Radiation Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Publication Date: June 18, 2024
Last Updated: June 25, 2024

Indications for systemic therapy with RT

For patients with HPV+ OPSCC and either T3-4 disease, ≥2 positive nodes, or a single node >3 cm receiving definitive RT, concurrent systemic therapy is recommended. (S, H )
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For patients with HPV+ OPSCC and T1-2 node-negative disease, or T1 disease and a single positive node ≤3 cm receiving definitive RT, RT alone is recommended. (S, L )
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For patients with HPV+ OPSCC and T2 disease with a single positive node ≤3 cm receiving definitive RT, either RT alone or concurrent systemic therapy is recommended. (S, L )
Implementation remark: Weigh the potential benefits of concurrent systemic therapy against toxicity risks given limited data regarding its efficacy in this population.
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For patients with HPV+ OPSCC who will receive definitive RT with or without concurrent systemic therapy, induction systemic therapy is not recommended. (S, H )
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For patients with HPV+ OPSCC who warrant definitive RT and concurrent systemic therapy, cisplatin is recommended. (S, H )
Implementation remark: Either 100 mg/m2 every 3 weeks or 40 mg/m2 weekly cisplatin is appropriate.
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For patients with HPV+ OPSCC who warrant definitive RT and concurrent systemic therapy but are not candidates for cisplatin, cetuximab or carboplatin/5-fluorouracil are conditionally recommended. (C, M )
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For patients with HPV+ OPSCC who warrant definitive RT and concurrent systemic therapy but are not candidates for cisplatin, taxane-based regimens are conditionally recommended. (C, CC)
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For patients with HPV+ OPSCC who will receive definitive RT, immunotherapy (either neoadjuvant, concurrent, or adjuvant) is not recommended regardless of PD-L1 status. (S, H )
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Indications for postoperative RT after curative-intent surgery

For patients with resected HPV+ OPSCC and pT3-4 or pathologic node-positive disease, and either a final microscopically positive margin (tumor on ink) or ENE, postoperative RT with concurrent cisplatin is recommended. (S, H )
Implementation remark: Either 100 mg/m2 every 3 weeks or 40 mg/m2 weekly cisplatin is appropriate.
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For patients with resected HPV+ OPSCC and pT1-2 node-negative disease with a final microscopically positive margin (tumor on ink), either RT alone or RT with concurrent cisplatin is recommended. (S, CC)
Implementation remark: Either 100 mg/m2 every 3 weeks or 40 mg/m2 weekly cisplatin is appropriate.
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For patients with resected HPV+ OPSCC and node-positive disease with either pT3-4 disease, ≥2 positive nodes, or a single positive node >3 cm, postoperative RT is recommended. (S, M )
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For patients with resected HPV+ OPSCC and pT3-4 node-negative disease, postoperative RT is recommended. (S, CC)
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For patients with resected HPV+ OPSCC and pT1-2 disease with either no positive nodes or a single positive node ≤3 cm without ENE, postoperative RT is conditionally recommended for perineural invasion and/or lymphovascular invasion. (C, CC)
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For patients with resected HPV+ OPSCC and microscopically close final margins, postoperative RT is conditionally recommended. (C, M )
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For patients with resected HPV+ OPSCC and pT1-2 disease with a single positive node ≤3 cm without other pathologic risk factors, observation is conditionally recommended. (C, M )
Implementation remark: Considerations before observation include the dissected nodal levels and number of dissected nodes.
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Dose-fractionation regimens and treatment volumes

For patients with HPV+ OPSCC receiving definitive RT with concurrent systemic therapy, 7000 cGy in 33-35 fractions to gross disease is recommended. (, )
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For patients with HPV+ OPSCC and T1-2 disease with either no positive nodes or a single positive node ≤3 cm receiving definitive RT alone, either 6600-7000 cGy with altered fractionation (accelerated or hypofractionated) or 6800-7000 cGy with conventional fractionation to gross disease is recommended. (, )
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For patients with HPV+ OPSCC receiving definitive RT, an EQD2 of at least 4600 cGy to clinically uninvolved nodal levels at risk for microscopic disease is conditionally recommended. (, )
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For patients with HPV+ OPSCC and T1-2 disease with a single positive node >3 cm or multiple nodes receiving definitive RT alone, altered fractionation (accelerated or hyperfractionated) is conditionally recommended. (C, M )
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For patients with HPV+ OPSCC and T3-4 disease with any nodal presentation receiving definitive RT alone, altered fractionation (accelerated or hyperfractionated) is recommended. (S, H )
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For patients with HPV+ OPSCC receiving postoperative RT, 6000-6600 cGy with daily fractionation to regions of microscopically positive primary site surgical margins (ie, tumor on ink) and/or ENE is recommended. (S, H )
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For patients with HPV+ OPSCC receiving postoperative RT, 5600-6000 cGy with daily fractionation to the postoperative primary bed and the pathologically involved nodal levels is recommended. (S, H )
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For patients with HPV+ OPSCC receiving postoperative RT, an EQD2 of at least 5000 cGy to pathologically uninvolved nodal levels in the dissected pathologically node-positive neck is conditionally recommended. (C, CC)
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For patients with HPV+ OPSCC, eliminating areas with a low risk of microscopic disease from CTV targets is recommended. (S, M )
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For patients with HPV+ T1-2 palatine tonsil OPSCC confined to the tonsillar fossa and either no positive nodes or a single positive node ≤3 cm without ENE treated with definitive or postoperative RT, unilateral RT is recommended. (S, L )
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For patients with HPV+ T1-2 palatine tonsil OPSCC without base of tongue involvement treated with definitive or postoperative RT, unilateral RT is conditionally recommended for: disease involving minimal soft palate and/or a single positive node >3 cm but ≤6 cm or multiple positive nodes, without evidence of ENE in all nodes. (C, L )
Implementation remark: Consideration for unilateral RT may include the number and size of involved nodes and extent of involved nodal levels.
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Preferred techniques and appropriate normal tissue considerations

