Human papillomavirus (HPV) infections are the primary cause of almost all cervical cancers, anal cancers, and a variable proportion of other anogenital tumors, as well as head and neck cancers. Circulating HPV DNA (cHPV-DNA) is emerging as a biomarker with extensive potential in the management of HPV-driven malignancies. There has been a rapid advancement in the development of techniques for analyzing cHPV-DNA for the detection, characterization, and monitoring of HPV-associated cancers. As clinical evidence accumulates, it is becoming evident that cHPV-DNA can be used as a diagnostic tool. By conducting clinical trials assessing the clinical utility of cHPV-DNA, the full potential of cHPV-DNA for the screening, diagnosis, and treatment of HPV-related malignancies can be corroborated. In this review, we examine the current landscape of applications for cHPV-DNA liquid biopsies throughout the cancer care continuum, highlighting future opportunities for research and integration into clinical practice.