Women's Health Research Institute, BC Women's Hospital and Health Service, Vancouver, British Columbia, Canada; Faculty of Health Sciences, Simon Fraser University, Vancouver, British Columbia, Canada.
Women's Health Research Institute, BC Women's Hospital and Health Service, Vancouver, British Columbia, Canada; Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Am J Obstet Gynecol. 2021 Nov;225(5):511.e1-511.e7. doi: 10.1016/j.ajog.2021.05.038. Epub 2021 Jun 1.
Cervical cancer, a preventable disease associated with the human papillomavirus, is responsible for significant morbidity and mortality globally. Primary human papillomavirus testing is more sensitive in detecting precancerous cervical lesions than cytologic screening and can be conducted using either DNA- or RNA-based assays. Screening programs must select the most appropriate assay from several available assays for their population. It is not yet known whether these assays perform equivalently in the long term, particularly among women with a negative human papillomavirus test result. This study aims to compare long-term safety after a negative human papillomavirus test result across both DNA- and RNA-based testing assays.
This study aimed to compare long-term high-grade cervical intraepithelial neoplasia (grade 2 or higher and grade 3 or higher) outcomes of 2 DNA-based assays (Digene Hybrid Capture 2 High-Risk HPV DNA Test and cobas 4800 HPV Test) and 1 messenger RNA-based assay (Aptima HPV Assay) using data from the Human Papillomavirus For Cervical Cancer Trial-DECADEl (FOCAL-DECADE) cohort, by first comparing the positive and negative rates between the assays and then investigating the cumulative incidence of cervical intraepithelial neoplasia grade 2 and higher and grade 3 or higher detection among participants in the FOCAL DECADE cohort over follow-up according to human papillomavirus testing assays.
The FOCAL Trial was a randomized controlled trial that evaluated human papillomavirus testing for primary cervical cancer screening. The FOCAL-DECADE cohort subsequently followed FOCAL Trial participants passively through the British Columbia Cervix Screening Program Database for approximately 10 years after the FOCAL Trial study exit to examine the rates of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher. For this study, eligible participants had baseline human papillomavirus-negative results from at least 1 assay and had 1 or more cytologic screens after baseline (9509 participants for DNA-based and 3473 participants for DNA- vs RNA-based assay comparisons). We constructed cumulative incidence curves and compared the hazard ratios for cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher detection according to the assays.
Over 10 years of follow-up, the cumulative incidence of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher did not significantly differ between the DNA-based assays (hazard ratio, 0.95; 95% confidence interval, 0.84-1.06; P=.35 and hazard ratio, 0.82; 95% confidence interval, 0.66-1.01; P=.06 for cervical intraepithelial neoplasia grade 2 or higher and cervical intraepithelial neoplasia grade 3 or higher, respectively) or between the DNA- and RNA-based assays (hazard ratio, 0.97; 95% confidence interval, 0.87-1.06; P=.48 and hazard ratio, 0.94; 95% confidence interval, 0.79-1.13; P=.52 for cervical intraepithelial neoplasia grade 2 or higher and cervical intraepithelial neoplasia grade 3 or higher, respectively).
Among participants who tested negative for human papillomavirus at baseline, the long-term risk of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher did not significantly differ regardless of whether DNA- or RNA-based human papillomavirus testing assays were used. Screening program decision makers can be confident that for women who test negative for human papillomavirus, DNA- and RNA-based assays exhibit similar cervical intraepithelial neoplasia grade 2 or higher outcomes over several years.
宫颈癌是一种与人类乳头瘤病毒相关的可预防疾病，在全球范围内导致了显著的发病率和死亡率。与细胞学筛查相比，基于人乳头瘤病毒的检测对癌前宫颈病变的检测更敏感，并且可以使用 DNA 或 RNA 为基础的检测进行。筛查计划必须为其人群选择最合适的检测方法。目前尚不清楚这些检测方法在长期内是否具有等效性，特别是对于人乳头瘤病毒检测结果为阴性的女性。本研究旨在比较两种 DNA 检测方法（Digene Hybrid Capture 2 High-Risk HPV DNA Test 和 cobas 4800 HPV Test）和一种基于信使 RNA 的检测方法（Aptima HPV Assay）在人乳头瘤病毒阴性结果后的长期安全性。
本研究旨在比较两种 DNA 检测方法（Digene Hybrid Capture 2 High-Risk HPV DNA Test 和 cobas 4800 HPV Test）和一种基于信使 RNA 的检测方法（Aptima HPV Assay）在人乳头瘤病毒阴性结果后的长期高级别宫颈上皮内瘤变（2 级或更高级别和 3 级或更高级别）结局，通过比较检测方法之间的阳性和阴性率，然后根据人乳头瘤病毒检测方法，调查 FOCAL DECADE 队列中参与者在随访期间高级别宫颈上皮内瘤变 2 级或更高级别和 3 级或更高级别检测的累积发生率。
FOCAL 试验是一项随机对照试验，评估了人乳头瘤病毒检测在原发性宫颈癌筛查中的应用。随后，FOCAL-DECADE 队列通过不列颠哥伦比亚宫颈癌筛查计划数据库对 FOCAL 试验参与者进行了大约 10 年的被动随访，以检查高级别宫颈上皮内瘤变 2 级或更高级别和 3 级或更高级别的发生率。对于这项研究，合格的参与者至少有一项检测的基线人乳头瘤病毒为阴性，并且在基线后有一项或多项细胞学筛查（9509 名参与者用于 DNA 检测，3473 名参与者用于 DNA 与 RNA 检测比较）。我们构建了累积发病率曲线，并根据检测方法比较了高级别宫颈上皮内瘤变 2 级或更高级别和 3 级或更高级别检测的风险比。
在 10 年的随访期间，基于 DNA 的检测方法之间（高级别宫颈上皮内瘤变 2 级或更高级别和高级别宫颈上皮内瘤变 3 级或更高级别的风险比分别为 0.95；95%置信区间，0.84-1.06；P=.35 和风险比，0.82；95%置信区间，0.66-1.01；P=.06）或 DNA 与 RNA 检测方法之间（高级别宫颈上皮内瘤变 2 级或更高级别和高级别宫颈上皮内瘤变 3 级或更高级别的风险比分别为 0.97；95%置信区间，0.87-1.06；P=.48 和风险比，0.94；95%置信区间，0.79-1.13；P=.52）高级别宫颈上皮内瘤变 2 级或更高级别和高级别宫颈上皮内瘤变 3 级或更高级别的累积发病率均无显著差异。
在基线时人乳头瘤病毒检测阴性的参与者中，无论使用 DNA 或 RNA 为基础的人乳头瘤病毒检测方法，高级别宫颈上皮内瘤变 2 级或更高级别和 3 级或更高级别的长期风险均无显著差异。筛查计划决策者可以放心，对于人乳头瘤病毒检测阴性的女性，DNA 和 RNA 为基础的检测在数年内具有相似的高级别宫颈上皮内瘤变结局。
