```markdown THE UNIVERSITY OF WESTERN AUSTRALIA > J Oral Pathol Med. 2007 Nov;36(10):575-80. doi: 10.1111/j.1600-0714.2007.00582.x. # Nomenclature and classification of potentially malignant disorders of the oral mucosa S Warnakulasuriya ¹, Newell W Johnson, I van der Waal Affiliations + expand PMID: 17944749 DOI: 10.1111/j.1600-0714.2007.00582.x ## Abstract At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK issues related to terminology, definitions and classification of oral precancer were discussed by an expert group. The consensus views of the Working Group are presented here. The term, 'potentially malignant disorders', was recommended to refer to precancer as it conveys that not all disorders described under this term may transform into cancer. Critically evaluating all definitions proposed so far for oral leukoplakia, the Working Group agreed that the term leukoplakia should be used to recognize 'white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer'. An outline was proposed for diagnosing oral leukoplakia that will prevent other oral white disorders being misclassified as leukoplakia. The Working Group discussed the caveats involved in the current use of terminology and classification of oral potentially malignant disorders, deficiencies of these complex systems, and how they have evolved over the past several decades. The terminology presented in this report reflects our best understanding of multi-step carcinogenesis in the oral mucosa, and aspires to engender consistency in use. FULL TEXT LINKS WILEY Full Text Article ACTIONS “ Cite Collections SHARE Twitter Facebook Link PAGE NAVIGATION < Title & authors Abstract Similar articles Cited by ``` #### Publication Information - **Journal:** J Oral Pathol Med. 2007 Nov;36(10):575-80. - **DOI:** 10.1111/j.1600-0714.2007.00582.x - **Authors:** S Warnakulasuriya, Newell W Johnson, I van der Waal - **PMID:** 17944749 #### Expert Group Consensus and Terminology At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK, issues related to terminology, definitions, and classification of oral precancer were discussed by an expert group. The consensus views of the Working Group are presented here. The term "potentially malignant disorders" (OPMDs) was recommended to refer to precancer, as it conveys that not all disorders described under this term may transform into cancer. The terminology presented in this report reflects the current understanding of multi-step carcinogenesis in the oral mucosa and aspires to engender consistency in use. #### Clinical Definitions and Diagnosis Critically evaluating all definitions proposed so far for oral leukoplakia, the Working Group agreed that the term leukoplakia should be used to recognize "white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer." An outline was proposed for diagnosing oral leukoplakia to prevent other oral white disorders from being misclassified. The Working Group also discussed the caveats involved in the current use of terminology and classification of oral potentially malignant disorders, the deficiencies of these complex systems, and how they have evolved over the past several decades. ```markdown THE UNIVERSITY OF WESTERN AUSTRALIA # Nomenclature and classification - Definition - OPMIDs refer to a group of lesions and conditions characterised by a variably increased risk of developing cancers of the lip (C00) and the oral cavity (C02-C06) - ‘pre-cancer’, ‘precursor lesions’, ‘pre-malignant’, ‘intra epithelial neoplasia’ and ‘potentially malignant’ have been used in the international literature to broadly describe clinical presentations that may potentially become cancer. 17 ``` #### Definition of Potentially Malignant Disorders Oral Potentially Malignant Disorders (OPMDs) refer to a group of lesions and conditions characterized by a variably increased risk of developing cancers of the lip (C00) and the oral cavity (C02-C06). #### Historical and Alternative Terminology Various terms have been used in international literature to broadly describe clinical presentations that may potentially become cancer, including: - Pre-cancer - Precursor lesions - Pre-malignant - Intra-epithelial neoplasia - Potentially malignant ```markdown THE UNIVERSITY OF WESTERN AUSTRALIA > J Oral Pathol Med. 2007 Nov;36(10):575-80. doi: 10.1111/j.1600-0714.2007.00582.x. # Nomenclature and classification of potentially malignant disorders of the oral mucosa S Warnakulasuriya ¹, Newell W Johnson, I van der Waal Affiliations + expand PMID: 17944749 DOI: 10.1111/j.1600-0714.2007.00582.x ## Abstract At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK issues related to terminology, definitions and classification of oral precancer were discussed by an expert group. The consensus views of the Working Group are presented here. The term, 'potentially malignant disorders', was recommended to refer to precancer as it conveys that not all disorders described under this term may transform into cancer. Critically evaluating all definitions proposed so far for oral leukoplakia, the Working Group agreed that the term leukoplakia should be used to recognize 'white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer'. An outline was proposed for diagnosing oral leukoplakia that will prevent other oral white disorders being misclassified as leukoplakia. The Working Group discussed the caveats involved in the current use of terminology and classification of oral potentially malignant disorders, deficiencies of these complex systems, and how they have evolved over the past several decades. The terminology presented in this report reflects our best understanding of multi-step carcinogenesis in the oral mucosa, and aspires to engender consistency in use. FULL TEXT LINKS WILEY Full Text Article ACTIONS "Cite" "Collections" SHARE Twitter Facebook Link PAGE NAVIGATION < Title & authors Abstract Similar articles Cited by ``` #### Publication Information - **Journal:** J Oral Pathol Med. 2007 Nov;36(10):575-80. - **DOI:** 10.1111/j.1600-0714.2007.00582.x - **Authors:** S Warnakulasuriya, Newell W Johnson, I van der Waal - **PMID:** 17944749 #### Expert Group Consensus and Terminology At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK, issues related to terminology, definitions, and classification of oral precancer were discussed by an expert group. The consensus views of the Working Group are presented here. The term "potentially malignant disorders" was recommended to refer to precancer, as it conveys that not all disorders described under this term may transform into cancer. The terminology presented in this report reflects the current understanding of multi-step carcinogenesis in the oral mucosa and aspires to engender consistency in