Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20882, USA.
Lancet Oncol. 2011 Jul;12(7):663-72. doi: 10.1016/S1470-2045(11)70145-0. Epub 2011 Jun 16.
Concurrent testing for human papillomavirus (HPV) and cervical cytology (co-testing) is an approved alternative to cytology alone in women aged 30 years and older. We aimed to assess the safety in routine clinical practice of 3-year screening intervals for women testing negative for HPV with normal cytology and to assess if co-testing can identify women at high risk of cervical cancer or cervical intraepithelial neoplasia grade 3 (CIN3) or worse over 5 years.
We assessed the 5-year cumulative incidence, starting in 2003-05, of cervical cancer and CIN3 or worse for 331,818 women aged 30 years and older who enrolled in co-testing at Kaiser Permanente Northern California (Berkeley, CA, USA) and had adequate enrolment co-test results. Follow-up continued until Dec 31, 2009. We defined cumulative incidence to include prevalence at enrolment and incidence after enrolment. Prevalence at enrolment was defined as the ratio of women diagnosed with each outcome on the biopsy visit immediately after their enrolment screening visit to the total enrolled women. At screening visits only HPV test and Pap smear samples were collected, and at biopsy visits colposcopically directed biopsies were taken. To estimate post-enrolment incidence, we used Weibull survival models.
In 315,061 women negative by HPV testing, the 5-year cumulative incidence of cancer was 3.8 per 100,000 women per year, slightly higher than for the 306,969 who were both negative by HPV and Pap testing (3.2 per 100,000), and half the cancer risk of the 319,177 who were negative by Pap testing (7.5 per 100,000). 313,465 (99.5%) women negative by HPV testing had either normal cytology or equivocal abnormalities. Abnormal cytology greatly increased cumulative incidence of CIN3 or worse over 5 years for the 16,757 positive by HPV testing (12.1%vs 5.9%; p<0.0001). By contrast, although statistically significant, abnormal cytology did not increase 5-year risk of CIN3 or worse for women negative by HPV testing to a substantial level (0.86%vs 0.16%; p=0.004). 12,208 (73%) of the women positive by HPV testing had no cytological abnormality, and these women had 258 (35%) of 747 CIN3 or adenocarcinoma in situ, [corrected] 25 (29%) of 87 cancers, and 17 (63%) of 27 adenocarcinomas.
For women aged 30 years and older in routine clinical practice who are negative by co-testing (both HPV and cytology), 3-year screening intervals were safe because a single negative test for HPV was sufficient to reassure against cervical cancer over 5 years. Incorporating HPV testing with cytology also resulted in earlier identification of women at high risk of cervical cancer, especially adenocarcinoma. Testing for HPV without adjunctive cytology might be sufficiently sensitive for primary screening for cervical cancer.
Intramural Research Program of the US National Cancer Institute/NIH/DHHS, and the American Cancer Society.
人乳头瘤病毒（HPV）与宫颈细胞学联合检测（联合检测）已被批准用于 30 岁及以上女性替代单独细胞学检测。我们旨在评估在常规临床实践中，对于 HPV 阴性且细胞学正常的女性，3 年筛查间隔的安全性，并评估联合检测是否能在 5 年内识别出患有宫颈癌或高级别宫颈上皮内瘤变（CIN3）或更严重病变的高危女性。
我们评估了 2003-05 年期间在 Kaiser Permanente Northern California（加利福尼亚州伯克利市）参加联合检测且有足够的入组联合检测结果的 331818 名 30 岁及以上女性的 5 年累计宫颈癌和 CIN3 或更严重病变的发生率。随访持续到 2009 年 12 月 31 日。我们将累计发生率定义为包括入组时的患病率和入组后的发病率。入组时的患病率定义为在入组筛查就诊后立即进行活检的每位女性中每个结局的诊断比例。在筛查就诊时仅采集 HPV 检测和巴氏涂片样本，在活检就诊时进行阴道镜指导下的活检。为了估计入组后的发病率，我们使用威布尔生存模型。
在 315061 名 HPV 检测阴性的女性中，癌症的 5 年累计发病率为每年每 100000 名女性 3.8 例，略高于 HPV 和巴氏涂片检测均为阴性的 306969 名女性（每年每 100000 名女性 3.2 例），也低于巴氏涂片检测阴性的 319177 名女性（每年每 100000 名女性 7.5 例）。313465 名（99.5%）HPV 检测阴性且细胞学正常或有不明确异常的女性。对于 HPV 检测阳性的 16757 名女性，细胞学异常显著增加了 5 年 CIN3 或更严重病变的累计发病率（12.1%比 5.9%；p<0.0001）。相比之下，尽管具有统计学意义，但 HPV 检测阴性的女性的细胞学异常并未显著增加 5 年 CIN3 或更严重病变的风险，仅增加了 0.86%比 0.16%（p=0.004）。12208 名（73%）HPV 检测阳性的女性没有细胞学异常，这些女性中有 258 名（35%）患有 CIN3 或原位腺癌，[更正]25 名（29%）患有癌症，17 名（63%）患有腺癌。
在常规临床实践中，对于 HPV 联合检测（HPV 和细胞学）阴性的 30 岁及以上女性，3 年筛查间隔是安全的，因为 HPV 单次阴性检测足以在 5 年内排除宫颈癌的风险。HPV 联合细胞学检测也能更早地识别出宫颈癌高危女性，尤其是腺癌高危女性。HPV 检测不结合细胞学检测可能足以作为宫颈癌的一线筛查方法。
美国国立癌症研究所/国家卫生研究院/美国卫生与公众服务部的内部研究计划和美国癌症协会。
