Detection of cervical neoplasia by DNA methylation analysis in cervico-vaginal lavages, a feasibility study.

OBJECTIVE: To explore the feasibility of DNA methylation analysis for the detection of cervical neoplasia in self-obtained cervico-vaginal lavages. METHODS: Lavages collected by a self-sampling device and paired cervical scrapings were obtained from 20 cervical cancer patients and 23 patients referred with an abnormal cervical smear (15 with high-grade cervical intraepithelial neoplasia (CIN2+) and 8 without CIN). All lavages and scrapings were analyzed by liquid based cytology (LBC), Hybrid Capture II (HC-II) for hr-HPV DNA detection and by DNA methylation analysis (JAM3, TERT, EPB41L3 and C13ORF18). Concordance between lavages and scrapings was measured by Cohen's Kappa (k). RESULTS: In lavages and scrapings from cervical cancer patients (n=20), methylation analysis was positive in 19 (95%) and 19 (95%), HC-II in 16 (80%) and 15 (75%) and LBC in 15 (75%) and 19 (95%), respectively. In lavages and scrapings from CIN2+ patients (n=15), methylation analysis was positive in 10 (67%) and 12 (80%), HC-II in 15 (100%) and 15 (100%) and LBC in 11 (73%) and 12 (80%), respectively. Concordance between cervical scrapings and lavages (n=43) was for LBC k=0.522 (p<0.001), hr-HPV testing k=0.551 (p<0.001) and DNA methylation analysis k=0.653 (p<0.001). CONCLUSIONS: DNA methylation analysis in cervico-vaginal lavages obtained by a self-sampling device is feasible and its diagnostic performance appears to be at least comparable to the detection of cervical neoplasia by cytomorphology and hr-HPV. Our pilot study suggests that detection of cervical neoplasia by DNA methylation analysis in cervico-vaginal lavages warrants exploration of its use in large prospective studies.

Accuracy of a low priced liquid-based method for cervical cytology in 632 women referred for colposcopy after a positive Pap smear.

The aim of this quality controlling study was to determine the accuracy of liquid-based cytology (LBC) with the Turbitec cytocentrifuge technique. Cervical smears of 632 women, who were referred to our CIN outpatient department, after at least two smears with ASCUS or higher were evaluated and compared with the histological outcome. In 592 cases the smears revealed abnormalities of squamous epithelium, and in 40 cases the abnormalities of glandular epithelium. In the group of squamous epithelium abnormalities, the sensitivity for LSIL was 39.7% and the specificity was 89.2%; for the LSIL+ group, these values were 89.4% and 91.4%, respectively. For HSIL the sensitivity was 68.3% and the specificity 92.8%, for the HSIL+ group 82.3% and 92.3%, respectively. The ASCUS rate was low (2.4%). The Turbitec cytocentrifuge method was proved to be a very good LBC method for cervical smears. Because of a comparable accuracy together with a lower price, this LBC method outweighs commercial alternatives.