use. #### Clinical Definitions and Diagnosis Critically evaluating all definitions proposed so far for oral leukoplakia, the Working Group agreed that the term leukoplakia should be used to recognize "white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer." An outline was proposed for diagnosing oral leukoplakia to prevent other oral white disorders from being misclassified. The Working Group also discussed the caveats involved in the current use of terminology and classification of oral potentially malignant disorders, the deficiencies of these complex systems, and how they have evolved over the past several decades. ```markdown WHO classification 2005 - Classification of precancerous lesions and conditions | Precancerous lesions | Precancerous conditions | |----------------------|-------------------------| | Leukoplakia | Submucous fibrosis | | Erythroplakia | Actinic keratosis | | Palatal lesions in reverse smokers | Lichen planus | | | Discoid lupus erythematosus | | | Hereditary disorders with increased risk:<br>dyskeratosis congenita and epidermolysis bullosa | J Oral Pathology Medicine, Volume: 36, Issue: 10, Pages: 575-580, First published: 26 July 2007, DOI: (10.1111/j.1600-0714.2007.00582.x) ```  The 2005 classification distinguishes between precancerous lesions and precancerous conditions based on their clinical and pathological characteristics. #### Precancerous Lesions - Leukoplakia - Erythroplakia - Palatal lesions in reverse smokers #### Precancerous Conditions - Submucous fibrosis - Actinic keratosis - Lichen planus - Discoid lupus erythematosus - Hereditary disorders with increased risk: - Dyskeratosis congenita - Epidermolysis bullosa *Source: J Oral Pathology Medicine, Volume: 36, Issue: 10, Pages: 575-580 (2007).* Table classifying precancerous lesions and conditions according to the WHO classification 2005, with two columns: 'Precancerous lesions' including leukoplakia, erythroplakia, and palatal lesions in reverse smokers, and 'Precancerous conditions' including submucous fibrosis, actinic keratosis, lichen planus, discoid lupus erythematosus, and hereditary disorders like dyskeratosis congenita and epidermolysis bullosa. ```markdown THE UNIVERSITY OF WESTERN AUSTRALIA Review > Oral Dis. 2021 Nov;27(8):1862-1880. doi: 10.1111/odi.13704. Epub 2020 Nov 26. # Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer Saman Warnakulasuriya ¹, Omar Kujan ², José M Aguirre-Urizar ³, José V Bagan ⁴ ⁵, Miguel Ángel González-Moles ⁶ ⁷, Alexander R Kerr ⁸, Giovanni Lodi ⁹, Fernanda Weber Mello ¹⁰, Luis Monteiro ¹¹, Graham R Ogden ¹², Philip Sloan ¹³, Newell W Johnson ¹⁴ ¹⁵ Affiliations + expand PMID: 33128420 DOI: 10.1111/odi.13704 **Free article** ## Abstract Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative FULL TEXT LINKS WILEY Full Text Article AIR FREE Full Text ACTIONS “ Cite _Collections SHARE Twitter Facebook Link PAGE NAVIGATION < Title & authors Abstract Similar articles 20 ``` #### Consensus Report on Oral Potentially Malignant Disorders (OPMD) Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This report presents an updated nomenclature and classification of OPMDs, based predominantly on clinical features. #### Workshop Background - **Convening Body:** WHO Collaborating Centre for Oral Cancer (UK). - **Evolution of Terminology:** The 2005 workshop initially used the term "potentially malignant disorders of the oral mucosa" (PMD), which has now been refined to "oral potentially malignant disorders" (OPMD). - **Scope:** The classification includes a wide spectrum of disorders such as leukoplakia, erythroplakia, and proliferative disorders. *Source: Oral Dis. 2021 Nov;27(8):1862-1880. doi: 10.1111/odi.13704.* ```markdown WHO classification 2020 <div align="right"> <img src="https://upload.wikimedia.org/wikipedia/commons/thumb/8/8a/The_University_of_Western_Australia_crest.svg/1200px-The_University_of_Western_Australia_crest.svg.png" alt="The University of Western Australia" width="150" /> </div> --- <table border="1" cellpadding="10" cellspacing="0" style="border-collapse: collapse; width: 100%; background-color: #f2f2f2;"> <thead> <tr> <th style="background-color: #d4af37; color: white; text-align: left;">Remove from the 2021 classification due to limited evidence</th> </tr> </thead> <tbody> <tr> <td style="background-color: #f5f5f5;">Oral Epidermolysis Bullosa</td> </tr> <tr> <td style="background-color: #f9f9f9;">Chronic hyperplastic candidosis</td> </tr> <tr> <td style="background-color: #f5f5f5;">Exophytic verrucous hyperplasia/verrucous hyperplasia</td> </tr> </tbody> </table> --- Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis. 2021 Nov;27(8):1862-1880. doi: 10.1111/odi.13704. 21 ```  #### Exclusions from the 2021 Classification Based on the consensus report, the following conditions were removed from the classification due to limited evidence regarding their malignant potential: - Oral Epidermolysis Bullosa - Chronic hyperplastic candidosis - Exophytic verrucous hyperplasia / verrucous hyperplasia *Source: Oral Dis. 2021 Nov;27(8):1862-1880.* A table with a yellow header titled 'Remove from the 2021 classification due to limited evidence' lists three conditions: Oral Epidermolysis Bullosa, Chronic hyperplastic candidosis, and Exophytic verrucous hyperplasia/verrucous hyperplasia. The table is part of a presentation on the WHO classification 2020, indicating items removed from the 2021 classification due to limited evidence. ```markdown WHO classification 2020 <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"> <thead> <tr> <th style="background-color: #d4a017; color: #ffffff;">Classification of oral potentially malignant disorders</th> <th style="background-color: #d4a017; color: #ffffff;">Newly included in 2021 classification</th> </tr> </thead> <tbody> <tr> <td>Leukoplakia</td> <td>Oral Lichenoid Lesion</td> </tr> <tr> <td>Proliferative verrucous leukoplakia</td> <td>Oral Graft versus Host Disease</td> </tr> <tr> <td>Erythroplakia</td> <td style="background-color: #d4a017; color: #ffffff;">Remove from the 2021 classification due to limited evidence</td> </tr> <tr> <td>Oral submucous fibrosis</td> <td>Oral Epidermolysis Bullosa</td> </tr> <tr> <td>Oral lichen planus</td> <td>Chronic hyperplastic candidosis</td> </tr> <tr> <td>Actinic Keratosis (Actinic Cheilitis)</td> <td>Exophytic verrucous hyperplasia/verrucous hyperplasia</td> </tr> <tr> <td>Palatal changes in reverse smoking</td> <td></td> </tr> <tr> <td>Oral Lupus Erythematosus</td> <td></td> </tr> <tr> <td>Dyskeratosis Congenita</td> <td></td> </tr> </tbody> </table> Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis. 2021 Nov;27(8):1862-1880. doi: 10.1111/odi.13704. ```  #### Comprehensive Classification of OPMDs This updated list includes established disorders and new additions to the 2021 consensus classification. **Established Oral Potentially Malignant Disorders:** - Leukoplakia - Proliferative verrucous leukoplakia - Erythroplakia - Oral submucous fibrosis - Oral lichen planus - Actinic Keratosis (Actinic Cheilitis) - Palatal changes in reverse smoking - Oral Lupus Erythematosus - Dyskeratosis Congenita **Newly Included in 2021 Classification:** - Oral Lichenoid Lesion - Oral Graft versus Host Disease #### Summary of Removals (Limited Evidence) - Oral Epidermolysis Bullosa - Chronic hyperplastic candidosis - Exophytic verrucous hyperplasia / verrucous hyperplasia *Source: Oral Dis. 2021 Nov;27(8):1862-1880.