What question did this study set out to answer?

To determine if on-treatment HPV circulating tumor DNA can personalize radiation doses for patients with HPV-positive oropharyngeal cancer.

May 9, 2026Open Access

Risk-adapted therapy guided by human papillomavirus (HPV) circulating tumor DNA in HPV-positive oropharyngeal cancer (ReACT 1.0): an exploratory phase II trial

Key Points

To determine if on-treatment HPV circulating tumor DNA can personalize radiation doses for patients with HPV-positive oropharyngeal cancer.
Exploratory phase II trial involving 102 patients with HPV-positive oropharyngeal carcinoma.
Patients reclassified based on HPV ctDNA dynamics after treatment, leading to de-intensified therapy for low-risk groups.
Primary outcome measured was progression-free survival (PFS) among patients receiving reduced treatment.
Two-year progression-free survival among de-escalated patients was 93% (95% CI, 87-99).
Intermediate-risk patients reclassified as low-risk based on HPV ctDNA showed significantly favorable outcomes.
HPV ctDNA dynamics correlated with distinct treatment responses in reclassified patients, allowing for better risk stratification.

Abstract

Circulating tumor DNA (ctDNA) has an expanding role in oncology. It is unknown whether on-treatment ctDNA can be used to personalize radiation dose. This phase 2 exploratory clinical trial enrolled 102 patients with human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC). Intermediate-risk patients (T4 disease or >10 pack-year smokers with pre-treatment HPV ctDNA scores >200) were reclassified as low-risk if HPV ctDNA cleared by >95% mid-treatment. All clinically low-risk and reclassified patients received de-intensified (chemo)radiation. The primary outcome was progression-free survival (PFS) among de-escalated patients; secondary outcomes included tolerability, distant metastatic-free, and overall survival. Eighty-nine patients received de-escalated treatment (60 low-risk, 29 reclassified). Two-year PFS among de-escalated patients was 93% (95%CI, 87-99). Post-hoc analyses suggested that intermediate-risk patients reclassified as low-risk and treated with de-escalation had distinct HPV ctDNA dynamics and favorable outcomes. HPV ctDNA is an emerging biomarker that might improve risk stratification for patients with intermediate-risk HPV-positive OPC. Registration number: NCT04900623. The ReACT 1.0 clinical trial shows that HPV ctDNA clearance (>95%) may be a useful biomarker to guide treatment de-escalation in intermediate-risk HPV+ oropharyngeal cancer.

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