HPV cfDNA testing shows high specificity but moderate sensitivity for cervical cancer detection

This systematic review and meta-analysis evaluated the diagnostic and prognostic performance of HPV circulating free DNA (cfDNA) testing in HPV-positive cervical cancer patients. The analysis included 20 studies (11 for diagnostic analysis, 6 for prognostic analysis), though specific study settings and comparators were not reported. For diagnostic performance, the pooled sensitivity was 0.47 (95% CI, 0.43-0.52) and specificity was 0.96 (95% CI, 0.92-0.98), with a diagnostic odds ratio of 71.31 and area under the SROC curve of 0.9825.

For prognostic analysis with 3.0 months follow-up, HPV cfDNA positivity at 3 months post-treatment was associated with reduced progression-free survival, with a hazard ratio of 8.50 (95% CI, 4.69-15.41). The positive likelihood ratio was 10.49 and negative likelihood ratio was 0.28 for diagnostic performance. Safety and tolerability data were not reported in the included studies.

Key limitations include the moderate diagnostic sensitivity of 0.47, which suggests HPV cfDNA testing may miss approximately half of cervical cancer cases when used alone. The analysis was based on observational diagnostic and prognostic studies, and heterogeneity was assessed with I² statistic (I² = 0% for prognostic analysis). The prognostic analysis reports association, not causation, between cfDNA positivity and reduced progression-free survival.

Practice relevance is restrained: while HPV cfDNA shows high specificity and strong prognostic association, its moderate sensitivity limits standalone diagnostic use. The evidence supports potential clinical utility in treatment surveillance rather than primary detection. Clinicians should interpret these findings as preliminary evidence from a meta-analysis of existing studies, not as definitive guidance from new clinical trials.