Hearing Outcomes in a Deintensification Trial of Adjuvant Therapy for HPV-Related Oropharyngeal Squamous Cell Carcinoma

David S. Lee, Rajwant S. Mahal, Theresa Tharakan, C. Cathryn, Dorina Kallogjeri, Wade L. Thorstad, Douglas R. Adkins, Peter Oppelt, Jessica Ley, Cameron C. Wick, Jose Zevallos

Research output: Contribution to journalArticlepeer-review


Objective: To explore whether deintensification of adjuvant therapy reduces ototoxicity among patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Study Design: Retrospective cohort study. Setting: Single academic center. Methods: The ototoxicity rate among adult patients with HPV-related OPSCC enrolled in the Minimalist Trial (MINT), a prospective phase 2 trial of surgery followed by risk-adjusted deintensified adjuvant therapy (42 Gy radiation given alone or with a single 100 mg/m2 dose of cisplatin), was compared to that among a historical cohort treated with standard adjuvant therapy (60-66 Gy radiation with up to three 100 mg/m2 doses of cisplatin). Ototoxicity was defined as Common Terminology Criteria for Adverse Events v5.0 ≥ Grade 2. Mixed model analysis was performed to investigate the association between deintensified adjuvant therapy and treatment-related hearing loss. Results: A total of 29 patients (58 ears) were analyzed in the MINT cohort, and 27 patients (54 ears) in the historical cohort. The ototoxicity rate was 5% (n = 3/58 ears) in the MINT cohort and 46% (n = 25/54 ears) in the historical cohort (difference, 41%; 95% confidence interval [CI] = 27%-56%). Patients in the MINT cohort demonstrated a 95% decrease in risk of ototoxicity compared to those in the historical cohort (adjusted odds ratio: 0.05, 95% CI = 0.01-0.31). Differences in estimated marginal mean threshold shifts were statistically and clinically significant at frequencies ≥ 3 kHz. Conclusion: The deintensified adjuvant therapy given in MINT led to less ototoxicity than standard adjuvant therapy among patients with HPV-related OPSCC.

Original languageEnglish
Pages (from-to)1089-1096
Number of pages8
JournalOtolaryngology - Head and Neck Surgery (United States)
Issue number5
StatePublished - May 2023


  • HPV-related oropharyngeal squamous cell carcinoma
  • cisplatin ototoxicity
  • hearing outcomes
  • p16+
  • treatment deintensification


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