在HPV阳性女性中，比较自我样本与宫颈刮片的FAM19A4甲基化分析以检测宫颈（癌前）病变。
FAM19A4 methylation analysis in self-samples compared with cervical scrapes for detecting cervical (pre)cancer in HPV-positive women.
作者信息
Luttmer Roosmarijn, De Strooper Lise M A, Dijkstra Maaike G, Berkhof Johannes, Snijders Peter J F, Steenbergen Renske D M, van Kemenade Folkert J, Rozendaal Lawrence, Helmerhorst Theo J M, Verheijen René H M, Ter Harmsel W Abraham, van Baal W Marchien, Graziosi Peppino G C M, Quint Wim G V, Spruijt Johan W M, van Dijken Dorenda K E, Heideman Daniëlle A M, Meijer Chris J L M
机构信息
Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Department of Obstetrics and Gynaecology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
出版信息
Br J Cancer. 2016 Aug 23;115(5):579-87. doi: 10.1038/bjc.2016.200. Epub 2016 Jul 14.
BACKGROUND
High-risk human papillomavirus (hrHPV)-positive women require triage to identify those with cervical high-grade intraepithelial neoplasia and cancer (⩾CIN3 (cervical intraepithelial neoplasia grade 3)). FAM19A4 methylation analysis, which detects advanced CIN and cancer, is applicable to different sample types. However, studies comparing the performance of FAM19A4 methylation analysis in hrHPV-positive self-samples and paired physician-taken scrapes are lacking.
METHODS
We compared the performance of FAM19A4 methylation analysis (and/or HPV16/18 genotyping) in self-samples and paired physician-taken scrapes for ⩾CIN3 detection in hrHPV-positive women (n=450,18-66 years).
RESULTS
Overall FAM19A4 methylation levels between sample types were significantly correlated, with strongest correlation in women with ⩾CIN3 (Spearman's ρ 0.697, P<0.001). The performance of FAM19A4 methylation analysis and/or HPV16/18 genotyping did not differ significantly between sample types. In women ⩾30 years, ⩾CIN3 sensitivity of FAM19A4 methylation analysis was 78.4% in self-samples and 88.2% in scrapes (ratio 0.89; CI: 0.75-1.05). In women <30 years, ⩾CIN3 sensitivities were 37.5% and 45.8%, respectively (ratio 0.82; CI: 0.55-1.21). In both groups, ⩾CIN3 specificity of FAM19A4 methylation analysis was significantly higher in self-samples compared with scrapes.
CONCLUSIONS
FAM19A4 methylation analysis in hrHPV-positive self-samples had a slightly lower sensitivity and a higher specificity for ⩾CIN3 compared with paired physician-taken scrapes. With a similarly good clinical performance in both sample types, combined FAM19A4 methylation analysis and HPV16/18 genotyping provides a feasible triage strategy for hrHPV-positive women, with direct applicability on self-samples.
背景
高危型人乳头瘤病毒（hrHPV）阳性女性需要进行分流，以识别那些患有宫颈高级别上皮内瘤变和癌症（≥CIN3，即宫颈上皮内瘤变3级）的患者。FAM19A4甲基化分析可检测高级别CIN和癌症，适用于不同的样本类型。然而，缺乏比较FAM19A4甲基化分析在hrHPV阳性自我采集样本和医生采集的配对刮片样本中性能的研究。
方法
我们比较了FAM19A4甲基化分析（和/或HPV16/18基因分型）在自我采集样本和医生采集的配对刮片样本中对hrHPV阳性女性（n = 450，年龄18 - 66岁）≥CIN3检测的性能。
结果
不同样本类型之间的总体FAM19A4甲基化水平显著相关，在≥CIN3的女性中相关性最强（斯皮尔曼ρ系数为0.697，P < 0.001）。FAM19A4甲基化分析和/或HPV16/18基因分型在不同样本类型中的性能没有显著差异。在30岁及以上的女性中，FAM19A4甲基化分析对≥CIN3的敏感性在自我采集样本中为78.4%，在刮片样本中为88.2%（比值为0.89；CI：0.75 - 1.05）。在30岁以下的女性中，≥CIN3的敏感性分别为37.5%和45.8%（比值为0.82；CI：0.55 - 1.21）。在两组中，FAM19A4甲基化分析对≥CIN3的特异性在自我采集样本中均显著高于刮片样本。
结论
与医生采集的配对刮片样本相比，hrHPV阳性自我采集样本中的FAM19A4甲基化分析对≥CIN3的敏感性略低，特异性更高。由于两种样本类型的临床性能同样良好，则FAM19A4甲基化分析与HPV16/18基因分型相结合，为hrHPV阳性女性提供了一种可行的分流策略，且可直接应用于自我采集样本。
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