Authors' Affiliations: Departments of Pathology and Epidemiology and Biostatistics, VU University Medical Center; Department of Obstetrics and Gynaecology, St. Lukas Andreas Ziekenhuis, Amsterdam; Department of Pathology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; and Department of Pathology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Cancer Epidemiol Biomarkers Prev. 2014 Jan;23(1):55-63. doi: 10.1158/1055-9965.EPI-13-0173. Epub 2013 Jun 3.
High-risk human papillomavirus (hrHPV) testing has higher sensitivity but lower specificity than cytology for cervical (pre)-cancerous lesions. Therefore, triage of hrHPV-positive women is needed in cervical cancer screening.
A cohort of 1,100 hrHPV-positive women, from a population-based screening trial (POBASCAM: n = 44,938; 29-61 years), was used to evaluate 10 triage strategies, involving testing at baseline and six months with combinations of cytology, HPV16/18 genotyping, and/or repeat hrHPV testing. Clinical endpoint was cervical intraepithelial neoplasia grade 3 or worse (CIN3(+)) detected within four years; results were adjusted for women not attending repeat testing. A triage strategy was considered acceptable, when the probability of no CIN3(+) after negative triage (negative predictive value, NPV) was at least 98%, and the CIN3(+) risk after positive triage (positive predictive value, PPV) was at least 20%.
Triage at baseline with cytology only yielded an NPV of 94.3% [95% confidence interval (CI), 92.0-96.0] and a PPV of 39.7% (95% CI, 34.0-45.6). An increase in NPV, against a modest decrease in PPV, was obtained by triaging women with negative baseline cytology by repeat cytology (NPV 98.5% and PPV 34.0%) or by baseline HPV16/18 genotyping (NPV 98.8% and PPV 28.5%). The inclusion of both HPV16/18 genotyping at baseline and repeat cytology testing provided a high NPV (99.6%) and a moderately high PPV (25.6%).
Triaging hrHPV-positive women by cytology at baseline and after 6 to 12 months, possibly in combination with baseline HPV16/18 genotyping, seems acceptable for cervical cancer screening.
Implementable triage strategies are provided for primary hrHPV screening in an organized setting.
高危型人乳头瘤病毒（hrHPV）检测在宫颈癌前病变方面的敏感性高于细胞学检查，但特异性较低。因此，宫颈癌筛查中需要对 hrHPV 阳性女性进行分流。
使用来自基于人群的筛查试验（POBASCAM：n=44938；29-61 岁）的 1100 名 hrHPV 阳性女性队列，评估了 10 种分流策略，涉及基线和 6 个月时的检测，细胞学、HPV16/18 基因分型和/或重复 hrHPV 检测的组合。临床终点是在四年内检测到宫颈上皮内瘤变 3 级或更高级别（CIN3+）；结果根据未参加重复检测的女性进行了调整。当阴性分流后的无 CIN3+（阴性预测值，NPV）概率至少为 98%，阳性分流后的 CIN3+风险（阳性预测值，PPV）至少为 20%时，可认为分流策略是可接受的。
仅在基线时进行细胞学检查的分流，NPV 为 94.3%（95%CI，92.0-96.0），PPV 为 39.7%（95%CI，34.0-45.6）。通过对基线时细胞学检查阴性的女性进行重复细胞学检查（NPV 为 98.5%，PPV 为 34.0%）或基线时 HPV16/18 基因分型（NPV 为 98.8%，PPV 为 28.5%），NPV 略有增加，PPV 略有降低。在基线时同时进行 HPV16/18 基因分型和重复细胞学检查，可提供高 NPV（99.6%）和中高 PPV（25.6%）。
在有组织的环境中，通过基线时的细胞学检查和 6-12 个月后的细胞学检查，可能结合基线时的 HPV16/18 基因分型，对 hrHPV 阳性女性进行分流，似乎可用于宫颈癌筛查。
为有组织的 HPV 初筛提供了可行的分流策略。
