Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer
Authors: Jared Weiss
Roi Dagan
Shetal Patel
Xianming M Tan
Sunil Kumar
Wendell Yarbrough
Nathan Sheets
Bhishamjit S Chera
Mark Weissler
Jeff Blumberg
William Mendenhall
Rebecca Green
Samip Patel
Juneko Grilley-Olson
Adam Zanation
Robert Amdur
Colette Shen
Emily Goldman
Brian Thorp
Gaorav P Gupta
Trevor Hackman
Journal: Journal of Clinical Oncology (2020)
Discipline: CLINICAL MEDICINE
Keywords: Plasma ctHPVDNA; HPV-associated oropharyngeal squamous cell carcinoma; longitudinal monitoring; clinical disease recurrence; biomarker clinical trial
Affiliations: Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC., Lineberger Comprehensive Cancer Center, University of North Carolina Hospitals, Chapel Hill, NC., Department of Radiation Oncology, University of Florida Hospitals, Gainesville, FL., University of North Carolina at Chapel Hill, Chapel Hill, NC., Department of Medicine, Division of Hematology Oncology, University of North Carolina School of Medicine, Chapel Hill, NC., Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, NC., Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, NC., Rex/UNC Hospital, Raleigh, NC.

Abstract:  Purpose: Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence. Methods and materials: A prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance. Results: One hundred fifteen patients were enrolled, and 1,006 blood samples were analyzed. After a median follow-up time of 23 months (range, 6.1-54.7 months), 15 patients (13%) developed disease recurrence. Eighty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 96% to 100%). Twenty-eight patients developed a positive ctHPVDNA during post-treatment surveillance, 15 of whom were diagnosed with biopsy-proven recurrence. Sixteen patients had 2 consecutively positive ctHPVDNA blood tests, 15 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 94% (95% CI, 70% to 99%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months (range, 0.37-12.9 months). Conclusion: Detection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy. 

Retracted: No

PubPeer comments:
 ![file] Figure 2C, and all the survival curves do not match with the table below. For example, by 20 month, half of the ctHPVDNA pos should have been censored, while the tick marks do not show that. Furthermore, by 40 months there are 0 patients at risk in the ctHPVDNA neg, but the KM lines keeps going. I think the labels may be switched. ,