Gertrude H Sergievsky Center, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA; Vagelos College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA.
Department of Obstetrics and Gynecology, University of Cape Town, Cape Town, South Africa.
Lancet Glob Health. 2020 Feb;8(2):e296-e304. doi: 10.1016/S2214-109X(19)30527-3.
HPV-based screen and treat is the recommended approach for cervical cancer screening in low-resource settings, but quite low specificity of human papillomavirus (HPV) testing, particularly in women living with HIV, leads to overtreatment. We evaluated whether HPV type restriction and more stringent cutoffs on Xpert HPV optimise performance characteristics of this assay for screen and treat.
We recruited HIV-negative and HIV-positive women aged 30-65 years from a primary care facility and a referral colposcopy clinic in Cape Town, South Africa. Women included had no history of any anogenital cancer or treatment for cervical dysplasia, had no hysterectomy, and were not pregnancy at the time of recruitment. All women had cervical samples collected for Xpert HPV (an assay that detects high-risk HPV types in five channels: HPV type 16; HPV types 18 or 45, or both; HPV types 31, 33, 35, 52, or 58, or more than one of these types; HPV types 51 or 59, or both; and HPV types 39, 56, 66, or 68, or more than one of these types) and underwent colposcopy and histological sampling with consensus pathology review. Logistic regression and receiver operating characteristic curves were used to evaluate improvements in specificity attained by modifying cycle threshold cutoffs to define screen-positive results.
We recruited 1121 women aged 30-65 years, 586 of whom were HIV-negative and 535 HIV-positive. Sensitivity of detecting cervical intraepithelial neoplasia grade 2 or greater in HIV-negative women using manufacturer-defined cycle threshold cutoffs for all channels was 88·7% (95% CI 83·1-94·3), and specificity was 86·9% (83·4-90·4). Sensitivity was 93·6% (90·0-97·3) and specificity 59·9% (54·1-65·7) in HIV-positive women. Cycle threshold values from channels detecting HPV type 16, HPV types 18 or 45 (or both), and HPV types 31, 33, 35, 52, or 58 (or more than one of these types) were informative to predict cervical intraepithelial neoplasia grade 2 or greater. Shifting cycle threshold cutoffs on these three channels allowing sensitivity to decline to 75-85%, led to specificities of 91·3-95·3% in HIV-negative women and 77·0-85·8% in HIV-positive women.
More stringent cycle threshold cutoffs on selected channels in Xpert HPV improve specificity with only modest losses in sensitivity, making this assay an optimal choice for HPV-based screen and treat in settings with a high prevalence of HIV. These modifications can be made from standard output with no need for new engineering. Decision making about performance characteristics of HPV testing can be shifted to programme implementers and cutoffs selected according to resource availability and community preferences.
Supported by the National Cancer Institute UH2/3 CA189908.
在资源匮乏的环境中，HPV 检测和治疗是宫颈癌筛查的推荐方法，但 HPV 检测的特异性相当低，尤其是在 HIV 感染者中，这导致了过度治疗。我们评估了 HPV 类型限制和 Xpert HPV 检测更严格的截止值是否可以优化该检测方法用于筛查和治疗的性能特征。
我们招募了来自南非开普敦的一家初级保健机构和一家转诊阴道镜诊所的 30-65 岁的 HIV 阴性和 HIV 阳性女性。入组的女性没有任何肛门生殖器癌症病史或宫颈发育不良的治疗史，没有子宫切除术，并且在招募时没有怀孕。所有女性均采集宫颈样本进行 Xpert HPV（一种可在五个通道中检测高危 HPV 类型的检测方法：HPV 16 型；HPV 18 或 45 型，或两者均有；HPV 31、33、35、52 或 58 型，或这些类型中的一种以上；HPV 51 或 59 型，或两者均有；HPV 39、56、66 或 68 型，或这些类型中的一种以上）检测，并进行阴道镜检查和组织学取样，通过共识病理学评估。使用逻辑回归和受试者工作特征曲线来评估通过修改循环阈值截止值来定义阳性筛查结果以提高特异性的效果。
我们招募了 1121 名年龄在 30-65 岁的女性，其中 586 名为 HIV 阴性，535 名为 HIV 阳性。使用制造商定义的所有通道的循环阈值截止值检测 HIV 阴性女性的宫颈上皮内瘤变 2 级或更高级别时，灵敏度为 88.7%（95%CI 83.1-94.3），特异性为 86.9%（83.4-90.4）。在 HIV 阳性女性中，灵敏度为 93.6%（90.0-97.3），特异性为 59.9%（54.1-65.7）。HPV 16 型、HPV 18 或 45 型（或两者均有）和 HPV 31、33、35、52 或 58 型（或这些类型中的一种以上）检测通道的循环阈值值可用于预测宫颈上皮内瘤变 2 级或更高级别，具有信息性。将这些三个通道上的循环阈值截止值降低至 75-85%，可使 HIV 阴性女性的特异性达到 91.3-95.3%，HIV 阳性女性的特异性达到 77.0-85.8%。
在 Xpert HPV 中选择的通道上更严格的循环阈值截止值可以提高特异性，而敏感性仅略有下降，这使得该检测方法成为资源丰富的 HIV 流行地区 HPV 检测和治疗的理想选择。这些修改可以从标准输出中进行，无需新的工程设计。HPV 检测性能特征的决策可以转移到方案实施者手中，并根据资源可用性和社区偏好选择截止值。
由美国国立癌症研究所 UH2/3 CA189908 资助。
