134 results on '"Rosin MP"'
Search Results
2. Gender- and ethnicity-specific survival trends of oral cavity and oropharyngeal cancers in British Columbia.
- Author
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Auluck A, Hislop G, Bajdik C, Hay J, Bottorff JL, Zhang L, and Rosin MP
- Published
- 2012
- Full Text
- View/download PDF
3. Oral submucous fibrosis, a clinically benign but potentially malignant disease: report of 3 cases and review of the literature.
- Author
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Auluck A, Rosin MP, Zhang L, and Kn S
- Published
- 2008
4. Primary malignant melanoma of maxillary gingiva--a case report and review of the literature.
- Author
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Auluck A, Zhang L, Desai R, and Rosin MP
- Published
- 2008
5. New hope for an oral cancer solution: together we can make a difference.
- Author
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Rosin MP, Poh CF, Elwood JM, Williams PM, Gallagher R, MacAulay C, Lam WW, Auluck A, Zhang L, Hislop TG, Rosin, Miriam P, Poh, Catherine F, Elwood, J Mark, Williams, P Michele, Gallagher, Richard, MacAulay, Calum, Lam, Wan W, Auluck, Ajit, Zhang, Lewei, and Hislop, T Gregory
- Abstract
Oral cancer is associated with high mortality and morbidity rates, largely as a result of late diagnosis. Although dental practitioners are trained to identify premalignant and malignant lesions, an organized system is needed to offer guidance and to improve access to experts in diagnosis and management of these lesions. In this article, we describe the many ways in which the British Columbia Oral Cancer Prevention Program (BC OCPP) is addressing this challenge: by linking community dental practices and referral centres, by creating partnerships between scientists and clinicians that already have resulted in new technologies to enhance early diagnosis, by involving a broad range of stakeholders to ensure population-based screening and by engaging in provincial, national and international outreach. [ABSTRACT FROM AUTHOR]
- Published
- 2008
6. Oral cancer screening in a high-risk underserved community: vancouver downtown eastside.
- Author
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Poh CF, Hislop G, Currie B, Lee R, Sikorski S, Zed C, Zhang L, Macaulay C, and Rosin MP
- Abstract
The objective of this study was to evaluate a clinic-centered oral cancer screening initiative in one of the poorest communities in Canada, assessing the need for screening and the acceptance of screening and identifying hindrances to both screening and follow-up. The study group included 204 people in the Vancouver Downtown Eastside (DTES). This was shown to be a high-risk community based on risk factors, lack of access to care, and the high frequency of oral mucosal anomalies. Acceptance of screening was high (98%); however, acceptance of biopsy for abnormal findings and follow-up was low. Among the 12 patients with clinical leukoplakia who were biopsied, 10 showed cancer or precancer. In summary, these data show a need for screening in this population and an ability to recruit patients to screening. They support a future expansion of this initiative to create a more comprehensive strategy for outreach to this underserved community that extends to screening, diagnostic work-up, and treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
7. Strengthening the quality of oral cancer screening.
- Author
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Laronde DM, Williams PM, Hislop TG, Bottorff JL, and Rosin MP
- Published
- 2009
8. Oral cancer awareness among immigrant Indo-Canadian community of Vancouver, BC.
- Author
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Auluck A, Rosin MP, and Hislop G
- Published
- 2008
9. Correction: Exploring the microbiome of oral epithelial dysplasia as a predictor of malignant progression.
- Author
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Wright RJ, Pewarchuk ME, Marshall EA, Murray B, Rosin MP, Laronde DM, Zhang L, Lam WL, Langille MGI, and Rock LD
- Published
- 2024
- Full Text
- View/download PDF
10. Exploring the microbiome of oral epithelial dysplasia as a predictor of malignant progression.
- Author
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Wright RJ, Pewarchuk ME, Marshall EA, Murrary B, Rosin MP, Laronde DM, Zhang L, Lam WL, Langille MGI, and Rock LD
- Subjects
- Cohort Studies, Humans, Child, RNA, Ribosomal, 16S genetics, Male, Female, Infant, Child, Preschool, Mouth Neoplasms, Microbiota genetics
- 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., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
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11. Predicting Progression of Low-Grade Oral Dysplasia Using Brushing-Based DNA Ploidy and Chromatin Organization Analysis.
- Author
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Datta M, Laronde DM, Rosin MP, Zhang L, Chan B, and Guillaud M
- Subjects
- Chromatin genetics, DNA genetics, Humans, Ploidies, Mouth Neoplasms diagnosis, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Precancerous Conditions diagnosis, Precancerous Conditions genetics, Precancerous Conditions pathology
- Abstract
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., (©2021 American Association for Cancer Research.)
- Published
- 2021
- Full Text
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12. Intraoral Photography Recommendations for Remote Risk Assessment and Monitoring of Oral Mucosal Lesions.
- Author
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Lin I, Datta M, Laronde DM, Rosin MP, and Chan B
- Subjects
- Humans, Mass Screening, Referral and Consultation, Risk Assessment, Mouth Neoplasms diagnosis, Photography, Dental
- Abstract
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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
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13. Basement membrane degeneration is common in lichenoid mucositis with dysplasia.
- Author
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Lin I, Laronde DM, Zhang L, Rosin MP, Yim I, and Rock LD
- Subjects
- Basement Membrane, Case-Control Studies, Humans, Lichen Planus, Oral, Mouth Neoplasms, Mucositis
- Abstract
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 (L
1 D2 ), and the other with primary dysplastic and secondary lichenoid features (D1 L2 ), 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., Competing Interests: The authors declare no known conflicts of interest., (Copyright © 2021 CDHA | ACHD.)- Published
- 2021
14. Effect of Fluorescence Visualization-Guided Surgery on Local Recurrence of Oral Squamous Cell Carcinoma: A Randomized Clinical Trial.
- Author
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Durham JS, Brasher P, Anderson DW, Yoo J, Hart R, Dort JC, Seikaly H, Kerr P, Rosin MP, and Poh CF
- Subjects
- Aged, Carcinoma in Situ mortality, Carcinoma in Situ pathology, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell pathology, Female, Humans, Incidence, Male, Middle Aged, Mouth Neoplasms mortality, Mouth Neoplasms pathology, Neoplasm Grading, Neoplasm Staging, Survival Rate, Carcinoma in Situ surgery, Carcinoma, Squamous Cell surgery, Mouth Neoplasms surgery, Neoplasm Recurrence, Local epidemiology, Optical Imaging, Surgery, Computer-Assisted
- Abstract
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.
- Published
- 2020
- Full Text
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15. Dysplasia and Lichenoid Mucositis: The Chicken or the Egg?
