Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ:: a nested case-control study
Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ:: a nested case-control study
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DOI：
10.1016/s0140-6736(00)02402-8
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发表时间：
2000-06-24
期刊：
影响因子：
168.9
通讯作者：
Melbye, M
中科院分区：
文献类型：
--
作者：
Ylitalo, N;Sorensen, P;Melbye, M
背景某些类型的人乳头瘤病毒(HPV)的持续感染被认为是宫颈肿瘤发生的先决条件。持久性可能取决于某些特征，例如病毒载量，到目前为止，这一点几乎没有得到关注。我们在现场调查了HPV16病毒载量与宫颈癌的关系。方法我们对瑞典参加细胞学筛查的妇女进行了嵌套式病例对照研究。我们使用了一种灵敏的定量聚合酶链式反应方法来估计每名妇女在确诊前长达26年的多次涂片中HPV16的载量。我们计算了C-t值，它随着病毒DNA拷贝数的增加而减少。我们检测了478例患者的2081份涂片和608名对照的1754份涂片。在病例中，我们发现在确诊前13年或更长时间，当许多涂片检查仍在细胞学上正常时，HPV16的载量一直在增加。HPV-16病毒载量高的女性在确诊前十多年的相对风险至少是HPV-16阴性女性的30倍。随着时间的推移，相对风险的增加是恒定的。在25岁以前感染高病毒载量的妇女中，约25%(95%可信区间0.12~0.32)在15年内发展为宫颈原位癌。与HPV-16相关的宫颈原位癌主要发生在长期高病毒载量的HPV-16阳性妇女中。除了细胞学筛查外，还可以使用定量HPV检测来确定高危妇女。
Background Persistent infection with certain types of human papillomavirus (HPV) is believed to be a prerequisite for the development of cervical neoplasia. Persistence may depend on certain characteristics, such as viral load, which has so far been given little attention. We investigated the association between HPV 16 viral load and cervical carcinoma in situ.Methods We did a nested case-control study of women participating in cytological screening in Sweden. We used a sensitive quantitative PCR assay to estimate HPV 16 load in multiple smears for each woman, taken during a period of up to 26 years before diagnosis. We calculated C-t values, which decrease as the number of viral DNA copies increases.Findings 2081 smears from 478 cases and 1754 smears from 608 controls were tested. Among cases, we found a consistently increased load of HPV 16 already 13 years or more before diagnosis, and when many smears were still cytologically normal. Women with high HPV 16 viral loads were at least 30 times the relative risk of HPV-16-negative women more than a decade before diagnosis. The increase in relative risk was constant over time. About 25% of women (95% CI 0.12-0.32) infected with a high viral load before age 25 years developed cervical carcinoma in situ within 15 years.Interpretation Cervical carcinoma in situ associated with HPV 16 occurs mainly in HPV-16-positive women who have consistently high viral loads long term. Women at high risk could be identified by use of a quantitative HPV test in addition to cytological screening.