HPV16 ctDNA assay predicts treatment response in metastatic head and neck cancer

Reviewed by Emily Henderson, B.Sc.Aug 2 2021

Oncotarget published "Human papilloma virus circulating tumor DNA assay predicts treatment response in recurrent/metastatic head and neck squamous cell carcinoma" which reported that despite the rising incidence of human papillomavirus related oropharyngeal squamous cell carcinoma, 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, the authors developed and analytically validated a new droplet digital PCR -based assay for HPV16 circulating tumor DNA and evaluated plasma HPV16 ctDNA for predicting treatment response in metastatic HPV OPSCC.

The authors developed and analytically validated a new droplet digital PCR -based assay for HPV16 circulating tumor DNA

The Oncotarget authors found that longitudinal changes of HPV16 ctDNA correlate with treatment response and that ctDNA responses are observed earlier than conventional imaging.

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.

Head and neck squamous cell carcinomas (HNSCC) constitute 3–5% of all malignancies worldwide and there are approximately 600,000 newly diagnosed cases annually."

Dr. Paul L. Swiecicki, The University of Michigan

The most studied ctDNA biomarker in HPV OPSCC is HPV ctDNA.

Limited prior data demonstrate that a rapid clearance profile of HPV ctDNA is associated with decreased risk of locoregional recurrence in patients receiving chemoradiation for locally advanced HPV OPSCC, and that levels may increase at the time of recurrence.

Small studies have suggested that HPV ctDNA levels correlate with total disease burden and levels mirror fluctuations in disease status in patients with R/M HPV OPSCC.

However, no study has prospectively examined the potential of HPV ctDNA changes during the course of treatment to predict treatment outcome.

The authors hypothesized that:

1. A HPV16 ctDNA test would offer a precise assay for detection of HPV OPSCC and
2. The assay would predict progressive disease prior to radiographic imaging in patients undergoing treatment for R/M HPV OPSCC.

The Swiecicki Research Team concluded in their Oncotarget Research Output that this data suggests that changes in HPV16 ctDNA may be predictive of progressive disease in patients with R/M HNSCC receiving systemic therapy.

Changes in HPV16 ctDNA appear to precede radiographic response and thus have the potential to be used as an early predictive biomarker to guide treatment decisions, potentially improving survival and sparing toxicity.

While larger prospective studies are required for validation and clinical utility analyses, this data offers a promising glimpse into the future potential clinical utility of HPV16 ctDNA in HNSCC.