Human papillomavirus (HPV) testing is very sensitive for primary cervical screening but has low specificity. Triage tests that improve specificity but maintain high sensitivity are needed. Women enrolled in the experimental arm of Phase 2 of the New Technologies for Cervical Cancer randomized controlled cervical screening trial were tested for high‐risk HPV (hrHPV) and referred to colposcopy if positive. hrHPV‐positive women also had HPV genotyping (by polymerase chain reaction with GP5+/GP6+ primers and reverse line blotting), immunostaining for p16 overexpression and cytology. We computed sensitivity, specificity and positive predictive value (PPV) for different combinations of tests and determined potential hierarchical ordering of triage tests. A number of 1,091 HPV‐positive women had valid tests for cytology, p16 and genotyping. Ninety‐two of them had cervical intraepithelial neoplasia grade 2+ (CIN2+) histology and 40 of them had CIN grade 3+ (CIN3+) histology. The PPV for CIN2+ was >10% in hrHPV‐positive women with positive high‐grade squamous intraepithelial lesion (61.3%), positive low‐grade squamous intraepithelial lesion (LSIL+) (18.3%) and positive atypical squamous cells of undetermined significance (14.8%) cytology, p16 positive (16.7%) and, hierarchically, for infections by HPV33, 16, 35, 59, 31 and 52 (in decreasing order). Referral of women positive for either p16 or LSIL+ cytology had 97.8% sensitivity for CIN2+ and women negative for both of these had a 3‐year CIN3+ risk of 0.2%. Similar results were seen for women being either p16 or HPV16/33 positive. hrHPV‐positive women who were negative for p16 and cytology (LSIL threshold) had a very low CIN3+ rate in the following 3 years. Recalling them after that interval and referring those positive for either test to immediate colposcopy seem to be an efficient triage strategy. The same applies to p16 and HPV16.

中文翻译：

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结合使用细胞学、p16 免疫染色和基因分型，对初次筛查时高危人乳头瘤病毒呈阳性的女性进行分类。


人乳头瘤病毒 (HPV) 检测对于初级宫颈筛查非常敏感，但特异性较低。需要提高特异性但保持高灵敏度的分类测试。参加宫颈癌新技术随机对照宫颈筛查试验第 2 期实验组的女性接受了高危 HPV (hrHPV) 检测，如果呈阳性则转诊至阴道镜检查。 hrHPV 阳性女性还进行了 HPV 基因分型（通过使用 GP5+/GP6+ 引物的聚合酶链反应和反向线印迹）、p16 过度表达的免疫染色和细胞学检查。我们计算了不同测试组合的敏感性、特异性和阳性预测值 (PPV)，并确定了分类测试的潜在分层顺序。对 1,091 名 HPV 阳性女性进行了有效的细胞学、p16 和基因分型检测。其中 92 例具有宫颈上皮内瘤变 2+ 级 (CIN2+) 组织学，40 例具有 CIN 3+ 级 (CIN3+) 组织学。在具有高度鳞状上皮内病变阳性 (61.3%)、低度鳞状上皮内病变阳性 (LSIL+) (18.3%) 和意义未明的非典型鳞状细胞阳性 (14.8) 的 hrHPV 阳性女性中，CIN2+ 的 PPV > 10%。 %) 细胞学检查，p16 阳性 (16.7%)，按等级划分，HPV33、16、35、59、31 和 52 感染（按降序排列）。转诊 p16 或 LSIL+ 细胞学阳性的女性对 CIN2+ 的敏感性为 97.8%，而这两项均为阴性的女性的 3 年 CIN3+ 风险为 0.2%。 p16 或 HPV16/33 阳性的女性也出现类似的结果。 p16 和细胞学（LSIL 阈值）阴性的 hrHPV 阳性女性在接下来的 3 年内 CIN3+ 率非常低。 在此间隔后回忆它们并将那些测试呈阳性的人立即进行阴道镜检查似乎是一种有效的分类策略。这同样适用于 p16 和 HPV16。