- Author
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Zhang L, Rock LD, Rosin MP, and Laronde DM
- Subjects
- Humans, Hyperplasia, Lichen Planus, Oral, Mouth Neoplasms, Mucositis
- Published
- 2018
- Full Text
- View/download PDF
16. Dysplasia Should Not Be Ignored in Lichenoid Mucositis.
- Author
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Rock LD, Laronde DM, Lin I, Rosin MP, Chan B, Shariati B, and Zhang L
- Subjects
- Adult, Disease Progression, Female, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, Lichen Planus, Oral pathology, Mucositis pathology, Precancerous Conditions pathology
- Abstract
Oral lichen planus is categorized as a potentially malignant condition by the World Health Organization; however, some argue that only lichen planus with dysplasia have malignant potential. Many pathologists call lichen planus with dysplasia "dysplasia with lichenoid mucositis (LM)" or "LM with dysplasia." Previous research has shown that certain high-risk patterns of loss of heterozygosity (LOH) in dysplastic lesions are associated with significantly increased cancer risk. However, LM without dysplasia lacks such molecular patterns, supporting the hypothesis that LM, by itself, is not potentially malignant and that only those with dysplasia have malignant potential. To further investigate the premalignant nature of LM with dysplasia, this study compared the rate of malignant progression of dysplasia with LM with that of dysplasia without LM. Patients from a population-based prospective cohort study with >10 y of follow-up were analyzed. Study eligibility included a histological diagnosis of a primary low-grade dysplasia with or without LM. A total of 446 lesions in 446 patients met the selection criteria; 373 (84%) were classified as dysplasia without LM, while 73 (16%) were classified as dysplasia with LM. Demographic and habit information, clinical information, and outcome (progression) were compared between the 2 groups. Forty-nine of 373 cases of dysplasia (13%) progressed compared to 8% (6/73) of dysplasia with LM. However, the difference was not statistically different ( P = 0.24). The 3- and 5-y rate of progression did not differ between the groups (6.7% and 12.5% for dysplasia without LM and 2.9% and 6.6% for those with LM; P = 0.36). Progression was associated with nonsmoking, location at a high-risk site, and diagnosis of moderate dysplasia regardless of whether LM was present or not. Dysplasia with or without LM had similar cancer risk, and dysplasia should not be discounted in the presence of LM.
- Published
- 2018
- Full Text
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17. Using quantitative tissue phenotype to assess the margins of surgical samples from a pan-Canadian surgery study.
- Author
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Guillaud M, MacAulay CE, Berean KW, Bullock M, Guggisberg K, Klieb H, Puttagunta L, Penner C, Kwan K, Rosin MP, and Poh CF
- Subjects
- Adult, Aged, Aged, 80 and over, Canada, Female, Fluorescence, Humans, Male, Middle Aged, Mouth Neoplasms diagnostic imaging, Neoplasm Staging, Phenotype, Young Adult, Margins of Excision, Mouth Neoplasms pathology, Mouth Neoplasms surgery
- Abstract
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., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2018
- Full Text
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18. Characterization of epithelial oral dysplasia in non-smokers: First steps towards precision medicine.
- Author
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Rock LD, Rosin MP, Zhang L, Chan B, Shariati B, and Laronde DM
- Subjects
- Adult, Female, Humans, Longitudinal Studies, Male, Middle Aged, Mouth Neoplasms pathology, Non-Smokers, Precancerous Conditions pathology, Precision Medicine
- Abstract
Objectives: Tobacco usage is the strongest risk factor in the development of oral squamous cell carcinoma (OSCC), which mandates careful screening for oral cancers in smokers. However, there are indications that oral potentially malignant lesions, such as oral epithelial dysplasia (OED), in non-smokers (NS) have a higher cancer risk than those in smokers. Without tobacco as an etiology, the development of these lesions in NS may suggest genetic susceptibility. The increasing incidence of OSCC in NS calls for a better understanding of the natural history of OED in NS as compared to that of smokers., Materials and Methods: Patients from a population-based longitudinal study with more than 10 years of follow up were analyzed. Of the 455 patients with primary OED (233 mild and 212 moderate dysplasia), 139 were NS and 306 were smokers. Demographic and habit information, clinical information (lesion site, size and appearance; toluidine blue and fluorescent visualization), microsatellite analysis for loss of heterozygosity (LOH) and outcome (progression) were compared between the two groups., Results and Conclusions: The majority of patients with OED were smokers. Of these, more were males, non-Caucasians and heavy drinkers. A significantly higher number of OED in NS were in the tongue, whereas a significantly higher number of OED in smokers were in the floor of mouth (FOM). OED in NS showed a greater than 2-fold increase in cancer progression. Strikingly, OED located in the FOM in NS showed a 38-fold increase in cancer progression as compared to those in smokers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
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19. Optimizing Fixation Protocols to Improve Molecular Analysis from FFPE Tissues.
- Author
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Maraschin BJ, Silva VP, Rock L, Sun H, Visioli F, Rados PV, and Rosin MP
- Subjects
- Humans, Paraffin Embedding, Tissue Fixation
- 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.
- Published
- 2017
- Full Text
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20. Oral Squamous Cell Carcinomas are Associated with Poorer Outcome with Increasing Ages.
- Author
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Lubpairee T, Poh CF, Laronde DM, Rosin MP, and Zhang L
- Abstract
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., Competing Interests: 9. Conflict of Interest: None to declare.
- Published
- 2017
21. Should severe epithelial dysplasia be treated?
- Author
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Zhang L, Lubpairee T, Laronde DM, and Rosin MP
- Subjects
- Adult, Aged, Aged, 80 and over, British Columbia, Carcinoma, Squamous Cell pathology, Disease Progression, Female, Humans, Male, Middle Aged, Mouth Neoplasms pathology, Carcinoma, Squamous Cell therapy, Mouth Neoplasms therapy
- Abstract
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., Competing Interests: Conflicts of Interest: None declared., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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22. Fluorescence Visualization-Guided Surgery for Early-Stage Oral Cancer.
