An update of the American Joint Committee on Cancer and Union for International Cancer Control (AJCC/UICC) staging guidelines for human papillomavirus (HPV-) positive oropharyngeal carcinoma (throat cancer) will make treatment of early-stage disease more consistent and appropriate.
Although exhibiting markedly different clinical behaviors, HPV plays a pivotal role in the development of both cervical squamous cell carcinoma and oropharyngeal squamous cell carcinoma, the latter, according to the American Cancer Society (ACS), being now more common in the U.S. than the former.[1][2][3]
A multicentre registry analysis leading to the staging update was published in The Lancet Oncology.[4]
Allen Ho, MD. Photo courtesy: © 2025 Cedars-Sinai. Used with permission.Answering questions
“Staging helps clinicians answer two questions,” said Allen Ho, MD, professor of Surgery, director of the Head and Neck Cancer Program at Cedars-Sinai, and lead author of the analysis.
“The first: How serious is the cancer? The second: What is the best treatment?”
Previous staging guidelines for HPV-positive throat cancer were so broad that as many as 80% of patients were classified as stage 1, with three different possible treatment strategies. Some stage 1 patients were treated with surgery alone, some with surgery plus radiation therapy, and some with surgery and radiation plus chemotherapy.
Improved information
“The new staging will better inform clinicians and patients about a patient’s prognosis and will minimize inconsistencies in the treatments patients are offered,” Ho said. “Currently, a patient diagnosed as stage 1 might be offered surgery plus radiation and chemotherapy, while another stage 1 patient may be offered surgery alone. The new guidelines will help ensure each patient receives the most appropriate treatment.”
Investigators divided the huge group of stage 1 patients into three separate groups, Ho explained. They created new subdivisions of nodal staging, which consider whether cancer has spread to lymph nodes, and paired a more cohesive treatment recommendation with each.
Zachary Zumsteg, MD. Photo courtesy: © 2025 Cedars-Sinai Used with permission.Extranodal extension
“Perhaps the biggest change in the new staging system is that it takes into account something called extranodal extension, where the cancer has not only spread to the lymph nodes, but has progressed further to destroy the lymph node capsule and spill into the surrounding tissue. Inclusion of this factor is important, because it often changes both prognosis and the recommended treatment following surgery,” noted Zachary Zumsteg, MD, professor of Radiation Oncology and Biomedical Sciences at Cedars-Sinai and senior author of the paper.
Ho noted that cases of HPV-positive throat cancer, caused by the same virus that causes cervical cancer, have outpaced cervical cancer because women are routinely screened for cervical cancer. They are also more likely than men to receive the HPV vaccine, which can prevent both cancer types.
New guidelines
The new guidelines were developed by an international committee led by Ho that analyzed data on more than 14,000 patients from 984 healthcare facilities in the United States. Patient data from patients treated between 2010 and 2019, was divided into a derivation cohort (n=7768) and validation cohort (n=6679).
Based on the outcome of a multivariable analysis the AJCC Expert Panel on HPV-positive oropharyngeal carcinoma endorsed the proposal by Delphi consensus, resulting in the guidelines set to become the official worldwide staging guidance in the coming year.
“These findings represent compelling evidence for staging modification,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer and the Steven Spielberg Family Chair in Hematology Oncology. “It is a challenging endeavor, but it improves the information and care that we are able to offer our patients; Cedars-Sinai Cancer is honored to be part of this international effort.”
Ho suggested that patients with newly diagnosed HPV-positive throat cancer ask their care team how these new guidelines have shaped their staging and treatment options.
“Patients should ask their caregivers how these new guidelines impact the clinician’s thinking about the patient’s staging, prognosis and which treatment to offer,” Ho concluded.
Reference
[1] Martinelli C, Ercoli A, Parisi S, Iatì G, Pergolizzi S, Alfano L, Pentimalli F, De Laurentiis M, Giordano A, Cortellino S. Molecular Mechanisms and Clinical Divergences in HPV-Positive Cervical vs. Oropharyngeal Cancers: A Critical Narrative Review. BMC Med. 2025 Jul 7;23(1):405. doi: 10.1186/s12916-025-04247-z. PMID: 40619351; PMCID: PMC12232849.
[2] Rettig EM, Sethi RKV. Cancer of the Oropharynx and the Association with Human Papillomavirus. Hematol Oncol Clin North Am. 2021 Oct;35(5):913-931. doi: 10.1016/j.hoc.2021.05.004. Epub 2021 Jul 7. PMID: 34244016.
[3] Roman BR, Aragones A. Epidemiology and incidence of HPV-related cancers of the head and neck. J Surg Oncol. 2021 Nov;124(6):920-922. doi: 10.1002/jso.26687. Epub 2021 Sep 23. PMID: 34558067; PMCID: PMC8552291.
[4] Ho AS, Huang SH, O’Sullivan B, Luu M, Evans M, Ferris RL, Lewis JS, Jr, Seethala RR, Yom SS, Mehanna H, Branstetter BF, Saba NF, Patel SG, Lydiatt WM, Zumsteg ZS. The Lancet Oncology, July 8, 2025. DOI: 10.1016/S1470-2045(25)00281-5
Featured image: Cedars-Sinai investigators led an update of staging guidelines for HPV-positive throat cancer that will make treatment more consistent. Photo courtesy: © 2025 Cedars-Sinai/Getty. Used with permission.
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