Department of Viruses, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
J Natl Cancer Inst. 2010 Oct 6;102(19):1478-88. doi: 10.1093/jnci/djq356. Epub 2010 Sep 14.
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.
背景：高危型人乳头瘤病毒（HPV）感染是高级别宫颈上皮内瘤变（CIN）和宫颈癌的主要原因。有研究表明，关于高危型 HPV 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 感染也可能是一种有用的筛查标志物。我们评估了一次性检测高危型 HPV DNA 后和持续性感染个别高危型 HPV 后发生高级别 CIN 的长期风险。
方法：来自丹麦普通人群的 8656 名女性进行了两次检查，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）。女性接受妇科检查和宫颈细胞学检查，并进行 HPV DNA 分析，采用杂交捕获 2 和线探针分析。通过全国丹麦病理学数据库对女性进行了长达 13.4 年的宫颈癌前病变随访。在给定的时间之前发生宫颈病变的绝对风险被估计为随时间变化的函数。
结果：对于细胞学检查正常且第二次检查时同时 HPV16 DNA 阳性的女性，在 12 年的随访中发展为 CIN3 或更高级别病变的估计概率为 26.7%（95%置信区间 [CI] = 21.1%至 31.8%）。HPV18 感染的相应风险为 19.1%（95%CI=10.4%至 27.3%），HPV31 为 14.3%（95%CI=9.1%至 19.4%），HPV33 为 14.9%（95%CI=7.9%至 21.1%）。除 HPV16、HPV18、HPV31 或 HPV33 以外的高危型 HPV 感染后发生 CIN3 或更高级别病变的绝对风险为 6.0%（95%CI=3.8%至 8.3%）。第二次检查时 HPV16 DNA 均为阳性的女性在 12 年内发生 CIN3 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 检测阴性的女性发生 CIN3 或更高级别病变的风险为 3.0%（95%CI=2.5%至 3.5%）。
结论：HPV16、HPV18、HPV31 和 HPV33 感染，尤其是 HPV16 的持续性感染，与进展为高级别宫颈病变的高绝对风险相关。结果表明 HPV 基因分型在宫颈癌筛查中有潜在价值。鉴于 HPV DNA 阴性的女性多年来保持着发生 CIN3 或更高级别病变的低风险，对这些女性进行频繁筛查可能没有必要。
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