Circulating tumor DNA for human papilloma virus-positive disease: ready for prime time?

Oropharyngeal squamous cell carcinomas (OPSCC) are caused by human papillomavirus (HPV) infection with increasing frequencies. HPV-positive OPSCC is often treated by definitive radiotherapy or chemoradiotherapy. Three to four months after treatment, response imaging is performed by MRI or PET-CT. In 10-15% of cases, residual disease is observed, causing subsequent diagnostic procedures and even treatments that were sometimes not necessary in retrospect. In 10-15% of cases, recurrences develop later in follow-up that are generally detected late. Liquid biopsies might be applied in HPV-positive OPSCC for early cancer detection, disease monitoring, and adaptive treatment.

A variety of studies has been published on the various applications, either using (droplet) digital PCR or DNA sequencing. In this review, an overview of the mostly used methods and current state of the art is provided. In addition, we will propose how we might deal with early molecular diagnosis of recurrence by ctHPV-DNA detection in plasma.

Disease monitoring in HPV-positive OPSCC has a very promising outlook, but published studies are generally small, and assays have not been standardized well. It is unknown whether ddPCR or DNA sequencing are the most suitable assays, as both have their advantages and limitations, and it might well depend on the specific application. We are awaiting large studies and preferably direct comparisons of ddPCR and DNA sequencing in clinical practice. In addition, we will have to develop a standardized method that can be rolled out. Only then it will be ready for prime time.