Circulating microRNA Profiles as Diagnostic Tools for High-Grade Cervical Lesions and HPV Genotype Stratification

Area of Science:

• Oncology
• Molecular Biology
• Gynecology

Background:

• Persistent high-risk human papillomavirus (hr-HPV) infection is a primary driver of cervical carcinogenesis.
• Improved molecular biomarkers are crucial for identifying individuals at high risk for cervical cancer.
• Circulating microRNAs (miRNAs) are stable in blood and implicated in carcinogenic pathways, making them potential liquid biopsy biomarkers.

Purpose of the Study:

• To evaluate five circulating miRNAs as biomarkers for distinguishing high-grade squamous cell intraepithelial lesions (HSIL) and cervical cancer from healthy controls.
• To assess the utility of these miRNAs for stratifying patients based on HPV status.
• To determine the diagnostic performance of single and combined miRNA markers.

Main Methods:

• Quantification of circulating miRNAs in blood samples from 80 women (38 HSIL, 10 cervical cancer, 32 controls) using RT-qPCR.
• Normalization of miRNA expression data to miRNA-23a.
• Evaluation of diagnostic performance using logistic regression and ROC curve analysis.

Main Results:

• Three miRNAs (miR-21, miR-205, and miR-218) were significantly dysregulated in patient cohorts compared to controls.
• A combination of these three miRNAs demonstrated strong diagnostic value for HSIL (AUC 0.81) and cervical cancer (AUC 0.81).
• The combined miRNA model showed high sensitivity and specificity for detecting HSIL and cancer, and was particularly effective for multiple HPV infections.

Conclusions:

• Circulating miRNA signatures hold significant potential as non-invasive liquid biopsy biomarkers for cervical dysplasia detection.
• These miRNA panels can aid in stratifying patients with HSIL based on HPV status.
• Further validation in larger prospective studies is warranted to confirm these promising findings.