P. Michele Williams

Simple device for the direct visualization of oral-cavity tissue fluorescence.

Early identification of high-risk disease could greatly reduce both mortality and morbidity due to oral cancer. We describe a simple handheld device that facilitates the direct visualization of oral-cavity fluorescence for the detection of high-risk precancerous and early cancerous lesions. Blue excitation light (400 to 460 nm) is employed to excite green-red fluorescence from fluorophores in the oral tissues. Tissue fluorescence is viewed directly along an optical axis collinear with the axis of excitation to reduce inter- and intraoperator variability. This robust, field-of-view device enables the direct visualization of fluorescence in the context of surrounding normal tissue. Results from a pilot study of 44 patients are presented. Using histology as the gold standard, the device achieves a sensitivity of 98% and specificity of 100% when discriminating normal mucosa from severe dysplasia/carcinoma in situ (CIS) or invasive carcinoma. We envisage this device as a suitable adjunct for oral cancer screening, biopsy guidance, and margin delineation.

DIRECT FLUORESCENCE VISUALIZATION OF CLINICALLY OCCULT HIGH-RISK ORAL PREMALIGNANT DISEASE USING A SIMPLE HAND-HELD DEVICE

A considerable proportion of oral cancer and precancer is not clinically apparent and could contribute significantly to the late diagnosis and high mortality of oral cancer. A simple method to identify such occult change is needed.

Visualization and Other Emerging Technologies as Change Makers for Oral Cancer Prevention

Abstract:  The genomic era has fueled a rapid emergence of new information at the molecular level with a great potential for developing innovative approaches to detection, risk assessment, and management of oral cancers and premalignant disease. As yet, however, little research has been done on complementary approaches that would use different technology in conjunction with molecular approaches to create a rapid and cost‐effective strategy for patient assessment and management. In our ongoing 8‐year longitudinal study, a set of innovative technologies is being validated alone and in combination to best correlate with patient outcome. The plan is to use these devices in a step‐by‐step sequence to guide key clinicopathological decisions on patient risk and treatment. The devices include a hand‐held visualization device that makes use of tissue autofluorescence to detect and delineate abnormal lesions and fields requiring follow‐up, to be used in conjunction with optical contrast agents such as toluidine blue. In addition, two semi‐automated high‐resolution computer microscopy systems will be used to quantitate the protein expression phenotype of cell nuclei in tissue sections and exfoliated cell brushings. Previously identified risk‐associated molecular changes are being used to validate these systems as well as to establish their place in a population‐based triage program that will filter out high‐risk cases in the community and funnel them to dysplasia clinics where higher‐cost molecular tools will guide intervention. A critical development for the translation of this technology into community settings is the establishment of an effective methodology for education and training of health practitioners on the front lines.

Erythema Multiforme: A Review of Epidemiology, Pathogenesis, Clinical Features, and Treatment

Erythema multiforme (EM) is an acute, immune-mediated disorder affecting the skin and/or mucous membranes, including the oral cavity. Target or iris lesions distributed symmetrically on the extremities and trunk characterize the condition. Infections are the most common cause of EM and the most frequently implicated infectious agent causing clinical disease is the herpes simplex virus. The diagnosis of EM is typically based on the patients history and clinical findings. Management involves controlling the underlying infection or causative agent, symptom control, and adequate hydration. The epidemiology, pathogenesis, clinical features, diagnosis, and treatment of EM are reviewed in this article.

Squamous cell carcinoma and precursor lesions: diagnosis and screening in a technical era.

Oral cancer is a substantial, though often unrecognized issue globally, with close to 300,000 new cases reported annually (18). The disease presents a management conundrum. It occurs at a site that is easily accessible for examination, yet, regrettably, is often diagnosed at an advanced stage when functional impairment due to treatment and mortality rates are high. Late stage identification is associated with high mortality with 5-year survival rates ranging from 30- 60%, depending on the global locale (64; 76). It is also associated with high rates of second oral malignancies, with up to a third of such patients suffering a recurrence of the tumor or the development of a second primary despite intensive follow-up (11; 36; 56). These figures have shown little improvement over the past few decades. Despite these statistics, there is hope for change in the not-too-distant future. This hope is fueled by recent strides being made in our understanding of cancer and in the emergence of promising technologies that could aid clinicians in detection, risk assessment and management of this disease. Several alternative detection and diagnostic aids for examining the oral cavity are commercially available or in development. The current challenge is to recognize that these devices are still evolving, yet in many cases they already are moving into the clinical arena. There is a need for the clinician to better understand these new innovations: the biology underlying their function, their strengths and weaknesses, and the scenarios under which they may demonstrate clinical utility. The intent of this paper is to highlight parameters to be considered when utilizing such technology and to indicate where we are in the development and validation of such approaches and in their incorporation into clinical practice. The paper will explore more recent concepts with respect to tissue change that underlies evident disease, briefly summarize difficulties with the current clinicopathological approaches for detection and diagnostic management of disease and then present an overview of current and developing diagnostic and screening methods. There have been several recent reviews of some of these devices (16; 32; 33; 40; 41). Our intent is not to duplicate this activity but rather to supplement it by building a framework for technology assessment that integrates data summarized in these papers.

