PURPOSE: Blood-borne, cell-free DNA has been proposed as a means of individualizing the management of human papillomavirus (HPV)-positive oropharyngeal carcinoma. METHODS AND MATERIALS: This study was designed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A comprehensive literature search of peer-reviewed publications from January 2013 to January 2024 was undertaken to identify prospective studies pertaining to the use of circulating HPV-DNA for oropharyngeal carcinoma. RESULTS: A total of 11 prospective studies were identified and differed in their clinical design, methods, and endpoints. Five included patients treated by chemoradiation; 3 by surgery; 2 by both; and 1 not specified. The timing and frequency of HPV-DNA draws was highly variable. The sample size ranged from 16 to 262 (mean, 99 patients). CONCLUSIONS: While interest is growing with integrating circulating HPV-DNA into clinical practice, the supporting evidence is limited by the heterogeneity of the evidence.
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