Using CircuLating Tumor DNA to Risk Adapt Post-Operative Therapy for HPV-associated Oropharyngeal Cancer

This study uses liquid biopsy — a blood test that detects fragments of tumor DNA linked to HPV — to determine how much follow-up radiation and chemotherapy patients need after surgery for HPV-positive throat cancer (oropharyngeal cancer). The goal is to reduce unnecessary treatment for those at low risk of recurrence. **You may be eligible if...** - You have HPV-positive (p16-positive) squamous cell carcinoma of the throat or an unknown primary site with lymph node involvement in the neck - You have had or will have surgery to remove the cancer - Your cancer has certain higher-risk features (positive nodes, lymphovascular invasion, close margins, etc.) - You are 18 or older, in reasonable health, and have adequate blood counts and organ function **You may NOT be eligible if...** - Your cancer is very advanced (stage T4 or N3) - There is evidence it has spread to other organs - You have had prior radiation to the head and neck above 30 Gy - You are pregnant or breastfeeding - You have a severe heart condition, active connective tissue disease, or moderate-to-severe hearing loss Talk to your doctor to see if this trial is right for you.