Abstract B05: Influence of fluorescence on screening decisions for oral lesions in community dental practices

Oral cancer is a global issue, with almost 300,000 new cases reported annually. While the oral cavity is cancer site that is easily examined, >40% of oral cancers are diagnosed at a late stage when prognosis is poor and treatment can be devastating. Opportunistic screening within the dental office could lead to earlier diagnosis and intervention with improved survival. Tools to aid screening are available but it is vital to validate them within the general dental office amongst clinicians with less experience than specialists in high-risk clinics. Fluorescence visualization (FV) is a tool used to assess alterations to tissue fluorescence. The goal of this study was to determine how clinicians made decisions about referral based on the risk classification of the lesion, how FV was integrated and how it affected the decision to refer. Information on FV rates in private practice and how FV affects decision making is vital to determine the feasibility of using this tool in a general practice setting. Methods: 15 dental offices participated in a 1-day workshop on oral cancer screening, including an introduction to and use of FV. Participants then screened patients (medical history, convention oral exam, fluorescent visualization exam) in-office for 11 months. Participants were asked to triage lesions by apparent risk: low, intermediate and high. Low-risk (LR) lesions were common and benign conditions including geographic tongue, candidiasis and known trauma. High-risk (HR) lesions were white or red lesions or ulcers without apparent cause and lichenoid lesions. Clinicians then made the decision on which lesions to reassess in 3 weeks based on risk assessment and clinical judgment. Lesions of concern were seen by a community facilitator or referred to an oral medicine specialist. Results: Of 2404 patients screened, 357 had lesions with 325 (15%) identified as low risk (LR) and 32 (9%) as high risk (HR). 192 of the 357 lesions were FV+ (54%), 26 FVE (7%) and 139 FV= (39%). Factors significantly associated with the presence of lesion included older age, history of smoking, and history of drinking alcohol. Lesions which were not white in colour were more apt to be FV+ (RR=5.6; 95%CI: 3.0 – 10.4) while a rough texture was associated with FV- (RR=0.47; 95%CI: 0.25-0.88). However, rough lesions were more likely to persist to the reassessment appointment (RR=3.7; 95%CI: 1.2-11.2), as did lesions assessed at the initial appointment as HR (RR=2.7; 95%CI: 1.4-5.1). The most predictive model for lesion persistence included both FV status (FV+) and lesion risk assessment (HR). Conclusion: A protocol for screening: assess risk, reassess and refer is recommended for the screening of abnormal intraoral lesions. Integrating FV into a process of assessing and reassessing lesions significantly improved this model. With education, clinicians can eliminate low risk FV+ lesions at either the initial screening appointment or at reassessment. Citation Format: Denise M. Laronde, P Michele Williams, T Greg Hislop, Catherine Poh, Samson Ng, Chris Badjik, Lewei Zhang, Calum MacAuley, Miriam Rsoin. Influence of fluorescence on screening decisions for oral lesions in community dental practices. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B05.

Abstract 2901: Visualization and delineation of high-risk fields in the oral cavity

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Oral cancer is a substantial, though often unrecognized issue globally, with close to 300,000 new cases reported annually. The disease represents a management conundrum: this is a cancer site that is easily examined; yet more that 40% of oral cancers are diagnosed at a late stage when the chance of death is high and treatment can be disfiguring and devastating. Visualization of high-risk fields can be improved by application of contrast agents, such as toluidine blue (TB) or through use of devices that measure alteration to tissue optics, such as fluorescence visualization (FV) both of which could facilitate assessment of abnormalities. This studys objective was to evaluate FV, within a high-risk clinic, to look for associations between loss of autofluorescence (FVL) and alterations to clinical, histological and molecular features and to determine its ability to detect high-risk oral premalignant fields and cancer. Methods: The study involved 170 patients, with 192 oral lesions (64 cancers, 28 severe dysplasia, 66 low-grade (mild/moderate) dysplasia and 34 nondysplasia), being followed in the ongoing Oral Cancer Prediction Longitudinal Study. Four categories of data were collected: 1) demographic and habit information (age, gender, ethnicity and tobacco habits); 2) lesion histology; 3) clinicopathological features at time of biopsy (lesion size, site, appearance, toluidine blue (TB) staining and FV status); and 4) molecular risk patterns of the lesions (loss of heterozygosity, LOH). Results: Demographics and smoking habit were not associated with FV status. Clinicopathological features of the lesion, appearance (P 2) arms (P=0.009). TB positivity was found to be highly associated with FVL (P<0.001). To date, 7 premalignant lesions have progressed to a high-grade lesion or SCC and all were FVL at time of low-grade dysplasia biopsy (FVL and progression, P=0.047). Six of the 7 progressing lesions were TB+. Conclusion: FV was found to be a very useful adjunctive tool when used by experienced clinicians in high-risk clinics. Integrating TB and FV results may aid in the detection of low-grade lesions at risk of progression. Further study of FV in low-grade and nondysplasia with a larger sample size is required. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2901.