Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
Int J Cancer. 2018 Jul 15;143(2):333-342. doi: 10.1002/ijc.31326. Epub 2018 Mar 9.
Human papilloma virus (HPV) testing is more sensitive but less specific than cytology. We evaluated stand-alone genotyping as a possible triage method. During a multicentre randomised controlled trial comparing HPV testing to conventional cytology, HPV-positive women were referred to colposcopy and followed up if no high-grade lesion was detected. HPV-positive samples were genotyped by GP5+/GP6+ primed polymerase chain reaction followed by reverse line blot. Genotypes were hierarchically ordered by positive predictive value (PPV) for CIN grade 2 or more (CIN2+), and grouped by cluster analysis into three groups (A, B and C in decreasing order). Receiver operating characteristic curves were computed. Among 2,255 HPV-positive women with genotyping, 239 CIN2+ (including 113 CIN3+) were detected at baseline or during a 3-year follow-up. HPV33 had the highest PPV with CIN2+ and CIN3+ as the endpoint and when considering lesions detected at baseline or also during follow-up. HPV16 and HPV35 were the second and third, respectively. Cross-sectional sensitivity for CIN2+ at baseline was 67.3% (95% CI 59.7-74.2), 91.8% (95% CI 86.6-95.5) and 94.7% (95% CI 90.2-97.6), respectively, when considering as "positive" any of the HPV types in group A (33, 16 and 35), A or B (31, 52, 18, 59 and 58) and A or B or C (39, 51, 56, 45 and 68). The corresponding cross-sectional PPVs for CIN2+ were 15.8% 95% (CI 13.2-18.7), 12.0% (95% CI 10.3-13.9) and 9.6% (95% CI 8.2-11.1), respectively. HPV33, 16 and 35 confer a high probability of CIN2+ but this rapidly decreases when adding other genotypes.
人乳头瘤病毒(HPV)检测的敏感性高于细胞学检查,但特异性较低。我们评估了单独的基因分型作为一种可能的分流方法。在一项比较 HPV 检测与传统细胞学的多中心随机对照试验中,HPV 阳性的女性被转诊行阴道镜检查,如果未发现高级别病变,则进行随访。HPV 阳性样本采用 GP5+/GP6+引物聚合酶链反应(PCR)进行基因分型,然后采用反向线印迹进行分析。根据对 2 级或更高级别宫颈上皮内瘤变(CIN2+)的阳性预测值(PPV),对基因型进行分层排序,并通过聚类分析分为三组(A、B 和 C,依次递减)。计算受试者工作特征曲线。在 2255 名 HPV 阳性且进行基因分型的女性中,基线时或随访 3 年内共发现 239 例 CIN2+(包括 113 例 CIN3+)。HPV33 对 CIN2+和 CIN3+的 PPV 最高,当考虑基线时或随访期间发现的病变时也是如此。HPV16 和 HPV35 分别位列第二和第三。基线时 CIN2+的横断敏感性分别为 67.3%(95%CI 59.7-74.2)、91.8%(95%CI 86.6-95.5)和 94.7%(95%CI 90.2-97.6),当考虑任何一种 A 组 HPV 类型(33、16 和 35)、A 组或 B 组(31、52、18、59 和 58)或 A 组、B 组或 C 组(39、51、56、45 和 68)为“阳性”时。相应的 CIN2+的横断 PPV 分别为 15.8%(95%CI 13.2-18.7)、12.0%(95%CI 10.3-13.9)和 9.6%(95%CI 8.2-11.1)。HPV33、16 和 35 预示着发生 CIN2+的可能性较高,但当加入其他基因型时,这种可能性迅速降低。