Performance of high-risk human papillomavirus DNA testing as a primary screen for cervical cancer: a pooled analysis of individual patient data from 17 population-based studies from China.
Performance of high-risk human papillomavirus DNA testing as a primary screen for cervical cancer: a pooled analysis of individual patient data from 17 population-based studies from China.
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DOI：
10.1016/s1470-2045(10)70256-4
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发表时间：
2010-12
期刊：
影响因子：
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通讯作者：
Cervical Cancer Screening Group in China
中科院分区：
文献类型：
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作者：
Zhao FH;Lin MJ;Chen F;Hu SY;Zhang R;Belinson JL;Sellors JW;Franceschi S;Qiao YL;Castle PE;Cervical Cancer Screening Group in China
关于高危型人乳头瘤病毒（HPV）DNA检测是否应用作宫颈癌的主要筛查，仍存在争议。我们研究的目的是评估HPV DNA检测是否可以应用于中国以及其他类似发展中国家的宫颈癌筛查项目。我们对1999年至2008年在中国大陆进行的基于人群的宫颈癌筛查研究进行了汇总分析，同时进行了HPV DNA检测（Hybrid Capture 2检测; Qiagen，盖瑟斯堡，MD，USA），液基细胞学（LBC）和醋酸目视检查（VIA）。符合条件的女性性活跃，未怀孕，子宫完整，无宫颈上皮内瘤变（CIN）、宫颈癌或盆腔放疗史。所有检测呈阳性的妇女均接受阴道镜检查和活检。宫颈病变通过直接或随机活检确诊。我们评估了HPV DNA检测对CIN 3级或以上的诊断准确性。对来自中国不同地区的17项横断面、基于人群的研究的30371名妇女进行了筛查。随后排除了1523名女性，因为HPV DNA样本不足或未进行活检，其中包括具有不确定意义的非典型鳞状细胞的女性;低度鳞状上皮内病变或更糟; HPV阳性，细胞学阴性，阴道镜检查结果缺失或阳性;以及细胞学结果不满意。HPV DNA检测的敏感性较高，为97.5%，（95% CI 95.7-98.7）检测CIN 3级或更差，特异性较低，为85.1%（82.3-87.9），与细胞学相比（敏感性87.9% [95%CI 84.7-90.7]，特异性94.7% [93.5-96.0]）和VIA（54.6% [48.0-61.2]，89.9% [86.8-93.0]）。敏感性不因研究或年龄（<35岁，35-49岁，≥50岁）而异;然而，特异性确实随年龄而异（p<0.0001），并且在35岁以下的女性中最高（89.4%; 95%CI 86.1-91.5）。将阳性临界点从生产商推荐的1 pg/mL增加到2 pg/mL，导致总体HPV DNA阳性率从16.3%下降到13.9%（p<0.0001），这可能导致转诊率下降，尽管敏感性略低（97.5%至95.2%）。在年龄小于35岁的女性中，将临界点增加至10 pg/mL，保持了97.7%（95% CI 87.7-99.9）的高灵敏度，并将特异性增加至93.5%（95% CI 91.9-94.6）。HPV DNA检测对CIN 3级或更严重的患者具有高度敏感性和中度特异性，在各研究中心和年龄组（包括35岁以下的女性）中结果一致。临界点的提高可能对中国未来的筛查项目有益，特别是在筛查35岁以下的女性时。Fogarty国际临床研究学者项目（美国国立卫生研究院Fogarty国际中心，通过范德比尔特大学国际临床研究员项目）;北京市教育委员会学术能力发展项目;中国医学科学院肿瘤研究所和医院。
Controversy remains over whether high-risk human papillomavirus (HPV) DNA testing should be used as a primary screen for cervical cancer. The aims of our study were to assess whether HPV DNA testing could be applied to cervical-cancer screening programmes in China, as well as other similar developing countries. We did a pooled analysis of population-based cervical cancer screening studies done in mainland China from 1999 to 2008 with concurrent HPV DNA testing (Hybrid Capture 2 assay; Qiagen, Gaithersburg, MD, USA), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Eligible women were sexually active, not pregnant, had an intact uterus, and had no history of cervical intraepithelial neoplasia (CIN), cervical cancer, or pelvic irradiation. All women positive for any test were referred for colposcopy and biopsy. Cervical lesions were diagnosed by directed or random biopsy. We assessed the diagnostic accuracy of HPV DNA testing for the detection of CIN grade 3 or greater. 30 371 women from 17 cross-sectional, population-based studies in various parts of China were screened. 1523 women were subsequently excluded because of inadequate HPV DNA specimens or they did not have a biopsy taken, which included women with atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesion or worse; positive HPV, negative cytology, and missing or positive colposcopy results; and unsatisfactory cytology results. HPV DNA testing had a higher sensitivity of 97.5% (95% CI 95.7–98.7) for detection of CIN grade 3 or worse, and a lower specificity of 85.1% (82.3–87.9), compared with cytology (sensitivity 87.9% [95% CI 84.7–90.7], specificity 94.7% [93.5–96.0]) and VIA (54.6% [48.0–61.2], 89.9% [86.8–93.0]). Sensitivity did not vary by study or age (<35 years, 35–49 years, ≥50 years); however, specificity did vary with age (p<0.0001) and was highest in women younger than 35 years (89.4%; 95% CI 86.1–91.5). An increase in the positive cutoff point from the manufacturer recommended 1 pg/mL to 2 pg/mL led to a decrease in the overall HPV DNA positivity from 16.3% to 13.9% (p<0.0001), which could result in a decrease in referral rates, although sensitivity was slightly lower (97.5% to 95.2%). An increase in the cutoff point to 10 pg/mL in women younger than 35 years maintained a high sensitivity 97.7% (95% CI 87.7–99.9) and increased specificity to 93.5% (95% CI 91.9–94.6). HPV DNA testing is highly sensitive and moderately specific for CIN grade 3 or worse, with consistent results across study sites and age groups—including women younger than 35 years. A rise in the cutoff point might be beneficial for future screening programmes in China, especially when screening women younger than 35 years. Fogarty International Clinical Research Scholars Program (Fogarty International Center, US National Institutes of Health, through the International Clinical Research Fellows Program at Vanderbilt University); Academic Capacity Development Program of the Beijing Municipal Commission of Education; and Cancer Institute and Hospital of the Chinese Academy of Medical Sciences.