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Publication Detail

Title: Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer.

Authors: Chera, Bhishamjit S; Kumar, Sunil; Beaty, Brian T; Marron, David; Jefferys, Stuart; Green, Rebecca; Goldman, Emily C; Amdur, Robert; Sheets, Nathan; Dagan, Roi; Hayes, D Neil; Weiss, Jared; Grilley-Olson, Juneko E; Zanation, Adam; Hackman, Trevor; Blumberg, Jeffrey M; Patel, Samip; Weissler, Mark; Tan, Xianming M; Parker, Joel S; Mendenhall, William; Gupta, Gaorav P

Published In Clin Cancer Res, (2019 08 01)

Abstract: 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.

PubMed ID: 31088830 Exiting the NIEHS site

MeSH Terms: Case-Control Studies; Chemoradiotherapy/mortality*; Circulating Tumor DNA/blood; Circulating Tumor DNA/genetics*; DNA, Viral/blood*; DNA, Viral/genetics; Female; Humans; Kinetics; Male; Middle Aged; Oropharyngeal Neoplasms/blood*; Oropharyngeal Neoplasms/pathology; Oropharyngeal Neoplasms/prevention & control*; Oropharyngeal Neoplasms/virology; Papillomaviridae/genetics*; Papillomaviridae/isolation & purification; Papillomavirus Infections/complications*; Papillomavirus Infections/genetics; Papillomavirus Infections/virology; Prognosis; Prospective Studies; Survival Rate

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