Long-term Absolute Risk of Cervical Intraepithelial Neoplasia Grade 3 or Worse Following Human Papillomavirus Infection: Role of Persistence
Long-term Absolute Risk of Cervical Intraepithelial Neoplasia Grade 3 or Worse Following Human Papillomavirus Infection: Role of Persistence
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DOI：
10.1093/jnci/djq356
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发表时间：
2010-10-01
影响因子：
10.3
通讯作者：
Iftner, Thomas
中科院分区：
文献类型：
--
作者：
Kjaer, Susanne K.;Frederiksen, Kirsten;Iftner, Thomas
背景高危型人乳头瘤病毒（HPV）感染是高度宫颈上皮内瘤变（CIN）和宫颈癌的主要原因。有人建议，有关高危HPV类型特异性感染的信息可能会使宫颈癌筛查更有效。持续性HPV感染也可能是一个有用的筛查标志物。我们评估了高危型HPV DNA一次性检测后和个体高危型HPV持续感染后高级别CIN的长期风险。方法对来自丹麦普通人群的8656名女性进行两次检查，间隔2年（第一次研究检查：1991年5月15日至1993年1月31日;第二次研究检查：1993年10月1日至1995年1月31日）。这些妇女接受了妇科检查和宫颈细胞学检查，并通过Hybrid Capture 2和线性探针检测法采集拭子进行HPV DNA分析。这些妇女通过丹麦全国病理学数据库进行了长达13.4年的宫颈肿瘤随访。在一个给定的时间之前，发展宫颈病变的绝对风险估计作为一个函数的time.Results的妇女与正常的细胞学结果同时HPV 16 DNA阳性的第二次检查，估计的概率发展CIN 3级（CIN 3）或更糟的12年内的后续行动是26.7%（95%置信区间[CI] = 21.1%至31.8%）。HPV 18感染者的相应风险为19.1%（95%CI = 10.4%~ 27.3%），HPV 31感染者的相应风险为14.3%（95%CI = 9.1%~ 19.4%），HPV 33感染者的相应风险为14.9%（95%CI = 7.9%~ 21.1%）。除HPV 16、HPV 18、HPV 31或HPV 33以外的高危型HPV感染后发生CIN 3或更严重的绝对风险为6.0%（95% CI = 3.8%至8.3%）。在两次检查均为HPV 16 DNA阳性的妇女中，在第二次检查后12年内发生CIN 3或癌症的估计绝对风险为47.4%。（95% CI = 34.9%至57.5%）;相比之下，杂交捕获2试验阴性后CIN 3或更差的风险为3.0%结论HPV 16、HPV 18、HPV 31和HPV 33感染，尤其是HPV 16持续感染与宫颈病变进展的绝对危险性相关。结果表明，基因分型在宫颈癌筛查中的潜在价值。鉴于HPV DNA阴性的妇女多年来保持其CIN 3或更糟的低风险，因此对这些妇女进行频繁的筛查可能是不必要的。
Background Infection with high-risk human papillomavirus (HPV) is the main cause of high-grade cervical intraepithelial neoplasia (CIN) and cancer. It has been suggested that information about high-risk HPV type-specific infection might make cervical cancer screening more effective. Persistent HPV infection could also be a useful screening marker. We estimated the long-term risk of high-grade CIN after one-time detection of high-risk HPV DNA and after persistent infection with individual high-risk HPV types.Methods A cohort of 8656 women from the general population of Denmark was examined twice, 2 years apart (first study examination: May 15, 1991, to January 31, 1993; second study examination: October 1, 1993, to January 31, 1995). The women underwent a gynecological examination and cervical cytology and had swabs taken for HPV DNA analysis by the Hybrid Capture 2 and line probe assays. The women were followed up through the nationwide Danish Pathology Data Bank for cervical neoplasia for up to 13.4 years. The absolute risk of developing cervical lesions before a given time was estimated as a function of time.Results For women with normal cytological findings who were concurrently HPV16 DNA positive at the second examination, the estimated probability of developing CIN grade 3 (CIN3) or worse within 12 years of follow-up was 26.7% (95% confidence interval [CI] = 21.1% to 31.8%). The corresponding risks among those infected with HPV18 was 19.1% (95% CI = 10.4% to 27.3%), with HPV31 was 14.3% (95% CI = 9.1% to 19.4%), and with HPV33 was 14.9% (95% CI = 7.9% to 21.1%). The absolute risk of CIN3 or worse after infection with high-risk HPV types other than HPV16, HPV18, HPV31, or HPV33 was 6.0% (95% CI = 3.8% to 8.3%). The estimated absolute risk for CIN3 or cancer within 12 years of the second examination among women who were HPV16 DNA positive at both examinations was 47.4% (95% CI = 34.9% to 57.5%); by contrast, the risk of CIN3 or worse following a negative Hybrid Capture 2 test was 3.0% (95% CI = 2.5% to 3.5%).Conclusion HPV16, HPV18, HPV31, and HPV33 infection and especially HPV16 persistence were associated with high absolute risks for progression to high-grade cervical lesions. The results indicate the potential value of genotyping in cervical cancer screening. Given that HPV DNA-negative women retained their low risk of CIN3 or worse for many years, frequent screening of these women may be unnecessary.