* A table comparing the WHO classification of oral potentially malignant disorders from 2020 with the newly included or removed items in the 2021 classification. The table lists conditions such as leukoplakia, erythroplakia, and oral lichen planus, indicating which are newly included or removed in the updated classification. # OPM D Epidemiology A recent systematic review included 22 epidemiological surveys that estimated a global prevalence of OPM Ds at **4.47%** (95% CI = 2.43–7.08). It was noted that prevalence may vary between populations and was generally higher in Asians and males. Prevalence of oral potentially malignant disorders: a systematic review and meta-analysis. J Oral Pathol Med 2018 Aug; 47: pp. 633-640. 22 #### Global Prevalence and Distribution A recent systematic review of 22 epidemiological surveys estimated the global prevalence of Oral Potentially Malignant Disorders (OPMDs) at **4.47%** (95% CI = 2.43–7.08). #### Demographic Variations Research indicates that prevalence rates are not uniform across all groups. Key findings regarding distribution include: - **Geographic Variation**: Prevalence varies significantly between different populations. - **Ethnic and Regional Factors**: Rates are generally higher among Asian populations. - **Gender Distribution**: There is a higher observed prevalence in males compared to females. #### Source Reference - Macey R, et al. Prevalence of oral potentially malignant disorders: a systematic review and meta-analysis. *J Oral Pathol Med*. 2018 Aug; 47(7): 633-640. ```markdown # Risk factors ## Pure nicotine based ### Vaping products ## Tobacco based ### Heated tobacco products "Heat-not-burn" ## Oral nicotine products ## Smokeless tobacco Items are not shown to scale THE UNIVERSITY OF WESTERN AUSTRALIA Kujan, O. (2017). Human Oral Cancer (Epidemiology and Characteristic). In: Al Moustafa, AE. (eds) Development of Oral Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-48054-1_1 ```  Tobacco and nicotine products are categorized into several delivery methods, each contributing to the risk profile of oral potentially malignant disorders. #### Pure Nicotine Based Products - **Vaping products**: Electronic delivery systems utilizing nicotine-based liquids. #### Tobacco Based Products - **Heated tobacco products**: Often referred to as "Heat-not-burn" devices. - **Smokeless tobacco**: Various forms of tobacco consumed without combustion. #### Oral Nicotine Products - Non-tobacco nicotine pouches or similar delivery formats. The image displays a 2x2 grid figure categorizing various nicotine products based on two axes: 'Pure nicotine based' vs. 'Tobacco based' and 'Heated aerosol' vs. 'Unheated'. The top-left quadrant shows vaping products like e-cigarettes and hookahs under 'Pure nicotine based' and 'Heated aerosol'. The top-right quadrant features heated tobacco products such as 'Heat-not-burn' devices under 'Tobacco based' and 'Heated aerosol'. The bottom-left quadrant includes oral nicotine products like nicotine pouches and gums under 'Pure nicotine based' and 'Unheated'. The bottom-right quadrant presents smokeless tobacco products such as snus and chewing tobacco under 'Tobacco based' and 'Unheated'. The figure is labeled with the title 'Risk factors' and includes a note stating 'Items are not shown to scale'. ```markdown Smokers are also at **10 times** higher risk for oral cancer compared to non-smokers. ``` #### Comparative Risk of Smoking Smokers are at a **10 times** higher risk for developing oral cancer compared to non-smokers. ```markdown Smokers are also at **10 times** higher risk for oral cancer compared to non-smokers. <img src="https://i.imgur.com/1234567.png" alt="As an active substance, nicotine, on a milligram for milligram basis is 10 times more potent than heroin.... Sachs, DPL. Advances in smoking cessation treatment. In: Simmons, ed. Current Pulmonology. Chicago: Year book medical publishers, 1991; 12: 139 - 198."> ```  #### Potency and Risk - Smokers are at a **10 times** higher risk for oral cancer compared to non-smokers. - As an active substance, nicotine is 10 times more potent than heroin on a milligram-for-milligram basis. A black and white image with swirling smoke patterns, featuring a quote about nicotine being 10 times more potent than heroin on a milligram-for-milligram basis, attributed to Sachs, DPL. The text is overlaid on the image, which visually represents the theme of smoking and its effects. ```markdown Risk factors Moderate drinkers have 1.8-fold higher risks of oral cavity and pharynx cancers and 1.4-fold higher risks of larynx cancers than non-drinkers, and **heavy drinkers** have 5-fold higher risks of oral cavity and pharynx cancers and 2.6-fold higher risks of larynx cancers <img src="https://i.imgur.com/placeholder.jpg" alt="A display of various alcohol bottles, including gin, vodka, and other spirits, arranged on shelves in a bar setting." /> Kujan, O. (2017). Human Oral Cancer (Epidemiology and Characteristic). In: Al Moustafa, AE. (eds) Development of Oral Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-48054-1_1 ```  #### Alcohol Consumption Risk Levels - **Moderate Drinkers**: - 1.8-fold higher risk of oral cavity and pharynx cancers. - 1.4-fold higher risk of larynx cancers compared to non-drinkers. - **Heavy Drinkers**: - 5-fold higher risk of oral cavity and pharynx cancers. - 2.6-fold higher risk of larynx cancers compared to non-drinkers. A photo displaying various alcohol bottles, including gin, vodka, and other spirits, arranged on shelves in a bar setting. This image is used to illustrate the topic of alcohol consumption as a risk factor for oral cavity and pharynx cancers, with text indicating that moderate drinkers have 1.8-fold higher risks and heavy drinkers have 5-fold higher risks compared to non-drinkers. ```markdown Risk factors - The combination of smoking and drinking is the most important aetiological factor for oral cancer and OPMDs - Many patients smoke and drink heavily (>5 