Could Immunotherapy Help Patients Avoid Surgery for Precancerous Oral Lesions?
Injecting immunotherapy directly into precancerous oral lesions may reduce the need for surgery, according to new research presented at the American Association for Cancer Research Annual Meeting.
In a phase 1 clinical trial led by researchers at The University of Texas MD Anderson Cancer Center, intralesional nivolumab reduced lesion size in most patients and allowed many to avoid surgical resection, currently the standard approach for managing high-risk oral premalignant lesions.
A new Phase 1 trial found that immunotherapy is effective and safe for cancer prevention. It can spare patients with oral pre-malignancies from having surgery and demonstrated an 85% clinical response rate, our Dr. Moran Amit presented at #AACR26. More about his research:… pic.twitter.com/mxnhUD027a
— UT MD Anderson (@UTMDAnderson) April 21, 2026
“Immunotherapy has transformed cancer treatment, but only a subset of patients benefit from it, and predicting who will respond remains challenging,” said presenting author Moran Amit, MD, PhD. “Our findings demonstrate that intralesional delivery of nivolumab is safe, well tolerated, and results in efficacy rates unparalleled by other nonsurgical methods.”
A Significant Shift From Surgery
For surgeons who remove these abnormalities, the implications are hard to ignore.
“This would be a significant change in practice for oral premalignant lesions,” said Caitlin McMullen, MD, a head and neck surgeon at Moffitt Cancer Center. “Currently, our only real option is surgical resection, but recurrence rates are high and there can be functional consequences. Even with limited resections.”
Those consequences can be significant. The oral cavity plays a central role in daily life, from eating and speaking to breathing. Even small surgical removals can add up over time, particularly for patients with recurrent or multifocal lesions.
“There are very few noninvasive agents to prevent or treat these lesions, and it is difficult to predict which ones will progress,” McMullen said. “Hence, most high-risk lesions are treated with surgery.”
An Unmet Need and a New Approach
That reality has left a noticeable gap in care.
Caitlin McMullen, MD
“This is a significant unmet need,” McMullen said. “I personally have a large cohort of patients with oral premalignant lesions where our options are mainly surgery or ongoing close observation.”
The approach tested in this study aims to change that equation. Instead of delivering nivolumab systemically, where it can cause significant immune-related toxicities, the drug is injected directly into the lesion at a much lower dose.
The results showed 85% of patients experienced a reduction in lesion size, with an average decrease of 60%. Some lesions showed complete pathologic response, and most remained cancer-free at one year.
Patients also reported stable or improved quality of life, with no dose-limiting toxicities observed.
Treatment and Prevention
While the therapy targets precancerous disease, McMullen views it firmly as a treatment strategy.
“These lesions already cause problems such as irritation and pain,” she said. “This data shows the injection also can prevent transformation to oral cancer, which is the biggest concern.”
That dual role treating existing symptoms while potentially intercepting cancer before it develops reflects a growing interest in earlier intervention across oncology.
Promising, but Early
Experts still caution that the findings are preliminary.
“There is no other agent I am aware of that has this high of a response rate,” McMullen said. “But it is important to understand the limitations of this study.”
The trial included just 29 patients, and many had lower-risk lesions with a relatively low likelihood of progressing to cancer.
“We do have to understand the costs and risks better,” she added. “I look forward to seeing the complete data published.”
Key questions remain about durability, long-term cancer prevention and how best to select patients in the absence of reliable biomarkers.
