Genome-wide microRNA analysis of HPV-positive self-samples yields novel triage markers for early detection of cervical cancer

Barbara C. Snoek, Wina Verlaat, Iris Babion, Putri W. Novianti, Mark A. van de Wiel, Saskia M. Wilting, Nienke E. van Trommel, Maaike C.G. Bleeker, Leon F.A.G. Massuger, Willem J.G. Melchers, Daoud Sie, Daniëlle A.M. Heideman, Peter J.F. Snijders, Chris J.L.M. Meijer, Renske D.M. Steenbergen

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

Offering self-sampling for HPV testing improves the effectiveness of current cervical screening programs by increasing population coverage. Molecular markers directly applicable on self-samples are needed to stratify HPV-positive women at risk of cervical cancer (so-called triage) and to avoid over-referral and overtreatment. Deregulated microRNAs (miRNAs) have been implicated in the development of cervical cancer, and represent potential triage markers. However, it is unknown whether deregulated miRNA expression is reflected in self-samples. Our study is the first to establish genome-wide miRNA profiles in HPV-positive self-samples to identify miRNAs that can predict the presence of CIN3 and cervical cancer in self-samples. Small RNA sequencing (sRNA-Seq) was conducted to determine genome-wide miRNA expression profiles in 74 HPV-positive self-samples of women with and without cervical precancer (CIN3). The optimal miRNA marker panel for CIN3 detection was determined by GRridge, a penalized method on logistic regression. Six miRNAs were validated by qPCR in 191 independent HPV-positive self-samples. Classification of sRNA-Seq data yielded a 9-miRNA marker panel with a combined area under the curve (AUC) of 0.89 for CIN3 detection. Validation by qPCR resulted in a combined AUC of 0.78 for CIN3+ detection. Our study shows that deregulated miRNA expression associated with CIN3 and cervical cancer development can be detected by sRNA-Seq in HPV-positive self-samples. Validation by qPCR indicates that miRNA expression analysis offers a promising novel molecular triage strategy for CIN3 and cervical cancer detection applicable to self-samples.

Original languageEnglish
Pages (from-to)372-379
Number of pages8
JournalInternational Journal of Cancer
Volume144
Issue number2
Early online date7 Sept 2018
DOIs
Publication statusPublished - 15 Jan 2019

Keywords

  • cervical intraepithelial neoplasia
  • human papillomavirus
  • microRNA profiling
  • self-sampling

Cite this