Injectable immunotherapy delivered directly into precancerous lesions in the mouth significantly reduced their size and helped the majority of patients avoid surgery, according to results from a phase I clinical trial presented at the American Association for Cancer Research Annual Meeting in April 2026.
Roughly 5 percent of the general population carries precancerous lesions in the mouth at any given time, and depending on the severity of abnormal cell growth and other individual factors, those lesions carry a progression risk to oral cancer of anywhere between 1 and 36 percent. Because no reliable biological markers exist to predict which lesions will progress, many patients are routinely referred for surgical removal, a procedure that carries significant consequences. Approximately 60 percent of patients present with multiple lesions, and the recurrence rate after surgery can reach as high as 40 percent. Each additional surgery removes tissue from the oral cavity, most commonly the tongue, with cumulative effects on a patient’s ability to speak, swallow, and eat.
How the injectable treatment works
The drug used in the trial is an immune checkpoint inhibitor that has been approved for use in cancer treatment when delivered intravenously. Systemic delivery at full doses carries a toxicity profile that researchers considered unacceptable for patients who do not yet have cancer. The trial tested whether injecting a fraction of that dose directly into the lesion could achieve a therapeutic effect while keeping drug levels in the bloodstream dramatically lower.
The trial enrolled 29 patients, each with at least one confirmed precancerous oral lesion considered high risk due to its size, location, or degree of cellular abnormality. More than half of the lesions were located on the tongue. Patients received injectable doses directly into one lesion every three weeks for four total cycles, at one of two dosage levels. Where multiple lesions were present, the largest was selected for treatment, allowing researchers to assess whether the injectable drug’s effects remained localized or spread systemically.
The results
After a median follow-up period of just over 14 months, 85 percent of patients showed a measurable reduction in lesion size. The average reduction across treated lesions was 60 percent, with 19 of 29 patients experiencing reductions greater than 50 percent. Six patients achieved complete pathologic response, meaning their treated lesion showed no remaining signs of abnormal cell growth at follow-up. Responses were observed across both high-grade and low-grade lesions.
Twelve months after treatment, more than 82 percent of treated lesions remained cancer free. Six patients whose lesions did progress to cancer had those lesions detected early and surgically removed. None of the patients whose lesions did not progress required surgery during the follow-up period.
Drug levels in the bloodstream were consistently around ten times lower than those observed with standard intravenous treatment. No dose-limiting toxicities occurred. The most common side effects were fatigue, diarrhea, and rash. Injection-site reactions occurred in 40 percent of injections but resolved within 48 hours without intervention. Patient-reported outcomes indicated that symptoms related to swallowing, voice, taste, and nutrition either improved or remained stable throughout treatment, and patients reported greater enjoyment of life and increased physical activity compared to their baseline.
Implications beyond the mouth
Tissue analysis from 23 participants revealed meaningful immune activation exclusively at the sites of injection, with no corresponding changes observed in untreated lesions from the same patients. That localization suggests the approach successfully confined the drug’s immunological activity to its target, which is central to the treatment’s safety advantage over systemic delivery.
Researchers noted that the implications of the findings may extend well beyond oral lesions. Many cancer types are preceded by precancerous changes, including those affecting the skin, cervix, and colon. The results raise the possibility that localized immunotherapy could serve as an early interception strategy across multiple disease sites, potentially reshaping how medicine approaches the window between abnormal cell growth and cancer diagnosis.
The study was supported by the Cancer Prevention and Research Institute of Texas. Limitations include the trial’s single-arm design and relatively short follow-up period.
