Cervical, Anal & Oral HPV Persistence/Adolescent Girls

描述(由申请人提供)：青少年和年轻女性的宫颈HPV感染率最高，包括感染HPV型，导致显著的发病率和死亡率。FDA批准的针对HPV16和HPV18(65%的宫颈癌存在的高危类型)以及HPV6和11(与大多数生殖器疣有关)的四价疫苗Gardasil(默克公司，新泽西州)的推出，有可能减轻生殖器HPV和疾病的负担。然而，HPV疫苗临床试验只集中在性伴数量有限的低风险女性身上，她们高度遵守疫苗接种时间表；这些女性并不代表那些最有可能患上HPV相关疾病的人。事实上，西班牙裔和非裔美国女性的宫颈癌发病率在美国分别是最高和第二高的，而从 宫颈癌。此外，与HPV相关的肛门和口咽部病变的相关性是一个重要的公共卫生问题，但很少有针对女性的疫苗研究评估肛门和/或口腔HPV。在Gardasil获得批准和释放后，我们启动了一项前瞻性队列研究，对象是住在西奈山青少年健康中心(MSAHC)的性活跃的市中心青少年女性，主要是西班牙裔和非裔美国人。MSAHC是美国最大的综合性青少年初级保健机构。到目前为止，该项目已经招募了640多名性活跃的青少年。在登记时，54%的宫颈、41%的肛门和21%的口腔标本检测到普遍的HPV感染，而疫苗类型(HPV6/11、16和18型)分别在7%、7%和1%的青少年中出现。宫颈HPV疫苗类型的横断面基线检测与接种次数呈负相关。然而，尽管接种了疫苗，但仍有相当多的事件(新的)检测到宫颈HPV16/18感染，尽管接种了疫苗(HPV16/18发病率=每100人年4.2例)；这一比率大大高于疗效试验中报告的比率。我们建议解决少数族裔年轻女性中HPV的健康差距问题，并继续我们对参加MSAHC HPV免疫计划的高危青少年女性进行的队列研究。我们建议延长前瞻性随访(每6个月重复访问一次)，以评估较长期的感染负担，并将样本量增加到略高于1400名受试者，以提高统计能力。这将使我们能够确定突破性HPV感染的风险因素，并整合一个新的目标，以评估青少年发展的心理社会因素和高危青少年的危险行为。从这项研究中获得的数据对于了解大型疫苗试验中没有研究过的HPV疫苗接种对这一群体的真实影响至关重要，并将为未来的HPV和宫颈癌筛查实践提供生物学基础，以及估计疫苗对肛门和口咽部HPV感染的潜在影响。

DESCRIPTION (provided by applicant): Adolescents and young women have the highest rates of cervical HPV, including infection with the HPV types causing significant morbidity and mortality. Introduction of the FDA-approved quadrivalent vaccine GARDASIL (Merck & Co., NJ) targeting HPV16 and HPV18 (high-risk types present in >65% of cervical cancers), as well as HPV6 and 11 (associated with most genital warts), has the potential to reduce the burden of genital HPV and disease. However, HPV vaccine clinical trials focused exclusively on low-risk women with limited numbers of sexual partners, who were highly compliant with the vaccine schedule; these females were not representative of those most at risk to suffer from HPV-related disease. In fact, Hispanic and African-American women have the highest and second highest incidence rates of cervical cancer in the U.S., respectively, and high mortality rates from cervical cancer. In addition, the association of HPV-related anal and oropharyngeal lesions is an important public health concern, yet few if any vaccine studies in women evaluated anal and/or oral HPV. Subsequent to the approval and release of GARDASIL, we initiated a prospective cohort study of sexually-active inner-city, predominantly Hispanic and African-American adolescent women attending the Mount Sinai Adolescent Health Center (MSAHC), the largest comprehensive adolescent primary care facility in the U.S. To date, this project has enrolled more than 640 sexually active teens. Prevalent HPV infection at enrollment was detected in 54% of cervical, 41% of anal, and 21% of oral specimens, with vaccine types (HPV 6/11, 16 & 18) present in 7%, 7% and 1% of adolescents, respectively. The cross-sectional baseline detection of vaccine HPV types in the cervix was inversely associated with the number of vaccinations. However, there was considerable incident (new) detection of cervical HPV 16/18 infection in the cervix not present at enrollment despite vaccination (HPV16/18 incidence=4.2 per 100 person years); a rate substantially above that reported in the efficacy trials. We propose to address the health disparities of HPV in minority young women and continue our cohort study of high-risk adolescent women participating in an HPV immunization program at MSAHC. We propose to extend the prospective follow-up (with repeated visits every 6 months) to evaluate longer term burden of infection, and increase the sample size to just over 1,400 subjects to improve statistical power. This will allow us to determine risk factors for break-through HPV infections, and integrate a new aim to evaluate psychosocial elements of adolescent development and risk behaviors in high-risk teens. The data obtained from this study will be essential to understanding the real-world impact of HPV vaccination in this group not studied in the large vaccine trials and will provide the biological underpinnings for future HPV and cervical cancer screening practices, as well as estimating the potential impact of vaccine on anal and oropharyngeal HPV infections.