Research Papers:

Human papilloma virus circulating tumor DNA assay predicts treatment response in recurrent/metastatic head and neck squamous cell carcinoma

Catherine T. Haring, Chandan Bhambhani, Collin Brummel, Brittany Jewell, Emily Bellile, Molly E. Heft Neal, Erin Sandford, Ryan M. Spengler, Apurva Bhangale, Matthew E. Spector, Jonathan McHugh, Mark E. Prince, Michelle Mierzwa, Francis P. Worden, Muneesh Tewari, Paul L. Swiecicki _ and J. Chad Brenner

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Oncotarget. 2021; 12:1214-1229. https://doi.org/10.18632/oncotarget.27992

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Catherine T. Haring1,#, Chandan Bhambhani2,#, Collin Brummel1, Brittany Jewell1, Emily Bellile3, Molly E. Heft Neal1, Erin Sandford2, Ryan M. Spengler2, Apurva Bhangale1, Matthew E. Spector1,4, Jonathan McHugh4,5, Mark E. Prince1, Michelle Mierzwa4,6, Francis P. Worden2,4, Muneesh Tewari2,4,8,9,*, Paul L. Swiecicki2,4,* and J. Chad Brenner1,4,7,*

1 University of Michigan, Department of Otolaryngology- Head and Neck Surgery, Ann Arbor, MI 48109, USA

2 University of Michigan, Department of Internal Medicine, Division of Hematology and Oncology, Ann Arbor, MI 48109, USA

3 University of Michigan, Department of Biostatistics, Ann Arbor, MI 48109, USA

4 University of Michigan, Rogel Cancer Center, Ann Arbor, MI 48109, USA

5 University of Michigan, Department of Pathology, Ann Arbor, MI 48109, USA

6 University of Michigan, Department of Radiation Oncology, Ann Arbor, MI 48109, USA

7 University of Michigan, Department of Pharmacology, Ann Arbor, MI 48109, USA

8 University of Michigan, Department of Biomedical Engineering, Ann Arbor, MI 48109, USA

9 University of Michigan, Center for Computational Medicine and Bioinformatics, Ann Arbor, MI 48109, USA

# Co-First Authors

* Co-Senior Authors

Correspondence to:

Paul L. Swiecicki,email: [email protected]

Keywords: HPV; head and neck cancer; oropharyngeal cancer; ctDNA; circulating tumor DNA

Received: March 24, 2021     Accepted: June 02, 2021     Published: June 22, 2021

Copyright: © 2021 Haring et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Despite the rising incidence of human papillomavirus related (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), treatment of metastatic disease remains palliative. Even with new treatments such as immunotherapy, response rates are low and can be delayed, while even mild tumor progression in the face of an ineffective therapy can lead to rapid death. Real-time biomarkers of response to therapy could improve outcomes by guiding early change of therapy in the metastatic setting. Herein, we developed and analytically validated a new droplet digital PCR (ddPCR)-based assay for HPV16 circulating tumor DNA (ctDNA) and evaluated plasma HPV16 ctDNA for predicting treatment response in metastatic HPV+ OPSCC. We found that longitudinal changes HPV16 ctDNA correlate with treatment response and that ctDNA responses are observed earlier than conventional imaging (average 70 days, range: 35–166). With additional validation in multi-site studies, this assay may enable early identification of treatment failure, allowing patients to be directed promptly toward clinical trials or alternative therapies.

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