Chera BS, Amdur RJ, Green R, et al. - In this work, the results of phase 2 clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma were reported. Inclusion was done of patients who were having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N0-N2, M0), (2) p16 positive, and (3) reporting minimal or remote smoking history. Participants (n = 114) were treated with 60 Gy intensity-modulated radiotherapy with concurrent intravenous cisplatin 30 mg/m² once per week. Ten or fewer tobacco pack-years was reported among 80% of patients. Two-year local-regional control, distant metastasis-free survival, progression-free survival, and overall survival were 95%, 91%, 86%, and 95%, respectively. Clinical outcomes among these patients were in favor of the de-intensified chemoradiotherapy regimen of 60 Gy intensity-modulated radiotherapy with concurrent low-dose cisplatin. To obtain favorable results with de-escalation, thre was no requirement for either neoadjuvant chemotherapy or routine surgery.