Liquid Biopsies with Circulating Plasma HPV–DNA Measurements—A Clinically Applicable Surveillance Tool for Patients with HPV-Positive Oropharyngeal Cancer

Purpose: To evaluate the accuracy of cell-free human papilloconcordance between HPV genotype in tumor tissue and plasma. mavirus-DNA (cfHPV-DNA) measurements in liquid biopsies in Fifty-four patients were followed with serial blood samples for a predicting disease in patients with HPV-positive/p16-positive median of 19.7 months (interquartile range, 13.5–25.5 months). (HPVþ/p16þ) oropharyngeal squamous cell carcinoma (OPSCC). Forty-one patients had undetectable plasma cfHPV-DNA in all Experimental Design: This was a prospective cohort study. follow-up samples, and none developed recurrences. Thirteen Plasma samples were collected before treatment, serially after curapatients were classified as cfHPV-DNA–positive in a follow-up tive intended therapy at follow-up visits 2 weeks, and 6, 9, 12, 18, 24, plasma sample. Of these, five patients developed a recurrence, and and 30 months after treatment. A droplet digital PCR assay comprthree had residual cancer. It was possible to detect cfHPV-DNA in ising eight HPV genotypes was used. HPV genotypes found in plasma plasma 97 to 166 days prior to the proven recurrence. and tumor tissue were compared. We correlated biopsy- or imaging-Conclusions: To our knowledge, to date, our study, comprising verified tumor progression to cfHPV-DNA in follow-up samples. the largest study of patients with HPVþ/p16þ OPSCC, using an Results: We enrolled 72 patients with HPVþ/p16þ OPSCC. ultrasensitive multiplex HPV gene panel, revealed a high sensitivity Baseline sensitivity for cfHPV-DNA detection was 97.2% (95% of cfHPV-DNA detection in the liquid biopsies. We recommend confidence interval, 90.3%–99.6%). CfHPV-DNA copy number/ serial plasma HPV samples for clinical monitoring of patients with milliliter plasma correlated with tumor stage. We found a 100% HPVþ/p16þ OPSCC.