Diagnostic and prognostic significance of circulating HPV cfDNA in cervical cancer: A systematic review and meta-analysis

Importance Human papillomavirus circulating free DNA (HPV cfDNA) is an emerging biomarker with potential utility in the detection and treatment monitoring of cervical cancer. Objective To conduct a systematic review and meta-analysis evaluating the diagnostic and prognostic performance of HPV cfDNA in cervical cancer. Methods A comprehensive literature search was conducted in PubMed, CINAHL, Cochrane Library, Scopus, and Embase through April 2025. Eligible studies reported or allowed calculation of diagnostic performance of HPV cfDNA in HPV-positive cervical cancer patients and/or included serial HPV cfDNA testing during post-treatment follow-up. Meta-analyses were conducted using a random-effects model. Heterogeneity was assessed with the I² statistic. The review followed PRISMA guidelines, and study quality was assessed using QUADAS-2. Results Of 106 studies screened, 20 met the inclusion criteria. Eleven studies contributed to the diagnostic meta-analysis and six to the prognostic analysis. The pooled sensitivity and specificity of HPV cfDNA for cervical cancer detection were 0.47 (95 % CI, 0.43–0.52) and 0.96 (95 % CI, 0.92–0.98), respectively. Positive and negative likelihood ratios were 10.49 and 0.28, with a diagnostic odds ratio of 71.31. The area under the SROC curve was 0.9825, indicating excellent overall diagnostic performance. Prognostically, HPV cfDNA positivity at 3 months post-treatment was significantly associated with reduced progression-free survival (HR = 8.50; 95 % CI, 4.69–15.41; I² = 0 %). Conclusions and relevance HPV cfDNA shows high specificity and strong prognostic value, supporting its clinical utility in cervical cancer detection and treatment surveillance.