Topical 5-FU in Odontogenic Keratocyst: Clinical Outcomes and Molecular Insights.

Odontogenic keratocyst (OKC) is a locally aggressive jaw cyst with a high recurrence rate. This study evaluated the efficacy of topical 5-fluorouracil (5-FU) as an adjunct to enucleation in 12 OKC patients. After cyst removal, residual bone cavities were packed with 5% 5-FU-coated iodoform gauze for 72 hours. Over a mean follow-up of 14 months, all patients healed uneventfully, and one recurrence occurred (8.3%; 95% CI: 0.2%-38.5%) at 12 months. Bulk RNA sequencing revealed enrichment of necroptosis and cellular senescence pathways, with upregulation of pro-apoptotic genes (FAS, TNFRSF10A, TNFRSF10D) and downregulation of proliferation-related genes (TOP2A, CDK1, CDK5) after 5-FU treatment in OKC tissues. These findings support topical 5-FU as a safe, cost-effective, adjuvant therapy that potentially reducing recurrence risk. Validation in larger multicenter studies with extended follow-up is warranted.