HPV16 L1 and L2 DNA methylation predicts high-grade cervical intraepithelial neoplasia in women with mildly abnormal cervical cytology.
HPV16 L1 and L2 DNA methylation predicts high-grade cervical intraepithelial neoplasia in women with mildly abnormal cervical cytology.
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DOI：
10.1002/ijc.28050
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发表时间：
2013-08-01
影响因子：
6.4
通讯作者：
Sasieni, Peter
中科院分区：
文献类型：
--
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
人乳头瘤病毒16型（HPV 16）DNA中的DNA甲基化变化很常见，对于识别宫颈癌风险增加的女性可能很重要。利用最近发表的来自哥斯达黎加的数据，我们开发了一种分类评分，以区分患有宫颈上皮内瘤变2级或3级（CIN 2/3）的妇女与没有明显高级别病变的妇女。在这里，我们的目标是调查的成绩使用来自英国的数据。对84名妇女进行基线和6个月随访时的宫颈脱落细胞进行分析，这些妇女是从一项随机临床试验中选出的，这些妇女正在接受低级别细胞学监测。甲基化研究的女性选择是基于基线样本中可检测到的HPV 16。在实验室人员对临床数据设盲的情况下，将纯化的DNA在病毒基因组中的选定CpG位点（URR、E6、L1和L2）进行亚硫酸氢盐转化、扩增和焦磷酸测序。主要测量是结合L1中的平均甲基化和L2中的任何甲基化的预定义评分。在第二次随访时，73/84（87%）名妇女为HPV 16阳性，其中25人的组织病理学诊断为CIN 2/3。评分与CIN 2/3显著相关（曲线下面积= 0.74，p = 0.002）。对于92%敏感性的临界值，40%（95% CI 27-54%）的HPV 16阳性且无CIN 2/3的女性可以避免阴道镜检查;阳性预测值为44%（32-58%），阴性预测值为90%（71-97%）。我们的结论是，定量DNA甲基化检测可能有助于改善HPV 16阳性妇女的分诊。
DNA methylation changes in human papillomavirus type 16 (HPV16) DNA are common and might be important for identifying women at increased risk of cervical cancer. Using recently published data from Costa Rica we developed a classification score to differentiate women with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) from those with no evident high-grade lesions. Here, we aim to investigate the performance of the score using data from the UK. Exfoliated cervical cells at baseline and 6-months follow-up were analyzed in 84 women selected from a randomized clinical trial of women undergoing surveillance for low-grade cytology. Selection of women for the methylation study was based on detectable HPV16 in the baseline sample. Purified DNA was bisulfite converted, amplified and pyrosequenced at selected CpG sites in the viral genome (URR, E6, L1 and L2), with blinding of laboratory personnel to the clinical data. The primary measure was a predefined score combining the mean methylation in L1 and any methylation in L2. At the second follow-up visit, 73/84 (87%) women were HPV16 positive and of these 25 had a histopathological diagnosis of CIN2/3. The score was significantly associated with CIN2/3 (area under curve = 0.74, p = 0.002). For a cutoff with 92% sensitivity, colposcopy could have been avoided in 40% (95% CI 27–54%) of HPV16 positive women without CIN2/3; positive predictive value was 44% (32–58%) and negative predictive value was 90% (71–97%). We conclude that quantitative DNA methylation assays could help to improve triage among HPV16 positive women.
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