TY - JOUR
T1 - Methylation markers FAM19A4 and miR124-2 as triage strategy for primary human papillomavirus screen positive women
T2 - A large European multicenter study
AU - Bonde, Jesper
AU - Floore, Arno
AU - Ejegod, Ditte
AU - Vink, Frederique J
AU - Hesselink, Albertus
AU - van de Ven, Peter M
AU - Oštrbenk Valenčak, Anja
AU - Pedersen, Helle
AU - Doorn, Saskia
AU - Quint, Wim G
AU - Petry, K Ulrich
AU - Poljak, Mario
AU - Stanczuk, Grazyna
AU - Cuschieri, Kate
AU - de Sanjosé, Silvia
AU - Bleeker, Maaike
AU - Berkhof, Johannes
AU - Meijer, Chris J L M
AU - Heideman, Daniëlle A M
AU - Alcaniz, Elia
AU - Rothe, Beate
AU - Hortal, Montserrat Torres
AU - Del Pino, Marta
AU - Bhatia, Ramya
N1 - © 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.
PY - 2021/1/15
Y1 - 2021/1/15
N2 - In human papillomavirus (HPV) cervical cancer screening, cytology is used as triage to counter the low specificity of HPV testing. VALID-SCREEN is a EU-multicenter, retrospective study conducted to evaluate the clinical performance of the FAM19A4/miR124-2 methylation-based molecular triage test as a substitute or addition to cytology as reflex testing of HPV screen positive women. FAM19A4/miR124-2 methylation test (QIAsure Methylation Test) was evaluated in 2384 HPV-positive cervical screening samples, from women 29-76 years of age, derived from four EU countries. Specimens were collected in ThinPrep or SurePath media, HPV-status, concurrent cytology, and histology diagnosis were provided by the parent institutes. The control population consisted of women with no evidence of disease within 2 years of follow-up. A total of 899 histologies were retrieved; 527 showed no disease, 124 CIN2 (5.2%), 228 CIN3 (9.6%) and 20 cervical cancers (0.8%); 19 of 20 screen-detected cervical cancers were found methylation-positive (sensitivity 95%). Overall specificity of FAM19A4/miR124-2 methylation test was 78.3% (n = 2013; 95%CI: 76-80). The negative predictive value of hrHPV positive, methylation-negative outcomes were 99.9% for cervical cancer (N = 1694; 95%CI: 99.6-99.99), 96.9% for ≥CIN3 (95%CI: 96-98), and 93.0% for ≥CIN2 (95%CI: 92-94). Overall sensitivity for CIN3 using FAM19A4/miR124-2 methylation test was 77% (n = 228; 95%CI: 71-82). CIN3 sensitivity was uniform between centers independent of sample collection medias, DNA extraction methods and HPV screening tests. Being objectively reported compared to the subjectivity of cytology, equally performing across settings and screening methods, the FAM19A4/miR124-2 methylation constitute an alternative/supplement to cytology as triage method to be investigated in real-life pilot implementation.
AB - In human papillomavirus (HPV) cervical cancer screening, cytology is used as triage to counter the low specificity of HPV testing. VALID-SCREEN is a EU-multicenter, retrospective study conducted to evaluate the clinical performance of the FAM19A4/miR124-2 methylation-based molecular triage test as a substitute or addition to cytology as reflex testing of HPV screen positive women. FAM19A4/miR124-2 methylation test (QIAsure Methylation Test) was evaluated in 2384 HPV-positive cervical screening samples, from women 29-76 years of age, derived from four EU countries. Specimens were collected in ThinPrep or SurePath media, HPV-status, concurrent cytology, and histology diagnosis were provided by the parent institutes. The control population consisted of women with no evidence of disease within 2 years of follow-up. A total of 899 histologies were retrieved; 527 showed no disease, 124 CIN2 (5.2%), 228 CIN3 (9.6%) and 20 cervical cancers (0.8%); 19 of 20 screen-detected cervical cancers were found methylation-positive (sensitivity 95%). Overall specificity of FAM19A4/miR124-2 methylation test was 78.3% (n = 2013; 95%CI: 76-80). The negative predictive value of hrHPV positive, methylation-negative outcomes were 99.9% for cervical cancer (N = 1694; 95%CI: 99.6-99.99), 96.9% for ≥CIN3 (95%CI: 96-98), and 93.0% for ≥CIN2 (95%CI: 92-94). Overall sensitivity for CIN3 using FAM19A4/miR124-2 methylation test was 77% (n = 228; 95%CI: 71-82). CIN3 sensitivity was uniform between centers independent of sample collection medias, DNA extraction methods and HPV screening tests. Being objectively reported compared to the subjectivity of cytology, equally performing across settings and screening methods, the FAM19A4/miR124-2 methylation constitute an alternative/supplement to cytology as triage method to be investigated in real-life pilot implementation.
KW - biomarker
KW - cervical carcinoma
KW - cervical screening
KW - DNA hypermethylation
KW - human genome methylation
KW - human papillomavirus
UR - http://www.scopus.com/inward/record.url?scp=85092905660&partnerID=8YFLogxK
U2 - 10.1002/ijc.33320
DO - 10.1002/ijc.33320
M3 - Journal article
C2 - 32997803
VL - 148
SP - 396
EP - 405
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
M1 - 33320
ER -