Introduction The objective of this study is to investigate the association between circulating human papillomavirus (HPV) cell-free DNA and oncological outcomes of cervical cancer patients.

Methods Searches in MEDLINE, Embase, and CENTRAL were conducted until November 26, 2023. Inclusion criteria were: (1) pathologically confirmed cervical cancer with available HPV test results; (2) detection of HPV cell-free DNA was performed in serum/plasma before treatment or at end of treatment; (3) studies reported oncological outcomes of cervical cancer patients based on HPV cell-free DNA levels. Two authors independently handled data extraction and study quality assessment. Pooled hazard ratios and 95% confidence intervals were calculated by the inverse-variance method for survival outcomes.

Results Five studies were finally included in this meta-analysis. Blood samples pre-treatment were collected from 237 patients, with 150 having end-of-treatment samples. Additionally, 82 patients had samples at 3 months post-treatment. Results indicated that positive HPV cell-free DNA at end of treatment correlated with poorer progression-free survival (pooled hazard ratio: 5.49; 95% CI: 2.85-10.58; I2: 0%). Similar findings were found at 3 months post-treatment (pooled hazard ratio: 7.86; 95% CI: 3.32-18.60; I2: 0%). However, pre-treatment positive HPV cell-free DNA wasn’t significantly linked to progression-free survival (pooled hazard ratio: 0.97; 95% CI: 0.55-1.71; I2: 0%).

Conclusion/Implications In conclusion, cervical cancer patients with positive HPV cell-free DNA detection post-treatment exhibited notably poorer oncological outcomes compared to negative patients. Personalized HPV cell-free DNA monitoring holds promise as a prognostic biomarker for these patients.