Type-specific associations of human papillomavirus load with risk of developing cervical carcinoma in situ

Type-specific associations of human papillomavirus load with risk of developing cervical carcinoma in situ
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DOI:
10.1002/ijc.20480
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发表时间:
2004-12-10
影响因子:
6.4
通讯作者:
Gyllensten, U
Gyllensten, U
中科院分区:
医学1区
文献类型:
--
作者:
Moberg, M;Gustavsson, I;Gyllensten, U

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我们先前已经证明,在不典型增生阴性的Papanicolaou涂片中,人类乳头瘤病毒(HPV)16的高载量与宫颈原位癌(CIS)的风险密切相关。在这里,我们研究了一些最常见的高危HPV类型的HPVDNA的数量,作为进展到宫颈CIS的决定因素。采用实时荧光定量聚合酶链式反应检测457例宫颈鳞状细胞癌和552例正常对照HPV16、18、31、33、35、39、45、52、58和67的标准化病毒载量。在长达26年的时间里收集了2747份妇科健康检查的巴氏涂片档案,对其进行了分析,以评估感染历史期间的病毒载量。宫颈涂片样本在DNA含量上差异很大,强调了HPV载量与样本中细胞数量正常化的必要性。对于所研究的大多数HPV类型,随着病毒载量的增加,发生宫颈CIS的风险增加。每个细胞的拷贝数范围在不同的HPV类型之间没有差异,但HPV16(OR=36.9;95%CI=8.9-153.2)的优势比显著高于HPV31(OR=3.2;95%CI=1.1-9.1)或HPV18/45(OR=2.6;95%CI=1.0-6.4)。因此,HPV病毒载量可能在宫颈鳞状细胞异常涂片阴性的阶段预测未来宫颈CIS的风险,但HPV类型之间的差异需要更密切的关注。(C)2004年Wiley-Liss公司
We have previously shown that high human papillomavirus (HPV) 16 load in Papanicolaou smears negative for dysplasia is strongly associated with risk for carcinoma in situ (CIS) of the cervix. Here we study the amount of HPV DNA for some of the most frequent high-risk HPV types as determinants of progression to cervical CIS. Real-time PCR is used to estimate the normalized viral load of HPV 16, 18, 31, 33, 35, 39, 45, 52, 58 and 67 in 457 cases of cervical CIS and 552 matched population controls. A total of 2,747 archival Pap smears from gynecologic health examinations, collected over a period of up to 26 years, were analyzed to assess viral load during the infection history. Cervical smear samples differ widely in amount of DNA, underscoring the need for normalization of HPV load to number of cells in the sample. The risk of developing cervical CIS increases with higher viral load for most of the HPV types studied. The range of copy numbers per cell does not differ between HPV types but the odds ratio for CIS in the percentile with highest viral load is substantially higher for HPV 16 (OR = 36.9; 95% CI = 8.9-153.2) than for HPV 31 (OR = 3.2; 95% CI = 1.1-9.1) or HPV 18/45 (OR = 2.6; 95% CI = 1.0-6.4). Therefore, HPV viral load may be predictive of future risk of cervical CIS at a stage when smears are negative for squamous abnormalities, but differences between HPV types need closer attention. (C) 2004 Wiley-Liss, Inc.