journal contribution
posted on 2025-08-01, 07:28 authored by Ari J. Rosenberg, Evgeny Izumchenko, Aditya Juloori, Rohan Katipally, John Cursio, Noura Choudhury, Zhen Gooi, Elizabeth Blair, Jeffrey Chin, Rifat Hasina, Augustin Vannier, Anna Starus, Frederick S. Jones, Emily L. Gramiccioni, Yuxuan Miao, Daniel J. Haraf, Everett E. Vokes, Alexander T. Pearson, Nishant Agrawal <p>Supplementary Figure 1. Progression free survival Kaplan-meier estimates for patients that rapidly clear ctHPV-DNA (≥95% ctHPV-DNA reduction) after cycles 1 and 2 (red) versus patients that do not achieve rapid ctHPV-DNA clearance after cycles 1 and 2 (blue).</p>
Funding
American Cancer Society (ACS)
National Cancer Institute (NCI)
United States Department of Health and Human Services
Find out more...U.S. Department of Defense (DOD)
V Foundation for Cancer Research (VFCR)
Grant Achatz and Nick Kokonas
Center for Cancer Research (CCR)
History
ARTICLE ABSTRACT
Human papillomavirus–associated (HPV+) oropharyngeal carcinoma is associated with excellent survival, yet treatment drives substantial toxicity. Improved biomarkers are needed to select patients for de-escalated treatment. Circulating tumor HPV DNA (ctHPV-DNA) represents a promising noninvasive biomarker to gauge treatment response and surveil for disease recurrence.
A prospective biomarker clinical trial of response-stratified de-escalation was conducted. Eligible patients with non-metastatic HPV+ oropharyngeal carcinoma received neoadjuvant chemotherapy, followed by risk/response-stratified de-escalation with transoral robotic surgery, de-escalated radiation with or without chemotherapy to 50 Gy, or standard chemoradiation to 70 Gy. Deep response (≥50% tumor shrinkage per RECIST v1.1) qualified patients for de-escalation. ctHPV-DNA was measured using HPV-SEQ in plasma at baseline, during neoadjuvant chemotherapy, radiation, and following treatment. The primary endpoint was the correlation of ctHPV-DNA kinetics and radiographic response.
Forty-six eligible patients were enrolled, and 488 ctHPV-DNA samples were analyzed (median 11 per patient). The median follow-up was 30 months, and five recurrences were observed (10.9%). Baseline ctHPV-DNA was detected in 95% of evaluable patients. Rapid early ctHPV-DNA clearance after one cycle of neoadjuvant therapy (≥95% reduction) predicted radiographic deep response (P = 0.04). Detection of ctHPV-DNA 3 months or later after treatment was associated with worse progression-free and overall survival (P < 0.001). Sensitivity, specificity, and positive and negative predictive values of longitudinal ctHPV-DNA were 100%. The longest lead time from positive ctHPV-DNA to detection of recurrent disease was 25 months.
Rapid early clearance of ctHPV-DNA during neoadjuvant therapy demonstrates utility in predicting response to treatment. Detectable ctHPV-DNA following treatment is predictive of both disease recurrence and worse survival.
