TY - JOUR
T1 - Evaluation of six methylation markers derived from genome-wide screens for detection of cervical precancer and cancer
AU - Dick, Stèfanie
AU - Verhoef, Lisanne
AU - De Strooper, Lise Ma
AU - Ciocănea-Teodorescu, Iuliana
AU - Wisman, G Bea A
AU - Meijer, Chris Jlm
AU - Bleeker, Maaike Cg
AU - Steenbergen, Renske Dm
AU - Heideman, Daniëlle Am
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Aim: To evaluate the triage performance of six host-cell DNA methylation markers derived from two genome-wide discovery screens for detection of cervical precancer (cervical intraepithelial neoplasia 3 [CIN]) and cancer. Materials & methods: Human papillomavirus-positive cervical scrapes of controls (≤CIN1; n = 352) and women diagnosed with CIN3 (n = 175) or cervical cancer (n = 50) were analyzed for methylation of ASCL1, LHX8, ST6GALNAC5, GHSR, SST and ZIC1. Results: Methylation levels increased significantly with disease severity (all markers p < 0.001). Three markers (ASCL1, LHX8, ZIC1) showed receiver operating characteristic curves with area under the curve >0.800 after leave-one-out cross-validation. Bi-marker panel ASCL1/LHX8 had highest area under the curve (0.882), and detected 83.4% of CIN3 and all cervical cancers at specificity of 82.4%. Conclusion: All six methylation markers showed an equivalent, high performance for the triage of human papillomavirus-positive women using cervical scrapes with complementarity between markers.
AB - Aim: To evaluate the triage performance of six host-cell DNA methylation markers derived from two genome-wide discovery screens for detection of cervical precancer (cervical intraepithelial neoplasia 3 [CIN]) and cancer. Materials & methods: Human papillomavirus-positive cervical scrapes of controls (≤CIN1; n = 352) and women diagnosed with CIN3 (n = 175) or cervical cancer (n = 50) were analyzed for methylation of ASCL1, LHX8, ST6GALNAC5, GHSR, SST and ZIC1. Results: Methylation levels increased significantly with disease severity (all markers p < 0.001). Three markers (ASCL1, LHX8, ZIC1) showed receiver operating characteristic curves with area under the curve >0.800 after leave-one-out cross-validation. Bi-marker panel ASCL1/LHX8 had highest area under the curve (0.882), and detected 83.4% of CIN3 and all cervical cancers at specificity of 82.4%. Conclusion: All six methylation markers showed an equivalent, high performance for the triage of human papillomavirus-positive women using cervical scrapes with complementarity between markers.
KW - ASCL1
KW - DNA methylation markers
KW - LHX8
KW - cervical cancer
KW - cervical intraepithelial neoplasia
KW - cervical screening
KW - human genome methylation
KW - human papillomavirus
KW - triage testing
UR - http://www.scopus.com/inward/record.url?scp=85092119820&partnerID=8YFLogxK
U2 - https://doi.org/10.2217/epi-2019-0331
DO - https://doi.org/10.2217/epi-2019-0331
M3 - Article
C2 - 32938193
SN - 1750-1911
VL - 12
SP - 1569
EP - 1578
JO - Epigenomics
JF - Epigenomics
IS - 18
ER -