Measurable Residual Disease Detection Using Tumor-Informed ctDNA Surveillance After Curative-Intent Treatment in HPV-Independent Squamous Cell Carcinoma of the Head and Neck

This study tests whether a blood test that detects tiny fragments of tumor DNA (called ctDNA) can identify leftover cancer cells after surgery or radiation in people with head and neck squamous cell carcinoma (mouth, throat, or voice box cancer) that is NOT related to HPV. Early ctDNA detection may help doctors catch cancer recurrence sooner. **You may be eligible if...** - You have been newly diagnosed with Stage III–IVB head and neck squamous cell carcinoma (cancers of the oral cavity, nose, sinuses, throat, or voice box) - You are planning to receive standard treatment (surgery or chemoradiation) at Massachusetts Eye and Ear Institute or Mass General Brigham hospitals - Tumor tissue is available for the DNA test **You may NOT be eligible if...** - You are under 18 - You have previously received surgery, radiation, or chemotherapy for this cancer - Your cancer has already spread to distant organs (Stage IVC) - You are currently in another interventional trial - You are pregnant Talk to your doctor to see if this trial is right for you.