评价 HPV 血清学多克隆 ELISA 检测作为人乳头瘤病毒暴露的生物标志物。
Evaluation of the polyclonal ELISA HPV serology assay as a biomarker for human papillomavirus exposure.
机构信息
Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20852, USA.
出版信息
Sex Transm Dis. 2011 Oct;38(10):976-82. doi: 10.1097/OLQ.0b013e31822545c0.
BACKGROUND
Seropositivity to human papillomavirus (HPV)16 and 18 antibodies is used as a measure of cumulative HPV exposure and as a stratifier of HPV exposure for vaccine efficacy analyses. Overall performance of these assays, as a measure of HPV exposure, has not been evaluated.
METHODS
Using data from the enrollment phase of the HPV16/18 vaccine trial in Costa Rica, we evaluated the performance of the polyclonal enzyme-linked immunosorbent assay (ELISA) HPV16 and 18 serological assays as a measure of HPV exposure. Biologic (e.g., HPV infection at the cervix) and behavioral characteristics (e.g., lifetime number of sexual partners) with known associations with current and past HPV infection were used to define cases and controls (HPV exposed vs. not exposed). Prevaccination serum was measured for antibodies against HPV16 and 18 by ELISA; cervical samples were tested for HPV DNA using PCR SPF10/LiPA25. ELISA results were analyzed using receiver-operator characteristic curves; performance was evaluated at the manufacturer set cut point (HPV16 = 8, HPV18 = 7) and at cut points chosen to optimize sensitivity and specificity (HPV16 = 34, HPV18 = 60).
RESULTS
Defining cases as type-specific HPV DNA positive with high-grade abnormal cytology (i.e., combined molecular and microscopic markers of infection), HPV16-ELISA gave sensitivity that was lower at the optimal cut point than the manufacturer cut point (62.2 compared with 75.7, respectively; P = 0.44). However, specificity was higher (85.3 compared with 70.4, respectively; P < 0.0001). Similarly, HPV18-ELISA gave sensitivity that was lower at the optimal cut point than the manufacturer cut point (34.5 compared with 51.7, respectively; P = 0.40), with higher specificities (94.9 compared with 72.6, respectively; P < 0.0001).
CONCLUSIONS
Modifying cut points did not improve the low sensitivity. The low sensitivity of this assay does not support its use for risk stratification or clinical settings.
背景
人乳头瘤病毒（HPV）16 和 18 抗体的血清阳性被用作累积 HPV 暴露的衡量标准，并作为 HPV 疫苗效力分析的 HPV 暴露分层因素。这些检测作为 HPV 暴露的衡量标准，其整体性能尚未得到评估。
方法
我们使用哥斯达黎加 HPV16/18 疫苗试验入组阶段的数据，评估了多克隆酶联免疫吸附试验（ELISA）HPV16 和 18 血清学检测作为 HPV 暴露衡量标准的性能。使用与当前和过去 HPV 感染具有已知关联的生物学（例如宫颈 HPV 感染）和行为学特征（例如终生性伴侣数）来定义病例和对照（HPV 暴露与未暴露）。使用 ELISA 检测 HPV16 和 18 的预疫苗血清抗体；使用 PCR SPF10/LiPA25 检测宫颈样本的 HPV DNA。使用受试者工作特征曲线分析 ELISA 结果；在制造商设定的临界点（HPV16 = 8，HPV18 = 7）和优化灵敏度和特异性的临界点（HPV16 = 34，HPV18 = 60）进行性能评估。
结果
将 HPV 特定型别 DNA 阳性且伴有高级别异常细胞学（即感染的分子和显微镜学标志物的综合组合）的病例定义为病例，与制造商临界点相比，HPV16-ELISA 在最佳临界点的灵敏度较低（分别为 62.2%和 75.7%；P = 0.44）。然而，特异性更高（分别为 85.3%和 70.4%；P < 0.0001）。类似地，HPV18-ELISA 在最佳临界点的灵敏度也低于制造商临界点（分别为 34.5%和 51.7%；P = 0.40），但特异性更高（分别为 94.9%和 72.6%；P < 0.0001）。
结论
改变临界点并不能提高低灵敏度。该检测的低灵敏度不支持其用于风险分层或临床环境。
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