Combined plasma and liquid-based cytology microRNA signatures as biomarkers of high-grade cervical lesions: association with HPV infection and p16 expression.
- 1Department of Basic Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia.
- 2Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Abstract
MicroRNA (miRNA) dysregulation may provide complementary molecular information for cervical lesion assessment and triage. This prospective observational study evaluated six candidate miRNAs in paired plasma and liquid-based cytology (LBC) specimens and their associations with cytological severity, high-risk human papillomavirus (hrHPV), and p16 expression. Among 328 women, cytology was classified as normal (n = 52), atypical squamous cells of undetermined significance (ASC-US; n = 44), low-grade squamous intraepithelial lesion (LSIL; n = 42), high-grade squamous intraepithelial lesion (HSIL; n = 82), or squamous cell carcinoma (SCC; n = 108). hrHPV positivity increased from 0% in normal cytology to 93.5% in SCC and p16 positivity from 0% to 95.4% (both P < 0.001). In paired plasma and LBC specimens, miR-21-5p, miR-155-5p, miR-9-5p, and miR-15b-5p progressively increased with cytological severity, whereas miR-375-3p and miR-145-5p decreased (all p < 0.001). For discrimination of HSIL/SCC from normal/ASC-US/LSIL, individual-miRNA areas under the curve (AUCs) ranged from 0.970 to 0.993. After stratified 10-fold cross-validation, AUCs were 0.818 (95% CI, 0.765-0.869) for hrHPV, 0.807 (0.751-0.860) for p16, and 0.840 (0.789-0.888) for hrHPV + p16. The six-miRNA LBC panel achieved an AUC of 0.9999 (0.9996-1.000), 99.5% sensitivity, 100.0% specificity, and a Brier score of 0.006. These findings demonstrate strong internal discrimination by LBC-derived miRNAs; however, validation against histologically confirmed endpoints in independent, clinically representative populations is required before clinical application.
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BibTeX
@article{hasan2026combined,
title = {{Combined plasma and liquid-based cytology microRNA signatures as biomarkers of high-grade cervical lesions: association with HPV infection and p16 expression.}},
author = {Tabinda Hasan and Huda Eltayeb and Amal N Alanazi and Ghaida S AlSugair and Nidhi Anand and Sridhar Mishra},
journal = {The journal of liquid biopsy},
year = {2026},
month = oct,
doi = {10.1016/j.jlb.2026.100673},
url = {https://europepmc.org/article/MED/42903652},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Combined plasma and liquid-based cytology microRNA signatures as biomarkers of high-grade cervical lesions: association with HPV infection and p16 expression.
AU - Tabinda Hasan
AU - Huda Eltayeb
AU - Amal N Alanazi
AU - Ghaida S AlSugair
AU - Nidhi Anand
AU - Sridhar Mishra
PY - 2026
DA - 2026/10/06
JO - The journal of liquid biopsy
DO - 10.1016/j.jlb.2026.100673
UR - https://europepmc.org/article/MED/42903652
AB - MicroRNA (miRNA) dysregulation may provide complementary molecular information for cervical lesion assessment and triage. This prospective observational study evaluated six candidate miRNAs in paired plasma and liquid-based cytology (LBC) specimens and their associations with cytological severity, high-risk human papillomavirus (hrHPV), and p16 expression. Among 328 women, cytology was classified as normal (n = 52), atypical squamous cells of undetermined significance (ASC-US; n = 44), low-grade squamous intraepithelial lesion (LSIL; n = 42), high-grade squamous intraepithelial lesion (HSIL; n = 82), or squamous cell carcinoma (SCC; n = 108). hrHPV positivity increased from 0% in normal cytology to 93.5% in SCC and p16 positivity from 0% to 95.4% (both P < 0.001). In paired plasma and LBC specimens, miR-21-5p, miR-155-5p, miR-9-5p, and miR-15b-5p progressively increased with cytological severity, whereas miR-375-3p and miR-145-5p decreased (all p < 0.001). For discrimination of HSIL/SCC from normal/ASC-US/LSIL, individual-miRNA areas under the curve (AUCs) ranged from 0.970 to 0.993. After stratified 10-fold cross-validation, AUCs were 0.818 (95% CI, 0.765-0.869) for hrHPV, 0.807 (0.751-0.860) for p16, and 0.840 (0.789-0.888) for hrHPV + p16. The six-miRNA LBC panel achieved an AUC of 0.9999 (0.9996-1.000), 99.5% sensitivity, 100.0% specificity, and a Brier score of 0.006. These findings demonstrate strong internal discrimination by LBC-derived miRNAs; however, validation against histologically confirmed endpoints in independent, clinically representative populations is required before clinical application.
SN - 2950-1954
ER -