The clinical landscape of head and neck cancer has shifted, with HPV-positive disease now dominating new cases. The American Society for Radiation Oncology (ASTRO) has released specific recommendations for the treatment of HPV-associated oropharyngeal cancer, emphasizing the importance of systemic therapy alongside radiation. Guideline Focus on HPV-Positive Disease The latest ASTRO guideline focuses solely on HPV-positive oropharyngeal cancer, unlike previous guidelines that covered both HPV-negative and HPV-positive cases. Dr. David Sher from UT Southwestern Medical Center highlighted the incorporation of new prospective trials into the updated guideline, offering detailed recommendations on treatment volumes, techniques, and patient reassessment post-treatment. Unique Radiation Dosing for Minimal Tissue Damage Notable in the guideline is the detailed radiation dosing recommendations for patients undergoing radiation therapy on one side of the neck. This approach aims to minimize normal tissue damage during treatment, setting a new standard in care. Comprehensive Recommendations for Treatment and Assessment The guideline also provides guidance on postoperative radiation or chemoradiotherapy for specific pathologic findings, optimal dosing regimens, and post-treatment assessments using advanced imaging methods. Patient-Centric Approach Throughout the guideline, there is an emphasis on shared decision-making with patients, ensuring personalized care and treatment plans. The guideline is now available in Practical Radiation Oncology, offering a comprehensive resource for healthcare professionals. These new guidelines are set to revolutionize the treatment approach to HPV-positive oropharyngeal cancer, paving the way for improved outcomes and patient care.