Validation of a DNA methylation HPV triage classifier in a screening sample
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- 作者：Attila T. Lorincz ; Adam R. Brentnall ; Dorota Scibior-Bentkowska ; Caroline Reuter ; Rawinder Banwait ; Louise Cadman ; Janet Austin ; Jack Cuzick and Natasa Vasiljević
- 关键词：HPV ; DNA methylation ; cervical cancer ; triage ; biomarkers
- 刊名：International Journal of Cancer
- 出版年：2016
- 出版时间：June 01 2016
- 年：2016
- 卷：138
- 期：11
- 页码：2745-2751
- 全文大小：328K
- ISSN：1097-0215
文摘
High-risk human papillomavirus (hrHPV) DNA tests have excellent sensitivity for detection of cervical intraepithelial neoplasia 2 or higher (CIN2+). A drawback of hrHPV screening, however, is modest specificity. Therefore, hrHPV-positive women might need triage to reduce adverse events and costs associated with unnecessary colposcopy. We compared the performance of HPV16/18 genotyping with a predefined DNA methylation triage test (S5) based on target regions of the human gene EPB41L3, and viral late gene regions of HPV16, HPV18, HPV31 and HPV33. Assays were run using exfoliated cervical specimens from 710 women attending routine screening, of whom 38 were diagnosed with CIN2+ within a year after triage to colposcopy based on cytology and 341 were hrHPV positive. Sensitivity and specificity of the investigated triage methods were compared by McNemar's test. At the predefined cutoff, S5 showed better sensitivity than HPV16/18 genotyping (74% vs 54%, P = 0.04) in identifying CIN2+ in hrHPV-positive women, and similar specificity (65% vs 71%, P = 0.07). When the S5 cutoff was altered to allow equal sensitivity to that of genotyping, a significantly higher specificity of 91% was reached (P < 0.0001). Thus, a DNA methylation test for the triage of hrHPV-positive women on original screening specimens might be a valid approach with better performance than genotyping.