- Author
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Poh CF, Anderson DW, Durham JS, Chen J, Berean KW, MacAulay CE, and Rosin MP
- Subjects
- British Columbia epidemiology, Carcinoma, Squamous Cell pathology, Disease-Free Survival, Female, Fluorescence, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Mouth Neoplasms pathology, Neoplasm Recurrence, Local epidemiology, Retrospective Studies, Survival Rate trends, Treatment Outcome, Carcinoma, Squamous Cell surgery, Mouth Neoplasms surgery, Neoplasm Staging methods, Optical Imaging methods, Oral Surgical Procedures methods, Surgery, Computer-Assisted methods
- Abstract
Importance: The prevalence of genetically altered cells in oral cancers has a negative influence on the locoregional recurrence rate and lowers survival. Fluorescence visualization (FV) can identify clinically occult, high-risk oral lesions by allowing health care professionals and surgeons to visualize and map occult disease. This process may improve overall survival by decreasing rates of locoregional recurrence., Objective: To assess the efficacy of FV-guided surgery in reducing locoregional recurrence and improving overall survival., Design, Setting, and Participants: A retrospective, case-control observational study was conducted on patients registered at a single oral oncology clinic from September 1, 2004, to August 31, 2009. The study included 246 patients 18 years or older with a diagnosis of a high-grade lesion (severe dysplasia or carcinoma in situ) or squamous cell carcinoma of less than 4 cm who underwent curative surgical treatment with at least 1 follow-up visit. Among these patients, 154 underwent surgery with FV guidance (FV group) and the other 92 underwent conventional surgery (control group). Demographic and lesional characteristics and outcomes were collected, and the key factors for the efficacy of FV-guided surgery were examined. Follow-up was completed on December 31, 2011, and data were analyzed from May 1 to November 30, 2013., Main Outcomes and Measures: Local recurrence of oral lesions with a histologic grade of severe dysplasia or higher, the presence of regional failure (ie, a metastatic lesion in the cervical lymph nodes), or disease-free survival after surgery., Results: Among the 246 patients included in the study (mean [SD] age, 60 [12] years; 108 women and 138 men), 156 had squamous cell carcinoma and 90 had high-grade lesions. There were no significant differences between the FV (n = 154) and control (n = 92) groups in age, smoking history, anatomical site of the lesion, tumor size, and previous oral cancer. Among the 156 patients with squamous cell carcinoma, the 92 patients in the FV group showed significant reduction in the 3-year local recurrence rate, from 40.6% (26 of 64 patients) to 6.5% (6 of 92 patients) (P < .001). Among the 90 patients with high-grade lesions, the 62 patients in the FV group showed a reduction in local recurrence rate from 11 of 28 patients (39.3%) to 5 of 62 patients (8.1%) (P < .001). The data also indicated that, compared with conventional surgery, the FV-guided approach for squamous cell carcinoma was associated with less regional failure (14 of 92 patients [15.2%] vs 16 of 64 [25.0%]; P = .08) and death (12 of 92 patients [13.0%] vs 13 of 64 [20.3%]; P = .22), although these differences were not statistically significant., Conclusions and Relevance: In this study, the use of FV as part of the surgical margin decision process significantly reduced the rate of local recurrence in preinvasive high-grade and early-stage oral cancers. An ongoing multicenter, phase 3, randomized surgical trial has completed accrual, and the data will be used to validate the results of this study.
- Published
- 2016
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23. Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation.
- Author
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Kang SYC, Kannan N, Zhang L, Martinez V, Rosin MP, and Eaves CJ
- Subjects
- Adolescent, Adult, Cell Proliferation, Cells, Cultured, Child, Child, Preschool, Epithelial Cells metabolism, Epithelial Cells pathology, Epithelial Cells virology, Humans, Hyaluronan Receptors analysis, Middle Aged, Nerve Tissue Proteins analysis, Palatine Tonsil metabolism, Palatine Tonsil pathology, Palatine Tonsil virology, Papillomavirus Infections metabolism, Receptors, Nerve Growth Factor analysis, Stem Cells metabolism, Stem Cells pathology, Stem Cells virology, Transcriptome, Young Adult, Epithelial Cells cytology, Human papillomavirus 16 physiology, Oncogene Proteins, Viral metabolism, Palatine Tonsil cytology, Papillomavirus E7 Proteins metabolism, Papillomavirus Infections pathology, Repressor Proteins metabolism, Stem Cells cytology
- Abstract
Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44(+)NGFR(+) and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44(+)NGFR(+) cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44(+)NGFR(+) cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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24. Targeting of chemoprevention to high-risk potentially malignant oral lesions: challenges and opportunities.
- Author
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Martinez VD, MacAulay CE, Guillaud M, Lam WL, Zhang L, Corbett KK, and Rosin MP
- Subjects
- Humans, Precancerous Conditions genetics, Risk Assessment methods, Risk Factors, Biomarkers, Tumor analysis, Disease Progression, Mouth Neoplasms prevention & control, Precancerous Conditions pathology
- Abstract
Worldwide, oral cancer is responsible for 170,000 deaths per year. Intervention to prevent this disease is a long sought after goal. Chemoprevention studies have focused on clinicopathological features of potentially malignant lesions (PML) in an effort to prevent their progression to cancer. However, prediction of future behavior for such lesions is difficult and remains a major challenge to such intervention. Different approaches to this problem have been tested in the past 20years. Early genetic progression models identified critical regions of allelic imbalance at 3p and 9p, and provided the basis for molecular markers to identify progressing PMLs. Subsequently, technological advances, such as genome-wide high-throughput array platforms, computer imaging, visualization technology and next generation sequencing, have broadened the scope for marker development and have the potential of further improving our ability to identify high-risk lesions in the near future either alone or in combination. In this article, we examine the milestones in the development of markers for PML progression. We emphasize the critical importance of networks among scientists, health professionals and community to facilitate the validation and application of putative markers into clinical practice. With a growing number of new agents to validate, it is necessary to coordinate the design and implementation of strategies for patient recruitment, integration of marker assessment, and the final translation of such approaches into clinical use., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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25. Decision making on detection and triage of oral mucosa lesions in community dental practices: screening decisions and referral.
- Author
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Laronde DM, Williams PM, Hislop TG, Poh C, Ng S, Zhang L, and Rosin MP
- Subjects
- British Columbia, Female, Humans, Male, Middle Aged, Decision Making, Education, Dental, Continuing, Mass Screening statistics & numerical data, Mouth Neoplasms diagnosis, Referral and Consultation statistics & numerical data, Risk Assessment statistics & numerical data, Triage
- Abstract
Unlabelled: Oral cancer is a substantial, often unrecognized issue globally, with close to 300 000 new cases reported annually. It is a management conundrum: a cancer site that is easily examined; yet more than 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., Objective: To describe how clinicians make decisions about referral based on the risk classification of the lesion., Methods: Eighteen dentists from 15 dental offices participated in a 1-day workshop on oral cancer screening. Participants then screened patients (medical history, conventional oral exam, fluorescent visualization examination) in-office for 11 months, triaging patients by apparent clinical risk: low risk (common benign conditions, geographic tongue, candidiasis, trauma), intermediate risk (lichenoid lesions) and high risk (white or red lesions or ulcers without apparent cause). Clinicians 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 2542 patients were screened, and 389 lesions were identified (15% of patients). 350 were determined to be low risk (90%), 19 intermediate risk (IR) (5%), and 20 high risk (HR) (5%). One hundred and sixty-six (43%) patients were recalled for 3-week reassessment: 90% of HR lesions, 63% of IR lesions (63%), and 39% of low-risk lesions. Compliance to recall was high (92% of cases). Reassessment eliminated the referral of 99/166 (60%) of lesions that had resolved. six lesions were biopsied with three low-grade dysplasias identified., Conclusions: Three key decision points were tested: risk assessment, need for reassessment, and need for referral. A 3-week reassessment appointment was invaluable to prevent the unnecessary referral due to confounders. There is a need for a well-defined triage pathway to facilitate oral cancer screening and a methodical and consistent approach to opportunistic screening in the dental office., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2014
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26. Influence of fluorescence on screening decisions for oral mucosal lesions in community dental practices.
