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Liquid Biopsies with Circulating Plasma HPV–DNA Measurements—A Clinically Applicable Surveillance Tool for Patients with HPV-Positive Oropharyngeal Cancer
PURPOSETo evaluate the accuracy of cell-free human papillomavirus-DNA (cfHPV-DNA) measurements in liquid biopsies in predicting disease in patients with HPV-positive/p16-positive (HPV+/p16+) oropharyngeal squamous cell carcinoma (OPSCC). EXPERIMENTAL DESIGNThis was a prospective cohort study. Plasma...
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Published in: | Clinical cancer research 2023-10, Vol.29 (19), p.3914-3923 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | PURPOSETo evaluate the accuracy of cell-free human papillomavirus-DNA (cfHPV-DNA) measurements in liquid biopsies in predicting disease in patients with HPV-positive/p16-positive (HPV+/p16+) oropharyngeal squamous cell carcinoma (OPSCC). EXPERIMENTAL DESIGNThis was a prospective cohort study. Plasma samples were collected before treatment, serially after curative intended therapy at follow-up visits 2 weeks, and 6, 9, 12, 18, 24, and 30 months after treatment. A droplet digital PCR assay comprising eight HPV genotypes was used. HPV genotypes found in plasma and tumor tissue were compared. We correlated biopsy- or imaging-verified tumor progression to cfHPV-DNA in follow-up samples. RESULTSWe enrolled 72 patients with HPV+/p16+ OPSCC. Baseline sensitivity for cfHPV-DNA detection was 97.2% (95% confidence interval, 90.3%-99.6%). CfHPV-DNA copy number/milliliter plasma correlated with tumor stage. We found a 100% concordance between HPV genotype in tumor tissue and plasma. Fifty-four patients were followed with serial blood samples for a median of 19.7 months (interquartile range, 13.5-25.5 months). Forty-one patients had undetectable plasma cfHPV-DNA in all follow-up samples, and none developed recurrences. Thirteen patients were classified as cfHPV-DNA-positive in a follow-up plasma sample. Of these, five patients developed a recurrence, and three had residual cancer. It was possible to detect cfHPV-DNA in plasma 97 to 166 days prior to the proven recurrence. CONCLUSIONSTo our knowledge, to date, our study, comprising the largest study of patients with HPV+/p16+ OPSCC, using an ultrasensitive multiplex HPV gene panel, revealed a high sensitivity of cfHPV-DNA detection in the liquid biopsies. We recommend serial plasma HPV samples for clinical monitoring of patients with HPV+/p16+ OPSCC. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-23-1064 |