Clinical Validation of the HPV-Risk Assay, a Novel Real-Time PCR Assay for Detection of High-Risk Human Papillomavirus DNA by Targeting the E7 Region
Clinical Validation of the HPV-Risk Assay, a Novel Real-Time PCR Assay for Detection of High-Risk Human Papillomavirus DNA by Targeting the E7 Region
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DOI：
10.1128/jcm.03195-13
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发表时间：
2014-03-01
影响因子：
9.4
通讯作者：
Heideman, D. A. M.
中科院分区：
文献类型：
--
作者：
Hesselink, A. T.;Berkhof, J.;Heideman, D. A. M.
HPV- risk检测是一种新的实时PCR检测方法，针对15种高危人乳头瘤病毒（HPV）类型（即HPV16、-18、-31、-33、-35、-39、-45、-51、-52、-56、-58、-59、-66、-67和-68）的E7区域，并提供HPV16和HPV18的额外基因型信息。本研究评估了宫颈刮痧标本hpv风险测定的临床表现和可重复性，以及其在自体阴道标本（宫颈）中的实用性。与高危HPV GP5+/6+ PCR相比，根据国际宫颈癌筛查HPV检测要求指南，通过非劣效性分析评估宫颈刮痧标本中2级或更严重宫颈上皮内瘤变（CIN2+）的HPV风险检测的临床表现。HPV-Risk检测显示CIN2+的临床敏感性为97.1%（95%可信区间[CI]， 89.1 - 99.3%； 67/69个样本），CIN2+的临床特异性为94.3% （95% CI, 92.5 - 95.7%； 777/824个样本）。临床敏感性和特异性均不逊于GP5+/6+ PCR（非劣效性评分检验，P分别为0.006和0.0003）。宫颈刮痧标本HPV-Risk检测的实验室内重复性（99.5% [95% CI, 98.6 ~ 99.8%]； 544/547个样本，kappa = 0.99）和实验室间一致性（99.2% [95% CI, 98.6 ~ 99.8%]； 527/531个样本，kappa = 0.98）较高。自采（宫颈）阴道标本与临床获得的宫颈刮痧标本的HPV-Risk检测结果一致性也很高，自采灌洗标本的一致性为95.9% (95% CI, 85.1 ~ 99.0%； 47/49个样本，kappa = 0.90)，自采刷刷标本的一致性为91.6% （95% CI, 84.6 ~ 95.6%； 98/107个样本，kappa = 0.82）。总之，HPV风险检测符合HPV检测要求的国际指南的横截面临床和可重复性标准，可以被认为是临床验证的宫颈筛查目的。HPV风险测定与自采集标本的兼容性支持其用于HPV自采样的效用。
The HPV-Risk assay is a novel real-time PCR assay targeting the E7 region of 15 high-risk human papillomavirus (HPV) types (i.e., HPV16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -67, and -68), and provides additional genotype information for HPV16 and HPV18. This study evaluated the clinical performance and reproducibility of the HPV-Risk assay with cervical scraping specimens and its utility with self-collected (cervico) vaginal specimens. The clinical performance of the HPV-Risk assay for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) with cervical scraping specimens was evaluated by a noninferiority analysis, relative to high-risk HPV GP5+/6+ PCR, following international guidelines for HPV test requirements for cervical cancer screening. The HPV-Risk assay showed clinical sensitivity for CIN2+ of 97.1% (95% confidence interval [CI], 89.1 to 99.3%; 67/69 samples) and a clinical specificity for CIN2+ of 94.3% (95% CI, 92.5 to 95.7%; 777/824 samples). The clinical sensitivity and specificity were noninferior to those of GP5+/6+ PCR (noninferiority score test, P = 0.006 and 0.0003, respectively). Intralaboratory reproducibility over time (99.5% [95% CI, 98.6 to 99.8%]; 544/547 samples, kappa = 0.99) and interlaboratory agreement (99.2% [95% CI, 98.6 to 99.8%]; 527/531 samples, kappa = 0.98) for the HPV-Risk assay with cervical scraping specimens were high. The agreement of the HPV-Risk assay results for self-collected (cervico) vaginal specimens and clinician-obtained cervical scraping specimens was also high, i.e., 95.9% (95% CI, 85.1 to 99.0%; 47/49 samples, kappa = 0.90) for self-collected lavage samples and 91.6% (95% CI, 84.6 to 95.6%; 98/107 samples, kappa = 0.82) for self-collected brush samples. In conclusion, the HPV-Risk assay meets the cross-sectional clinical and reproducibility criteria of the international guidelines for HPV test requirements and can be considered clinically validated for cervical screening purposes. The compatibility of the HPV-Risk assay with self-collected specimens supports its utility for HPV self-sampling.