Screening for cervical cancer by primary high-risk HPV (hrHPV) testing has just been introduced in the Netherlands. Because hrHPV testing also results in the identification of women with clinically irrelevant transient hrHPV infections, additional triage markers are required to identify women at risk of high-grade cervical intraepithelial neoplasia (CIN) or cancer. We expect microRNAs (miRNAs) to provide promising triage markers, since they are 1) often deregulated in cancer and 2) easily detectable in small amounts of clinical material. We previously identified 8 miRNAs with altered expression in cervical (pre)cancer due to either methylation-mediated silencing or chromosomal alterations. In this study, we evaluated the clinical value of the 8 miRNAs to triage hrHPV-positive women in cervical screening.
Quantitative TaqMan RT-PCR was used to determine expression levels of the 8 candidate miRNAs in RNA isolated from cervical scrapes of hrHPV-positive women without disease (n=66), with high-grade CIN (n=121), cervical squamous cell carcinoma (SCC, n=29) and cervical adenocarcinoma (AC, n=9).
Six out of 8 miRNAs showed significantly (p < 0.05) differential expression between scrapes of hrHPV-positive women with and without high-grade CIN and cancer. Using logistic regression analysis a miRNA classifier was built, which detected a major subset of high-grade CIN (~65%), all but two SCC (93%) and all AC (100%).
Altered miRNA expression is detectable in hrHPV-positive cervical scrapes of women with underlying high-grade CIN and cancer. Our miRNA classifier provides promising results for the triage of hrHPV-positive women.