ObjectiveTo compare the performance of cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for the triage of high‐risk HPV‐positive cervical samples.DesignRetrospective analyses of archival samples collected from a large‐scale prospective randomised controlled trial.Setting/SampleHPV‐positive women recruited from the general cervical screening population.Methods403 HPV‐positive samples including 113 normal, 173 low‐grade cervical intraepithelial neoplasia (LG‐CIN), 114 HG‐CIN and three cervical cancers. All samples were assessed by liquid‐based cytology, HPV genotyping and PAX1/SOX1 methylation.Main Outcome MeasuresAUC (area under the curve), sensitivity and specificity for cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for high‐grade (HG) premalignant cervical lesions.ResultsPAX1 was more sensitive than cytology and HPV16/18 genotyping in detecting a HG lesion (CIN2+). The sensitivity for PAX1, SOX1, cytology and HPV16/18 were 73.5% (95% CI: 65.5–81.5), 41.9% (95% CI: 32.9–50.8), 48.7% (95% CI: 39.7–57.8) and 36.8% (95% CI: 28.0–45.5), respectively, and their respective specificities were 70.3% (95% CI: 65.0–75.6), 83.6% (95% CI: 79.3–87.9), 77.6% (95% CI: 72.8–82.5) and 67.1% (95% CI: 61.7–72.6), respectively. Overall, PAX1 gave the best AUC at 0.72. Adding SOX1 to PAX1 did not improve the AUC (0.68). Three hundred and twenty‐two women who did not have a HG lesion at baseline were followed up for two rounds of screening. Fewer women developed a HG lesion with a normal baseline PAX1 compared to women with a normal baseline cytology or negative HPV16/18 (8.4% vs. 14.5% and 17.5%, respectively).ConclusionPAX1 triage for referral to colposcopy in HPV‐positive women may be superior to cytology and HPV16/18 genotyping.

中文翻译：

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PAX1/SOX1 DNA 甲基化与细胞学和 HPV16/18 基因分型在宫颈癌筛查中对高危 HPV 阳性女性进行分类：档案样本的回顾性分析


目的比较细胞学、HPV16/18 基因分型和 PAX1/SOX1 甲基化在高危 HPV 阳性宫颈样本分类中的表现。设计对从大规模前瞻性随机对照试验中收集的档案样本进行回顾性分析。设置/样本HPV 阳性从一般宫颈筛查人群中招募女性。方法 403 例 HPV 阳性样本，包括 113 例正常样本、173 例低度宫颈上皮内瘤样病变 (LG-CIN)、114 例 HG-CIN 和 3 例宫颈癌。所有样本均通过液基细胞学、HPV 基因分型和 PAX1/SOX1 甲基化进行评估。主要结果指标 AUC（曲线下面积）、细胞学的敏感性和特异性、HPV16/18 基因分型和高级别 (HG) 的 PAX1/SOX1 甲基化结果PAX1 在检测 HG 病变 (CIN2+) 方面比细胞学和 HPV16/18 基因分型更敏感。 PAX1、SOX1、细胞学和 HPV16/18 的敏感性分别为 73.5% (95% CI: 65.5–81.5)、41.9% (95% CI: 32.9–50.8)、48.7% (95% CI: 39.7–57.8) 和 36.8 %（95% CI：28.0-45.5），其特异性分别为 70.3%（95% CI：65.0-75.6）、83.6%（95% CI：79.3-87.9）、77.6%（95% CI：72.8） –82.5) 和 67.1% (95% CI: 61.7–72.6)。总体而言，PAX1 的 AUC 最好，为 0.72。将 SOX1 添加到 PAX1 并没有改善 AUC (0.68)。对基线时没有 HG 病变的 322 名女性进行了两轮筛查的随访。与基线细胞学正常或 HPV16/18 阴性的女性相比，基线 PAX1 正常且出现 HG 病变的女性较少（分别为 8.4% vs. 14.5% 和 17.5%）。优于细胞学和HPV16/18基因分型。