Intralesional nivolumab generated responses in precancerous oral lesions in a phase I study presented at AACR 2026. Researchers reported that injecting Opdivo directly into lesions reduced lesion size and decreased the need for additional interventions, testing a localized strategy that differs from systemic checkpoint blockade. The approach targets early disease biology in the oral cavity while potentially limiting systemic exposure associated with standard immune checkpoint regimens. For the trial, nivolumab was delivered directly into lesions to engage local immune activity. The early dataset supports continued evaluation of checkpoint inhibition as a preventative or early-intervention strategy in head and neck precancer, an area where escalation beyond watch-and-wait has been limited by risk–benefit concerns.