OBJECTIVE: The aim of this study was to determine whether circulating tumor human papillomavirus (HPV) DNA is a potential specific biomarker for cervical cancer (CC). METHODS: This retrospective matched study included 87 patients with cervical intraepithelial neoplasia (CIN), 29 CC patients (FIGO IA1-IVA) and 29 HPV-negative controls at Yuhuangding Hospital of Qingdao University (from July 2022 to September 2023). The digital droplet PCR (ddPCR) was used to detect and quantify ctHPV DNA in the plasma of patients with HPV16, 18, 33, 52, or 58-associated CC. RESULTS: The ctHPV DNA was exclusively detectable in HPV-positive samples, with no detection in patients across various CIN stages (n = 87) or HPV-negative controls (n = 29). Additionally, ctHPV DNA was identified in nine out of 10 late-stage patients (90%) and six out of 19 early-stage patients (31.6%). CONCLUSION: The ctHPV DNA serves as a specific biomarker for the diagnosis CC. Additionally, this discovery addresses the knowledge gap in ctHPV DNA research in the early stages of CC and promotes clinical diagnosis and treatment strategies.