Improving the detection and triage of oral premalignant lesions in high-Risk clinics and community dental practices

Oral cancer occurs at a cancer site that is easily examined; yet more than 40% of oral cancers are diagnosed at a late stage when the chance of death is high and treatment can be devastating. Although oral cancer screening is part of every oral health professional’s (OHP) training, it is often difficult for OHPs to differentiate high-risk oral premalignant lesions (OPLs) from benign reactive lesions. A primary goal of this thesis was to evaluate two approaches to enhancing visualization of clinical lesions: the application of toluidine blue (TB) stain, used to improve contrast of suspicious mucosal areas in normal tissue (Project 1), and fluorescence visualization (FV), used to identify an alteration to tissue optics that is associated with morphological and biochemical change seen in cancers and premalignant disease (Projects 2 and 4). A second goal was to develop and evaluate an educational strategy for oral cancer screening in community dental clinics aimed at strengthening conventional screening activities and providing a framework for integration and assessment of visualization techniques in community settings (Projects 3 and 4). Studies were conducted on patients within two settings: referral clinics of the BC Oral Cancer Prevention Program (Projects 1 and 2) and community dental clinics in the Vancouver lower mainland (Projects 3 and 4). Use of two settings is important: technology developed within high-risk referral settings needs to be re-evaluated in community clinics where the spectrum of disease is different and expertise is variable. Among key results of these studies were: a strong association between TB positive staining and increased (6-fold) cancer risk for OPLs; an association of FV and high-risk clinical, histological and molecular change; and; identification of barriers and facilitators for oral cancer screening in OHPs with evaluation of a triaging framework to support key decision points in community practices. In summary this thesis data supports the use of TB and FV visualization approaches in high-risk clinics to improve detection of OPLs. In addition, the community studies have produced a framework for transfer of new technology into general dental practice building upon an enhanced triage and referral system

Clinical indicators of the development of a second oral malignancy at a previously treated cancer site : early results of a longitudinal study

Oral squamous cell carcinoma (SCC) has a poor 5-year survival rate of just over 50%, largely due to a high rate of second oral malignancies (SOM) including both recurrences and second primary tumours. Current dinicopathological indicators for oral premalignant lesions (OPLs) at high-risk of progressing into cancer are based on primary OPLs. Little is known whether these risk indicators apply to OPLs at previously treated cancer sites, which are particularly difficult to differentiate from reactive changes resulting from aggressive treatment of the tumours. Objective, to discover which clinicopathological indicators, if any, could significantly predict a SOM at the previously treated cancer site at around 1 year (8 - 16 months) after treatment of the cancer. Method. 84 patients with oral cancer (treated with intent to cure) being followed prospectively in the Oral Oncology/Oral Dysplasia Clinic were used in this thesis. Three categories of data were collected: (1) demographic and habit information (age, gender, ethnicity and tobacco habits) (2) primary tumour information (stage, site, histology and treatment of the tumour) and (3) dinicopathological features of post-treatment cancer site during follow up (the presence of an OPL, size, appearance, toluidine blue (TB) staining, histopathology and treatment of the OPLs). Results. 18 patients (21%) have developed a SOM at the treated cancer site (SOM group) within an average of 26 (± 14) months. Follow-up time for 66 patients who did not develop SOM (non-SOM group) was 28 (± 15) months. Demographics, smoking habit and features of the primary oral cancer did not predict SOM. Of the clinicopathological features of post-treatment cancer site during follow up, appearance, histopathology and treatment of OPLs did not predict SOM. There was a trend in increasing size of OPLs in the SOM group (14 ± 16 mm in diameter vs. 6 ± 5 for non-SOM group, P =0.07). However, 2 significant predictors were found. The presence of leukoplakia at the prior cancer site was significantly associated with SOM both at one-year post tumour treatment (72% vs. 15% in non-SOM group, P< 0.001) and ever during follow up (83% vs. 36%, P= 0.001). Uptake of TB stain was also significantly associated with SOM both at one-year post tumour treatment (50% vs. 11% in non-SOM group, P- 0.001) and during the entire follow-up (67% vs. 25%, P= 0.002). Conclusion: The results showed that presence of an OPL at the previous tumour site (regardless of its appearance and size) and TB positivity were significant risk predictors for SOM.Dentistry, Faculty ofGraduat

Parental psychosocial factors, unmet dental needs and preventive dental care in children and adolescents with special health care needs: A stress process model

Background Children and adolescents with special health care needs (SHCN) have higher unmet dental needs, but the potential mechanisms by which parental factors can influence dental care use have not been determined. Parenting a child with SHCN can present special demands that affect parents’ well-being and, in turn, their caregiving. Hence, the study's overall aim was to apply the stress process model to examine the role of parental psychosocial factors in the association between child SHCN and dental care. Specifically, the study tested hypotheses regarding how (a) children’s SHCN status is associated with child dental care (unmet dental needs and lack of preventive dental visits), both directly and indirectly via parental psychosocial factors (parenting stress, instrumental, and emotional social support) and (b) parental social support buffers the association between parenting stress and child dental care. Methods A secondary data analysis of the 2011–2012 US National Survey of Children’s Health was performed for 6- to 11-year-old children (n = 27,874) and 12- to 17-year-old adolescents (n = 31,328). Our age-stratified models estimated associations between child SHCN status and parental psychosocial factors with two child dental care outcomes: parent-reported unmet child dental needs and lack of preventive dental care. Results Parents of children with (vs without) SHCN reported higher unmet child dental needs, higher parenting stress, and lower social support (instrumental and emotional). Instrumental, but not emotional, parental support was associated with lower odds of their child unmet dental needs in both age groups. The association between parenting stress and child dental care outcomes was modified by parental social support. Conclusion Differences existed in child unmet dental needs based on SHCN status, even after adjusting for parental psychosocial factors. SHCN status was indirectly associated with unmet dental needs via parental instrumental support among adolescents, and parental instrumental support buffered the negative association between parenting stress and both child dental care outcomes. Hence, parental social support was an important determinant of child dental care and partially explained the dental care disparities in adolescents with SHCN.Dentistry, Faculty ofNon UBCOral Biological and Medical Sciences (OBMS), Department ofOral Health Sciences (OHS), Department ofReviewedFacult

