Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-associated Oropharyngeal Cancer

Presentation: AHNS-010
Topic: Mucosal - HPV Positive
Type: Oral
Date: Wednesday, May 1, 2019
Session: 1:00 PM - 1:10 PM Best of Mucosal HPV Positive Abstracts
Authors: Gaorav P Gupta, MD, PhD1, Sunil Kumar, PhD1, Colette Shen, MD, PhD1, Robert Amdur, MD2, Roi Dagan, MD2, Jared Weiss, MD1, Juneko Grilley-Olson, MD1, Adam Zanation, MD1, Trevor Hackman, MD1, Jeff Blumberg, MD1, Samip Patel, MD1, Brian Thorp, MD1, Mark Weissler, MD1, Sheets Nathan, MD3, William Mendenhall, MD2, Bhishamjit S Chera, MD1
Institution(s): 1University of North Carolina at Chapel Hill, 2University of Florida Hospitals, 3Rex/UNC Hospitals

Purpose/Objectives: To assess the performance of plasma circulating tumor HPV DNA (ctHPVDNA) testing to identify patients with disease recurrence during post-treatment surveillance in a cohort of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

Materials/Methods: A prospective biomarker trial was conducted in 89 patients with p16 positive OPSCC who had no evidence of distant metastatic disease at baseline. All patients received definitive chemoradiotherapy (CRT) with 78 receiving de-intensified CRT on clinical trial (60Gy).  Remaining patients received standard CRT (70Gy). All patients had a 3 month post-CRT PET/CT and were thereafter followed with clinical examinations every 2 - 4 months for years 1 - 2, then every 6 months for years 3 - 5.  Chest x-rays or chest CT’s were performed every 6 months. Multianalyte droplet digital PCR assays were developed for ultra-sensitive detection of ctHPVDNA -16, -18, -31, -33, and -35 DNA on the Bio-Rad QX200 platform. Additional imaging was obtained if ctHPVDNA became detectable in the blood.  Surveillance ctHPVDNA testing was initiated 4 months after completing CRT in patients who were clinically disease-free. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of ctHPVDNA testing at detecting recurrence were calculated.  Disease recurrence was defined as biopsy-proven relapse that occurred at least 4 months after completion of CRT.

Results:  Clinical characteristics were the following:  89% T0-2, 79% N1, 15% N2, 80% never/≤ 10 pack years.  Mean f/u was 20.2 months (range 6.4 – 40.6). Baseline ctHPVDNA was detectable in 51/58 (88%), with a median value of 582 copies/mL (range 8 - 22,579). All evaluable patients (n=57) had undetectable ctHPVDNA within 6 months of completing CRT.  70/89 patients (79%) in the surveillance cohort had undetectable ctHPVDNA at all timepoints during post-CRT surveillance.  All 70 of these patients remain disease-free by clinical exam and radiographic imaging. 19/89 patients (21%) developed a positive ctHPVDNA test result with a median interval from CRT of 16.7 months (range 7.8 – 30.4) and a median value of 75 copies/mL (range 9 – 28,369). 8/19 patients who developed a positive ctHPVDNA test result during surveillance were diagnosed with recurrent disease (0 local, 1 regional, 3 regional and distant, and 4 distant).  11 patients developed detectable ctHPVDNA (range 23 – 28,369 copies/ml), with no evidence of disease recurrence on radiographic imaging. Four of these patients subsequently cleared their ctHPVDNA on a followup blood test, suggesting a possibility of immunological clearance. Sensitivity, specificity, NPV, and PPV of ctHPVDNA testing for detection of disease recurrence was:  100%, 90%, 100%, 53%.

Conclusions: Performance of an optimized multianalyte ctHPVDNA blood test to identify patients who remain cancer-free after curative-intent therapy was excellent (NPV = 100%).  Future studies should be done to evaluate whether ctHPVDNA testing may improve early detection of cancer recurrence while also reducing costs by targeting radiographic surveillance to the subset of patients who are at greatest risk of relapse.