Gustinucci Daniela, Giorgi Rossi Paolo, Cesarini Elena, Broccolini Massimo, Bulletti Simonetta, Carlani Angela, D'angelo Valentina, D'amico Maria Rosaria, Di Dato Eugenio, Galeazzi Paola, Malaspina Morena, Martinelli Nadia, Spita Nicoletta, Tintori Beatrice, Giaimo Maria Donata, Passamonti Basilio
From Azienda USL Umbria 1 Perugia, Laboratorio Unico Di Screening, Perugia, Italy.
Servizio Interaziendale Di Epidemiologia, AUSL Reggio Emilia, Italy, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy,
Am J Clin Pathol. 2016 Jan;145(1):35-45. doi: 10.1093/ajcp/aqv019.
We measured the accuracy of p16(INK4a)-Ki67 (CINtec PLUS, Roche, Mannheim, Germany), and E6/E7mRNA (types 16/18/31/33/45 NucliSENS easyQ, bioMérieux, Boxtel, The Netherlands) as triage test, alone and combined with cytology.
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.
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 undetermined 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 p16INK4a-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.
The high sensitivity of combined strategies probably allows longer intervals in HPV-positive, triage-negative women.
我们测量了p16（INK4a）-Ki67（CINtec PLUS，德国罗氏公司，曼海姆）和E6/E7mRNA（16/18/31/33/45型NucliSENS easyQ，荷兰生物梅里埃公司，博克斯泰尔）作为分流检测单独使用以及与细胞学联合使用时的准确性。
在一项以人群为基础的筛查中招募了6272名女性，以HPV DNA作为初筛检测；396人呈阳性，并接受了细胞学和生物标志物检测。所有检测均在同一样本上进行。细胞学阳性的女性被转诊至阴道镜检查；细胞学阴性的女性被转诊至一年后的HPV复查。终点是基线或随访时的CIN2+。
对于意义不明确的非典型鳞状细胞（ASC-US）和高级别阈值的细胞学检查，敏感性分别为77.6%（95%置信区间（CI）65.3 - 86.7）和53.2%（95%CI：40.3 - 65.4），对于p16INK4a - Ki67和E6/E7mRNA，敏感性分别为87.6%（95%CI：75.7 - 93.6）和80.8%（95%CI：67.6 - 89.8）。对于ASC-US和高级别阈值的细胞学检查，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），对于p16（INK4a）- Ki67和E6/E7mRNA，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）。将高级别细胞学或生物标志物阳性的女性转诊至阴道镜检查的策略达到了接近100%的敏感性，同时阴道镜转诊率有适度增加。
联合策略的高敏感性可能允许HPV阳性、分流阴性的女性延长检查间隔时间。