- Author
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Laronde DM, Williams PM, Hislop TG, Poh C, Ng S, Bajdik C, Zhang L, MacAulay C, and Rosin MP
- Subjects
- Adult, Alcohol Drinking, Clinical Competence, Color, Community Dentistry, Decision Making, Education, Dental, Continuing, Female, Fluorescence, Follow-Up Studies, Humans, Light, Male, Medical History Taking, Mouth Neoplasms pathology, Physical Examination, Practice Patterns, Dentists', Precancerous Conditions pathology, Referral and Consultation, Risk Assessment, Smoking, Tobacco, Smokeless, Early Detection of Cancer, Mass Screening methods, Mouth Neoplasms diagnosis, Precancerous Conditions diagnosis
- Abstract
Background: Quality of oral screening examinations is dependent upon the experience of the clinician and can vary widely. Deciding when a patient needs to be referred is a critical and difficult decision for general practice clinicians. A device to aid in this decision would be beneficial. The objective of this study was to to examine the utility of direct fluorescence visualization (FV) by dental practitioners as an aid in decision-making during screening for cancer and other oral lesions., Methods: Dentists were trained to use a stepwise protocol for evaluation of the oral mucosa: medical history, head, neck and oral exam, and fluorescent visualization exam. They were asked to use clinical features to categorize lesions as low (LR), intermediate (IR), or high (HR) risk and then to determine FV status of these lesions. Clinicians made the decision of which lesions to reassess in 3 weeks and based on this reassessment, to refer forward., Results: Of 2404 patients screened over 11 months, 357 initially had lesions with 325 (15%) identified as LR, 16 (4.5%) IR, and 16 (4.5%) HR. Lesions assessed initially as IR and HR had a 2.7-fold increased risk of FV loss persisting to the reassessment appointment versus the LR lesions. The most predictive model for lesion persistence included both FV status and lesion risk assessment., 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., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2014
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27. Predicting progression of oral dysplasia--response.
- Author
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Rosin MP, Zhang L, and Mao L
- Subjects
- Animals, Female, Humans, Male, Biomarkers, Tumor analysis, Loss of Heterozygosity genetics, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Neoplasm Recurrence, Local pathology, Neoplasms pathology, Neoplastic Cells, Circulating pathology, Precancerous Conditions genetics, Precancerous Conditions pathology
- Published
- 2013
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28. Loss of heterozygosity (LOH) profiles--validated risk predictors for progression to oral cancer.
- Author
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Zhang L, Poh CF, Williams M, Laronde DM, Berean K, Gardner PJ, Jiang H, Wu L, Lee JJ, and Rosin MP
- Subjects
- Disease Progression, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Proportional Hazards Models, ROC Curve, Risk Factors, Loss of Heterozygosity genetics, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Precancerous Conditions genetics, Precancerous Conditions pathology
- Abstract
A major barrier to oral cancer prevention has been the lack of validated risk predictors for oral premalignant lesions (OPL). In 2000, we proposed a loss of heterozygosity (LOH) risk model in a retrospective study. This paper validated the previously reported LOH profiles as risk predictors and developed refined models via the largest longitudinal study to date of low-grade OPLs from a population-based patient group. Analysis involved a prospective cohort of 296 patients with primary mild/moderate oral dysplasia enrolled in the Oral Cancer Prediction Longitudinal Study. LOH status was determined in these OPLs. Patients were classified into high-risk or low-risk profiles to validate the 2000 model. Risk models were refined using recursive partitioning and Cox regression analyses. The prospective cohort validated that the high-risk lesions (3p and/or 9p LOH) had a 22.6-fold increase in risk (P = 0.002) compared with low-risk lesions (3p and 9p retention). Addition of another 2 markers (loci on 4q/17p) further improved the risk prediction, with five-year progression rates of 3.1%, 16.3%, and 63.1% for the low-, intermediate-, and high-risk lesions, respectively. Compared with the low-risk group, intermediate- and high-risk groups had 11.6-fold and 52.1-fold increase in risk (P < 0.001). LOH profiles as risk predictors in the refined model were validated in the retrospective cohort. Multicovariate analysis with clinical features showed LOH models to be the most significant predictors of progression. LOH profiles can reliably differentiate progression risk for OPLs. Potential uses include increasing surveillance for patients with elevated risk, improving target intervention for high-risk patients while sparing a large number of low-risk patients from needless screening and treatment.
- Published
- 2012
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29. High throughput image cytometry for detection of suspicious lesions in the oral cavity.
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Macaulay C, Poh CF, Guillaud M, Michele Williams P, Laronde DM, Zhang L, and Rosin MP
- Subjects
- Humans, Mouth Neoplasms genetics, Reproducibility of Results, Sensitivity and Specificity, DNA, Neoplasm analysis, Flow Cytometry methods, Image Interpretation, Computer-Assisted methods, Microscopy methods, Molecular Imaging methods, Mouth Neoplasms diagnosis, Pattern Recognition, Automated methods
- Abstract
The successful management of oral cancer depends upon early detection, which relies heavily on the clinician's ability to discriminate sometimes subtle alterations of the infrequent premalignant lesions from the more common reactive and inflammatory conditions in the oral mucosa. Even among experienced oral specialists this can be challenging, particularly when using new wide field-of-view direct fluorescence visualization devices clinically introduced for the recognition of at-risk tissue. The objective of this study is to examine if quantitative cytometric analysis of oral brushing samples could facilitate the assessment of the risk of visually ambiguous lesions. About 369 cytological samples were collected and analyzed: (1) 148 samples from pathology-proven sites of SCC, carcinoma in situ or severe dysplasia; (2) 77 samples from sites with inflammation, infection, or trauma, and (3) 144 samples from normal sites. These were randomly separated into training and test sets. The best algorithm correctly recognized 92.5% of the normal samples, 89.4% of the abnormal samples, 86.2% of the confounders in the training set as well as 100% of the normal samples, and 94.4% of the abnormal samples in the test set. These data suggest that quantitative cytology could reduce by more than 85% the number of visually suspect lesions requiring further assessment by biopsy.