standard drinks/day) - Both of these account for up to 75% of all OPMD cases Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis. 2021 Nov;27(8):1862-1880. doi: 10.1111/odi.13704. ``` #### Synergistic Effects of Tobacco and Alcohol - The combination of smoking and drinking is the most important aetiological factor for oral cancer and Oral Potentially Malignant Disorders (OPMDs). - A significant number of patients engage in heavy consumption of both substances (defined as >5 standard drinks per day). - Combined tobacco and alcohol use accounts for up to 75% of all OPMD cases. ```markdown # Risk factors ## Betel quid/Areca nut - Areca nut - Abundant copper and flavonoids - Stabilize and enhance cross-linking of collagen - Fibrosis - Alkaloids (arecoline) - Stimulate collagen synthesis and reduce collagen degradation - Can be converted to carcinogenic nitrosamines - Gutka - Powdered tobacco, slaked lime, and spices wrapped in *Piper betle* leaf, also referred to as “betel leaf” - more rapid development of oral lesions <img src="https://i.imgur.com/7ZjX7Xe.jpg" alt="Areca nuts and gutka packets displayed for sale."> The University of Western Australia 27 ```   #### Areca Nut - Contains abundant copper and flavonoids which stabilize and enhance the cross-linking of collagen, leading to fibrosis. - Contains alkaloids (such as arecoline) which: - Stimulate collagen synthesis. - Reduce collagen degradation. - Can be converted to carcinogenic nitrosamines. #### Gutka - Consists of powdered tobacco, slaked lime, and spices wrapped in *Piper betle* leaf (betel leaf). - Associated with a more rapid development of oral lesions. A close-up photo of areca nuts, showing their rough, brown exterior and the distinctive white and brown patterned interior when cut open. This image illustrates the physical appearance of areca nuts, which are discussed in the context of their role in betel quid and their health effects. A photo of various packaged gutka products displayed on a shelf. The packages are colorful and arranged in rows, representing the commercial forms of gutka, a mixture of powdered tobacco, slaked lime, and spices wrapped in a betel leaf, which is associated with the rapid development of oral lesions. ```markdown # Risk factors <img src="https://i.imgur.com/5JzQlXz.png" alt="Illustration of HPV virus particles"> HPV is thought to cause 70% of oropharyngeal cancers in the United States. --- Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis. 2021 Nov;27(8):1862-1880. doi: 10.1111/odi.13704. 28 ```  #### Oropharyngeal Cancer Association Human Papillomavirus (HPV) is estimated to cause 70% of oropharyngeal cancers in the United States. A detailed illustration of HPV virus particles, depicted as spherical structures with a complex, lattice-like surface. The image is presented in a scientific context, accompanying text that states HPV is thought to cause 70% of oropharyngeal cancers in the United States. ```markdown THE UNIVERSITY OF WESTERN AUSTRALIA # Clinical types ## Leukoplakia Persistent white patch that cannot be rubbed off. Generally asymptomatic - 1-4% in Western countries - Higher prevalence in SE Asia - Global prevalence: 2-3% ## Homogeneous leukoplakia : Uniformly white, flat and thin, have a smooth surface and may exhibit shallow cracks. ## Nodular leukoplakia : Small polypoid or rounded outgrowths, red or white excrescences. ## Verrucous leukoplakia : The surface is raised, exophytic, wrinkled or corrugated <img src="https://i.imgur.com/9ZzJQfL.jpg" alt="Clinical image of leukoplakia showing a white patch on the tongue." /> <img src="https://i.imgur.com/7lXzRkY.jpg" alt="Clinical image of leukoplakia showing nodular white patches on the oral mucosa." /> ```   #### Leukoplakia Overview Leukoplakia is a persistent white patch that cannot be rubbed off. It is generally asymptomatic. - **Global Prevalence:** 2-3% - **Western Countries:** 1-4% - **South East Asia:** Higher prevalence noted #### Clinical Morphologies - **Homogeneous leukoplakia:** Uniformly white, flat, and thin. These lesions have a smooth surface and may exhibit shallow cracks. - **Nodular leukoplakia:** Characterized by small polypoid or rounded outgrowths, presenting as red or white excrescences. - **Verrucous leukoplakia:** The surface is raised, exophytic, wrinkled, or corrugated. Clinical image showing a white patch on the tongue, illustrating homogeneous leukoplakia with a uniformly white, flat, and thin appearance on the oral mucosa. Clinical image displaying nodular leukoplakia with small polypoid or rounded outgrowths, appearing as white patches on the oral mucosa. ```mermaid graph TD %% Clinical Categories Top[Clinical appearance] --> Homogenous Top --> NonHomogenous[Non-homogenous] %% Homogenous sub-categories Homogenous --> Normal[Normal mucosa] Homogenous --> Thin[Thin, smooth leukoplakia] Homogenous --> Thick[Thick, fissured leukoplakia] %% Non-homogenous sub-categories NonHomogenous --> Verrucous[Verrucous or nodular leukoplakia] NonHomogenous --> Erythroleukoplakia[Erythroleukoplakia speckled leukoplakia] NonHomogenous --> Erythroplakia[Erythroplakia] %% Histopathologic Features Mapping Normal --- H1[Hyperkeratosis<br/>Acanthosis<br/>Lymphocytes variable] Thin --- H2[Hyperkeratosis<br/>Acanthosis<br/>Dysplasia minimal, mild, or moderate<br/>Lymphocytes variable] Thick --- H3[Hyperkeratosis<br/>Verrucous epithelial hyperplasia<br/>Bulbous rete ridges<br/>Dysplasia minimal, mild, or moderate<br/>Lymphocytes moderate numbers, often band-like] Verrucous --- H3 Erythroleukoplakia --- H4[Variable hyperkeratosis<br/>Bulbous rete ridges<br/>Epithelial atrophy on right<br/>Dysplasia mild to severe<br/>Lymphocytes moderate numbers, often band-like] Erythroplakia --- H5[Minimal keratosis<br/>Epithelial atrophy or bulbous rete ridges<br/>Dysplasia moderate to severe or carcinoma in situ<br/>Lymphocytes moderate numbers, often band-like] ```  #### Classification by Clinical Appearance Oral lesions are categorized based on their clinical presentation, which correlates with specific histopathologic features. 1. **Homogenous Lesions** - **Normal mucosa:** Associated with hyperkeratosis, acanthosis, and variable lymphocytes. - **Thin, smooth leukoplakia:** Associated with hyperkeratosis, acanthosis, minimal to moderate dysplasia, and variable lymphocytes. - **Thick, fissured leukoplakia:** Associated with hyperkeratosis, verrucous epithelial hyperplasia, bulbous rete ridges, minimal to moderate dysplasia, and moderate, often band-like lymphocyte infiltration. 