Clinical evaluation of modifications to a human papillomavirus assay to optimise its utility for cervical cancer screening in low-resource settings: a diagnostic accuracy study.
Clinical evaluation of modifications to a human papillomavirus assay to optimise its utility for cervical cancer screening in low-resource settings: a diagnostic accuracy study.
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DOI：
10.1016/s2214-109x(19)30527-3
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发表时间：
2020-03
期刊：
影响因子：
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通讯作者：
Denny L
中科院分区：
文献类型：
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作者：
Kuhn L;Saidu R;Boa R;Tergas A;Moodley J;Persing D;Campbell S;Tsai WY;Wright TC;Denny L
HPV-based screen-and-treat is the recommended approach for cervical cancer screening in low resource settings, but relatively low specificity of HPV testing, particularly in women living with HIV leads to over-treatment. We evaluated whether HPV type restriction and more stringent cut-offs on Xpert HPV optimizes performance characteristics of this assay for screen-and-treat. In a clinical study in Cape Town, South Africa, 586 HIV-negative and 535 HIV-positive women, aged 30–65 years, were recruited. All women had cervical samples collected for Xpert HPV and underwent colposcopy and histological sampling with consensus pathology review. Logistic regression and receiver operating characteristic curves (ROC) were used to evaluate improvements in specificity attained by modifying cycle threshold (Ct) cut-offs to define screen-positive. Sensitivity of detecting cervical intraepithelial lesions grade 2 or greater (CIN2+) at manufacturer-defined Ct cut-offs for all channels was 88.7% (95% CI: 83.1–94.3) and specificity 86.9% (95% CI: 83.4–90.4) in HIV-negative women. Sensitivity was 93.6% [95% CI: 90.0–97.3] and specificity 59.9% [95% CI: 54.1–65.7] in HIV-positive women. Ct values from channels detecting (1) HPV 16, (2) HPV 18 and/or 45, and (3) HPV 31, 33, 35, 52, and/or 58 were informative to predict CIN2+. Shifting Ct cut-offs on these three channels allowing sensitivity to decline to 85–75%, led to specificities of 91.3–95.3% in HIV-negative and 77.0–85.8% in HIV-positive women. More stringent Ct cut-offs 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 program implementers and cutoffs selected for appropriate to resource availability and community preferences.
