Does location or dysplasia define the risk for oral cancer in oral leukoplakia?

Dysplasia is the Primary Risk Factor for Oral Cancer in Oral Leukoplakia, with Location as a Secondary Factor

The presence and grade of dysplasia is the most significant risk factor for malignant transformation of oral leukoplakia, with location being a secondary but important risk factor. 1, 2

Risk Factors for Malignant Transformation

Dysplasia as the Primary Risk Factor

• The risk of progression to oral cancer significantly increases with the grade of dysplasia, with 5-year competing risk-adjusted absolute risks of: 2.2% for no dysplasia, 11.9% for mild dysplasia, 8.7% for moderate dysplasia, and 32.2% for severe dysplasia 1
• High-risk dysplastic oral leukoplakia is associated with a 4.57-fold increased risk of malignant transformation compared with low-risk dysplasia 3
• The new binary system for grading dysplasia (low-risk vs. high-risk) shows significant value in predicting malignant transformation risk, with high-risk dysplastic lesions having significantly higher malignant incidence, particularly during the first 2-3 years of follow-up 3
• Incorporation of differentiated dysplasia (alongside classic WHO-defined dysplasia) improves risk prediction, increasing the hazard ratio from 3.26 to 7.43 2

Location as a Secondary Risk Factor

• Leukoplakias on the tongue and floor of mouth have a 2.72-fold higher risk of harboring malignancy compared to those on buccal mucosa 4
• Historically, leukoplakias of the tongue have shown the highest incidence of malignant change 5
• The tongue and lips are the most common sites for severe dysplasia 5

Synergistic Effect of Multiple Risk Factors

• There is a synergistic effect between clinical appearance and lesion site: nonhomogeneous leukoplakia on the tongue/floor of mouth has a 43.10-fold higher risk compared to homogeneous lesions on buccal mucosa 4
• Loss of Keratin 13 (CK13) expression, when combined with the presence of dysplasia, is associated with a greater risk of malignant progression 2

Clinical Implications for Management

• All oral leukoplakias should be biopsied regardless of visual or clinical impression, as the decision to biopsy based on clinical features alone has low sensitivity (59.6%) and specificity (62.1%) 1
• Even homogeneous leukoplakias in the buccal mucosa still have the possibility of harboring carcinoma, emphasizing the need for microscopic analysis of all lesions 4
• Patients with oral leukoplakia, particularly those with dysplasia, need close monitoring for signs of early cancer 1
• In oral lesions without dysplasia and with retained CK13 staining, the risk for progression is very low 2

Treatment Considerations

• Photodynamic therapy (ALA-PDT) has emerged as an alternative therapeutic approach for managing oral leukoplakia, especially for lesions in regions with underlying functional structures where surgical methods may be less feasible 6
• Traditional treatment approaches include non-surgical (chemoprevention or observation) and surgical methods (traditional excision, electrocauterization, CO2 laser ablation, and cryosurgery) 6

Important Caveats

• Despite the strong association between dysplasia and malignant transformation, 39.6% of cancers can arise from biopsied leukoplakias without dysplasia, highlighting the need for surveillance of all leukoplakia patients 1
• The prevalence of dysplasia in non-cancerous leukoplakias can be as high as 45.6% 4
• No clinical attributes can provide absolute certainty regarding malignant potential, emphasizing the need for histopathological examination 4