Identification of microRNAs as biomarkers for triage of cervical intraepithelial neoplasia in cervical scrape samples from high-risk HPV-positive women.

BACKGROUND

Cervical cancer (CC) is the fourth leading cause of cancer death in women worldwide. High-risk human papillomavirus (HR-HPV) testing is highly sensitive but lacks specificity for identifying women at risk of progression. Reliable biomarkers are urgently needed to identify HR-HPV-positive women most likely to develop cervical cancer. Aberrant microRNA (miRNA) expression contributes to HPV-driven carcinogenesis and represents a promising diagnostic tool.

METHODS

Cervical scrape samples from HR-HPV-positive women were histologically classified as low-grade (≤CIN1) or high-grade (CIN2/3). Total RNA was extracted and small RNA sequencing performed to identify differentially expressed miRNAs. Bioinformatic analyses included clustering, ROC curves, logistic regression, and functional enrichment. Selected candidates were validated byRT-qPCR in independent samples.

RESULTS

Nineteen dysregulated miRNAs distinguished low- from high-grade lesions, six linked to viral and cancer pathways. Three (hsa-miR-501-3p, hsa-miR-1271-5p, hsa-miR-9-5p) were validated by RT-qPCR and showed strong discriminatory capacity. hsa-miR-501-3p reached high diagnostic accuracy (AUC = 0.88), which improved to 0.94 when combined with the others. The validated signature achieved high sensitivity and specificity for detecting high-grade lesions.

CONCLUSION

This pioneering study in Colombia using cervical scrapes demonstrates that miRNAs are potential biomarkers for high-grade cervical lesions and that this clinically relevant, minimally invasive sample routinely collected in screening supports their use.