title: Detection of cervical neoplasia by DNA methylation analysis in cervico-vaginal lavages, a feasibility study.
abstract: 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.
authors.affiliation: Department of Gynaecological Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: J J H
authors.initials: JJ
authors.lastname: Eijsink
authors.forename: N
authors.initials: N
authors.lastname: Yang
authors.forename: A
authors.initials: A
authors.lastname: Lendvai
authors.forename: H G
authors.initials: HG
authors.lastname: Klip
authors.forename: H H
authors.initials: HH
authors.lastname: Volders
authors.forename: H J
authors.initials: HJ
authors.lastname: Buikema
authors.forename: B M
authors.initials: BM
authors.lastname: van Hemel
authors.forename: M
authors.initials: M
authors.lastname: Voll
authors.forename: H J T
authors.initials: HJ
authors.lastname: Coelingh Bennink
authors.forename: E
authors.initials: E
authors.lastname: Schuuring
authors.forename: G B A
authors.initials: GB
authors.lastname: Wisman
authors.forename: A G J
authors.initials: AG
authors.lastname: van der Zee
mesh_terms: D019175:DNA Methylation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D010865:Pilot Projects; D016353:Self-Examination; D007507:Therapeutic Irrigation / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology*; D014621:Vagina / Q000473:pathology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology*