Radiation Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma: An ASTRO Clinical Practice Guideline

PurposeHPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct disease from other head and neck tumors. This guideline provides evidence-based recommendations on the critical decisions in its curative treatment, including both definitive and postoperative radiation therapy (RT) management.MethodsThe American Society for Radiation Oncology convened a task force to address 5 key questions on the use of RT for management of HPV-associated OPSCC. These questions included indications for definitive and postoperative RT and chemoradiation; dose-fractionation regimens and treatment volumes; preferred RT techniques and normal tissue considerations; and post-treatment management decisions. The task force did not address indications for primary surgery versus RT. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.ResultsConcurrent cisplatin is recommended for patients receiving definitive RT with T3-4 disease and/or one node >3 cm, or multiple nodes. For similar patients who are ineligible for cisplatin, concurrent cetuximab, carboplatin/5-fluorouracil, or taxane-based systemic therapy are conditionally recommended. In the postoperative setting, RT with concurrent cisplatin (either schedule) is recommended for positive surgical margins (PSM) or extranodal extension (ENE). Postoperative RT alone is recommended for pT3-4 disease, >2 nodes, or a single node >3 cm. Observation is conditionally recommended for pT1-2 disease and a single node ≤3 cm without other risk factors. For patients treated with definitive RT with concurrent systemic therapy, 7000 cGy in 33 to 35 fractions is recommended, and for patients receiving postoperative RT without PSM and ENE, 5600-6000 cGy is recommended. For all patients receiving RT, intensity modulated RT over 3-D techniques with reduction in dose to critical organs-at-risk (including salivary and swallowing structures) is recommended. Reassessment with positron emission tomography-computed tomography (PET-CT) is recommended approximately 3 months following definitive RT/chemoradiation, and neck dissection is recommended for convincing evidence of residual disease; for equivocal PET-CT findings, either neck dissection or repeat imaging is recommended.ConclusionsThe role and practice of RT continues to evolve for HPV-associated OPSCC, and these guidelines inform best clinical practice based on the available evidence.