- Published
- 2012
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30. Unique FISH patterns associated with cancer progression of oral dysplasia.
- Author
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Poh CF, Zhu Y, Chen E, Berean KW, Wu L, Zhang L, and Rosin MP
- Subjects
- Biomarkers, Tumor, Carcinoma, Squamous Cell genetics, Case-Control Studies, Centromere pathology, Chromosomal Instability genetics, Cyclin D1 genetics, Disease Progression, ErbB Receptors genetics, Female, Humans, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Male, Middle Aged, Mouth Mucosa pathology, Mouth Neoplasms genetics, Polyploidy, Precancerous Conditions genetics, Proportional Hazards Models, Retrospective Studies, Risk Factors, Sensitivity and Specificity, Carcinoma, Squamous Cell pathology, Cell Transformation, Neoplastic genetics, Gene Dosage genetics, Mouth Neoplasms pathology, Precancerous Conditions pathology
- Abstract
Subgroups of patients with oral pre-malignant lesions (OPLs) are at extremely high risk for developing invasive cancer in spite of surgical excision. The objective of this study was to evaluate the utility of specific genes and their associated centromeres as markers to stratify OPLs for their cancer risk. Samples used in this study included 35 oral dysplasia with known outcome and 20 normal oral mucosa. Of the dysplasias, 20 were from an ongoing longitudinal study showing progression. The remaining 15 cases (2 of which progressed) were chosen from the population-based, provincial BC Oral Biopsy Service (OBS). Copy number alterations at EGFR, CEP7, CCND1, and CEP11 were evaluated by fluorescent in situ hybridization (FISH). There was no significant difference in demographics between progressors and non-progressors. Specific FISH profiles at these genes and their corresponding centromeres were associated with progression. High gene gain of CCND1 was associated with an 8-fold elevated risk of progression compared with those with no gain in time-to-progression analysis. Numerical alterations of EGFR and CCND1 and their centromeres might be an effective means for identifying OPLs at risk. Future studies will expand on this analysis and set the stage for application of this approach in routine clinical practice.
- Published
- 2012
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31. Long non-coding RNAs are expressed in oral mucosa and altered in oral premalignant lesions.
- Author
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Gibb EA, Enfield KS, Stewart GL, Lonergan KM, Chari R, Ng RT, Zhang L, MacAulay CE, Rosin MP, and Lam WL
- Subjects
- Chromosome Mapping, Humans, Mouth Mucosa metabolism, Mouth Neoplasms genetics, RNA, Untranslated classification, Gene Expression Profiling, Mouth Diseases genetics, Precancerous Conditions genetics, RNA, Untranslated genetics
- Abstract
Oral epithelial dysplasias are believed to progress through a series of histopathological stages; from mild to severe dysplasia, to carcinoma in situ, and finally to invasive OSCC. Underlying this change in histopathological grade are gross chromosome alterations and changes in gene expression of both protein-coding genes and non-coding RNAs. Recent papers have described associations of aberrant expression of microRNAs, one class of non-coding RNAs, with oral cancer. However, expression profiling of long non-coding RNAs (lncRNAs) has not been reported. Long non-coding RNAs are a novel class of mRNA-like transcripts with no protein coding capacity, but with a variety of functions including roles in epigenetics and gene regulation. In recent reports, the aberrant expression of lncRNAs has been associated with human cancers, suggesting a critical role in tumorigenesis. Here, we present the first long non-coding RNA expression map for the human oral mucosa. We describe the expression of 325 long non-coding RNAs, suggesting lncRNA expression contributes significantly to the oral transcriptome. Intriguingly, ∼60% of the detected lncRNAs show aberrant expression in oral premalignant lesions. A number of these lncRNAs have been previously associated with other human cancers., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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32. Canadian Optically-guided approach for Oral Lesions Surgical (COOLS) trial: study protocol for a randomized controlled trial.
- Author
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Poh CF, Durham JS, Brasher PM, Anderson DW, Berean KW, MacAulay CE, Lee JJ, and Rosin MP
- Subjects
- Canada, Cost-Benefit Analysis, Double-Blind Method, Humans, Neoplasm Recurrence, Local, Quality-Adjusted Life Years, Squamous Cell Carcinoma of Head and Neck, Surgery, Computer-Assisted economics, Carcinoma in Situ surgery, Carcinoma, Squamous Cell surgery, Fluorescence, Head and Neck Neoplasms surgery, Mouth Neoplasms surgery, Surgery, Computer-Assisted methods
- Abstract
Background: Oral cancer is a major health problem worldwide. The 5-year survival rate ranges from 30-60%, and has remained unchanged in the past few decades. This is mainly due to late diagnosis and high recurrence of the disease. Of the patients who receive treatment, up to one third suffer from a recurrence or a second primary tumor. It is apparent that one major cause of disease recurrence is clinically unrecognized field changes which extend beyond the visible tumor boundary. We have previously developed an approach using fluorescence visualization (FV) technology to improve the recognition of the field at risk surrounding a visible oral cancer that needs to be removed and preliminary results have shown a significant reduction in recurrence rates., Method/design: This paper describes the study design of a randomized, multi-centre, double blind, controlled surgical trial, the COOLS trial. Nine institutions across Canada will recruit a total of 400 patients with oral severe dysplasia or carcinoma in situ (N = 160) and invasive squamous cell carcinoma (N = 240). Patients will be stratified by participating institution and histology grade and randomized equally into FV-guided surgery (experimental arm) or white light-guided surgery (control arm). The primary endpoint is a composite of recurrence at or 1 cm within the previous surgery site with 1) the same or higher grade histology compared to the initial diagnosis (i.e., the diagnosis used for randomization); or 2) further treatment due to the presence of severe dysplasia or higher degree of change at follow-up. This is the first randomized, multi-centre trial to validate the effectiveness of the FV-guided surgery., Discussion: In this paper we described the strategies, novelty, and challenges of this unique trial involving a surgical approach guided by the FV technology. The success of the trial requires training, coordination, and quality assurance across multiple sites within Canada. The COOLS trial, an example of translational research, may result in reduced recurrence rates following surgical treatment of early-stage oral cancer with significant impacts on survival, morbidity, patients' quality of life and the cost to the health care system., Trial Registration: Clinicaltrials.gov NCT01039298.
- Published
- 2011
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33. Squamous cell carcinoma and precursor lesions: diagnosis and screening in a technical era.
