Department of Obstetrics and Gynecology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Obstetrics and Gynecology, Academician Expert Workstation, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
JAMA Netw Open. 2021 Dec 1;4(12):e2140644. doi: 10.1001/jamanetworkopen.2021.40644.
High-risk human papillomavirus (hrHPV) persistent infection is the major etiology of cervical precancer and cancer. Noninvasive self-sampling HPV testing is a promising alternative cervical cancer screening for avoiding stigma and improving patient willingness to participate.
To investigate the feasibility and accuracy of menstrual blood (MB) hrHPV capture sequencing in hrHPV detection.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study collected 137 sanitary pads from 120 women who were premenopausal and had hrHPV as detected by cervical HPV GenoArray testing. Patients were recruited from September 1, 2020, to April 1, 2021, at Central Hospital of Wuhan, China. Target capture sequencing was performed to determine hrHPV genotypes in MB. Sanger sequencing was performed as the criterion standard for detecting hrHPV genotypes among enrolled women. Data were analyzed from April 1 through June 1, 2021.
Complete concordance, incomplete concordance, and discordance of MB hrHPV capture sequencing and conventional HPV testing were defined according to genotype overlapping levels. Concordance of the 2 detection methods and comparative power of MB hrHPV capture sequencing during different menstrual cycle days (MCDs) were the main outcomes.
A total of 120 enrolled women with hrHPV (mean [SD; range] age, 33.9 [6.9; 20.0 -52.0] years) provided 137 sanitary pads. The overall concordance rate of MB hrHPV capture sequencing and cervical HPV testing was 92.7% (95% CI, 88.3%-97.1%), with a κ value of 0.763 (P < .001). Among 24 samples with incomplete concordance or discordant results, 11 samples with additional hrHPV genotypes (45.8%), 5 true-negative samples (20.8%), and the correct hrHPV genotypes of 2 samples (8.3%) were correctly identified by MB hrHPV capture sequencing. MB hrHPV detection of hrHPV was equivalent on different MCDs, with an MB hrHPV-positive rate of 27 of 28 patients (96.4%) for MCD 1, 52 of 57 patients (91.2%) for MCD 2, 27 of 28 patients for MCD 3, 4 of 4 patients (100%) for MCD 4, and 3 of 3 patients (100%) for MCD 5 (P = .76). The sensitivity of the MB hrHPV capture sequencing was 97.7% (95% CI, 95.0%-100%).
These findings suggest that MB hrHPV capture sequencing is a feasible and accurate self-collected approach for cervical cancer screening. This study found that this method is associated with superior performance in identification of HPV genotypes and true-negative events compared with cervical HPV testing.
高危型人乳头瘤病毒（hrHPV）持续感染是宫颈癌前病变和癌症的主要病因。非侵入性的自我采样 HPV 检测是一种很有前途的替代宫颈癌筛查方法，可以避免污名化，并提高患者参与的意愿。
研究月经血（MB）hrHPV 捕获测序在 hrHPV 检测中的可行性和准确性。
设计、地点和参与者：这项队列研究从 120 名患有 hrHPV 的绝经前女性中收集了 137 片卫生棉条，这些女性的 hrHPV 是通过宫颈 HPV GenoArray 检测发现的。患者于 2020 年 9 月 1 日至 2021 年 4 月 1 日在中国武汉中心医院招募。采用靶向捕获测序来确定 MB 中的 hrHPV 基因型。Sanger 测序作为检测入组女性 hrHPV 基因型的标准。数据的分析是在 2021 年 4 月 1 日至 6 月 1 日进行的。
根据基因型重叠程度，定义了 MB hrHPV 捕获测序与常规 HPV 检测的完全一致性、不完全一致性和不一致性。主要的研究结果是 2 种检测方法的一致性和 MB hrHPV 捕获测序在不同月经周期日（MCD）的比较能力。
共有 120 名患有 hrHPV 的入组女性（平均[SD；范围]年龄，33.9[6.9；20.0-52.0]岁）提供了 137 片卫生棉条。MB hrHPV 捕获测序与宫颈 HPV 检测的总体一致性率为 92.7%（95%CI，88.3%-97.1%），κ 值为 0.763（P<0.001）。在 24 个存在不完全一致性或不一致结果的样本中，11 个样本存在额外的 hrHPV 基因型（45.8%）、5 个真阴性样本（20.8%）和 2 个正确的 hrHPV 基因型（8.3%）被 MB hrHPV 捕获测序正确识别。在不同的 MCD 中，MB hrHPV 检测 hrHPV 的结果是等效的，在 MCD 1 中，28 名患者中有 27 名（96.4%）为 MB hrHPV 阳性，在 MCD 2 中，57 名患者中有 52 名（91.2%）为 MB hrHPV 阳性，在 MCD 3 中，28 名患者中有 27 名，在 MCD 4 中，4 名患者中有 4 名（100%），在 MCD 5 中，3 名患者中有 3 名（100%）（P=0.76）。MB hrHPV 捕获测序的灵敏度为 97.7%（95%CI，95.0%-100%）。
这些发现表明，MB hrHPV 捕获测序是一种可行且准确的宫颈癌筛查自我采集方法。本研究发现，与宫颈 HPV 检测相比，该方法在识别 HPV 基因型和真阴性事件方面具有更好的性能。
