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MicroRNA-Based Triage of HPV-Positive Women Using Liquid-Based Cytology: Diagnostic Performance and Network-Level
Justyna Pisarska1, Aleksandra Kożańska1, Rafał Rzepka2
1Department of Microbiology and Molecular Biology, Institute of Health Sciences, Collegium Medicum, University of Zielona Góra, 65-046 Zielona Góra, Poland.
Cancers
|February 27, 2026
Summary
MicroRNAs (miRNAs) can improve cervical cancer screening by identifying high-grade lesions. Network analysis reveals changes in miRNA regulation during disease progression, offering better triage markers.
Area of Science:
- Gynecologic Oncology
- Molecular Diagnostics
- Biomarker Discovery
Background:
- Human papillomavirus (HPV)-based screening for cervical cancer lacks specificity, leading to unnecessary colposcopy referrals.
- MicroRNAs (miRNAs) show promise as biomarkers for improved triage of HPV-positive women.
- This study investigates diagnostic and regulatory roles of miRNAs in cervical lesions using liquid-based cytology (LBC) specimens.
Purpose of the Study:
- To evaluate the diagnostic performance of selected miRNAs in cervical lesions.
- To analyze the regulatory roles and network dynamics of miRNAs during cervical lesion progression.
- To identify robust miRNA biomarkers for triaging HPV-positive women.
Main Methods:
- Expression analysis of six miRNAs (miR-15a-5p, miR-16-5p, miR-20b-5p, miR-155-5p, miR-34a-5p, miR-140-3p) in NILM, CIN II, CIN III, and cervical cancer (CC) samples.
- Utilized residual LBC specimens, avoiding additional sampling.
- Assessed diagnostic performance via ROC analysis and employed network analyses (correlation, differential correlation) for regulatory insights.
Main Results:
- Stage-dependent miRNA expression changes were observed, but expression magnitude alone was insufficient for diagnosis.
- Upregulated miRNAs (miR-16-5p, miR-20b-5p, miR-155-5p) showed high accuracy in distinguishing normal from high-grade lesions/cancer.
- miRNA co-expression networks underwent significant remodeling, particularly during CIN II to CIN III transition, indicating distinct roles as biomarkers versus regulators.
Conclusions:
- Cervical lesion progression involves both altered miRNA expression and stage-specific reorganization of miRNA regulatory networks.
- Integrating diagnostic performance with network analysis enhances identification of reliable triage markers.
- This approach provides insights into regulatory instability associated with cervical lesion progression.
Keywords:
HPV infectionSpearman correlationbiomarkercervical cancercervical intraepithelial neoplasia (CIN) lesionsmiRNAs expressionmicroRNAqPCRreceiver operating characteristic (ROC)regulatory network of miRNA
