Background: In the context of primary HPV cervical cancer screening, the identification of minor screening abnormalities necessitates triage tests to optimize management and mitigate overtreatment. Currently, reflex cytology and reflex p16/Ki67 dual-stain (DS) are under scrutiny for their applicability in primary HPV-based screening. However, there remains a dearth of comprehensive data for comparing their performance. Methods: Among 30,066 results from liquid-based cervical cancer screening tests, a cohort of 332 cases was meticulously selected based on available high-risk human papillomavirus (HPV) test results, limited genotyping for HPV 16 and 18, liquid-based cytology, DS, and histology outcomes from standardized colposcopy with biopsy. For cases positive for 12 other high-risk HPV genotypes, three retrospective triage approaches were analyzed. We computed the positive predictive value (PPV) for the detection of high-grade squamous intraepithelial lesions or worse (HSIL+). Results: Both triage models employing DS (reflex cytology followed by DS and reflex DS alone in all cases) exhibited significantly higher PPV for HSIL+ compared to the strategy with reflex cytology alone (35.9%/33.3% vs. 18.8%;p< 0.0001). Additionally, these DS-based models showed higher negative predictive values (NPV) (100%/96.2% vs. 69.2%;p= 0.0024/0.0079). In the DS-inclusive models, fewer colposcopies were necessitated (103/102 vs. 154), and fewer cases of HSIL+ were overlooked (0/3 vs. 8). Conclusions: Our findings suggest that p16/Ki67 dual-stain, either as a standalone or combined triage test, holds promise for the effective detection of HSIL+ in patients with minor screening abnormalities in primary HPV-based cervical cancer screening.
背景：在基于HPV的宫颈癌初筛中，针对轻微筛查异常结果的分流检测对于优化管理、避免过度治疗至关重要。目前，反射性细胞学检测和反射性p16/Ki67双染检测在HPV初筛中的应用价值正受到关注，但尚缺乏全面比较二者性能的数据。方法：从30,066例液基宫颈癌筛查结果中，我们根据高危型人乳头瘤病毒检测结果、HPV 16/18有限基因分型、液基细胞学、双染检测以及标准化阴道镜活检组织学结果，严格筛选出332例病例。针对其他12种高危HPV基因型阳性病例，我们分析了三种回顾性分流策略，并计算了其对高级别鳞状上皮内病变及以上病变的阳性预测值。结果：与单独采用反射性细胞学分流的策略相比，两种包含双染检测的分流模型在所有病例中采用反射性细胞学后接双染检测或单独采用反射性双染检测均显示出显著更高的高级别病变阳性预测值，同时这些基于双染的模型也表现出更高的阴性预测值。在包含双染的模型中，所需阴道镜检查数量更少，且漏诊的高级别病变病例更少。结论：我们的研究结果表明，在基于HPV的宫颈癌初筛出现轻微异常的患者中，p16/Ki67双染检测无论是作为独立还是联合分流检测，在有效检出高级别病变方面均展现出良好前景。
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