Castle Philip E, Lorincz Attila T, Scott David R, Sherman Mark E, Glass Andrew G, Rush Brenda B, Wacholder Sholom, Burk Robert D, Manos M Michele, Schussler John E, Macomber Paul, Schiffman Mark
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
J Clin Microbiol. 2003 Sep;41(9):4022-30. doi: 10.1128/JCM.41.9.4022-4030.2003.
We compared the performance of a prototype version of the Hybrid Capture 3 (HC3) human papillomavirus (HPV) DNA assay to the current generation Hybrid Capture 2 (HC2) assay, both of which target 13 oncogenic HPV types, for the detection of cervical intraepithelial neoplasia grade 3 and cancer (CIN3+) with cervicovaginal lavage specimens collected at enrollment into a 10-year cohort study at Kaiser Permanente (Portland, Oreg.). HC3 results for a risk-stratified sample (n = 4,364) were compared to HC2 results for the entire cohort (n = 20,810) with receiver operating characteristics curves, and the optimal cut points for both tests (relative light units [RLU]/positive control [PC]) for the detection of CIN3+ were determined. Specimens were also tested for HPV16 and HPV18 with separate HC3 type-specific probes. The optimal cut point for detecting CIN3+ was 1.0 RLU/PC for HC2, as previously shown, and was 0.6 RLU/PC for HC3. At the optimal cut points, HC3 and HC2 had similar screening performance characteristics for CIN3+ diagnosed at the enrollment visit. In analyses that included cases CIN3+ at enrollment and those diagnosed during early follow-up, HC3 had nonsignificantly higher sensitivity and equal specificity for the detection of CIN3+ compared to HC2; this increase in sensitivity was primarily the result of increased detection of CIN3+ in women who were 30 years of age or older and were cytologically negative (P = 0.006). We also compared the performance of the hybrid capture tests to MY09/11 L1 consensus primer PCR results (n = 1,247). HC3 was less likely than HC2 to test positive for specimens that tested positive by PCR for any untargeted types (P < 0.001). HC3 was less likely than HC2 to test positive for untargeted PCR-detected single infections with HPV53 (P = 0.001) and HPV66 (P = 0.01). There was good agreement between test positivity by PCR and by single type-specific HC3 probes for HPV16 (kappa = 0.76; 95% confidence interval [CI] = 0.71 to 0.82) and for HPV18 (kappa = 0.73; 95% CI = 0.68 to 0.79). In conclusion, we suggest that HC3 (>/=0.6 RLU/PC) may be slightly more sensitive than and equally specific test as HC2 (>/=1.0 RLU/PC) for the detection of CIN3+ over the duration of typical screening intervals.
我们将杂交捕获3（HC3）人乳头瘤病毒（HPV）DNA检测的原型版本与当前一代的杂交捕获2（HC2）检测进行了性能比较，这两种检测均针对13种致癌性HPV类型，用于检测在俄勒冈州波特兰市凯撒医疗集团开展的一项为期10年的队列研究入组时采集的宫颈阴道灌洗标本中的宫颈上皮内瘤变3级和癌症（CIN3+）。通过绘制受试者工作特征曲线，将风险分层样本（n = 4,364）的HC3检测结果与整个队列（n = 20,810）的HC2检测结果进行比较，并确定了两种检测用于检测CIN3+的最佳临界点（相对光单位[RLU]/阳性对照[PC]）。还使用单独的HC3型特异性探针检测标本中的HPV16和HPV18。如先前所示，检测CIN3+的HC2最佳临界点为1.0 RLU/PC，HC3为0.6 RLU/PC。在最佳临界点时，HC3和HC2对入组时诊断的CIN3+具有相似的筛查性能特征。在纳入入组时为CIN3+以及早期随访期间诊断为CIN3+病例的分析中，与HC2相比，HC3检测CIN3+的敏感性略高且特异性相同；敏感性的增加主要是由于30岁及以上且细胞学检查阴性的女性中CIN3+检出率增加所致（P = 0.006）。我们还将杂交捕获检测的性能与MY09/11 L1共识引物PCR结果（n = 1,247）进行了比较。对于PCR检测出任何非靶向类型呈阳性的标本，HC3检测呈阳性的可能性低于HC2（P < 0.001）。对于PCR检测出的HPV53（P = 0.001）和HPV66（P = 0.01）非靶向单感染，HC3检测呈阳性的可能性低于HC2。PCR检测阳性与HC3单一型特异性探针检测HPV16（kappa = 0.76；95%置信区间[CI] = 0.71至0.82）和HPV18（kappa = 0.73；95%CI = 0.68至0.79）的检测阳性之间具有良好的一致性。总之，我们建议在典型筛查间隔期间，HC3（≥0.6 RLU/PC）在检测CIN3+方面可能比HC2（≥1.0 RLU/PC）略敏感且特异性相同。
