Plasma Cell-Free Human Papillomavirus Oncogene E6 and E7 DNA Predicts Outcome in Oropharyngeal Squamous Cell Carcinoma

Persistent human papillomavirus (HPV) infection is associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), and increasing incidences of OPSCC are reported. The generally favorable treatment outcome in patients with HPV-driven OPSCC has brought de-escalation of treatment into discussion. Nevertheless, 13% to 25% develop a relapse within two years after current standard treatment. New biomarkers are urgently required to monitor therapy response, tumor burden, and minimal residual disease during follow-up. This observational study examined 50 patients with OPSCC to investigate plasma cell-free (cf) HPV-DNA derived from tumor cells before therapy and during follow-up. Real-time quantitative PCR was applied to quantify the DNA concentration of HPV oncogenes E6 and E7. A total of 85.7% of pretreatment samples from patients with HPV-driven OPSCC (n = 28) were positive for at least one marker, and cfHPV-DNA concentration increased with tumor size. Virtually no signals were detected in HPV-negative OPSCC patients (n = 20; P