- Author
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Poh CF, MacAulay CE, Laronde DM, Williams PM, Zhang L, and Rosin MP
- Subjects
- Carcinoma, Squamous Cell prevention & control, Coloring Agents, Diagnostic Imaging methods, Fluorescence, Humans, Image Processing, Computer-Assisted methods, Mouth Neoplasms prevention & control, Optical Devices, Precancerous Conditions prevention & control, Technology Assessment, Biomedical standards, Biomedical Technology, Carcinoma, Squamous Cell diagnosis, Mass Screening, Mouth Neoplasms diagnosis, Precancerous Conditions diagnosis
- Published
- 2011
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34. The epidermal growth factor receptor axis: support for a new target for oral premalignancy.
- Author
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Rosin MP and Califano JA
- Subjects
- Antineoplastic Agents therapeutic use, ErbB Receptors genetics, ErbB Receptors metabolism, Humans, Mouth Neoplasms metabolism, Precancerous Conditions metabolism, Precancerous Conditions pathology, ErbB Receptors antagonists & inhibitors, Mouth Neoplasms prevention & control, Precancerous Conditions drug therapy
- Abstract
This perspective on the report by Benchekroun et al. in this issue of the journal (beginning on page 800) examines new studies of factors in the epidermal growth factor receptor (EGFR) axis (including copy number alterations at the EGFR locus) that potentially predict the development of oral cancer; this work was conducted in a chemoprevention trial cohort of patients with oral premalignant lesions. The new data raise the possibility that a subset of oral premalignant lesions may benefit from specific therapeutic targeting of the EGFR axis., (2010 AACR.)
- Published
- 2010
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35. Multiple pathways in the FGF signaling network are frequently deregulated by gene amplification in oral dysplasias.
- Author
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Tsui IF, Poh CF, Garnis C, Rosin MP, Zhang L, and Lam WL
- Subjects
- Carcinoma, Squamous Cell genetics, Cyclin D1 genetics, ErbB Receptors genetics, Head and Neck Neoplasms genetics, Humans, Oligonucleotide Array Sequence Analysis, RNA, Messenger analysis, Fibroblast Growth Factors physiology, Gene Amplification, Mouth Neoplasms genetics, Precancerous Conditions genetics, Signal Transduction physiology
- Abstract
Genetic alteration in oral premalignant lesions (OPLs), the precursors of oral squamous cell carcinomas (OSCCs), may represent key changes in disease initiation and development. We ask if DNA amplification occurs at this early stage of cancer development and which oncogenic pathways are disrupted in OPLs. Here, we evaluated 50 high-grade dysplasias and low-grade dysplasias that later progressed to cancer for gene dosage aberrations using tiling-path DNA microarrays. Early occurrences of DNA amplification and homozygous deletion were frequently detected, with 40% (20/50) of these early lesions exhibiting such features. Expression for 88 genes in 7 recurrent amplicons were evaluated in 5 independent head and neck cancer datasets, with 40 candidates found to be overexpressed relative to normal tissues. These genes were significantly enriched in the canonical ERK/MAPK, FGF, p53, PTEN and PI3K/AKT signaling pathways (p = 8.95 x 10(-3) to 3.18 x 10(-2)). These identified pathways share interactions in one signaling network, and amplification-mediated deregulation of this network was found in 30.0% of these preinvasive lesions. No such alterations were found in 14 low-grade dysplasias that did not progress, whereas 43.5% (10/23) of OSCCs were found to have altered genes within the pathways with DNA amplification. Multitarget FISH showed that amplification of EGFR and CCND1 can coexist in single cells of an oral dysplasia, suggesting the dependence on multiple oncogenes for OPL progression. Taken together, these findings identify a critical biological network that is frequently disrupted in high-risk OPLs, with different specific genes disrupted in different individuals., ((c) 2009 UICC.)
- Published
- 2009
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36. Genomic imbalances in precancerous tissues signal oral cancer risk.
- Author
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Garnis C, Chari R, Buys TP, Zhang L, Ng RT, Rosin MP, and Lam WL
- Subjects
- Chromosome Aberrations, Comparative Genomic Hybridization, Disease Progression, Genetic Predisposition to Disease, Genome, Human, Humans, Mouth Neoplasms pathology, Precancerous Conditions pathology, Risk Factors, Mouth Neoplasms genetics, Precancerous Conditions genetics
- Abstract
Oral cancer develops through a series of histopathological stages: through mild (low grade), moderate, and severe (high grade) dysplasia to carcinoma in situ and then invasive disease. Early detection of those oral premalignant lesions (OPLs) that will develop into invasive tumors is necessary to improve the poor prognosis of oral cancer. Because no tools exist for delineating progression risk in low grade oral lesions, we cannot determine which of these cases require aggressive intervention. We undertook whole genome analysis by tiling-path array comparative genomic hybridization for a rare panel of early and late stage OPLs (n = 62), all of which had extensive longitudinal follow up (>10 years). Genome profiles for oral squamous cell carcinomas (n = 24) were generated for comparison. Parallel analysis of genome alterations and clinical parameters was performed to identify features associated with disease progression. Genome alterations in low grade dysplasias progressing to invasive disease more closely resembled those observed for later stage disease than they did those observed for non-progressing low grade dysplasias. This was despite the histopathological similarity between progressing and non-progressing cases. Strikingly, unbiased computational analysis of genomic alteration data correctly classified nearly all progressing low grade dysplasia cases. Our data demonstrate that high resolution genomic analysis can be used to evaluate progression risk in low grade OPLs, a marked improvement over present histopathological approaches which cannot delineate progression risk. Taken together, our data suggest that whole genome technologies could be used in management strategies for patients presenting with precancerous oral lesions.
- Published
- 2009
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37. Tracing the "at-risk" oral mucosa field with autofluorescence: steps toward clinical impact.
- Author
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Poh CF, MacAulay CE, Zhang L, and Rosin MP
- Subjects
- Fluorescence, Humans, Mouth Neoplasms diagnosis, Risk Factors, Cell Transformation, Neoplastic, Diagnostic Imaging methods, Mouth Mucosa pathology, Precancerous Conditions diagnosis
- Published
- 2009
- Full Text
- View/download PDF
38. Areca nut and betel quid chewing among South Asian immigrants to Western countries and its implications for oral cancer screening.
- Author
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Auluck A, Hislop G, Poh C, Zhang L, and Rosin MP
- Subjects
- Asia ethnology, Behavior, Addictive, Canada epidemiology, Culture, Health Knowledge, Attitudes, Practice, Humans, Life Style, Mouth Neoplasms epidemiology, Mouth Neoplasms etiology, Mouth Neoplasms physiopathology, Oral Health, Risk Assessment, Rural Population, Areca adverse effects, Mass Screening, Mastication, Mouth Neoplasms diagnosis
- Abstract
The South Asian community is the largest and one of the fastest growing minority groups in Canada, according to the 2006 census. These immigrants bring to Canada talents and skills that can promote Canada's economy and cultural diversity, but they also bring lifestyle habits that may lead to serious health issues. Chewing areca nut and betel quid (paan, with and without tobacco) is a known risk factor for oral cancer. This habit is common in the Indo-Canadian population, as evidenced by its sales in local Indian markets and restaurants. In this article, we present an overview of the sociocultural beliefs, knowledge and practices regarding betel quid/areca nut chewing, and discuss its implications for oral cancer screening among this immigrant population.
