Abstract：
Human papillomavirus (HPV)-based screening offers better protection against cervical cancer compared to cytology, but HPV screening assays must adhere to validation requirements of the international guidelines to ensure optimal performance. Allplex HPV HR Detection (Allplex) assay, launched in the late 2022, is a fully automated real-time PCR-based assay utilizing innovative technology that enables quantification and concurrent distinction of 14 high-risk HPV genotypes (HPV16,18,31,33,35,39,45,51,52,56,58,59,66 and 68). We assessed the validity of the Allplex for cervical cancer screening purposes, via comparison to a clinically validated comparator assay (Hybrid Capture 2; HC2), and through assessment of intra-laboratory reproducibility and inter-laboratory agreement. A clinical validation panel comprised of 973 residual ThinPrep samples was obtained from women aged 30-64 years participating in the organized Slovenian screening program, of these 863 were from women undergoing their regular screening visit after a previous negative screen test while 110 were from women with underlying cervical intraepithelial neoplasia grade 2 or worse (CIN2+) lesions. The Allplex\'s relative clinical sensitivity for detection of CIN2+ and CIN3+ were 1.01 (95%CI;0.98-1.04) and 0.98 (95%CI;0.95-1.02), compared to that of HC2. At recommended thresholds of ≥98% and ≥90%, the Allplex\'s clinical sensitivity and specificity (p=0.0004 and p=0.02, respectively) were non-inferior to HC2. High intra-laboratory reproducibility and inter-laboratory agreement, both overall (98.1% and 97.9%, respectively) and at genotype level (>98.7%) was observed. In addition, analytical genotype-specific performance of Allplex was compared to that of its predecessor Anyplex HPV HR; high overall agreement was observed (96.3%; kappa value 0.88), with some variations in performance. In conclusion, Allplex met all validation criteria described in the international guidelines on sensitivity, specificity and laboratory reproducibility and can be considered clinically validated for primary cervical cancer screening.
摘要：
与细胞学相比，基于人乳头瘤病毒（HPV）的筛查可以更好地预防宫颈癌。但HPV筛查试验必须遵守国际指南的验证要求,以确保最佳性能.AllplexHPVHR检测（Allplex）分析，在2022年末推出,是一种基于实时PCR的全自动检测方法,利用创新技术,能够对14种高危型HPV基因型(HPV16,18,31,33,35,39,45,51,52,56,58,59,66和68)进行定量和同时区分.我们评估了Allplex用于宫颈癌筛查目的的有效性，通过与临床验证的比较试验(混合捕获2；HC2)进行比较，并通过评估实验室内的可重复性和实验室间的协议。从参加有组织的斯洛文尼亚筛查计划的30-64岁女性中获得了由973个残留ThinPrep样本组成的临床验证小组，在这863名女性中,有110名女性是在既往筛查试验阴性后接受常规筛查访视的女性,而有2级或更严重的宫颈上皮内瘤变(CIN2+)病变的女性.Allplex检测CIN2+和CIN3+的相对临床灵敏度为1.01(95CI;0.98-1.04)和0.98(95CI;0.95-1.02)，与HC2相比。在≥98%和≥90%的推荐阈值下，Allplex的临床敏感性和特异性（分别为p=0.0004和p=0.02）均不劣于HC2。高实验室内可重复性和实验室间协议，两者总体(98.1%和97.9%，分别）和基因型水平（>98.7%）。此外,Allplex的分析基因型特异性表现与其前身AnyplexHPVHR比较;观察到高总体一致性(96.3%;κ值0.88),在性能上有一些变化。总之,Allplex符合关于敏感性的国际指南中描述的所有验证标准，特异性和实验室可重复性，可以被认为是原发性宫颈癌筛查的临床验证。
