NATURAL HISTORY STUDIES OF HPV INFECTION

HPV 感染的自然史研究

基本信息

批准号：
2886756
负责人：
Cosette M Wheeler
金额：
$ 40.11万
依托单位：
UNIVERSITY OF NEW MEXICO
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-09-30 至 2002-07-31
项目状态：
已结题

项目摘要

Because human papillomavirus (HPV) infections appear to be causally linked to most cervical intraepithelial neoplasia (CIN) and cervical carcinoma, it is important to identify determinants of HPV-associated cervical disease. A growing body of evidence suggests an important role for the major histocompatibility complex (MHC) in the etiology of cervical dysplasia and cancer. Further studies in this area are needed to determine the relationship between host-virus interaction and the risk for cervical disease. In addition to understanding host factors, we also need to understand the population dynamics of HPV infections. Currently, HPV "types" have been used as the exposure measure for HPV-associated risk for invasive cervical carcinoma. This level of exposure determination has not provided us with useful prognostic markers for determining risk of progression to invasive cervical carcinoma. Virtually no information is available concerning specific HPV sequences within HPV types associated with risk for invasive cervical carcinoma or presumed precursor lesions. Furthermore, sequence diversity of HPVs, the potential significance of HPV variants and subtypes, and relationships between HPV types have been given little consideration as factors important for determining risk for cervical disease. This grant application requests funding for studies that will examine host- and viral-specific risk factors of HPV-associated cervical disease. We have previously identified HPV-specific MHC associations with severe dysplasia/ClS and invasive cervical carcinoma in case-control studies of Hispanic women. We will characterize HLA class l and II loci in case-control studies of in situ and invasive cervical cancer in Hispanic and non-Hispanic white women from the same geographic location. We will also consider HPV sequence-specific risk factors for cervical disease. We have previously observed an amino acid change in the HPV-16 E6 open reading frame that is associated with high grade squamous intraepithelial lesions. We will examine this observation in a blinded investigation using specimens obtained through an ongoing longitudinal cohort study of HPV and cervical disease being conducted by the NCl. The proposed studies will form a basis for elucidating specific mechanisms of HPV-associated cervical cancer.

因为人乳头瘤病毒 (HPV) 感染似乎存在因果关系大多数宫颈上皮内瘤变（CIN）和宫颈癌，确定 HPV 相关宫颈癌的决定因素非常重要疾病。越来越多的证据表明，主要组织相容性复合体（MHC）在宫颈癌病因学中的作用发育不良和癌症。需要在该领域进行进一步研究以确定宿主与病毒相互作用与宫颈癌风险之间的关系疾病。除了了解宿主因素外，我们还需要了解了解 HPV 感染的群体动态。目前，HPV “类型”已被用作 HPV 相关风险的暴露量度浸润性宫颈癌。这种暴露程度的测定并未为我们提供了有用的预后标志物来确定风险进展为浸润性宫颈癌。几乎没有任何信息可获得有关 HPV 类型内特定 HPV 序列的相关信息有患浸润性宫颈癌或推测癌前病变的风险。此外，HPV 的序列多样性、HPV 的潜在意义已给出变异和亚型，以及 HPV 类型之间的关系很少考虑作为确定宫颈癌风险的重要因素疾病。该拨款申请要求为研究提供资金，这些研究将检查 HPV 相关宫颈癌的宿主和病毒特异性危险因素疾病。我们之前已经确定了 HPV 特异性 MHC 与病例对照中的严重不典型增生/ClS和浸润性宫颈癌对西班牙裔女性的研究。我们将描述 HLA l 类和 II 类基因座的特征西班牙裔原位宫颈癌和浸润性宫颈癌的病例对照研究和来自同一地理位置的非西班牙裔白人女性。我们将还要考虑宫颈疾病的 HPV 序列特异性危险因素。我们之前观察到 HPV-16 E6 开放阅读中的氨基酸变化与高级鳞状上皮内病变相关的框架。我们将使用样本进行盲法调查来检验这一观察结果通过一项正在进行的 HPV 和宫颈癌纵向队列研究获得疾病由 NCl 进行。拟议的研究将构成基础阐明 HPV 相关宫颈癌的具体机制。

项目成果

期刊论文数量（28）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Risk of anal carcinoma in situ in relation to human papillomavirus type 16 variants.

与人乳头瘤病毒 16 型变种相关的肛门原位癌风险。

DOI：
发表时间：
1998
期刊：
Cancer research.
影响因子：
0
作者：
Xi,LF;Critchlow,CW;Wheeler,CM;Koutsky,LA;Galloway,DA;Kuypers,J;Hughes,JP;Hawes,SE;Surawicz,C;Goldbaum,G;Holmes,KK;Kiviat,NB
通讯作者：
Kiviat,NB

Identification of five novel human papillomavirus sequences in the New Mexico triethnic population.

新墨西哥州三民族人群中五种新型人乳头瘤病毒序列的鉴定。

DOI：
10.1093/infdis/170.5.1089
发表时间：
1994
期刊：
The Journal of infectious diseases
影响因子：
0
作者：
Peyton,CL;Wheeler,CM
通讯作者：
Wheeler,CM

Human papillomavirus genotype distributions: implications for vaccination and cancer screening in the United States.

DOI：
10.1093/jnci/djn510
发表时间：
2009-04-01
期刊：
Journal of the National Cancer Institute
影响因子：
0
作者：
Wheeler CM;Hunt WC;Joste NE;Key CR;Quint WG;Castle PE
通讯作者：
Castle PE

A novel human papillomavirus sequence from an international cervical cancer study.

来自国际宫颈癌研究的新型人乳头瘤病毒序列。

DOI：
10.1093/infdis/170.5.1093
发表时间：
1994
期刊：
The Journal of infectious diseases
影响因子：
0
作者：
Peyton,CL;Jansen,AM;Wheeler,CM;Stewart,AC;Peto,J;Bosch,FX;Muñoz,N;Teyssie,AR;Torroella,M;Wabinga,HR
通讯作者：
Wabinga,HR

Hematopoiesis in larval Pseudoplusia includens and Spodoptera frugiperda.