TY - JOUR
T1 - FAM19A4/miR124-2 methylation in invasive cervical cancer
T2 - A retrospective cross-sectional worldwide study
AU - Vink, Frederique J
AU - Meijer, Chris J L M
AU - Clifford, Gary M
AU - Poljak, Mario
AU - Oštrbenk, Anja
AU - Petry, Karl Ulrich
AU - Rothe, Beate
AU - Bonde, Jesper
AU - Pedersen, Helle
AU - de Sanjosé, Silvia
AU - Torres, Montserrat
AU - Del Pino, Marta
AU - Quint, Wim G V
AU - Cuschieri, Kate
AU - Alcañiz Boada, Elia
AU - van Trommel, Nienke E
AU - Lissenberg-Witte, Birgit I
AU - Floore, Arno N
AU - Hesselink, Albertus T
AU - Steenbergen, Renske D M
AU - Bleeker, Maaike C G
AU - Heideman, Daniëlle A M
N1 - This article is protected by copyright. All rights reserved.
PY - 2020/8/15
Y1 - 2020/8/15
N2 - Widespread adoption of primary human papillomavirus (HPV)-based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124-2 genes has shown promise for the triage of high-risk (hr) HPV-positive women. In our study, we assessed the consistency of FAM19A4/miR124-2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation-specific PCR (qMSP)-based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7–99.2) tested FAM19A4/miR124-2 methylation-positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124-2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV-negative carcinomas. These results indicate that a negative FAM19A4/miR124-2 methylation assay result is likely to rule out the presence of cervical cancer.
AB - Widespread adoption of primary human papillomavirus (HPV)-based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124-2 genes has shown promise for the triage of high-risk (hr) HPV-positive women. In our study, we assessed the consistency of FAM19A4/miR124-2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation-specific PCR (qMSP)-based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7–99.2) tested FAM19A4/miR124-2 methylation-positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124-2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV-negative carcinomas. These results indicate that a negative FAM19A4/miR124-2 methylation assay result is likely to rule out the presence of cervical cancer.
KW - DNA hypermethylation
KW - biomarker
KW - cervical carcinoma
KW - cervical screening
KW - human genome methylation
KW - human papillomavirus
U2 - 10.1002/ijc.32614
DO - 10.1002/ijc.32614
M3 - Article
SN - 0020-7136
VL - 147
SP - 1215
EP - 1221
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -