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Published on: September 16, 2022
Liquid Biopsy Biomarkers for Cervical Cancer: A Systematic Review.
Jesús Alejandro Pineda-Migranas1, Juan Carlos Bravata-Alcántara2,3, Iliana Alejandra Cortés-Ortíz4
1Escuela Superior de Medicina, Instituto Politécnico Nacional (IPN), Salvador Díaz Mirón esq. Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomás, Mexico City 11340, Mexico.
Liquid biopsy shows promise for cervical cancer detection. Circulating cell-free HPV DNA (cfHPV-DNA) is the most promising biomarker for monitoring treatment and recurrence, while microRNAs and cytokines require further standardization.
Area of Science:
- Oncology
- Molecular Diagnostics
- Biomarker Discovery
Background:
- Cervical cancer is a major global health concern, especially in low- and middle-income countries.
- Liquid biopsy offers a minimally invasive alternative to traditional screening for detecting and monitoring cervical cancer.
- Biomarkers like serum cytokines, circulating microRNAs (miRNAs), and cell-free HPV DNA (cfHPV-DNA) are being investigated.
Purpose of the Study:
- To systematically review the role of serum cytokines, circulating miRNAs, and cfHPV-DNA in cervical cancer.
- To evaluate the diagnostic and prognostic performance of these liquid biopsy biomarkers.
- To assess the clinical readiness of these biomarkers for cervical cancer management.
Main Methods:
- Systematic review of 21 studies published between 2015 and 2025, adhering to the PRISMA 2020 statement.
- Analysis of studies investigating serum cytokines (TNF-α, IL-6, IL-10), circulating miRNAs (miR-21, miR-29a, miR-34a), and cfHPV-DNA.
- Evaluation of biomarker performance metrics, including sensitivity and specificity, particularly for cfHPV-DNA using ddPCR.
Main Results:
- Circulating miRNAs are linked to recurrence, progression, and survival but lack standardization for clinical use.
- Circulating cell-free HPV DNA (cfHPV-DNA), especially when detected by ddPCR, shows high specificity (100%) and good sensitivity (80-88%).
- Serum cytokines reflect tumor microenvironment but suffer from variability, limiting their use as standalone markers.
Conclusions:
- Liquid biopsy is a promising approach for cervical cancer management.
- Circulating cell-free HPV DNA (cfHPV-DNA) is the most clinically ready biomarker for post-treatment surveillance and early recurrence detection.
- MicroRNAs and cytokines require further multicenter validation and standardization before widespread clinical implementation.
