Cervical cancer risk in HPV-positive women after a negative FAM19A4/mir124-2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow-up

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Abstract

DNA methylation analysis of cervical scrapes using FAM19A4 and mir124-2 genes has shown a good clinical performance in detecting cervical cancer and advanced CIN lesions in need of treatment in HPV-positive women. To date, longitudinal data on the cancer risk of methylation test-negative women are lacking. In our study, we assessed the longitudinal outcome of FAM19A4/mir124-2 methylation analysis in an HPV-positive screening cohort with 14 years of follow-up. Archived HPV-positive cervical scrapes of 1,040 women (age 29-61 years), who were enrolled in the POBASCAM screening trial (ISRCTN20781131) were tested for FAM19A4/mir124-2 methylation. By linkage with the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), 35 cervical cancers were identified during 14 years of follow-up comprising three screens (baseline, and after 5 and 10 years). The baseline scrape of 36.1% (n = 375) women tested positive for FAM19A4/mir124-2 methylation, including 24 women with cervical cancer in follow-up, and 30.6% (n = 318) had abnormal cytology (threshold borderline dyskaryosis or ASCUS), including 14 women with cervical cancer in follow-up. Within screening round capability of FAM19A4/mir124-2 methylation to detect cervical cancer was 100% (11/11, 95% CI: 71.5-100). Kaplan-Meier estimate of 14-year cumulative cervical cancer incidence was 1.7% (95% CI: 0.66-3.0) among baseline methylation-negative and 2.4% (95% CI: 1.4-3.6) among baseline cytology-negative women (risk difference: 0.71% [95% CI: 0.16-1.4]). In conclusion, a negative FAM19A4/mir124-2 methylation test provides a low cervical cancer risk in HPV-positive women of 30 years and older. FAM19A4/mir124-2 methylation testing merits consideration as an objective triage test in HPV-based cervical screening programs.

Original languageEnglish
Pages (from-to)1541-1548
Number of pages8
JournalInternational Journal of Cancer
Volume143
Issue number6
Early online date16 Apr 2018
DOIs
Publication statusPublished - 15 Sep 2018

Cite this

@article{f8e864e534ac49c48a0c75952f3cafe8,
title = "Cervical cancer risk in HPV-positive women after a negative FAM19A4/mir124-2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow-up",
abstract = "DNA methylation analysis of cervical scrapes using FAM19A4 and mir124-2 genes has shown a good clinical performance in detecting cervical cancer and advanced CIN lesions in need of treatment in HPV-positive women. To date, longitudinal data on the cancer risk of methylation test-negative women are lacking. In our study, we assessed the longitudinal outcome of FAM19A4/mir124-2 methylation analysis in an HPV-positive screening cohort with 14 years of follow-up. Archived HPV-positive cervical scrapes of 1,040 women (age 29-61 years), who were enrolled in the POBASCAM screening trial (ISRCTN20781131) were tested for FAM19A4/mir124-2 methylation. By linkage with the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), 35 cervical cancers were identified during 14 years of follow-up comprising three screens (baseline, and after 5 and 10 years). The baseline scrape of 36.1{\%} (n = 375) women tested positive for FAM19A4/mir124-2 methylation, including 24 women with cervical cancer in follow-up, and 30.6{\%} (n = 318) had abnormal cytology (threshold borderline dyskaryosis or ASCUS), including 14 women with cervical cancer in follow-up. Within screening round capability of FAM19A4/mir124-2 methylation to detect cervical cancer was 100{\%} (11/11, 95{\%} CI: 71.5-100). Kaplan-Meier estimate of 14-year cumulative cervical cancer incidence was 1.7{\%} (95{\%} CI: 0.66-3.0) among baseline methylation-negative and 2.4{\%} (95{\%} CI: 1.4-3.6) among baseline cytology-negative women (risk difference: 0.71{\%} [95{\%} CI: 0.16-1.4]). In conclusion, a negative FAM19A4/mir124-2 methylation test provides a low cervical cancer risk in HPV-positive women of 30 years and older. FAM19A4/mir124-2 methylation testing merits consideration as an objective triage test in HPV-based cervical screening programs.",
author = "{De Strooper}, {Lise M A} and Johannes Berkhof and Steenbergen, {Renske D M} and Lissenberg-Witte, {Birgit I} and Snijders, {Peter J F} and Meijer, {Chris J L M} and Heideman, {Dani{\"e}lle A M}",
note = "{\circledC} 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.",
year = "2018",
month = "9",
day = "15",
doi = "10.1002/ijc.31539",
language = "English",
volume = "143",
pages = "1541--1548",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Cervical cancer risk in HPV-positive women after a negative FAM19A4/mir124-2 methylation test

