Use of Cytology, E6/E7 mRNA and p16INK4a-Ki-67 to Define the Management of Human Papillomavirus (HPV)-Positive Women in Cervical Cancer Screening
Use of Cytology, E6/E7 mRNA and p16INK4a-Ki-67 to Define the Management of Human Papillomavirus (HPV)-Positive Women in Cervical Cancer Screening
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DOI：
10.1093/ajcp/aqv019
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发表时间：
2016-01-01
影响因子：
3.5
通讯作者：
Passamonti, Basilio
中科院分区：
文献类型：
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作者：
Gustinucci, Daniela;Rossi, Paolo Giorgi;Passamonti, Basilio
目的：我们检测了p16（INK 4a）-Ki 67的准确性，（CINtec PLUS，Roche，曼海姆，德国）和E6/E7 mRNA（类型16/18/31/33/45 NucliSENS easyQ，bioMerieux，博克斯特尔，荷兰）作为分类检测，单独和与细胞学联合。396例为阳性，并进行了细胞学和生物标志物检测。所有试验均在同一样品上进行。细胞学阳性的妇女被称为阴道镜检查;细胞学阴性的妇女被称为一年的HPV复检。结果：敏感性为77.6%（95%置信区间（CI）65.3-86.7）和53.2%在细胞学上，不典型鳞状细胞的显著性（ASC-US）和高级别阈值（95%CI：40.3-65.4），p16（INK 4a）-Ki 67和E6/E7 mRNA的阳性率分别为80.8%（95%CI：75.7-93.6）和80.8%（95%CI：67.6-89.8）。ASC-US和高分级阈值细胞学检查的阴道镜转诊率分别为36%（95%CI：31.2-40.9）和11.2%（95%CI：7.8-14.1），p16（INK 4a）-Ki 67和E6/E7 mRNA的阴道镜转诊率分别为36.0%（95%CI：29.9-29.6）和47.5%（95%CI：32.5-42.4）。策略指高级别细胞学或生物标志物阳性的妇女阴道镜检查达到敏感性接近100%，适度增加阴道镜referreration.Conclusions：高敏感性的联合策略可能允许更长的时间间隔HPV阳性，分流阴性的妇女。
Objectives: We measured the accuracy of p16(INK4a)-Ki67 (CINtec PLUS, Roche, Mannheim, Germany), and E6/E7mRNA (types 16/18/31/33/45 NucliSENS easyQ, bioMerieux, Boxtel, The Netherlands) as triage test, alone and combined with cytology.Methods: Six thousand two hundred and seventy two women were recruited in a population-based screening using HPV DNA as primary test; 396 were positive and were tested for cytology and biomarkers. All tests were performed on the same sample. Cytology-positive women were referred to colposcopy; cytology-negative women were referred to one-year HPV re-testing. The endpoint was CIN2+ at baseline or follow up.Results: Sensitivity was 77.6% (95% confidence interval (CI) 65.3-86.7) and 53.2% (95%CI: 40.3-65.4) for cytology at atypical squamous cells of udetermined significance (ASC-US) and high-grade threshold, and 87.6% (95%CI:75.7-93.6), and 80.8% (95%CI: 67.6-89.8) for p16(INK4a)-Ki67, and E6/E7mRNA, respectively. Colposcopy referral was 36% (95%CI: 31.2-40.9) and 11.2% (95%CI: 7.8-14.1) for cytology at ASC-US and high-grade threshold, respectively, and 36.0% (95%CI: 29.9-29.6), and 47.5% (95%CI: 32.5-42.4) for p16(INK4a)-Ki67, and E6/E7mRNA, respectively. Strategies referring high-grade cytology or biomarker positive women to colposcopy reached sensitivity close to 100%, with modest increase in colposcopy referral.Conclusions: The high sensitivity of combined strategies probably allows longer intervals in HPV-positive, triage negative women.