What question did this study set out to answer?

The aim is to evaluate the effectiveness of circulating HPV DNA as a biomarker for monitoring cervical cancer recurrence.

February 9, 2026

Ultrasensitive next‐generation sequencing–based detection of circulating human papillomavirus DNA for cervical cancer recurrence monitoring

Key Points

The aim is to evaluate the effectiveness of circulating HPV DNA as a biomarker for monitoring cervical cancer recurrence.
Included 141 cervical cancer patients with varying treatment modalities.
Collected plasma samples before treatment, at early follow-up, and during longer follow-up.
Used next-generation sequencing to detect ccfHPV DNA.
Assessed associations between ccfHPV DNA status and recurrence using Cox proportional hazards models.
Recurrence risk associated with pretreatment ccfHPV DNA positivity was significantly higher, with an adjusted hazard ratio of 4.92.
At early follow-up, ccfHPV DNA positivity predicted recurrence strongly with an adjusted hazard ratio of 19.1.
Positive predictive value for recurrence was 83%, and negative predictive value was 90% within 50 months.
In 60.9% of recurrence cases, ccfHPV DNA was detectable before clinical signs, with an average lead time of 144 days.

Abstract

Abstract Background Circulating cell‐free human papillomavirus (ccfHPV) DNA is a promising biomarker for cervical cancer monitoring. This study used next‐generation sequencing (NGS) to assess its prognostic and surveillance value. Methods The authors included 141 cervical cancer patients (International Federation of Gynecology and Obstetrics IA1–IVB) grouped by treatment: primary surgery ( n = 50), primary surgery + adjuvant oncological ( n = 22), and primary oncological treatment ( n = 69). Plasma was collected pretreatment, at early follow‐up (first post‐treatment sample FPS), and during longer follow‐up. ccfHPV DNA was detected using an NGS‐based assay, enabling high sensitivity without prior knowledge of human papillomavirus (HPV) genotype. Associations between ccfHPV DNA status and recurrence were assessed using Cox proportional hazards models, and predictive accuracy was evaluated via sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results Pretreatment ccfHPV DNA positivity was detected in 8.0%, 36.4%, and 82.6% of patients across the groups, and ccfHPV DNA positivity was significantly associated with higher recurrence risk (adjusted hazard ratio HR, 4.92; 95% confidence interval CI, 1.29–18.7; p = .02). At FPS, ccfHPV DNA positivity strongly predicted recurrence (adjusted HR, 19.1; 95% CI, 7.27–50.2), with a PPV of 83% and NPV of 90% for recurrence within 50 months. Among patients who developed recurrence, ccfHPV DNA was detectable before clinical evidence of recurrence in 60.9% of cases with a mean lead time of 144 days. Conclusion ccfHPV DNA detected by NGS is a strong prognostic biomarker for residual disease or recurrence. Its strong performance, already at early follow‐up, supports its integration into individualized follow‐up strategies. Prospective multicenter studies should validate these findings and guide clinical implementation. Trial Registration The study was registered with ClinicalTrials.gov (identifiers: NCT03749720)

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