Parental psychosocial factors, unmet dental needs and preventive dental care in children and adolescents with special health care needs: A stress process model

BackgroundChildren and adolescents with special health care needs (SHCN) have higher unmet dental needs, but the potential mechanisms by which parental factors can influence dental care use have not been determined. Parenting a child with SHCN can present special demands that affect parents' well-being and, in turn, their caregiving. Hence, the study's overall aim was to apply the stress process model to examine the role of parental psychosocial factors in the association between child SHCN and dental care. Specifically, the study tested hypotheses regarding how (a) children's SHCN status is associated with child dental care (unmet dental needs and lack of preventive dental visits), both directly and indirectly via parental psychosocial factors (parenting stress, instrumental, and emotional social support) and (b) parental social support buffers the association between parenting stress and child dental care.MethodsA secondary data analysis of the 2011-2012 US National Survey of Children's Health was performed for 6- to 11-year-old children (n = 27,874) and 12- to 17-year-old adolescents (n = 31,328). Our age-stratified models estimated associations between child SHCN status and parental psychosocial factors with two child dental care outcomes: parent-reported unmet child dental needs and lack of preventive dental care.ResultsParents of children with (vs without) SHCN reported higher unmet child dental needs, higher parenting stress, and lower social support (instrumental and emotional). Instrumental, but not emotional, parental support was associated with lower odds of their child unmet dental needs in both age groups. The association between parenting stress and child dental care outcomes was modified by parental social support.ConclusionDifferences existed in child unmet dental needs based on SHCN status, even after adjusting for parental psychosocial factors. SHCN status was indirectly associated with unmet dental needs via parental instrumental support among adolescents, and parental instrumental support buffered the negative association between parenting stress and both child dental care outcomes. Hence, parental social support was an important determinant of child dental care and partially explained the dental care disparities in adolescents with SHCN

Oral Health and Psychosocial Predictors of Quality of Life and General Well-Being among Adolescents in Lesotho, Southern Africa

Background: Adolescents’ quality of life is reported to be significantly associated with physical and social wellbeing. Although adolescents are 30% of the Southern African population, no previous studies have focused on this group in relation to oral health and quality of life. Methods: A 40-item survey and clinical oral examinations were conducted in public schools in Maseru from 10 to 25 August 2016. Simple, bivariate, and multivariate regressions were used to evaluate the associations of oral health and psychosocial factors with self-reported general health status and quality of life. Results: A total of 526 participants, aged 12–19 years old, responded to the survey and participated in the clinical examinations. The majority reported a good (good/very good/excellent) quality of life (84%) and general health (81%). Bivariate results showed that self-reported general health in this population was significantly influenced by age. The presence of toothache and sensitivity in the adolescents were significantly associated with poor (fair/poor) self-reported general health and were found to be the best predictors for self-general health and quality of life. Conclusions: The absence of dental conditions such as toothache and tooth sensitivity can lead to a better perception of general health and Quality of Life in adolescents.Dentistry, Faculty ofNon UBCOral Biological and Medical Sciences (OBMS), Department ofReviewedFacult

Oral Health Status and Patterns of Dental Service Utilization of Adolescents in Lesotho, Southern Africa

This study aimed to characterize the best predictors for unmet dental treatment needs and patterns of dental service utilization by adolescents in the Kingdom of Lesotho, Southern Africa. A self-reported 40-item oral health survey was administered, and clinical oral examinations were conducted in public schools in Maseru from August 10 to August 25, 2016. Associations between psychosocial factors with oral health status and dental service utilization were evaluated using simple, bivariate, and multivariate regressions. Five hundred and twenty-six survey responses and examinations were gathered. The mean age of student participants was 16.4 years of age, with a range between 12 and 19 years of age. More than two thirds (68%; n = 355) of participants were female. The majority reported their quality of life (84%) and general health to be good/excellent (81%). While 95% reported that oral health was very important, only 11% reported their personal dental health as excellent. Three percent reported having a regular family dentist, with the majority (85%) receiving dental care in a hospital or medical clinic setting; only 14% had seen a dental professional within the previous two years. The majority of participants did not have dental insurance (78%). Clinical examination revealed tooth decay on 30% of mandibular and maxillary molars; 65% had some form of gingivitis. In multivariate analysis, not having dental education and access to a regular dentist were the strongest predictors of not visiting a dentist within the last year. Our results suggest that access to oral health care is limited in Lesotho. Further patient oral health education and regular dental care may make an impact on this population.Dentistry, Faculty ofNon UBCOral Biological and Medical Sciences (OBMS), Department ofOral Health Sciences (OHS), Department ofReviewedFacult

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

Abstract 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

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