Cuzick J, Beverley E, Ho L, Terry G, Sapper H, Mielzynska I, Lorincz A, Chan W K, Krausz T, Soutter P
Imperial Cancer Research Fund, London, UK.
Br J Cancer. 1999 Oct;81(3):554-8. doi: 10.1038/sj.bjc.6690730.
Certain types of the human papilloma virus (HPV) are well established as the primary cause of cervical cancer. Several studies have shown that HPV testing can improve the detection rate of high-grade cervical intraepithelial neoplasia (CIN), but these have been carried out primarily in younger women. In this study we evaluated the role of HPV testing as an adjunct to cytology in women aged 35 or over. An additional aim was to evaluate commercially available kits for HPV testing. A total of 2988 eligible women aged 34 or more attending for a routine smear in 40 general practitioner practices received HPV testing in addition to routine cytology, after having given written informed consent. Samples were assayed by polymerase chain reaction (PCR) and two versions of the Hybrid Capture test for HPV, and women were invited for colposcopy if there was any cytological abnormality (including borderline smears) or the PCR test was positive. Any apparent abnormality was biopsied and loop-excision was performed as necessary. CIN was judged by histology; 42 women had high-grade CIN, of which six were cytology negative (86% sensitivity for borderline or worse) and three had a borderline smear (79% sensitivity for mild dyskaryosis or worse). The positive predictive value of a borderline smear was only 3.1%. Eleven high-grade lesions were negative by the PCR HPV test (sensitivity 74%). The first generation Hybrid Capture II test had a similar sensitivity but an unacceptably high false positive rate (18.3%), while the newer Hybrid Capture II microtitre kit had a 95% sensitivity and a 2.3% positivity rate in normal women when used at a 2 pg ml(-1) cut-off (positive predictive value 27%). Cytology performed very well in this older cohort of women. The newer Hybrid Capture II microtitre test may be a useful adjunct, especially if the results reported here are reproducible in other studies. A combined screening test offers the possibility of greater protection and/or longer screening intervals, which could reduce the overall cost of the screening programme.
某些类型的人乳头瘤病毒（HPV）已被确认为宫颈癌的主要病因。多项研究表明，HPV检测可提高高级别宫颈上皮内瘤变（CIN）的检出率，但这些研究主要是在年轻女性中进行的。在本研究中，我们评估了HPV检测作为35岁及以上女性细胞学检查辅助手段的作用。另一个目的是评估市售的HPV检测试剂盒。共有2988名年龄在34岁及以上、在40家全科医生诊所接受常规涂片检查的符合条件的女性，在签署书面知情同意书后，除了接受常规细胞学检查外，还接受了HPV检测。样本通过聚合酶链反应（PCR）以及两种版本的HPV杂交捕获试验进行检测，如果存在任何细胞学异常（包括临界涂片）或PCR检测呈阳性，则邀请女性进行阴道镜检查。对任何明显异常进行活检，并根据需要进行环形切除术。CIN通过组织学判断；42名女性患有高级别CIN，其中6名细胞学检查为阴性（对临界或更严重病变的敏感性为86%），3名有临界涂片（对轻度核异质或更严重病变的敏感性为79%）。临界涂片的阳性预测值仅为3.1%。11例高级别病变的PCR HPV检测为阴性（敏感性74%）。第一代杂交捕获II试验的敏感性相似，但假阳性率高得令人无法接受（18.3%），而更新的杂交捕获II微量滴定试剂盒在以2 pg ml(-1)为临界值用于正常女性时，敏感性为95%，阳性率为2.3%（阳性预测值27%）。细胞学检查在这个年龄较大的女性队列中表现良好。更新的杂交捕获II微量滴定试验可能是一种有用的辅助手段，尤其是如果此处报告的结果在其他研究中具有可重复性。联合筛查试验有可能提供更大的保护和/或更长的筛查间隔，这可以降低筛查计划的总体成本。
