Sustained Locoregional Control With Deintensified Chemoradiotherapy for HPV Oropharyngeal Carcinoma

Standard treatment for human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) often includes 7 weeks of intensive chemoradiotherapy with substantial toxic effects. Lowering the radiation dose to gross disease may maintain cancer control with fewer toxic effects.

To evaluate long-term oncologic outcomes among patients with HPV-associated OPC treated with definitive deintensified (chemo)radiotherapy.

This cohort study evaluated consecutive patients treated with (chemo)radiotherapy between September 2014 and August 2022 at multiple institutions under one academic hospital system. Eligible patients had p16-positive OPC with a clinical stage from T0 to T3 and N0 to N2c (according to the American Joint Committee on Cancer [AJCC] Staging Manual, seventh edition) and favorable smoking history. Data were analyzed between August 2023 and October 2025.

Treatment was 60-Gy intensity-modulated radiotherapy with first-choice concurrent chemotherapy of weekly cisplatin, 30 mg/m2, or weekly cisplatin, 40 mg/m2. Patients with OPC with a clinical stage from T0 to T2 and N0 to N1 (according to AJCC, seventh edition) were recommended 60-Gy radiotherapy alone.

Evaluation of locoregional recurrence was the primary outcome. Distant recurrence, progression-free survival (PFS), and overall survival (OS) were secondary outcomes.

A total of 240 patients received definitive deintensified (chemo)radiotherapy (207 receiving prospective protocol-adherent treatment and 33 receiving non-protocol-adherent treatment). Mean (SD) patient age was 60.3 (9.9) years (range, 33.0-84.0 years); 206 (85.8%) were male, and 34 (14.2%) were female. The cohort included 139 never smokers (57.9%) and 101 former smokers (42.1%) (median smoking history, 9.0 pack-years [range, 0.25-50.0 pack-years]). Concurrent chemotherapy was prescribed for 205 patients (85.4%), with 185 (77.1%) receiving cisplatin, and 165 (68.8%) receiving weekly cisplatin, 30 mg/m2. Median follow-up for surviving patients was 6.5 years (range, 0.44-11.0 years; 208 of 210 [99.0%] with minimum 2-year follow-up). Outcomes were as follows: 2-year OS was 97.9% (95% CI, 96.1%-99.7%), and 5-year OS, 92.4% (95% CI, 89.0%-96.0%); 2-year PFS, 94.1% (95% CI, 91.2%-97.2%), and 5-year PFS, 86.5% (95% CI, 82.1%-91.0%); 2-year locoregional recurrence, 1.3% (95% CI, -0.2% to 2.7%), and 5-year locoregional recurrence, 3.4% (95% CI, 1.1%-5.8%); 2-year distant recurrence, 4.6% (95% CI, 1.9%-7.3%), and 5-year distant recurrence, 7.3% (95% CI, 3.9%-10.7%). The median time to progression events was 1.9 years (range, 0.3-5.1 years); 12 of 26 recurrences (46.2%) occurred after 2 years. Thirty-three patients with low-risk disease (clinical stage T0-T2, N0-N1, according to AJCC, seventh edition) received radiotherapy alone, which resulted in a 5-year PFS of 93.8%, with no patients experiencing a locoregional recurrence.

In this cohort study, modest dose deintensification of 60-Gy radiotherapy in patients with HPV-associated OPC shows favorable rates of locoregional control. These findings provide support for ongoing investigations of deintensified radiotherapy.