2. **Non-homogenous Lesions** - **Verrucous or nodular leukoplakia:** Shares histopathologic features with thick, fissured leukoplakia (hyperkeratosis, verrucous hyperplasia, bulbous rete ridges, and moderate dysplasia). - **Erythroleukoplakia (speckled leukoplakia):** Characterized by variable hyperkeratosis, bulbous rete ridges, epithelial atrophy, mild to severe dysplasia, and moderate, often band-like lymphocyte infiltration. - **Erythroplakia:** Characterized by minimal keratosis, epithelial atrophy or bulbous rete ridges, moderate to severe dysplasia or carcinoma in situ, and moderate, often band-like lymphocyte infiltration. A detailed anatomical diagram illustrating the clinical appearance and histopathologic features of various types of leukoplakia and erythroplakia. The diagram is divided into homogenous and non-homogenous categories, showing cross-sections of normal mucosa, thin smooth leukoplakia, thick fissured leukoplakia, verrucous or nodular leukoplakia, erythroleukoplakia, and erythroplakia. Each section includes labels for histopathologic features such as hyperkeratosis, acanthosis, dysplasia, and lymphocyte infiltration, with a legend explaining the color coding for keratin layer, erythema, normal epithelium, dysplastic epithelial cells, and lymphocytes. # Leukoplakia **Definition:** “A predominantly white plaque of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer” The following criteria should be considered when making a clinical diagnosis of oral leukoplakia: - A predominantly white patch/plaque that cannot be rubbed off. - Most homogeneous Leukoplakia affect a circumscribed area and have well-demarcated borders. A smaller subset can present with diffuse borders. - Non-homogeneous Leukoplakia typically present with more diffuse borders and may have red or nodular components. - No evidence of chronic traumatic irritation to the area (e.g., a sharp tooth rubbing on the tongue, a white patch on the alveolar ridge or retromolar pad from masticatory friction, a white patch on gingiva from overzealous toothbrushing). - Is not reversible on elimination of apparent traumatic causes, that is demonstrates a persistence feature. - Does not disappear or fade away on stretching (retracting) the tissue. - By exclusion of other white or white/red lesions #### Definition of Leukoplakia Leukoplakia is defined as "a predominantly white plaque of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer." #### Clinical Diagnostic Criteria The following criteria should be considered when making a clinical diagnosis: - **Physical Characteristics:** A predominantly white patch or plaque that cannot be rubbed off. - **Borders:** - Most homogeneous leukoplakia affect a circumscribed area and have well-demarcated borders. - A smaller subset may present with diffuse borders. - Non-homogeneous leukoplakia typically present with more diffuse borders and may have red or nodular components. - **Exclusion of Trauma:** No evidence of chronic traumatic irritation, such as: - Sharp teeth rubbing on the tongue. - Masticatory friction on the alveolar ridge or retromolar pad. - Overzealous toothbrushing on the gingiva. - **Persistence:** The lesion is not reversible upon elimination of apparent traumatic causes. - **Tissue Manipulation:** The lesion does not disappear or fade away upon stretching (retracting) the tissue. - **Differential Diagnosis:** Diagnosis is reached by the exclusion of other white or white/red lesions. ```markdown # Leukoplakia and Erythroplakia **THE UNIVERSITY OF WESTERN AUSTRALIA** ## Aetiology and pathogenesis - Tobacco (smoking or chewing) - Alcohol consumption - Areca nut/betel quid with or without tobacco - High-risk HPV infection is very rare in OPMs ## Epidemiology - Leukoplakia - 1-4% in Western countries - Higher prevalence in SE Asia - Global prevalence: 2-3% ``` #### Risk Factors and Aetiology - **Tobacco:** Both smoking and chewing varieties. - **Alcohol:** Regular consumption. - **Areca Nut:** Use of betel quid, with or without tobacco. - **Infection:** High-risk HPV infection is considered very rare in Oral Potentially Malignant Disorders (OPMDs). #### Epidemiology of Leukoplakia - **Global prevalence:** 2-3% - **Western countries:** 1-4% - **South East Asia:** Higher prevalence compared to Western regions. ```markdown Leukoplakia Clinical features - This means: - It cannot be attributed to - Reactive, frictional, traumatic, or other causes - Older individuals <img src="https://i.imgur.com/placeholder.jpg" alt="Clinical images of leukoplakia lesions in the oral cavity." /> ```  #### Clinical Presentation Leukoplakia is characterized by the following clinical parameters: - **Exclusionary Nature:** The lesion cannot be attributed to reactive, frictional, traumatic, or other known causes. - **Demographics:** Most commonly observed in older individuals. Clinical images of leukoplakia lesions in the oral cavity, showing white patches on the mucosal surfaces of the mouth, consistent with the condition's presentation in older individuals. ```markdown Erythroplakia Defined as “A predominantly fiery red patch that cannot be characterized clinically or pathologically as any other definable disease” Clinical features <img src="https://i.imgur.com/placeholder.png" alt="Clinical images of erythroplakia in the oral cavity"/> THE UNIVERSITY OF WESTERN AUSTRALIA ```  #### Definition of Erythroplakia Erythroplakia is defined as "a predominantly fiery red patch that cannot be characterized clinically or pathologically as any other definable disease." Two clinical photographs showing erythroplakia in the oral cavity, characterized by a fiery red patch on the mucosal surface. The images illustrate the appearance of the lesion in different areas of the mouth, with one showing a more extensive red area and the other highlighting a smaller, raised lesion near teeth. ```markdown # Leukoplakia and Erythroplakia ## Diagnosis - Diagnosis of exclusion - Diagnostic aids - Tolonium chloride or toluidine blue dye - Oral CDx brush biopsy kits <img src="https://i.imgur.com/8QzZQ.png" alt="Clinical images of oral lesions labeled a, b, and c. Image a shows a white patch on the tongue. Image b shows a red patch with blue dye applied. Image c shows a brush biopsy being performed on the tongue." /> ```  #### Diagnostic Process - **Diagnosis of Exclusion:** Clinical identification relies on ruling out other specific conditions. #### Diagnostic Aids To assist in the evaluation of suspicious lesions, the following tools may be utilized: - **Vital Staining:** Tolonium chloride or toluidine blue dye. - **Cytology:** Oral CDx brush biopsy kits. Clinical images of oral lesions labeled a, b, and c. Image a shows a white patch on the tongue. Image b shows a red patch with blue dye applied. Image c shows a brush biopsy being performed on the tongue. ```markdown Oral submucous fibrosis Aetiology and pathogenesis - Areca nut - Abundant