpest disparities were observed among the most deprived patient populations in suburban and rural areas. However, the establishment of new treatment centers has decreased overall travel times by 28% in recent decades. CONCLUSIONS: Residence in a neighborhood with high socioeconomic deprivation is strongly associated with head and neck cancer patients' spatial access to cancer treatment centers. Patients residing in the most socioeconomically deprived neighborhoods consistently have longer travel times in urban, suburban, and rural communities in the study area.

Optimizing Fixation Protocols to Improve Molecular Analysis from FFPE Tissues.

Most Departments of Pathology around the world have a considerable archive of formalin-fixed paraffin-embedded (FFPE) tissue suitable for molecular assessment. This article points out the potential DNA damage that may occur if basic steps are not followed during processing and storage of these samples. Furthermore, it hopes to establish parameters to optimize quality and quantity of DNA extracted from FFPE tissues.

Optimizing Fixation Protocols to Improve Molecular Analysis from FFPE Tissues

Abstract Most Departments of Pathology around the world have a considerable archive of formalin-fixed paraffin-embedded (FFPE) tissue suitable for molecular assessment. This article points out the potential DNA damage that may occur if basic steps are not followed during processing and storage of these samples. Furthermore, it hopes to establish parameters to optimize quality and quantity of DNA extracted from FFPE tissues.

Resumo A maioria dos Departamentos de Patologia em todo o mundo têm um considerável acervo de tecidos embebidos em parafina e fixados em formalina, que são passíveis para análises moleculares. Este artigo apresenta os danos ao DNA que podem ocorrer se passos básicos não forem seguidos durante o processamento e armazenamento destas amostras. Além disso, procura estabelecer parâmetros para otimizar a qualidade e quantidade do DNA extraído de tecidos FFPE.

Oral Squamous Cell Carcinomas are Associated with Poorer Outcome with Increasing Ages.

OBJECTIVES: 1.1.Although oral cancers traditionally occur in people between the age of 50 and 70, there are increasing incidences of this disease in younger and very old people. Objectives: to compare the demographics, habits, clinicopathological features, treatment and outcome of oral cancer in three age groups of patients: Young (≤ 45), Traditional (46 to 75), and Old (> 75). SUBJECTS: 1.2.Primary oral cancers (393 patients) in a longitudinal study were used. RESULTS: 1.3.Significant differences were noted in ethnicity (fewer Caucasian patients in Young), tobacco habit (more non-smokers in Young), location of cancer (more at tongue for Young and more at low-risk sites for Old) and treatment (more surgery for Young). Compared to Young (univariate analysis), Traditional and Old showed a 3- and 4.5-fold increase in local recurrences respectively; 1.9- and 2.7-fold increase in regional metastasis; 3.1- and 5.4-fold increase in death due to disease; and a 3.4- and 6.6-fold decrease in overall survival. Compared to Young (multivariate analysis), Traditional and Old showed a 2.4- and 3.3-fold increase in local recurrence; 2.7- and 5.4-fold increase in disease-specific survival; and 2.8- and 6.5-fold decrease in overall survival. CONCLUSION: 1.4.Oral cancer in different age groups showed differing ethnicity, habit, location, treatment and outcome.

Should severe epithelial dysplasia be treated?

OBJECTIVE: To identify clinical features associated with progression of primary severe epithelial dysplasia into invasive squamous cell carcinoma (SCC). DESIGN: Longitudinal population-based study. SETTING: Oral dysplasia clinics. PATIENTS: This study involved 118 patients with 118 severe dysplasia who were prospectively enrolled between 1996 and 2014, and the lesions were either completely removed surgically (treated) or actively followed (untreated). MEASUREMENTS: Demographics, habits, clinical information and outcome were compared between the treated and untreated groups. RESULTS: Of the 118 lesions, 77 were treated and 41 were not. The treated lesions showed significantly less progression when compared to the untreated: 5/77 (6%) treated lesions progressed into invasive SCC versus 12/41 (29%) untreated (P=0.004). The 5-year probability (confidence interval) of progression into SCC for the treated was 7.6 (1-14) as compared to 38.6 (16-55) for the untreated. Interestingly the clinical changes at the site of the disease also had strong predictive value for cancer progression. If the site showed no lesion after treatment or after incisional biopsy (40 cases), only 1 (3%) progressed into cancer. If the site showed ever disappearance of the lesion or marked decrease in the size of the lesion to ⩽10mm (29 cases), 4 (15%) progressed. If the site showed lesions with fluctuation in size or persistent in size or marked increase in size (25 cases), 18 (58%) progressed (P<0.001). CONCLUSION: Treatment significantly reduced cancer progression, and phenotypic changes at the site of the disease had significant predictive value for cancer progression.

Socio-economic deprivation: a significant determinant affecting stage of oral cancer diagnosis and survival.

BACKGROUND: Many factors contribute to socioeconomic status (SES), yet in most survival studies only income is used as a measure for determining SES. We used a complex, composite, census-based metric for socioeconomic deprivation to better distinguish individuals with lower SES and assess its impact on survival and staging trends of oral cancers. METHODS: Oropharyngeal (OPC) and oral cavity cancer (OCC) cases were identified from the British Columbia cancer registry between 1981-2009 and placed into affluent and deprived neighborhoods using postal codes linked to VANDIX (a composite SES index based on 7 census variables encompassing income, housing, family structure, education, and employment). Stage and cancer-specific survival rates were examined by sex, SES, and time period. RESULTS: Approximately 50 % of OPC and OCC cases of both sexes resided in SES deprived neighborhoods. Numbers of cases have increased in recent years for all but OCC in men. The deprivation gap in survival between affluent and deprived neighborhoods widened in recent years for OPC and OCC in men, while decreasing for OPC and increasing slightly for OCC in women. Greater proportions of OCC cases were diagnosed at later stage disease for both sexes residing in deprived neighborhoods, a trend not seen for OPC. CONCLUSION: SES remains a significant independent determinant of survival for both OPC and OCC when using a composite metric for SES. OPC survival rates among men have improved, albeit at slower rates in deprived communities. OCC screening programs need to be targeted towards SES-deprived neighborhoods where greater proportions of cases were diagnosed at a later stage and survival rates have significantly worsened in both sexes.

A Lifecourse Model of Multimorbidity Resilience: Theoretical and Research Developments.

The purpose of this article is to advance a Lifecourse Model of Multimorbidity Resilience. It focuses on the ways in which individuals face adversities associated with multimorbidity and regain a sense of wellness through a complex, dynamic phenomenon termed resilience. A comprehensive review of 112 publications (between 1995 and 2015) was conducted using several comprehensive electronic data bases. Two independent researchers extracted and synthesized resilience literature with specific applications to chronic illness. The article outlines five stages of theoretical development of resilience, synthesizes these with the aging and chronic illness literature, builds a rationale for a lifecourse approach to resilience, and applies the model to multimorbidity. Cultivating and maintaining resilience is fundamental to functioning and quality of life for those with multimorbidity. We found that there are a number of gaps in both basic and applied research that need to be filled to advance knowledge and practice based on resilience approaches.