American Association for Cancer Research
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Figure S5 from Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer

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journal contribution
posted on 2023-03-31, 20:44 authored by Bhishamjit S. Chera, Sunil Kumar, Brian T. Beaty, David Marron, Stuart Jefferys, Rebecca Green, Emily C. Goldman, Robert Amdur, Nathan Sheets, Roi Dagan, D. Neil Hayes, Jared Weiss, Juneko E. Grilley-Olson, Adam Zanation, Trevor Hackman, Jeffrey M. Blumberg, Samip Patel, Mark Weissler, Xianming M. Tan, Joel S. Parker, William Mendenhall, Gaorav P. Gupta

Lack of correlation between ctHPV16DNA clearance at week 6 and persistent/recurrent disease


UNC School of Medicine

UNC Lineberger Cancer Center

University Cancer Research Fund

University of Florida School of Medicine Department of Radiation Oncology




To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16-positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (types 16/18/31/33/35) in plasma. A control cohort of 55 healthy volunteers and 60 patients with non–HPV-associated malignancy was also analyzed. Baseline plasma ctHPVDNA had high specificity (97%) and high sensitivity (89%) for detecting newly diagnosed HPV-associated OPSCC. Pretreatment ctHPV16DNA copy number correlated with disease burden, tumor HPV copy number, and HPV integration status. We define a ctHPV16DNA favorable clearance profile as having high baseline copy number (>200 copies/mL) and >95% clearance of ctHPV16DNA by day 28 of CRT. Nineteen of 67 evaluable patients had a ctHPV16DNA favorable clearance profile, and none had persistent or recurrent regional disease after CRT. In contrast, patients with adverse clinical risk factors (T4 or >10 pack years) and an unfavorable ctHPV16DNA clearance profile had a 35% actuarial rate of persistent or recurrent regional disease after CRT (P = 0.0049). A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPV-associated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy.

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