copper and flavonoids - Stabilize and enhance cross-linking of collagen - Fibrosis - Alkaloids (arecoline) - Stimulate collagen synthesis and reduce collagen degradation - Can be converted to carcinogenic nitrosamines - Gutka - Powdered tobacco, slaked lime, and spices wrapped in *Piper betle* leaf, also referred to as “betel leaf” - more rapid development of oral lesions ``` #### Role of Areca Nut - **Areca nut components** - Abundant copper and flavonoids - Stabilize and enhance cross-linking of collagen, leading to fibrosis - Alkaloids (arecoline) - Stimulate collagen synthesis and reduce collagen degradation - Can be converted to carcinogenic nitrosamines #### Role of Gutka - **Composition and Impact** - Contains powdered tobacco, slaked lime, and spices wrapped in *Piper betle* leaf (betel leaf) - Associated with more rapid development of oral lesions ```html <table border="0" cellpadding="0" cellspacing="0"> <tr> <td><img src="https://via.placeholder.com/150x50?text=The+University+of+Western+Australia" alt="The University of Western Australia"></td> <td><img src="https://via.placeholder.com/150x50?text=The+University+of+Western+Australia" alt="The University of Western Australia"></td> </tr> </table> <h1>Clinical features</h1> <p>Farah CS, balasubramanian R, McCollough M. Contemporary Oral Medicine: A Comprehensive Approach to Clinical Practice. First edition. China. Springer 2019.</p> ```  Clinical features of oral submucous fibrosis are detailed in contemporary oral medicine literature, focusing on a comprehensive approach to clinical practice. The University of Western Australia logo is displayed in the top right corner, featuring a shield with a black swan and the text 'THE UNIVERSITY OF WESTERN AUSTRALIA' in blue. ```markdown Clinical features - Diffuse, pale, marble-like, and keratotic areas - Sites - Buccal mucosa - Soft palate - Tongue <img src="https://i.imgur.com/placeholder.jpg" alt="Clinical image showing oral mucosa with diffuse, pale, marble-like, and keratotic areas marked by a red dot."> Farah CS, balasubramanian R, McCollough M. Contemporary Oral Medicine: A Comprehensive Approach to Clinical Practice. First edition. China. Springer 2019. ```  #### Presentation and Localization - **Visual Characteristics** - Diffuse, pale, marble-like, and keratotic areas - **Commonly Affected Sites** - Buccal mucosa - Soft palate - Tongue Clinical image showing oral mucosa with diffuse, pale, marble-like, and keratotic areas, marked by a red dot. The image illustrates the clinical features described in the text, including affected sites such as the buccal mucosa, soft palate, and tongue. ```markdown THE UNIVERSITY OF WESTERN AUSTRALIA | Oral Health Centre of Western Australia Histopathologic features ``` Histopathologic features of the condition are assessed through microscopic examination of affected tissues at the Oral Health Centre. ```markdown Diagnosis and management - History and clinical presentation - Obtain good clinical images and write comprehensive clinical notes - Obtain a biopsy if indicated - Watchful monitoring - Temporomandibular disorder management Sadaksharam J, Mahalingam S. Evaluation of Oral Pentoxifylline in the Management of Oral Submucous Fibrosis - An Ultrasonographic Study. *Contemp Clin Dent*. 2017 Apr-Jun;8(2):200-204. ``` #### Clinical Protocol - **Assessment and Documentation** - Evaluate history and clinical presentation - Obtain good clinical images and write comprehensive clinical notes - **Intervention and Follow-up** - Obtain a biopsy if indicated - Watchful monitoring - Temporomandibular disorder management # Palatal lesions in reverse smokers ## Clinical features <img src="https://i.imgur.com/7zV1Q9p.png" alt="Clinical features of palatal lesions in reverse smokers: top image shows a lesion marked with a red dot on the hard palate; bottom image shows a raised, pinkish lesion on the hard palate." /> Bharath TS, Kumar NG, Nagaraja A, Saraswathi TR, Babu GS, Raju PR. Palatal changes of reverse smokers in a rural coastal Andhra population with review of literature. J Oral Maxillofac Pathol. 2015 May-Aug;19(2):182-7.  #### Clinical Presentation Palatal changes associated with reverse smoking typically manifest on the hard palate. These lesions can present with varying clinical appearances, including: - Distinct mucosal alterations often localized to the posterior hard palate. - Erythematous areas or red dots, which frequently represent the inflamed orifices of minor salivary gland ducts. - Raised, pinkish, or white keratotic lesions that may appear as diffuse thickening of the palatal epithelium. - Potential for ulceration or hyperkeratotic patches in chronic cases. #### Epidemiological Context These lesions are notably prevalent in specific geographic regions, such as rural coastal Andhra populations, where the habit of reverse smoking (placing the lit end of a cigarette or cheroot inside the mouth) is culturally practiced. The intense heat and concentrated combustion products directed toward the palatal mucosa contribute to the unique clinical profile of these disorders. Two clinical photographs showing palatal lesions in reverse smokers. The top image displays a dark, irregular lesion on the hard palate marked with a red dot, while the bottom image shows a raised, pinkish lesion on the hard palate. These images illustrate the clinical features of palatal changes associated with reverse smoking. # Actinic Cheilitis **Aetiology and pathogenesis** - UV light exposure - Aetiopathogenesis similar to that of actinic keratosis of the skin - Higher prevalence in - Closer to the equator - Middle-aged to elderly, fair complexioned men - Outdoor occupation - Certain genetic disorders - Xeroderma pigmentosum - Albinism - Porphyria cutanea tarda Neville B, Allen C, Damm D. Oral and maxillofacial pathology. Fourth edition.; Place of publication not identified Elsevier; 2016 #### Risk Factors and Mechanisms The aetiopathogenesis of actinic cheilitis is similar to that of actinic keratosis of the skin, primarily driven by chronic ultraviolet (UV) light exposure. #### High-Prevalence Demographics There is a higher prevalence of this condition among individuals with the following characteristics: - **Geographic and Environmental Factors** - Living in regions closer to the equator - Engagement in outdoor occupations - **Patient Demographics** - Middle-aged to elderly individuals - Fair-complexioned men - **Genetic Predispositions** - Xeroderma pigmentosum - Albinism - Porphyria cutanea tarda ```markdown Clinical features <img src="https://i.imgur.com/placeholder.png" alt="Clinical features of oral pathology: top image shows a lesion on the upper lip with a red dot indicating the site; bottom image shows a lesion on the lower lip." /> Neville B, Allen C, Damm D. Oral and maxillofacial pathology. . Fourth edition.; Place of publication not identified Elsevier; 2016 ```  #### Presentation of Lesions Clinical manifestations of actinic cheilitis typically involve the vermilion border of the lips. Observations from clinical cases include: - Lesions appearing on the upper lip, which may present with localized areas of irritation or distinct marking. - Involvement of the lower lip, which is more frequently affected due to its greater exposure to solar radiation. Two clinical photographs showing oral pathology on the lips. The top image displays a lesion on the upper lip with a red dot indicating the site, while the bottom image shows a lesion on the lower lip. Both images are part of a presentation on clinical features of oral pathology.  