ArticleBMC medicine2022
Targeted RNA next generation sequencing analysis of cervical smears can predict the presence of hrHPV-induced cervical lesions.
Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Cervicovaginal specimen biomarkers for early detection of ovarian and endometrial cancer: A review.Cancer medicine · 2024Pooled it
- Molecular detection of hrHPV-induced high-grade squamous intraepithelial lesions of the cervix through a targeted RNA next generation sequencing assay.Molecular medicine (Cambridge, Mass.) · 2025Article
- Vitamin D, immune microenvironment, and cervical lesions: mechanisms and therapeutic strategies from polyps to carcinoma.Frontiers in nutrition · 2025Review
- Gene expression analysis of ovarian follicles and stromal cells in girls with Turner syndrome.Molecular human reproduction · 2024Article
- Temporal composition of the cervicovaginal microbiome associates with hrHPV infection outcomes in a longitudinal study.BMC infectious diseases · 2024Article
- Biological functions, mechanisms, and clinical significance of circular RNA in colorectal cancer.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBecause most cervical cancers are caused by high-risk human papillomaviruses (hrHPVs), cervical cancer prevention programs increasingly employ hrHPV testing as a primary test. The high sensitivity of HPV tests is accompanied by low specificity, resulting in high rates of overdiagnosis and overtreatment. Targeted circular probe-based RNA next generation sequencing (ciRNAseq) allows for the quantitative detection of RNAs of interest with high sequencing depth. Here, we examined the potential of ciRNAseq-testing on cervical scrapes to identify hrHPV-positive women at risk of having or developing high-grade cervical intraepithelial neoplasia (CIN).
methodsWe performed ciRNAseq on 610 cervical scrapes from the Dutch cervical cancer screening program to detect gene expression from 15 hrHPV genotypes and from 429 human genes. Differentially expressed hrHPV- and host genes in scrapes from women with outcome "no CIN" or "CIN2+" were identified and a model was built to distinguish these groups.
resultsApart from increasing percentages of hrHPV oncogene expression from "no CIN" to high-grade cytology/histology, we identified genes involved in cell cycle regulation, tyrosine kinase signaling pathways, immune suppression, and DNA repair being expressed at significantly higher levels in scrapes with high-grade cytology and histology. Machine learning using random forest on all the expression data resulted in a model that detected 'no CIN' versus CIN2+ in an independent data set with sensitivity and specificity of respectively 85 ± 8% and 72 ± 13%.
conclusionsCiRNAseq on exfoliated cells in cervical scrapes measures hrHPV-(onco)gene expression and host gene expression in one single assay and in the process identifies HPV genotype. By combining these data and applying machine learning protocols, the risk of CIN can be calculated. Because ciRNAseq can be performed in high-throughput, making it cost-effective, it can be a promising screening technology to stratify women at risk of CIN2+. Further increasing specificity by model improvement in larger cohorts is warranted.
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