Natural History of CIN2 in Adolescents

这是一项为期5年的前瞻性研究，旨在：1）检查青少年中高度鳞状上皮内病变（HSIL）的CIN-2（宫颈上皮内病变）子集的自然史，2）确定与CIN 2病变消退相关的免疫学和行为因素。可能影响CIN 2消退的免疫学和行为学因素的研究将包括：持续的局部（宫颈）Th-1样细胞因子反应、对HPV的全身细胞毒性T淋巴细胞（CTL）反应（仅适用于HPV 16阳性女性）、诊断时病变大小、诊断时宫颈不成熟（异位）量和激素避孕。 其他将被监测的可能影响因素包括高风险性行为和结果（多个伴侣，物质使用，怀孕，性传播感染和细菌性阴道病）。 最后，本研究建议比较基线访视时诊断为CIN-1、CIN-2和活检组织学正常的妇女的局部免疫反应。预计约有40 000名19岁或19岁以下的年轻妇女将在北方加州Kaiser Permanente诊所接受为期24个月的宫颈细胞学筛查。将招募细胞学异常的13-19岁青少年（估计N=2680）。 基线检查将包括面谈和宫颈样本的HPV DNA检测和定量细胞因子研究使用逆转录酶聚合酶链反应技术。 将拍摄阴道照片以确定病变大小。 所有样本将在活检前获得。 活检证实CIN 2的患者（N=416）将每3个月接受一次随访，包括面谈、阴道镜检查、HPV DNA检测和细胞学检查，并接受免疫研究（使用实时RT-PCR进行宫颈细胞因子分析，对HPV 16感染的女性进行外周血CTL测定），直至研究结束。 患有CIN-3的女性退出标准治疗。 活检证实为低级别（L）SIL或更低的患者将退出。了解CIN 2的自然史对于构建青少年癌症筛查的成本效益策略至关重要。 此外，定义与CIN 2消退相关的免疫因素将对疫苗和治疗策略具有重要意义，定义临床（包括重复HPV DNA检测）和行为风险将对分诊和咨询策略具有重要意义。

This is a 5 year prospective study designed to: 1) examine the natural history of CIN-2 (cervical intra-epithelial lesions) subset of high grade squamous intra-epithelial lesions (HSIL) among adolescents, and 2) identify immunologic and behavioral factors associated with regression of CIN 2 lesions. The study of immunologic and behavioral factors that may influence CIN 2 regression will include: sustained local (cervical) Th-1 like cytokine response, systemic cytotoxic T lymphocyte (CTL) responses to HPV (for HPV 16 positive women only), size of lesion at diagnosis, amount of cervical immaturity (ectopy) at diagnosis, and hormonal contraception. Other factors that will be monitored for possible effects include high risk sexual behavior and outcomes (multiple partners, substance use, pregnancy, sexually transmitted infections, and bacterial vaginosis). Last, this study proposes to compare local immunologic responses among women who at baseline visit are diagnosed with CIN-1, CIN-2 and normal histology on biopsy. Approximately 40,000 young women 19 years or younger are expected to undergo cervical cytology screening within the Northern California Kaiser Permanente clinics over a 24 month period. Adolescents aged 13-19 years with abnormal cytology (estimated N=2680) will be recruited. Baseline examination will include interview and cervical samples for HPV DNA testing and quantitative cytokine studies using reverse transcriptase polymerase chain reaction techniques. Colpophotographs will be obtained to determine lesion size. All samples will be obtained prior to biopsy. Those with biopsy-confirmed CIN 2 (N=416) will be followed every 3 months using interview, colposcopy, HPV DNA testing, and cytology and undergo immune studies (cervical cell cytokine analysis using real-time RT-PCR and peripheral blood CTL assays on women with HPV 16 infection) until the end of the study. Women with CIN-3 are exited for standard therapy. Those with biopsied confirmed low grade (L) SIL or less will exited. Understanding of the natural history of CIN 2 will be critical in efforts to construct cost-effective strategies for cancer screening in adolescents. In addition, defining immunologic factors associated with CIN 2 regression will have important implications for vaccine and therapeutic strategies and defining clinical (including repeated HPV DNA testing) and behavioral risks will have important implications for triage and counseling strategies.