Format

Send to

Choose Destination
Clin Cancer Res. 2019 Aug 1;25(15):4682-4690. doi: 10.1158/1078-0432.CCR-19-0211. Epub 2019 May 14.

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

Author information

1
Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina. gaorav@med.unc.edu bchera@med.unc.edu.
2
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
3
Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
4
Lineberger Bioinformatics Core, University of North Carolina Hospitals, Chapel Hill, North Carolina.
5
Department of Radiation Oncology, University of Florida Hospitals, Gainesville, Florida.
6
Department of Radiation Oncology, UNC Rex Hospitals, Raleigh, North Carolina.
7
University of Florida Health Proton Therapy Institute, Jacksonville, Florida.
8
West Cancer Center, University of Tennessee, Memphis, Tennessee.
9
Division of Hematology Oncology, Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina.
10
Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
11
Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina.
12
Department of Genetics, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
#
Contributed equally

Abstract

PURPOSE:

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).

EXPERIMENTAL DESIGN:

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.

RESULTS:

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).

CONCLUSIONS:

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.

PMID:
31088830
PMCID:
PMC6679766
[Available on 2020-08-01]
DOI:
10.1158/1078-0432.CCR-19-0211

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center