Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Methodology, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
Cancer Epidemiol Biomarkers Prev. 2024 Aug 1;33(8):1037-1045. doi: 10.1158/1055-9965.EPI-24-0046.
High-risk human papillomavirus (hrHPV)-based cervical cancer screening in the Netherlands led to a substantial increase in number of colposcopy referrals and low-grade lesions detected. Genotyping strategies may be employed to lower the screening-related burden.
We evaluated 14 triage strategies with genotyping (HPV16/18 or HPV16/18/31/33/45/52/58) for hrHPV-positive borderlineormilddyskaryosis (BMD)ornormal cytology,usingdata from a population-based hrHPV-based screening trial with 5-year interval (POBASCAM). We considered colposcopy referral at baseline, after 6-month repeat cytology and after 5-year hrHPV testing. Performance was evaluated by one-round positive and negative predictive value (PPVandNPV) for CIN3+ and by two-roundcolposcopy referral rate. To identify efficient strategies, they were ordered by the one-round colposcopy referral rate. Adjacent strategies were compared by the marginal PPV for detecting one additional CIN3+ (mPPV).
The most conservative strategy (repeat cytology after BMD and HPV16/18/31/33/45/52/58-positive normal cytology, next round otherwise) yielded an mPPV of 28%, NPV of 98.2%, and two-round colposcopy referral rate of 47.2%. Adding direct referral after BMD or genotype-positive BMD yielded an mPPV ≤ 8.2%, NPV ≥ 98.5% and an increase in colposcopy referral rate of 1.9% to 6.5%. Adding direct referral after HPV16/18-positive normal cytology yielded an mPPV ≤ 3.5%, NPV ≥ 99.5% and an increase in colposcopy referral rate of 13.9%.
Direct colposcopy referral of women with BMD or normal cytology is unlikely to be efficient, but genotype-guided direct referral after BMD may be considered because the increase in colposcopies is limited.
hrHPV screening programs can become very efficient when immediate colposcopy referral is limited to women at highest CIN3+ risk. See related In the Spotlight, p. 979.
荷兰基于高危型人乳头瘤病毒（hrHPV）的宫颈癌筛查导致大量阴道镜转诊和低度病变的检出。基因分型策略可能被用于降低筛查相关的负担。
我们使用基于人群的hrHPV 筛查试验（POBASCAM）的数据，评估了 14 种基于基因分型（HPV16/18 或 HPV16/18/31/33/45/52/58）的用于 hrHPV 阳性边界型或轻度不典型鳞状上皮细胞（BMD）或正常细胞学的分流策略。我们考虑了基线时、6 个月重复细胞学检查和 5 年 hrHPV 检测后的阴道镜转诊。通过对 CIN3+的一轮阳性和阴性预测值（PPV 和 NPV）和两轮阴道镜转诊率来评估性能。通过一轮阴道镜转诊率对这些策略进行排序，以确定有效的策略。通过检测额外一个 CIN3+的边缘 PPV（mPPV）来比较相邻策略。
最保守的策略（BMD 后重复细胞学检查和 HPV16/18/31/33/45/52/58 阳性正常细胞学检查，否则进行下一轮检查）的 mPPV 为 28%，NPV 为 98.2%，两轮阴道镜转诊率为 47.2%。在 BMD 或基因型阳性 BMD 后直接转诊的策略 mPPV≤8.2%，NPV≥98.5%，阴道镜转诊率增加 1.9%至 6.5%。在 HPV16/18 阳性正常细胞学检查后直接转诊的策略 mPPV≤3.5%，NPV≥99.5%，阴道镜转诊率增加 13.9%。
BMD 或正常细胞学检查的妇女直接阴道镜转诊不太可能有效，但可以考虑在 BMD 后进行基于基因分型的直接转诊，因为阴道镜检查的增加是有限的。
当立即进行阴道镜转诊仅限于 CIN3+风险最高的妇女时，高危型人乳头瘤病毒（hrHPV）筛查计划可以变得非常有效。参见相关的“聚光灯下”，第 979 页。
