TY - JOUR
T1 - Long-term CIN3+ risk of HPV positive women after triage with FAM19A4/miR124-2 methylation analysis
AU - Dick, Stèfanie
AU - Kremer, Wieke W
AU - De Strooper, Lise M A
AU - Lissenberg-Witte, Birgit I
AU - Steenbergen, Renske D M
AU - Meijer, Chris J L M
AU - Berkhof, Johannes
AU - Heideman, Daniëlle A M
N1 - Copyright © 2019 Elsevier Inc. All rights reserved.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - OBJECTIVE: This study evaluates the long-term risk for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among HPV positive women triaged with FAM19A4/miR124-2 methylation analysis.METHODS: In a post hoc analysis, data on FAM19A4/miR124-2 methylation, cytology, and HPV16/18 genotyping of HPV positive women (n = 1025) from a large population-based screening cohort with 14-year follow-up were evaluated. Cumulative CIN3+ incidences over 3 screening rounds (5-year intervals) of 4 triage strategies were compared: FAM19A4/miR124-2 methylation analysis, cytology, HPV16/18 genotyping with FAM19A4/miR124-2 methylation, and HPV16/18 genotyping with cytology.RESULTS: Kaplan-Meier estimates of 14-year cumulative CIN3+ incidence of HPV positive women with a negative methylation and a negative cytology triage test were comparable (16.3% and 15.6%, respectively). The cumulative CIN3+ incidence of methylation positive and cytology positive women were 39.8% and 46.5%, respectively. HPV16/18 genotyping with methylation and HPV16/18 genotyping with cytology resulted in the lowest 14-year cumulative CIN3+ incidence among triage negative women (10.7% and 10.0%, respectively), but cumulative CIN3+ incidence among triage positive women was lower (33.4% and 35.7%, respectively) compared with triage by methylation alone and cytology alone.CONCLUSIONS: Among HPV positive women of 30 years and older, a negative FAM19A4/miR124-2 methylation triage test provides a similar long-term CIN3+ risk compared with a negative cytology triage test. Because of their high CIN3+ risk, women with a positive methylation triage test could be referred for colposcopy. Therefore, FAM19A4/miR124-2 methylation analysis is a promising alternative to cytology for triage of HPV positive women.
AB - OBJECTIVE: This study evaluates the long-term risk for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among HPV positive women triaged with FAM19A4/miR124-2 methylation analysis.METHODS: In a post hoc analysis, data on FAM19A4/miR124-2 methylation, cytology, and HPV16/18 genotyping of HPV positive women (n = 1025) from a large population-based screening cohort with 14-year follow-up were evaluated. Cumulative CIN3+ incidences over 3 screening rounds (5-year intervals) of 4 triage strategies were compared: FAM19A4/miR124-2 methylation analysis, cytology, HPV16/18 genotyping with FAM19A4/miR124-2 methylation, and HPV16/18 genotyping with cytology.RESULTS: Kaplan-Meier estimates of 14-year cumulative CIN3+ incidence of HPV positive women with a negative methylation and a negative cytology triage test were comparable (16.3% and 15.6%, respectively). The cumulative CIN3+ incidence of methylation positive and cytology positive women were 39.8% and 46.5%, respectively. HPV16/18 genotyping with methylation and HPV16/18 genotyping with cytology resulted in the lowest 14-year cumulative CIN3+ incidence among triage negative women (10.7% and 10.0%, respectively), but cumulative CIN3+ incidence among triage positive women was lower (33.4% and 35.7%, respectively) compared with triage by methylation alone and cytology alone.CONCLUSIONS: Among HPV positive women of 30 years and older, a negative FAM19A4/miR124-2 methylation triage test provides a similar long-term CIN3+ risk compared with a negative cytology triage test. Because of their high CIN3+ risk, women with a positive methylation triage test could be referred for colposcopy. Therefore, FAM19A4/miR124-2 methylation analysis is a promising alternative to cytology for triage of HPV positive women.
KW - Cervical intraepithelial neoplasia
KW - Cervical screening
KW - Cytology
KW - DNA methylation
KW - Genotyping
KW - Human papillomavirus
UR - http://www.scopus.com/inward/record.url?scp=85066875764&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ygyno.2019.06.002
DO - https://doi.org/10.1016/j.ygyno.2019.06.002
M3 - Article
C2 - 31182225
SN - 0090-8258
VL - 154
SP - 368
EP - 373
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -