Case Reports of Four Patients with HPV-Positive Head and Neck Cancer of Non-Oropharyngeal Origin Undergoing Liquid Biopsy for Circulating Cell-Free HPV-DNA before, during, and after Treatment.

INTRODUCTION: Human papillomavirus (HPV) is a risk factor for oropharyngeal squamous cell carcinoma (OPSCC) and is sometimes found in other head and neck squamous cell carcinomas (HNSCCs), where its role is not as clearly defined. To gain more knowledge regarding response to therapy, and the monitoring of cell-free HPV DNA (cfHPV-DNA) in plasma in HPV-positive (HPV+) non-OPSCC HNSCC, the presence and levels of cfHPV-DNA in the plasma of four patients were followed before, during, and after therapy and correlated to treatment response. CASE PRESENTATIONS: Two HPV+ nasopharyngeal cancer patients, one HPV+ lacrimal gland carcinoma patient, and one HPV+ hypopharyngeal carcinoma patient were examined for the presence of cfHPV-DNA in plasma using droplet digital PCR assaying for HPV16 or 35. At diagnosis, the HPV35+ nasopharyngeal carcinoma patient and the HPV16+ hypopharyngeal carcinoma patient were positive for cfHPV-DNA, which subsequently cleared rapidly after a favorable treatment response. The second patient with a nasopharyngeal carcinoma (HPV16+, T1N0M0) was cfHPV-DNA negative at all time points. The patient with an HPV16+ lacrimal duct carcinoma lacked a plasma sample at diagnosis, and the sample taken immediately after surgical removal of the patient's tumor was cfHPV-DNA negative. However, this patient turned cfHPV-DNA positive in plasma 3-4 weeks after initiation of radiotherapy, with increasing cfHPV-DNA values during further follow-up, but after treatment for a then detected locoregional relapse became cfHPV-DNA negative again. CONCLUSION: Monitoring cfHPV-DNA in plasma could be useful for following treatment response also in HPV+ non-OPSCC HNSCC; however, larger cohorts are needed to confirm these findings.