HPV33 DNA methylation measurement improves cervical pre-cancer risk estimation of an HPV16, HPV18, HPV31 and EPB41L3 methylation classifier
HPV33 DNA methylation measurement improves cervical pre-cancer risk estimation of an HPV16, HPV18, HPV31 and EPB41L3 methylation classifier
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DOI：
10.3233/cbm-150507
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发表时间：
2015-01-01
影响因子：
3.1
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;Lorincz, Attila T.
背景：持续感染高危人乳头瘤病毒（hrHPV）型可导致宫颈癌，但大多数检测呈阳性的妇女患宫颈癌的风险很低。需要一些策略，既能保持hrHPV检测的高灵敏度，又能减少假阳性的数量。我们之前的研究表明，结合HPV 16、18和31型和人类基因EPB41L3的DNA甲基化分类检测有助于识别高级别宫颈病变。目的：评估HPV 33型DNA甲基化检测是否能改善以往的分类方法。方法：伦敦阴道镜转诊组1493名妇女，其中556名（37%）有组织学证实的CIN（宫颈上皮内瘤变）2或3，其中包括114名HPV33阳性妇女，测量了3个L2 CpGs 5557、5560和5566的甲基化。通过将HPV33添加到先前的分类器中，对新分类器S5的识别性能进行了评估。结果：HPV33甲基化测量提高了HPV33阳性女性的预测。受试者工作特征分析显示，HPV33甲基化的曲线下面积（AUC）为0.68 （95% CI 0.57-0.78）。HPV33甲基化显著提高了早期风险评分（AUC = 0.82 vs 0.80; P < 0.001）。CIN2/3的灵敏度为90%，特异性为49% （95% CI 46-52%）。结论：HPV33 DNA甲基化检测可为EPB41L3与HPV16、HPV18、HPV31的诊断提供独立信息，且优于基因分型。其他HPV和人类甲基化靶区可能有助于进一步改善S5。
BACKGROUND: Persistent infection with high risk human papillomavirus (hrHPV) types causes cervical cancer but most women who test positive are at very low risk of neoplasia. Strategies are needed which can retain high sensitivity of hrHPV testing but reduce the number of false-positives. We showed previously that a combination DNA methylation triage assay for HPV types 16, 18 and 31 and human gene EPB41L3 was useful to identify high grade cervical lesions.OBJECTIVE: Assess whether measurement of DNA methylation in HPV type 33 can improve the previous classifier.METHODS: A London colposcopy referral group of 1493 women of whom 556 (37%) had histologically-confirmed CIN (cervical intraepithelial neoplasia) 2 or 3 that included 114 HPV33 positive women with methylation measured for three L2 CpGs 5557, 5560 and 5566. Discrimination performance was assessed for the new classifier S5, built by adding HPV33 to the earlier classifier.RESULTS: HPV33 methylation measurement improved prediction among HPV33 positive women. Receiver operating characteristic analyses showed an area under the curve (AUC) for HPV33 methylation of 0.68 (95% CI 0.57-0.78). The earlier risk score was significantly improved by HPV33 methytlation (AUC = 0.82 vs 0.80; P < 0.001). For 90% sensitivity the specificity for CIN2/3 was 49% (95% CI 46-52%).CONCLUSIONS: Measurement of HPV33 DNA methylation contributes independent diagnostic information to EPB41L3 and HPV16, HPV18 and HPV31, and is superior to genotyping. Other HPV and human methylation target regions might be useful to further improve S5.