Prospective study on viral load of cervical cancer

描述(由申请人提供)：我们的长期目标是通过提高对生物学的了解和更具成本效益的筛查策略来预防宫颈癌。虽然人乳头瘤病毒(HPV)感染是宫颈癌的一个公认的原因，但HPV的病毒载量是否影响从原位癌(CIS)到浸润性癌的进展和/或与遗传因素相互作用尚不完全清楚。因为临床干预排除了对这种进展的直接观察。我们需要非常规的方法。我们的主要目标是：1)量化自从检测到HPV和HPV 16高病毒载量以来，CIS和浸润性癌症的绝对和相对风险，2)评估持续的HPV 16高病毒载量是否是发展为CIS和浸润性癌症的决定因素，3)评估特定的HLADQ6/DR15单倍型是否与CIS和浸润性癌症的风险相关，以及这种关联是否通过更高的病毒载量和/或Hp V的持久性来调节，以及4)评估衣原体感染是否与CIS和浸润性癌症的风险相关。建立在早期独联体研究的经验基础上(由NCI资助)。我们将利用瑞典在计算机化登记中记录的广泛的以人口为基础的PAP涂片筛查所创造的独特先决条件。确定所有独联体和浸润性癌症的病例。以及获取档案涂片和组织样本。在这个大型研究基地中采用嵌套设计，并进行长达25年的完整随访，我们将确定600名浸润性癌症妇女、600名CIS妇女和600名与每个病例组匹配的对照妇女。使用有效和敏感的聚合酶链式反应分析，病毒DNA的存在--以及HPV16，以及病毒载量--将在每个参与者的所有可用涂片中进行分析(平均每个人四个，总共提供约9600个涂片)。人类白细胞抗原和沙眼衣原体将在所有包括在内的妇女的第一次涂片中进行分析。相对风险和相互作用将通过条件Logistic回归和绝对风险函数通过非参数方法进行估计。

DESCRIPTION (provided by applicant): Our long-term objective is to bring about prevention of cervix cancer through improved biologic understanding and more cost-effective screening strategies. Although human papilloma virus (HPV) infection is an established cause of cervical cancer, it is incompletely known if viral load of HPV influences progression from cancer in situ (CIS) to invasive cancer and/or interacts with genetic factors. Since clinical intervention precludes direct observation of this progression. unconventional approaches are needed. Our main specific aims are to ; 1) quantify the absolute and relative risks for CIS and invasive cancer as a function of time since detected HPV and HPV 16 high viral load, 2) assess whether persistent HPV 16 high viral load is a determinant for development of CIS and invasive cancer, 3) assess whether the specific HLA DQ6/DR15 haplotype is associated with risks for CIS and invasive cancer, and if the association is mediated via a higher viral load and/or persistence of HP V. and 4) assess whether Chlamydia infection is associated with risks for CIS and invasive cancer. Building on experience from an earlier study of CIS (funded by NCI). we will take advantage of unique prerequisites in Sweden created by extensive population-based PAP smear screening documented in computerised registers. ascertainment of all incident cases of CIS and invasive cancer. and access to archival smears and tissue specimens. Using a nested design in this large study base with up to 25 years of complete follow-up, we will identify 600 women with invasive cancer, 600 women with CIS and 600 individually matched control women to each case-group. Using validated and sensitive PCR assays, the presence of viral DNA - and for HPV 16, also the viral load -will be analyzed in all available smears from each participant (on average four per individual, giving a total of about 9600 smears). HLA and C trachomatis will be analyzed in the first smear from all included women. Relative risks and interactions will be estimated by conditional logistic regression and absolute risk functions by non-parametric methods.