Oreste Iocca1,2, Thomas P Sollecito3, Faizan Alawi4, Gregory S Weinstein5, Jason G Newman5, Armando De Virgilio1,2, Pasquale Di Maio6, Giuseppe Spriano1,2, Simón Pardiñas López7, Rabie M Shanti5,8. 1. Department of Otorhinolaryngology-Head and Neck Surgery, Humanitas Clinical and Research Center, Rozzano, Milano, Italy. 2. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy. 3. Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania. 4. Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania. 5. Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania. 6. Giovanni Borea Civil Hospital, Department of Otolaryngology-Head and Neck Surgery, Sanremo, Italy. 7. Periodontology and Oral Surgery, Clínica Médico Dental Pardiñas, Cell Therapy and Regenerative Medicine Group, Centre for Advanced Scientific Research (CICA) and Biomedical Research Institute of A Coruña (INIBIC) Strategic Group, Universidade da Coruña (UDC), University Hospital Complex of A Coruña (CHUAC), Galician Health Service (SERGAS), A Coruña, Spain. 8. Department of Oral and Maxillofacial Surgery, University of Pennsylvania School of Dental Medicine, Philadelphia, PA.
Abstract
IMPORTANCE: Potentially malignant disorders of the oral cavity (OPMD) are a heterogeneous group of lesions associated with a variable risk of malignant transformation (MT) to invasive cancer. Leukoplakia (LE), lichen planus (LP), oral lichenoid lesions (OLL), oral erythroplakia (OE), oral submucous fibrosis (OSF), and proliferative verrucous leukoplakia (PVL) are among the most common of these lesions. Oral dysplasia is a mucosal area characterized by cellular and architectural derangement, which may be associated with OPMDs or not. OBJECTIVE: To define the MT rate of OPMDs and the risk of development into cancer of mild vs moderate/severe oral dysplasia. This in order to implement adequate follow-up strategies and treatment decisions. STUDY DESIGN: We performed a systematic review and meta-analysis on studies reporting the MT rates of OPMDs and oral dysplasia. Ninety-two studies were included for the analysis. Cumulative rates were reported for OPMDs overall and as a subgroup, a comparison was made of mild vs moderate/severe dysplasia. Meta-regression on OPMD and year of publication was also performed. MAIN OUTCOME AND MEASURES: Overall MT rates of OPMDs and odds ratio of MT of mild vs moderate/severe dysplasia. RESULTS: Overall MT rate across all OPMD groups was 7.9% (99% confidence interval [CI] 4.9%-11.5%). MT rates of the specific OPMD subgroups were as follows: LP 1.4% (99% CI 0.9%-1.9%), LE 9.5 (5.9%-14.00%), OLL 3.8% (99% CI 1.6%-7.00%), OSF 5.2% (99% CI 2.9%-8.00%), OE 33.1% (99% CI 13.6%-56.1%), and PVL 49.5% (99% CI 26.7%-72.4%). Regarding the dysplasia grades comparison, the meta-analysis showed that moderate/severe dysplasia is meaningfully associated to a much greater risk of MT compared to mild dysplasia with an odds ratio of 2.4 (95% CI 1.5-3.8) [Correction added on 27 December 2019, after first online publication: CI updated from 99% to 95%.]. Heterogeneity was not significant. Annual MT rates were approximated based on the average follow-up as reported in the various subgroups. Lichen planus had an annual MT of 0.28%, OLL of 0.57%, leukoplakia of 1.56%, PVL of 9.3%, and OSF of 0.98%. Mild dysplasia had an annual MT of 1.7%, while severe dysplasia of 3.57%. Meta-regression showed a significant negative correlation of PVL MT rate and year of the study (P value <.001). CONCLUSIONS AND RELEVANCE: OPMDs and oral dysplasia are relatively common conditions that general practitioners, head and neck, and oral medicine specialists, face in their everyday practice. Our analysis confirms the significant risk of MT of these lesions, although variable among the subgroups. Moderate/severe dysplasia bears a much higher risk of cancer evolution than mild dysplasia. It is important to raise public health awareness on the MT rates of these conditions, at the same time efficacious communication with the patient is of utmost importance. This, coupled with strict follow-up measures and optimal treatment strategies, would help in reducing the transformation of these oral conditions into invasive cancer.
IMPORTANCE: Potentially malignant disorders of the oral cavity (OPMD) are a heterogeneous group of lesions associated with a variable risk of malignant transformation (MT) to invasive cancer. Leukoplakia (LE), lichen planus (LP), oral lichenoid lesions (OLL), oral erythroplakia (OE), oral submucous fibrosis (OSF), and proliferative verrucous leukoplakia (PVL) are among the most common of these lesions. Oral dysplasia is a mucosal area characterized by cellular and architectural derangement, which may be associated with OPMDs or not. OBJECTIVE: To define the MT rate of OPMDs and the risk of development into cancer of mild vs moderate/severe oral dysplasia. This in order to implement adequate follow-up strategies and treatment decisions. STUDY DESIGN: We performed a systematic review and meta-analysis on studies reporting the MT rates of OPMDs and oral dysplasia. Ninety-two studies were included for the analysis. Cumulative rates were reported for OPMDs overall and as a subgroup, a comparison was made of mild vs moderate/severe dysplasia. Meta-regression on OPMD and year of publication was also performed. MAIN OUTCOME AND MEASURES: Overall MT rates of OPMDs and odds ratio of MT of mild vs moderate/severe dysplasia. RESULTS: Overall MT rate across all OPMD groups was 7.9% (99% confidence interval [CI] 4.9%-11.5%). MT rates of the specific OPMD subgroups were as follows: LP 1.4% (99% CI 0.9%-1.9%), LE 9.5 (5.9%-14.00%), OLL 3.8% (99% CI 1.6%-7.00%), OSF 5.2% (99% CI 2.9%-8.00%), OE 33.1% (99% CI 13.6%-56.1%), and PVL 49.5% (99% CI 26.7%-72.4%). Regarding the dysplasia grades comparison, the meta-analysis showed that moderate/severe dysplasia is meaningfully associated to a much greater risk of MT compared to mild dysplasia with an odds ratio of 2.4 (95% CI 1.5-3.8) [Correction added on 27 December 2019, after first online publication: CI updated from 99% to 95%.]. Heterogeneity was not significant. Annual MT rates were approximated based on the average follow-up as reported in the various subgroups. Lichen planus had an annual MT of 0.28%, OLL of 0.57%, leukoplakia of 1.56%, PVL of 9.3%, and OSF of 0.98%. Mild dysplasia had an annual MT of 1.7%, while severe dysplasia of 3.57%. Meta-regression showed a significant negative correlation of PVL MT rate and year of the study (P value <.001). CONCLUSIONS AND RELEVANCE: OPMDs and oral dysplasia are relatively common conditions that general practitioners, head and neck, and oral medicine specialists, face in their everyday practice. Our analysis confirms the significant risk of MT of these lesions, although variable among the subgroups. Moderate/severe dysplasia bears a much higher risk of cancer evolution than mild dysplasia. It is important to raise public health awareness on the MT rates of these conditions, at the same time efficacious communication with the patient is of utmost importance. This, coupled with strict follow-up measures and optimal treatment strategies, would help in reducing the transformation of these oral conditions into invasive cancer.
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