HPV-Associated Oropharyngeal Cancer: Adjuvant Treatment Deintensification

Get Permission

Postoperative adjuvant therapy—both chemoradiotherapy and radiotherapy alone—for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma may be safely de-escalated, according to results presented by Thorstad et al at the 2024 Multidisciplinary Head and Neck Cancers Symposium (Abstract 14). This approach, using pathology-based risk stratification, resulted in significantly less weight loss than conventional treatment and rendered 90% of patients progression-free at 4 years in the nonrandomized phase II Minimally Invasive Minimum Therapy (MINT) trial.

The long-term efficacy results of the MINT trial were presented at the symposium by Wade Thorstad, MD, Professor of Radiation Oncology and Chief of the Head and Neck Cancer Service at Washington University School of Medicine in St. Louis, who said, “The primary objective of the study was met, with significantly less weight loss with de-escalated treatment.”

About the MINT Study

To help identify an optimal de-intensification treatment strategy for HPV-associated oral cancer, investigators from Washington University School of Medicine in St. Louis evaluated a risk-based strategy. They conducted a nonrandomized, multiarm phase II trial in which 58 patients with clinical stage I to III HPV-positive oropharyngeal squamous cell carcinoma (or positive neck node with unknown primary site) underwent either transoral robotic surgery or transoral laser microsurgery and selective neck dissection and then were stratified by pathological risk into three treatment arms.

The majority of patients were clinical and pathologic stage I, were nonsmokers, and had N1 disease and tonsils as the primary site. Patients with clinical stage T1-2N0, T4, and N3 disease were excluded. Patients were enrolled into three treatment arms, based on pathology:

  • Arm 1: High-risk pathology (extranodal extension and/or positive margins). These patients received de-escalated postoperative adjuvant chemoradiotherapy with cisplatin at 100 mg/m2 for one dose plus 42 Gy radiotherapy over 21 fractions (n = 20).
  • Arm 2: Intermediate-risk pathology (lymphovascular invasion, perineural invasion, at least two positive nodes, at least one positive node > 3 mm, T3 or N2 disease. These patients received de-escalated postoperative adjuvant radiotherapy with 42 Gy over 21 fractions (n = 30).
  • Arm 3: Highest-risk pathology (cT3-pT4). These patients received standard-of-care treatment with cisplatin at 100 mg/m2 for three doses plus 60 Gy radiotherapy delivered concurrently (n = 4).

The primary hypothesis was that, compared to standard treatment, de-escalated treatment would result in less weight loss, which is a quantitative surrogate of the severity of mucositis. Recurrence rate, progression-free survival, and overall survival were also endpoints. The recurrence rate was deemed acceptable if the 95% upper limit of the confidence interval was ≤ 20%.

Dr. Thorstad reported the results of the two experimental arms involving de-escalated chemoradiotherapy (arm 1) and de-escalated radiotherapy (arm 2). 

De-escalation: Safe and Effective

The mean percent weight loss during de-escalated postoperative adjuvant chemoradiotherapy was significantly less than in a similar historical cohort treated conventionally: 4.9% vs 7.4% (P = .0003). The mean percent weight loss during de-escalated radiotherapy was 3.18%, Dr. Thorstad reported.

At a median follow-up of 50 months, there were two recurrences out of 20 patients in arm 1 (de-escalated chemoradiotherapy); these were distant only and occurred at 12 and 19 months posttreatment, respectively. There was one recurrence out of 30 patients in arm 2 (de-escalated radiotherapy), which was both regional and distant and occurred 22 months after treatment. One patient in arm 2 died, though this patient was known to be disease-free 3 months earlier, Dr. Thorstad added.

This amounted to recurrence rates of 10% in arm 1 (95% confidence interval [CI] = 1.2%–31.7%) and 3.3% in arm 2 (95% CI = 0.1%–17.2%). At 4 years, 90.0% and 90.1% of patients, respectively, were progression-free and 100% and 94%, respectively, were alive. 

“Note that the 95% confidence interval in arm 2 was less than 20% as an upper limit [for significance], but we did not achieve that in arm 1, possibly due to low patient numbers,” Dr. Thorstad said. “We believe that further study of this de-escalated approach is warranted.”

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®.