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; J Chad Brenner

doi:10.18632/oncotarget.27992

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

Oncotarget. 2021 Jun 22;12(13):1214-1229. doi: 10.18632/oncotarget.27992.

Authors

Catherine T Haring^{1

2}, Chandan Bhambhani^{3

2}, Collin Brummel¹, Brittany Jewell¹, Emily Bellile⁴, Molly E Heft Neal¹, Erin Sandford³, Ryan M Spengler³, Apurva Bhangale¹, Matthew E Spector^{1

5}, Jonathan McHugh^{5

6}, Mark E Prince¹, Michelle Mierzwa^{5

7}, Francis P Worden^{3

5}, Muneesh Tewari^{3

5

8

9

10}, Paul L Swiecicki^{3

5

10}, J Chad Brenner^{1

5

11

10}

Affiliations

¹ University of Michigan, Department of Otolaryngology-Head and Neck Surgery, Ann Arbor, MI 48109, USA.
² Co-First Authors.
³ University of Michigan, Department of Internal Medicine, Division of Hematology and Oncology, Ann Arbor, MI 48109, USA.
⁴ University of Michigan, Department of Biostatistics, Ann Arbor, MI 48109, USA.
⁵ University of Michigan, Rogel Cancer Center, Ann Arbor, MI 48109, USA.
⁶ University of Michigan, Department of Pathology, Ann Arbor, MI 48109, USA.
⁷ University of Michigan, Department of Radiation Oncology, 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.
¹⁰ Co-Senior Authors.
¹¹ University of Michigan, Department of Pharmacology, Ann Arbor, MI 48109, USA.

Abstract

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.

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