A DNA methylation classifier of cervical precancer based on human papillomavirus and human genes.
A DNA methylation classifier of cervical precancer based on human papillomavirus and human genes.
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DOI：
10.1002/ijc.28790
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发表时间：
2014-09-15
影响因子：
6.4
通讯作者：
Lorincz, Attila T.
中科院分区：
文献类型：
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作者：
Brentnall, Adam R.;Vasiljevic, Natasa;Scibior-Bentkowska, Dorota;Cadman, Louise;Austin, Janet;Szarewski, Anne;Cuzick, Jack;Lorincz, Attila T.
关键词：
高危型人乳头瘤病毒（HPV）检测作为高级别宫颈上皮内瘤样病变（CIN 2/3）的筛查试验是高度敏感的，CIN 2/3是宫颈癌的前兆。然而，它具有相对较低的特异性。我们的目标是使用人类和HPV DNA甲基化的组合来开发具有更高特异性的预测规则。通过焦磷酸测序分析了来自伦敦阴道镜转诊队列的脱落宫颈标本中HPV 16、HPV 18、HPV 31的L1和L2区域以及人类基因EPB 41 L3、DPYS和ML的DNA甲基化水平。HPV 16阳性556例（CIN 2/3），HPV 18阳性201例（CIN 2/3），HPV 31阳性202例（CIN 2/3）。预测规则包括EPB 41 L3和HPV，曲线下面积为0.80（95%CI 0.78-0.82）。对于90%的灵敏度，特异性为36%（33-40），阳性预测值（PPV）为46%（43-48）。按HPV分型，90%的敏感性分别对应于以下特异性和PPV：HPV 16，38%（32-45）和67%（63-71）; HPV 18，53%（45-62）和52%（45-59）; HPV 31，39%（31-49）和58%（51-65）; HPV 16、18或31型，44%（40-49）和62%（59-65），其他hrHPV 17%（14-21）和21%（18-24）。我们的结论是，甲基化检测hrHPV阳性的妇女可能会改善PPV的敏感性损失最小。
Testing for high-risk (hr) types of human papillomavirus (HPV) is highly sensitive as a screening test of high-grade cervical intraepithelial neoplastic (CIN2/3) disease, the precursor of cervical cancer. However, it has a relatively low specificity. Our objective was to develop a prediction rule with a higher specificity, using combinations of human and HPV DNA methylation. Exfoliated cervical specimens from colposcopy-referral cohorts in London were analyzed for DNA methylation levels by pyrosequencing in the L1 and L2 regions of HPV16, HPV18, HPV31 and human genes EPB41L3, DPYS and MAL. Samples from 1,493 hrHPV-positive women were assessed and of these 556 were found to have CIN2/3 at biopsy; 556 tested positive for HPV16 (323 CIN2/3), 201 for HPV18 (73 CIN2/3) and 202 for HPV31 (98 CIN2/3). The prediction rule included EPB41L3 and HPV and had area under curve 0.80 (95% CI 0.78–0.82). For 90% sensitivity, specificity was 36% (33–40) and positive predictive value (PPV) was 46% (43–48). By HPV type, 90% sensitivity corresponded to the following specificities and PPV, respectively: HPV16, 38% (32–45) and 67% (63–71); HPV18, 53% (45–62) and 52% (45–59); HPV31, 39% (31–49) and 58% (51–65); HPV16, 18 or 31, 44% (40–49) and 62% (59–65) and other hrHPV 17% (14–21) and 21% (18–24). We conclude that a methylation assay in hrHPV-positive women might improve PPV with minimal sensitivity loss.
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影响因子：
3.8
作者：
Szarewski, Anne;Ambroisine, Laurence;Cuzick, Jack
通讯作者：
Cuzick, Jack
影响因子：
6.4
作者：
Lorincz, Attila T.;Brentnall, Adam R.;Vasiljevic, Natasa;Scibior-Bentkowska, Dorota;Castanon, Alejandra;Fiander, Alison;Powell, Ned;Tristram, Amanda;Cuzick, Jack;Sasieni, Peter
通讯作者：
Sasieni, Peter
影响因子：
6.4
作者：
Overmeer, Renee M.;Louwers, Jacqueline A.;Steenbergen, Renske D. M.
通讯作者：
Steenbergen, Renske D. M.
影响因子：
--
作者：
Vasiljević N;Wu K;Brentnall AR;Kim DC;Thorat MA;Kudahetti SC;Mao X;Xue L;Yu Y;Shaw GL;Beltran L;Lu YJ;Berney DM;Cuzick J;Lorincz AT
通讯作者：
Lorincz AT
四基因甲基化标记物组作为高危人乳头瘤病毒阳性患者的分类测试
影响因子：
6.4
作者：
Eijsink, J. J. H.;Lendvai, A.;Wisman, G. B. A.
通讯作者：
Wisman, G. B. A.