Updated ASTRO Clinical Guidelines on Radiation Therapy for HPV-Positive Oropharyngeal Cancer

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The American Society for Radiation Oncology (ASTRO) detailed best practices for using radiation therapy as a stand-alone curative treatment or in combination with surgery and/or chemotherapy to treat patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma, according to updated clinical guidelines published by Margalit et al in Practical Radiation Oncology.


HPV-associated oropharyngeal squamous cell carcinoma is the most common type of HPV-related cancer type among male patients and second only to cervical cancer among female patients. At least 70% of newly diagnosed oropharyngeal cancers are related to HPV. Patients diagnosed with HPV-positive oropharyngeal squamous cell carcinoma tend to be younger—with an average age at diagnosis of 55 years in the United States—and may experience better outcomes compared with patients diagnosed with HPV-negative disease.

In contrast to the decreasing incidence of tobacco- and alcohol-related oropharyngeal squamous cell carcinoma, incidence rates of HPV-associated oropharyngeal squamous cell carcinoma have been increasing rapidly in most developed nations—including the United States, where approximately 21,000 adult patients are diagnosed with this type of cancer each year. Current projections have estimated that the number of patients with HPV-associated disease will continue to rise over the next several decades before eventually decreasing as HPV vaccines become more globally accessible.

Since ASTRO published its 2017 guidelines for oropharyngeal cancer, HPV-associated oropharyngeal squamous cell carcinoma was recognized as a clinically separate disease from non-HPV–associated oropharyngeal squamous cell carcinoma. The updated clinical guidelines focus specifically on treating patients with HPV-associated disease.

Radiation therapy has proven effective in the treatment of tumors caused by HPV, which are typically more radiosensitive and responsive to therapy. With the increasing number of long-term survivors, modern clinical trials tend to focus on de-escalating treatments to reduce side effects while maintaining high cure rates.

“Radiation therapy plays a critical role in the treatment of HPV-[associated] oropharyngeal [squamous cell carcinoma], offering a highly effective option for patients seeking curative outcomes. This updated guideline underscores the importance of tailored radiation strategies that maximize patient survival while minimizing side effects,” highlighted lead study author Danielle N. Margalit, MD, MPH, Vice Chair of the guideline task force and a radiation oncologist at Brigham & Women’s/Dana-Farber Cancer Center. “The recommendations are informed by recent clinical trial data, providing a robust evidence base that empowers physicians and patients to make treatment decisions,” she continued.

Updated Clinical Guidelines

To develop the updated clinical guidelines, a multidisciplinary guideline task force—comprised of radiation and medical oncologists, head and neck surgeons, a medical physicist, and a patient representative—conducted a systematic evidence review of articles published between January 2000 and May 2023. 

The updated clinical guidelines covered:

  • Concurrent systemic therapy in patients treated for HPV-associated oropharyngeal squamous cell carcinoma undergoing definitive radiation therapy, which was recommended if the patients have certain indicators of higher risk such as more advanced tumor stages or involvement of multiple lymph nodes. The guideline task force also outlined criteria where radiation alone was recommended over chemoradiation therapy.
  • Postoperative radiation or chemoradiation therapy among patients treated with curative-intent surgery, which was recommended over observation if pathologic risk factors such as a positive surgical margin or certain tumor characteristics were present. The guideline task force discussed patient selection and provided direction for the dosing and scheduling of postoperative radiation and chemoradiation therapy.
  • Considerations for systemic therapy, including recommendations for chemotherapy drugs, dosing, and sequencing with radiation therapy—with an emphasis on shared decision-making weighing the potential benefits and risks of treatment between physicians and patients.
  • Optimal dosing and fractionation regimens for radiation and chemoradiation therapy in the definitive and postoperative settings. Taking into consideration data from recent dose de-escalation trials, the guideline task force suggested minimizing doses to areas that most impact patients’ quality of life, such as the organs responsible for swallowing and saliva production. Recommendations also addressed preferred radiation therapy techniques like intensity-modulated radiation therapy.
  • Posttreatment assessment, specifically guidance for patients’ initial restaging following completion of treatment and ongoing surveillance using advanced imaging or other methods.


“The optimal treatment for a patient with HPV-[associated] oropharyngeal [squamous cell carcinoma] involves collaboration between radiation oncologists, surgeons, medical oncologists, and other specialists. This guideline highlights the necessity of a multidisciplinary approach to ensure that each patient receives a comprehensive, personalized treatment plan,” underscored senior study author David J. Sher, MD, MPH, Chair of the guideline task force and a radiation oncologist at the University of Texas Southwestern Medical Center. “By working together, we can provide the highest quality care that aligns with the patient's unique needs and preferences, ultimately improving their quality of life and treatment outcomes," he concluded.

Disclosure: For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.