- Published
- 2009
39. Multiple aberrations of chromosome 3p detected in oral premalignant lesions.
- Author
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Tsui IF, Rosin MP, Zhang L, Ng RT, and Lam WL
- Subjects
- Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Comparative Genomic Hybridization, Disease Progression, Follow-Up Studies, Gene Deletion, Gene Dosage, Humans, Loss of Heterozygosity, Mouth Mucosa metabolism, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Precancerous Conditions pathology, Chromosome Aberrations, Chromosomes, Human, Pair 3, Mouth Mucosa pathology, Precancerous Conditions genetics
- Abstract
The study of oral premalignant lesions (OPL) is crucial to the identification of initiating genetic events in oral cancer. However, these lesions are minute in size, making it a challenge to recover sufficient DNA from microdissected cells for comprehensive genomic analysis. As a step toward identifying genetic aberrations associated with oral cancer progression, we used tiling-path array comparative genomic hybridization to compare alterations on chromosome 3p for 71 OPLs against 23 oral squamous cell carcinomas. 3p was chosen because although it is frequently altered in oral cancers and has been associated with progression risk, its alteration status has only been evaluated at a small number of loci in OPLs. We identified six recurrent losses in this region that were shared between high-grade dysplasias and oral squamous cell carcinomas, including a 2.89-Mbp deletion spanning the FHIT gene (previously implicated in oral cancer progression). When the alteration status for these six regions was examined in 24 low-grade dysplasias with known progression outcome, we observed that they occurred at a significantly higher frequency in low-grade dysplasias that later progressed to later-stage disease (P < 0.003). Moreover, parallel analysis of all profiled tissues showed that the extent of overall genomic alteration at 3p increased with histologic stage. This first high-resolution analysis of chromosome arm 3p in OPLs represents a significant step toward predicting progression risk in early preinvasive disease and provides a keen example of how genomic instability escalates with progression to invasive cancer.
- Published
- 2008
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- View/download PDF
40. Potential use of quantitative tissue phenotype to predict malignant risk for oral premalignant lesions.
- Author
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Guillaud M, Zhang L, Poh C, Rosin MP, and MacAulay C
- Subjects
- Carcinoma, Squamous Cell genetics, Disease Progression, Early Diagnosis, Humans, Loss of Heterozygosity, Mouth Neoplasms genetics, Precancerous Conditions genetics, Precancerous Conditions pathology, Prognosis, Regression Analysis, Risk Factors, Sensitivity and Specificity, Time Factors, Carcinoma, Squamous Cell diagnosis, Diagnostic Techniques and Procedures, Mouth Neoplasms diagnosis, Phenotype, Precancerous Conditions diagnosis
- Abstract
The importance of early diagnosis in improving mortality and morbidity rates of oral squamous cell carcinoma (SCC) has long been recognized. However, a major challenge for early diagnosis is our limited ability to differentiate oral premalignant lesions (OPL) at high risk of progressing into invasive SCC from those at low risk. We investigated the potential of quantitative tissue phenotype (QTP), measured by high-resolution image analysis, to identify severe dysplasia/carcinoma in situ (CIS; known to have an increased risk of progression) and to predict progression to cancer within hyperplasia or mild/moderate dysplasia. We generated a nuclear phenotype score (NPS), a combination of five nuclear morphometric features that best discriminate 4,027 "normal" nuclei (selected from 29 normal oral biopsies) from 4,298 "abnormal" nuclei (selected from 30 SCC biopsies). This NPS was then determined for a set of 69 OPLs. Severe dysplasia/CIS showed a significant increase in NPS compared with hyperplasia or mild/moderate dysplasia. However, within the latter group, elevated NPS was strongly associated with the presence of high-risk loss of heterozygosity (LOH) patterns. There was a statistical difference between NPS of hyperplasia or mild/moderate dysplasia that progressed to cancer and those that did not. Individuals with a high NPS had a 10-fold increase in relative risk of progression. In the multivariate Cox model, LOH and NPS together were the strongest predictors for cancer development. These data suggest that QTP could be used to identify lesions that require molecular evaluation and should be integrated with such approaches to facilitate the identification of hyperplasia or mild/moderate dysplasia OPLs at high risk of progression.
- Published
- 2008
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- View/download PDF
41. Oral cancer: just the facts.
- Author
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Laronde DM, Hislop TG, Elwood JM, and Rosin MP
- Subjects
- Age Factors, Alcohol Drinking adverse effects, Alphapapillomavirus pathogenicity, Canada epidemiology, Early Diagnosis, Humans, Incidence, Mouth Neoplasms etiology, Prevalence, Risk Factors, Sex Factors, Smoking adverse effects, Mass Screening, Mouth Neoplasms diagnosis, Mouth Neoplasms epidemiology
- Abstract
Oral cancer screening should be an integral part of a clinician's routine. This article reviews facts about oral cancer that are relevant to screening. The relevance of some issues in a particular dental practice will vary with the patient composition of the practice.
- Published
- 2008
42. Evaluation of a suspicious oral mucosal lesion.
- Author
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Williams PM, Poh CF, Hovan AJ, Ng S, and Rosin MP
- Subjects
- Alcohol Drinking, Biopsy, British Columbia, Coloring Agents, Diagnosis, Differential, Fluorescence, Humans, Medical History Taking, Mouth Neoplasms pathology, Physical Examination, Precancerous Conditions diagnosis, Precancerous Conditions pathology, Preventive Health Services, Smoking, Tolonium Chloride, Mouth Mucosa pathology, Mouth Neoplasms diagnosis
- Abstract
Dentists who encounter a change in the oral mucosa of a patient must decide whether the abnormality requires further investigation. In this paper, we describe a systematic approach to the assessment of oral mucosal conditions that are thought likely to be premalignant or an early cancer. These steps, which include a comprehensive history, step-by-step clinical examination (including use of adjunctive visual tools), diagnostic testing and formulation of diagnosis, are routinely used in clinics affiliated with the British Columbia Oral Cancer Prevention Program (BC OCPP) and are recommended for consideration by dentists for use in daily practice.
