Comparing the performance of FAM19A4 methylation analysis, cytology and HPV16/18 genotyping for the detection of cervical (pre)cancer in high-risk HPV-positive women of a gynecologic outpatient population (COMETH study).

Autor: Luttmer R; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., De Strooper LM; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Berkhof J; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands., Snijders PJ; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Dijkstra MG; Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands., Uijterwaal MH; Department of Obstetrics and Gynecology, Flevo Hospital, Almere, The Netherlands., Steenbergen RD; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., van Kemenade FJ; Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands., Rozendaal L; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Helmerhorst TJ; Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Verheijen RH; Department of Obstetrics and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands., Ter Harmsel WA; Department of Gynecology, Roosevelt Clinic, Leiden, The Netherlands., Van Baal WM; Department of Obstetrics and Gynecology, Flevo Hospital, Almere, The Netherlands., Graziosi PG; Department of Obstetrics and Gynecology, Sint Antonius Hospital, Nieuwegein, The Netherlands., Quint WG; DDL Diagnostic Laboratory, Rijswijk, The Netherlands., Heideman DA; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Meijer CJ; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2016 Feb 15; Vol. 138 (4), pp. 992-1002. Date of Electronic Publication: 2015 Sep 14.
DOI: 10.1002/ijc.29824
Abstrakt: Recently, DNA methylation analysis of FAM19A4 in cervical scrapes has been shown to adequately detect high-grade cervical intraepithelial neoplasia and cervical cancer (≥ CIN3) in high-risk HPV (hrHPV)-positive women. Here, we compared the clinical performance of FAM19A4 methylation analysis to cytology and HPV16/18 genotyping, separately and in combination, for ≥ CIN3 detection in hrHPV-positive women participating in a prospective observational multi-center cohort study. The study population comprised hrHPV-positive women aged 18-66 years, visiting a gynecological outpatient clinic. From these women, cervical scrapes and colposcopy-directed biopsies (for histological confirmation) were obtained. Cervical scrapes were analyzed for FAM19A4 gene promoter methylation, cytology and HPV16/18 genotyping. Methylation analysis was performed by quantitative methylation-specific PCR (qMSP). Sensitivities and specificities for ≥ CIN3 were compared between tests. Stratified analyses were performed for variables that potentially influence marker performance. Of all 508 hrHPV-positive women, the sensitivities for ≥ CIN3 of cytology, FAM19A4 methylation analysis, and cytology combined with HPV16/18 genotyping were 85.6, 75.6 and 92.2%, respectively, with corresponding specificities of 49.8, 71.1 and 29.4%, respectively. Both sensitivity and specificity of FAM19A4 methylation analysis were associated with age (p ≤ 0.001 each). In women ≥ 30 years (n = 287), ≥ CIN3 sensitivity of FAM19A4 methylation analysis was 88.3% (95%CI: 80.2-96.5) which was noninferior to that of cytology [85.5% (95%CI: 76.0-94.0)], at a significantly higher specificity [62.1% (95%CI: 55.8-68.4) compared to 47.6% (95%CI: 41.1-54.1)]. In conclusion, among hrHPV-positive women from an outpatient population aged ≥ 30 years, methylation analysis of FAM19A4 is an attractive marker for the identification of women with ≥ CIN3.
(© 2015 UICC.)
Databáze: MEDLINE
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