Oral Lichen Planus (OLP) is a chronic inflammatory condition affecting the oral mucosa. It is characterized by various clinical manifestations and is considered a potentially malignant disorder. A histopathologic image showing a tissue section with distinct layers, likely representing epithelial and underlying connective tissue. The upper layer appears as a stratified squamous epithelium with purple-stained nuclei, while the lower region shows a more loosely arranged, pale-staining connective tissue. A red circle highlights a specific area of interest within the tissue. ```markdown # Lichen Planus ## Aetiology and pathogenesis - Immune mediated - T lymphocytes mainly - Idiopathic vs drug induced - Prevalence - 0.22-5% worldwide - 30-80 year olds - Approximately 15% have cutaneous disease as well - Females > Males ``` #### Aetiology and Pathogenesis - Immune mediated condition involving primarily T lymphocytes. - Can be classified as idiopathic or drug-induced. #### Epidemiology - **Prevalence:** 0.22–5% worldwide. - **Age Demographic:** Typically affects individuals between 30 and 80 years of age. - **Gender:** More common in females than males. - **Systemic Involvement:** Approximately 15% of patients also present with cutaneous (skin) disease.  Lichen planus presents in several distinct clinical forms within the oral cavity, ranging from asymptomatic white striations to painful erosive lesions. Close-up photograph of the oral cavity, showing the tongue, palate, and surrounding tissues. The image appears to be taken during a medical examination, with a dental instrument visible in the lower portion of the frame. The tissue exhibits a reddish-pink coloration with some areas of inflammation or irritation.  Clinical evaluation of the oral mucosa is essential to identify the specific subtype of lichen planus present, as management strategies may vary based on the severity and symptoms. Close-up intraoral photograph showing a red, inflamed lesion on the oral mucosa, with a small red dot indicating a specific point of interest. The surrounding tissue appears pink and moist, with visible saliva and a tooth in the lower portion of the image. <img src="https://i.imgur.com/8QZzRzL.jpg" alt="Close-up view of teeth and gums showing signs of gingival inflammation and possible periodontal disease, with a red dot indicating a specific area of interest. The image is from The University of Western Ontario."/>  #### Gingival Involvement Clinical presentation often includes signs of gingival inflammation. This may manifest as desquamative gingivitis, where the gingiva appears erythematous and friable. Close-up view of teeth and gums showing signs of gingival inflammation and possible periodontal disease, with a red dot indicating a specific area of interest. The image is from The University of Western Ontario.  The distribution of lesions is often bilateral and symmetrical, a hallmark feature that helps distinguish oral lichen planus from other mucosal pathologies. A close-up photo of the oral cavity showing the palate and teeth, with a red dot indicating a specific point of interest on the tissue. The image appears to be from a medical or dental context, possibly illustrating a condition or procedure. <img src="https://i.imgur.com/5QzZ9dE.png" alt="Oral cavity showing teeth and gums with a red dot indicating a specific area on the soft tissue." />  #### Soft Tissue Manifestations Lesions can be observed on various soft tissue surfaces of the oral cavity, frequently appearing as white, lace-like patterns known as Wickham striae. A close-up photograph of the oral cavity showing teeth, gums, and a red dot indicating a specific area on the soft tissue, likely highlighting a lesion or abnormality. The image includes visible dental restorations and is marked with 'THE UNIVERSITY OF WESTERN' in the top right corner. <img src="https://i.imgur.com/5ZjKqfE.png" alt="Oral cavity showing the tongue with a red dot marking a specific area on the tongue surface." />  #### Lingual Presentation The tongue is a common site for lichen planus. It may present with white plaques or erosive areas on the dorsal or lateral surfaces. A close-up photograph of the oral cavity showing the tongue with a red dot marking a specific area on the tongue surface, likely indicating a lesion or point of interest for medical examination. <img src="https://i.imgur.com/5ZjKz6l.png" alt="Close-up of a human tongue with a red dot marking a specific area on the tongue surface, framed by facial hair. The University of Western Australia logo is visible in the top right corner." />  #### Tongue Surface Characteristics Detailed examination of the tongue surface may reveal atrophy of the papillae or hyperkeratotic patches associated with the disease. Close-up photograph of a human tongue with a red dot marking a specific area on the tongue surface, framed by facial hair. The image appears to be from a medical or scientific study, possibly related to oral health or research conducted at The University of Western Australia, as indicated by the logo in the top right corner. <img src="https://i.imgur.com/5ZjKz6l.png" alt="Close-up of teeth and gums with a red dot indicating a specific area of interest." />  #### Periodontal and Gingival Observations Specific areas of interest in the gingival tissues often show localized redness or ulceration, which can cause significant discomfort during oral hygiene procedures. Close-up photograph of the inside of a mouth showing teeth and gums, with a red dot indicating a specific area of interest on the gum tissue near a tooth. The image appears to be from a dental examination or educational material, as indicated by the 'The University of Western' logo in the top right corner. ```markdown Histopathologic features - Surface epithelial findings largely depends on clinical presentation - e.g., Hyperkeratosis in reticular, papular and plaque like and ulceration in atrophic Cheng YS, Gould A, Kurago Z, Fantasia J, Muller S. Diagnosis of oral lichen planus: a position paper of the American Academy of Oral and Maxillofacial Pathology.. ``` #### Surface Epithelial Findings The histopathologic appearance of the surface epithelium largely depends on the clinical presentation: - **Hyperkeratosis:** Typically seen in reticular, papular, and plaque-like forms. - **Ulceration:** Commonly observed in the atrophic (erosive) form. *Source: Cheng YS, Gould A, Kurago Z, Fantasia J, Muller S. Diagnosis of oral lichen planus: a position paper of the American Academy of Oral and Maxillofacial Pathology.