Biopsy for Suspicious Oral Lesions: A Review From the American Head and Neck Society-Cancer Prevention Service.

Abstract

Oral cancer is often preceded by a precursor lesion. This presents an opportunity for early diagnosis and intervention. Method of biopsy and interpretation are not well standardized and novel methods of analysis are now being investigated. We conducted a narrative review of PubMed/MEDLINE (last search August 31, 2025), focusing on adult oral precancerous lesions evaluated in outpatient settings. Incisional punch biopsy is reproducible and often provides the diagnostic information needed. However, scalpel biopsy should be considered when initial biopsy is equivocal, depth of invasion is desired, or to minimize sampling bias. Limited studies show improved sensitivity of combining saliva and plasma sampling. Targeted fluorescent imaging may aid in future biopsy site selection. AI has shown encouraging results in both automated detection of dysplasia and prediction of malignant progression, achieving performance comparable to clinically validated grading systems. This update serves to further inform biopsy of oral suspicious lesions and provide a framework for future investigation.