T2 - A post hoc analysis in the POBASCAM trial with 14 year follow-up

AU - De Strooper, Lise M A

AU - Berkhof, Johannes

AU - Steenbergen, Renske D M

AU - Lissenberg-Witte, Birgit I

AU - Snijders, Peter J F

AU - Meijer, Chris J L M

AU - Heideman, Daniëlle A M

N1 - © 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

PY - 2018/9/15

Y1 - 2018/9/15

N2 - DNA methylation analysis of cervical scrapes using FAM19A4 and mir124-2 genes has shown a good clinical performance in detecting cervical cancer and advanced CIN lesions in need of treatment in HPV-positive women. To date, longitudinal data on the cancer risk of methylation test-negative women are lacking. In our study, we assessed the longitudinal outcome of FAM19A4/mir124-2 methylation analysis in an HPV-positive screening cohort with 14 years of follow-up. Archived HPV-positive cervical scrapes of 1,040 women (age 29-61 years), who were enrolled in the POBASCAM screening trial (ISRCTN20781131) were tested for FAM19A4/mir124-2 methylation. By linkage with the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), 35 cervical cancers were identified during 14 years of follow-up comprising three screens (baseline, and after 5 and 10 years). The baseline scrape of 36.1% (n = 375) women tested positive for FAM19A4/mir124-2 methylation, including 24 women with cervical cancer in follow-up, and 30.6% (n = 318) had abnormal cytology (threshold borderline dyskaryosis or ASCUS), including 14 women with cervical cancer in follow-up. Within screening round capability of FAM19A4/mir124-2 methylation to detect cervical cancer was 100% (11/11, 95% CI: 71.5-100). Kaplan-Meier estimate of 14-year cumulative cervical cancer incidence was 1.7% (95% CI: 0.66-3.0) among baseline methylation-negative and 2.4% (95% CI: 1.4-3.6) among baseline cytology-negative women (risk difference: 0.71% [95% CI: 0.16-1.4]). In conclusion, a negative FAM19A4/mir124-2 methylation test provides a low cervical cancer risk in HPV-positive women of 30 years and older. FAM19A4/mir124-2 methylation testing merits consideration as an objective triage test in HPV-based cervical screening programs.

AB - DNA methylation analysis of cervical scrapes using FAM19A4 and mir124-2 genes has shown a good clinical performance in detecting cervical cancer and advanced CIN lesions in need of treatment in HPV-positive women. To date, longitudinal data on the cancer risk of methylation test-negative women are lacking. In our study, we assessed the longitudinal outcome of FAM19A4/mir124-2 methylation analysis in an HPV-positive screening cohort with 14 years of follow-up. Archived HPV-positive cervical scrapes of 1,040 women (age 29-61 years), who were enrolled in the POBASCAM screening trial (ISRCTN20781131) were tested for FAM19A4/mir124-2 methylation. By linkage with the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), 35 cervical cancers were identified during 14 years of follow-up comprising three screens (baseline, and after 5 and 10 years). The baseline scrape of 36.1% (n = 375) women tested positive for FAM19A4/mir124-2 methylation, including 24 women with cervical cancer in follow-up, and 30.6% (n = 318) had abnormal cytology (threshold borderline dyskaryosis or ASCUS), including 14 women with cervical cancer in follow-up. Within screening round capability of FAM19A4/mir124-2 methylation to detect cervical cancer was 100% (11/11, 95% CI: 71.5-100). Kaplan-Meier estimate of 14-year cumulative cervical cancer incidence was 1.7% (95% CI: 0.66-3.0) among baseline methylation-negative and 2.4% (95% CI: 1.4-3.6) among baseline cytology-negative women (risk difference: 0.71% [95% CI: 0.16-1.4]). In conclusion, a negative FAM19A4/mir124-2 methylation test provides a low cervical cancer risk in HPV-positive women of 30 years and older. FAM19A4/mir124-2 methylation testing merits consideration as an objective triage test in HPV-based cervical screening programs.

U2 - 10.1002/ijc.31539

DO - 10.1002/ijc.31539

M3 - Article

VL - 143

SP - 1541

EP - 1548

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 6

ER -