* ```markdown THE UNIVERSITY OF WESTERN AUSTRALIA # Histopathologic features - Surface epithelial findings largely depends on clinical presentation - e.g., Hyperkeratosis in reticular, papular and plaque like and ulceration in atrophic - Important criteria - Degeneration and loss (squamatisation) of the basal cell layer - Lymphocytic band of variable thickness <img src="https://i.imgur.com/4aZqj7L.png" alt="Histopathologic image of oral lichen planus showing degeneration and loss of basal cell layer with lymphocytic band"/> <img src="https://i.imgur.com/3rZj7Ql.png" alt="High magnification histopathologic image of oral lichen planus showing lymphocytic infiltration"/> Cheng YS, Gould A, Kurago Z, Fantasia J, Muller S. Diagnosis of oral lichen planus: a position paper of the American Academy of Oral and Maxillofacial Pathology.. ```   #### Diagnostic Criteria - **Surface Epithelial Findings:** These vary by clinical subtype (e.g., hyperkeratosis in reticular/plaque forms; ulceration in atrophic forms). - **Basal Cell Layer Changes:** Liquefaction degeneration and loss (squamatisation) of the basal cell layer. - **Inflammatory Infiltrate:** A well-defined, band-like zone of lymphocytic infiltration of variable thickness in the superficial connective tissue. *Source: Cheng YS, Gould A, Kurago Z, Fantasia J, Muller S. Diagnosis of oral lichen planus: a position paper of the American Academy of Oral and Maxillofacial Pathology.* Histopathologic image of oral lichen planus showing degeneration and loss of the basal cell layer with a lymphocytic band, illustrating key features like squamatisation and inflammatory infiltration. High magnification histopathologic image of oral lichen planus showing dense lymphocytic infiltration in the lamina propria, highlighting the characteristic lymphocytic band. [^1]: Original PDF page 1: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=1|L11 OPMDs and Oral Cancer II slides, p.1]] [^2]: Original PDF page 2: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=2|L11 OPMDs and Oral Cancer II slides, p.2]] [^3]: Original PDF page 3: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=3|L11 OPMDs and Oral Cancer II slides, p.3]] [^4]: Original PDF page 4: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=4|L11 OPMDs and Oral Cancer II slides, p.4]] [^5]: Original PDF page 5: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=5|L11 OPMDs and Oral Cancer II slides, p.5]] [^6]: Original PDF page 6: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=6|L11 OPMDs and Oral Cancer II slides, p.6]] [^7]: Original PDF page 7: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=7|L11 OPMDs and Oral Cancer II slides, p.7]] [^8]: Original PDF page 8: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=8|L11 OPMDs and Oral Cancer II slides, p.8]] [^9]: Original PDF page 9: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=9|L11 OPMDs and Oral Cancer II slides, p.9]] [^10]: Original PDF page 10: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=10|L11 OPMDs and Oral Cancer II slides, p.10]] [^11]: Original PDF page 11: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=11|L11 OPMDs and Oral Cancer II slides, p.11]] [^12]: Original PDF page 12: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=12|L11 OPMDs and Oral Cancer II slides, p.12]] [^13]: Original PDF page 13: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=13|L11 OPMDs and Oral Cancer II slides, p.13]] [^14]: Original PDF page 14: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=14|L11 OPMDs and Oral Cancer II slides, p.14]] [^15]: Original PDF page 15: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=15|L11 OPMDs and Oral Cancer II slides, p.15]] [^16]: Original PDF page 16: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=16|L11 OPMDs and Oral Cancer II slides, p.16]] [^17]: Original PDF page 17: [[L11 OPMDs and Oral Cancer 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II_slides.pdf#page=25|L11 OPMDs and Oral Cancer II slides, p.25]] [^26]: Original PDF page 26: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=26|L11 OPMDs and Oral Cancer II slides, p.26]] [^27]: Original PDF page 27: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=27|L11 OPMDs and Oral Cancer II slides, p.27]] [^28]: Original PDF page 28: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=28|L11 OPMDs and Oral Cancer II slides, p.28]] [^29]: Original PDF page 29: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=29|L11 OPMDs and Oral Cancer II slides, p.29]] [^30]: Original PDF page 30: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=30|L11 OPMDs and Oral Cancer II slides, p.30]] [^31]: Original PDF page 31: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=31|L11 OPMDs and Oral Cancer II slides, p.31]] [^32]: Original PDF page 32: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=32|L11 OPMDs and Oral Cancer II slides, p.32]] [^33]: Original PDF page 33: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=33|L11 OPMDs and Oral Cancer II slides, p.33]] [^34]: Original PDF page 34: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=34|L11 OPMDs and Oral Cancer II slides, p.34]] [^35]: Original PDF page 35: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=35|L11 OPMDs and Oral Cancer II slides, p.35]] [^36]: Original PDF page 36: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=36|L11 OPMDs and Oral Cancer II slides, p.36]] [^37]: Original PDF page 37: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=37|L11 OPMDs and Oral Cancer II slides, p.37]] [^38]: Original PDF page 38: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=38|L11 OPMDs and Oral Cancer II slides, p.38]] [^39]: Original PDF page 39: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=39|L11 OPMDs and Oral Cancer II slides, p.39]] [^40]: Original PDF page 40: [[L11 OPMDs and Oral Cancer II_slides.pdf#page=40|L11 OPMDs and Oral Cancer II slides, p.40]] [^41]: Original PDF page 41: [[L11 OPMDs and Oral Cancer 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