- Published
- 2008
43. Voices from the community--experiences from the dental office: initiating oral cancer screening.
- Author
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Laronde DM, Bottorff JL, Hislop TG, Poh CY, Currie B, Williams PM, and Rosin MP
- Subjects
- British Columbia, Dentist-Patient Relations, Education, Dental, Continuing, Humans, Patient Acceptance of Health Care, Professional Role, Time Management, Mass Screening, Mouth Neoplasms diagnosis, Practice Patterns, Dentists'
- Published
- 2008
44. Biopsy and histopathologic diagnosis of oral premalignant and malignant lesions.
- Author
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Poh CF, Ng S, Berean KW, Williams PM, Rosin MP, and Zhang L
- Subjects
- British Columbia, Epithelium pathology, Humans, Biopsy methods, Carcinoma, Squamous Cell pathology, Mouth Neoplasms pathology, Precancerous Conditions pathology, Preventive Health Services organization & administration
- Abstract
Accurate diagnosis of premalignant or malignant oral lesions depends on the quality of the biopsy, adequate clinical information and correct interpretation of the biopsy results. The purpose of this paper is to review the procedures for obtaining appropriate biopsy samples, and the criteria for diagnosing and grading dysplasias. The World Health Organization's description of the architectural and cytologic epithelial changes that characterize dysplasia is detailed, and guidelines for following up patients with premalignant and malignant lesions are provided. The benefits of using the centralized services and expertise of the British Columbia Oral Biopsy Service are also reviewed.
- Published
- 2008
45. Why should dentists screen for oral cancer?
- Author
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Musa Z, Johnston K, Peacock S, Rosin MP, and Elwood JM
- Subjects
- Age Factors, Alcohol Drinking, British Columbia, Early Diagnosis, Humans, Risk Factors, Smoking, Mass Screening, Mouth Neoplasms diagnosis, Practice Patterns, Dentists'
- Published
- 2008
46. A magic wand for the community dental office? Observations from the British Columbia Oral Cancer Prevention Program.
- Author
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Laronde DM, Poh CF, Williams PM, Hislop TG, Zhang L, MacAulay C, and Rosin MP
- Subjects
- British Columbia, Fluorescence, Humans, Light, Community Dentistry, Mass Screening instrumentation, Mouth Neoplasms prevention & control
- Published
- 2007
47. Visualization and other emerging technologies as change makers for oral cancer prevention.
- Author
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Rosin MP, Poh CF, Guillard M, Williams PM, Zhang L, and MacaUlay C
- Subjects
- Humans, Image Cytometry, Longitudinal Studies, Mass Screening methods, Microsatellite Repeats genetics, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Precancerous Conditions genetics, Precancerous Conditions pathology, Predictive Value of Tests, Mouth Neoplasms diagnosis, Mouth Neoplasms prevention & control, Precancerous Conditions diagnosis, Precancerous Conditions prevention & control
- 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.
- Published
- 2007
- Full Text
- View/download PDF
48. Direct fluorescence visualization of clinically occult high-risk oral premalignant disease using a simple hand-held device.
- Author
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Poh CF, Ng SP, Williams PM, Zhang L, Laronde DM, Lane P, Macaulay C, and Rosin MP
- Subjects
- Adult, Early Diagnosis, Equipment Design, Female, Follow-Up Studies, Humans, Male, Middle Aged, Luminescent Measurements instrumentation, Mouth Neoplasms diagnosis, Precancerous Conditions diagnosis, Spectrometry, Fluorescence instrumentation
- Abstract
Background: 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., Methods: Patients in the Oral Dysplasia Clinics at British Columbia are currently being examined with a simple hand-held device that permits the direct visualization of alterations to autofluorescence in the oral cavity. Tissue showing loss of autofluorescence is biopsied., Results: We present 3 representative cases in which occult lesions were identified with fluorescence visualization during longitudinal follow-up, resulting in the diagnosis of a primary dysplasia in case 1, a second primary cancer in case 2, and cancer recurrence in case 3., Conclusions: This is the first report of the diagnosis of occult oral disease using a simple noninvasive device. These early examples indicate the potential value of this technology to guide the management of patients with oral lesions, facilitating the detection of high-risk changes not apparent with white-light visualization.
- Published
- 2007
- Full Text
- View/download PDF
49. Fluorescence visualization detection of field alterations in tumor margins of oral cancer patients.
- Author
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Poh CF, Zhang L, Anderson DW, Durham JS, Williams PM, Priddy RW, Berean KW, Ng S, Tseng OL, MacAulay C, and Rosin MP
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor genetics, Carcinoma in Situ diagnosis, Carcinoma, Squamous Cell genetics, Female, Humans, Intraoperative Period, Loss of Heterozygosity, Male, Middle Aged, Mouth Neoplasms genetics, Risk Assessment, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell surgery, Fluorescence, Hydrocarbons, Mouth Neoplasms diagnosis, Mouth Neoplasms surgery
- Abstract
Purpose: Genetically altered cells could become widespread across the epithelium of patients with oral cancer, often in clinically and histologically normal tissue, and contribute to recurrent disease. Molecular approaches have begun to yield information on cancer/risk fields; tissue optics could further extend our understanding of alteration to phenotype as a result of molecular change., Experimental Design: We used a simple hand-held device in the operating room to directly visualize subclinical field changes around oral cancers, documenting alteration to fluorescence. A total of 122 oral mucosa biopsies were obtained from 20 surgical specimens with each biopsy being assessed for location, fluorescence visualization (FV) status, histology, and loss of heterozygosity (LOH; 10 markers on three regions: 3p14, 9p21, and 17p13)., Results: All tumors showed FV loss (FVL). For 19 of the 20 tumors, the loss extended in at least one direction beyond the clinically visible tumor, with the extension varying from 4 to 25 mm. Thirty-two of 36 FVL biopsies showed histologic change (including 7 squamous cell carcinoma/carcinomas in situ, 10 severe dysplasias, and 15 mild/moderate dysplasias) compared with 1 of the 66 FV retained (FVR) biopsies. Molecular analysis on margins with low-grade or no dysplasia showed a significant association of LOH in FVL biopsies, with LOH at 3p and/or 9p (previously associated with local tumor recurrence) present in 12 of 19 FVL biopsies compared with 3 of 13 FVR biopsies (P=0.04)., Conclusions: These data have, for the first time, shown that direct FV can identify subclinical high-risk fields with cancerous and precancerous changes in the operating room setting.
- Published
- 2006
- Full Text
- View/download PDF
50. Heads up! - a call for dentists to screen for oral cancer.
- Author
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Poh CF, Williams PM, Zhang L, and Rosin MP
- Subjects
- Canada epidemiology, Early Diagnosis, Humans, Middle Aged, Mouth Neoplasms mortality, Survival Rate, Dentists, Mass Screening, Mouth Neoplasms diagnosis, Professional Role
- Published
- 2006
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