For patients with HPV+ OPSCC receiving definitive or postoperative RT, IMRT over 3-D CRT is recommended. (S, H )
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For patients with HPV+ OPSCC receiving definitive or postoperative RT, reducing dose to xerostomia OARs is recommended, as target coverage permits. (S, H )
Implementation remark: Xerostomia OARs include parotid glands, submandibular glands, and oral cavity.
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For patients with HPV+ OPSCC receiving definitive or postoperative RT, reducing dose to dysphagia/swallowing OARs is recommended, as target coverage permits. (S, M )
Implementation remark: Swallowing OARs include pharyngeal constrictors, cervical esophagus, larynx, and oral cavity.
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For patients with HPV+ OPSCC receiving definitive or postoperative RT, reducing dose to the mandible to minimize risk of osteoradionecrosis is recommended, as target coverage permits. (S, M )
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For patients with HPV+ OPSCC receiving definitive or postoperative RT, optimizing RT prescription dose homogeneity in target volumes is recommended. (S, CC)
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Preferred approaches for initial post-treatment restaging and management of the neck

For patients with HPV+ OPSCC and node-positive disease receiving definitive RT with or without concurrent systemic therapy, reassessment with PET-CT approximately 3 months after completing treatment is recommended. (S, M )
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For patients with HPV+ OPSCC and node-negative disease receiving definitive RT with or without concurrent systemic therapy, reassessment with cross-sectional imaging approximately 3 months after completing treatment is recommended. (S, L )
Implementation remark: Imaging modalities include PET-CT and/or contrast-enhanced CT or MRI.
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For patients with HPV+ OPSCC who undergo surgery with or without postoperative RT, reassessment with cross-sectional imaging approximately 3-6 months after completing treatment is recommended. (S, CC)
Implementation remark: Imaging modalities include PET-CT and/or contrast-enhanced CT or MRI.
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For patients with HPV+ OPSCC and node-positive disease receiving definitive RT with or without systemic therapy, neck dissection is recommended when PET-CT approximately 3 months after treatment reports convincing evidence of residual or progressive isolated regional disease. (S, M )
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For patients with HPV+ OPSCC and node-positive disease receiving definitive RT with or without systemic therapy, either neck dissection or short interval repeat imaging is recommended when PET-CT approximately 3 months after treatment reports an equivocal response in regional disease. (S, M )
Implementation remark: Repeat imaging in 2-3 months with PET-CT and/or contrast-enhanced CT or MRI may avoid unnecessary surgical intervention.
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Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Radiation Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Authoring Organization

American Society for Radiation Oncology

Publication Month/Year

June 18, 2024

Last Updated Month/Year

June 26, 2024

Supplemental Implementation Tools

Document Type

Guideline

Country of Publication

US

Document Objectives

HPV-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.

PICO Questions

  1. For patients receiving definitive RT for HPV+ OPSCC, what are the indications for systemic therapy?

  2. Following curative-intent surgery for patients with HPV+ OPSCC, what are the indications for postoperative RT with or without systemic therapy?

  3. For patients receiving definitive or postoperative RT with or without systemic therapy for HPV+ OPSCC, what are the optimal dose-fractionation regimens and treatment volumes?

  4. For patients receiving definitive or postoperative RT with or without systemic therapy for HPV+ OPSCC, what are the preferred RT techniques and appropriate normal tissue considerations?

  5. Following definitive or postoperative RT with or without systemic therapy for patients with HPV+ OPSCC, what are the preferred approaches for initial post-treatment restaging and management of the neck?

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Outpatient, Radiology services, Operating and recovery room

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D002294 - Carcinoma, Squamous Cell

Keywords

squamous cell carcinoma, Oropharyngeal Squamous Cell Carcinoma

Source Citation

Danielle N. Margalit, Christopher J. Anker, Michalis Aristophanous, Musaddiq Awan, Gopal K. Bajaj, Lisa Bradfield, Joseph Califano, Jimmy J. Caudell, Christina H. Chapman, Adam S. Garden, Paul M. Harari, Amanda Helms, Alexander Lin, Ellie Maghami, Ranee Mehra, Lance Parker, Yelizaveta Shnayder, Sharon Spencer, Paul L. Swiecicki, Jillian Chiaojung Tsai, David J. Sher, Radiation Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma: An ASTRO Clinical Practice Guideline, Practical Radiation Oncology, 2024, ISSN 1879-8500, https://doi.org/10.1016/j.prro.2024.05.007.

Methodology

Number of Source Documents
159
Literature Search Start Date
January 1, 2000
Literature Search End Date
May 24, 2023