背景:在原发性HPV宫颈癌筛查的背景下,识别轻微的筛查异常需要进行分诊测试,以优化管理并减轻过度治疗.目前,反射细胞学和反射p16/Ki67双重染色(DS)在基于HPV的初次筛查中的适用性正在接受审查.然而,仍然缺乏全面的数据来比较他们的表现。
方法:在30,066个基于液体的宫颈癌筛查测试结果中,根据现有的高危型人乳头瘤病毒(HPV)检测结果,精心选择了332例病例,HPV16和18的有限基因分型,液基细胞学,DS,和标准化阴道镜活检的组织学结果。对于12种其他高危HPV基因型阳性的病例,分析了三种回顾性分诊方法.我们计算了检测高度鳞状上皮内病变或更严重病变(HSIL)的阳性预测值(PPV)。
结果:两种使用DS的分诊模型(在所有情况下都是反射细胞学,然后是DS和仅反射DS)与仅使用反射细胞学的策略相比,HSIL+的PPV明显更高(35.9%/33.3%vs.18.8%;p<0.0001)。此外,这些基于DS的模型显示出较高的阴性预测值(NPV)(100%/96.2%与69.2%;p=0.0024/0.0079)。在包含DS的型号中,需要更少的阴道镜检查(103/102vs.154),忽略HSIL+的病例较少(0/3vs.8).
结论:我们的研究结果表明p16/Ki67双重染色,作为独立或组合的分诊测试,在以HPV为基础的原发性宫颈癌筛查中,对轻度筛查异常患者的HSIL+有效检测具有前景。
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.