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宫颈癌的生物学认识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）感染是宫颈癌的确定原因，但不完全清楚HPV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。因为临床干预排除了直接观察这种进展。需要非常规的方法。我们的主要具体目标是；1)量化CIS和侵袭性癌症的绝对和相对风险，作为检测HPV和HPV 16高病毒载量的时间函数，2)评估持续的HPV 16高病毒载量是否是CIS和侵袭性癌症发展的决定因素，3)评估特异性HLA DQ6/DR15单倍型是否与CIS和侵袭性癌症的风险相关。如果这种关联是通过较高的病毒载量和/或HP v的持续存在介导的。4)评估衣原体感染是否与CIS和浸润性癌症的风险相关。基于早期CIS研究的经验（由NCI资助）。我们将利用瑞典独特的先决条件，在计算机登记册中记录了广泛的基于人群的PAP涂片筛查。确定所有CIS和浸润性癌症的病例。还能拿到档案涂片和组织标本。在这项长达25年的完整随访的大型研究基础中，我们将在每个病例组中确定600名患有浸润性癌症的女性，600名患有CIS的女性和600名单独匹配的对照女性。使用经过验证和敏感的PCR分析，将在每个参与者的所有可用涂片中分析病毒DNA的存在-以及HPV 16，以及病毒载量（平均每个人4个，总共约9600个涂片）。将在所有纳入的妇女的第一次涂片中分析HLA和沙眼C。相对风险和相互作用将通过条件逻辑回归估计，绝对风险函数将通过非参数方法估计。

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.