比较FAM19A4甲基化分析、细胞学检查和HPV16/18基因分型在妇科门诊高危HPV阳性女性中检测宫颈（癌前）病变的性能（COMETH研究）。
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).
作者信息
Luttmer Roosmarijn, De Strooper Lise M A, Berkhof Johannes, Snijders Peter J F, Dijkstra Maaike G, Uijterwaal Margot H, Steenbergen Renske D M, van Kemenade Folkert J, Rozendaal Lawrence, Helmerhorst Theo J M, Verheijen Rene H M, Ter Harmsel W Abraham, Van Baal W Marchien, Graziosi Peppino G C M, Quint Wim G V, Heideman Daniëlle A M, Meijer Chris J L M
机构信息
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
出版信息
Int J Cancer. 2016 Feb 15;138(4):992-1002. doi: 10.1002/ijc.29824. Epub 2015 Sep 14.
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.
最近的研究表明，对宫颈刮片进行FAM19A4的DNA甲基化分析能够充分检测出高危型人乳头瘤病毒（hrHPV）阳性女性中的高级别宫颈上皮内瘤变和宫颈癌（≥CIN3）。在此，我们在一项前瞻性观察性多中心队列研究中，比较了FAM19A4甲基化分析与细胞学检查以及HPV16/18基因分型单独及联合检测hrHPV阳性女性中≥CIN3的临床性能。研究人群包括年龄在18 - 66岁、前往妇科门诊就诊的hrHPV阳性女性。从这些女性中获取宫颈刮片和阴道镜引导下的活检组织（用于组织学确诊）。对宫颈刮片进行FAM19A4基因启动子甲基化、细胞学检查以及HPV16/18基因分型检测。甲基化分析采用定量甲基化特异性PCR（qMSP）方法。比较各检测方法对≥CIN3的敏感性和特异性。对可能影响标志物性能的变量进行分层分析。在所有508例hrHPV阳性女性中，细胞学检查、FAM19A4甲基化分析以及细胞学联合HPV16/18基因分型检测≥CIN3的敏感性分别为85.6%、75.6%和92.2%，相应的特异性分别为49.8%、71.1%和29.4%。FAM19A4甲基化分析的敏感性和特异性均与年龄相关（p值均≤0.001）。在年龄≥30岁的女性（n = 287）中，FAM19A4甲基化分析检测≥CIN3的敏感性为88.3%（95%CI：80.2 - 96.5），不低于细胞学检查的敏感性[85.5%（95%CI：76.0 - 94.0）]，而特异性显著更高[62.1%（95%CI：55.8 - 68.4）]，高于细胞学检查的特异性[47.6%（95%CI：41.1 - 54.1）]。总之，在年龄≥30岁的门诊hrHPV阳性女性中，FAM19A4甲基化分析是识别≥CIN3女性的一个有吸引力的标志物。
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