Cervical, Anal & Oral HPV Persistence/Adolescent Girls

描述（由研究者提供）：青少年和年轻女性的宫颈HPV感染率最高，包括感染可导致显著发病率和死亡率的HPV类型。引入FDA批准的四价疫苗（Gardasil（R），Merck & Co.）靶向HPV 16和HPV 18（>65%的宫颈癌中存在的高危[HR]类型）以及HPV 6和11（与大多数生殖器疣相关），有可能减少生殖器HPV和疾病的负担。HPV疫苗临床试验仅关注性伴侣数量有限的低风险女性，这些女性高度遵守疫苗接种计划;这些女性并不代表那些最有可能患HPV相关疾病的女性。事实上，西班牙裔和非洲裔美国妇女在美国的宫颈癌发病率最高和第二高，以及宫颈癌的高死亡率。此外，HPV相关肛门和/或口咽病变的关联是一个重要的公共卫生问题，但很少有女性疫苗研究评估了这些部位的HPV。继批准和发布GARDASIL后，我们开始了一项前瞻性队列研究，研究对象是在西奈山青少年健康中心（MSAHC）（美国最大的综合性青少年初级保健机构）就诊的性活跃的市中心少数民族青少年女性。迄今为止，该项目已招募了750多名12-19岁的性活跃青少年。在54%的宫颈、42%的肛门和20%的口腔标本中检测到了入组时的HPV感染，疫苗类型（HPV 6/11、16和18）分别在7%、6%和1%的青少年中存在。与未接种疫苗的青少年相比，接种三剂疫苗的青少年宫颈HPV疫苗类型的风险显著降低。关于宫颈外部位，当与未接种疫苗的青少年相比时，在肛门和口腔中观察到HR-HPV疫苗类型的非显著减少。尽管接种了疫苗，但在入组时仍有相当多的宫颈HPV 16/18感染事件（4.2/100人年）未检出;观察到的这一发生率大大高于疗效试验中报告的发生率。我们建议通过继续对在MSAHC参加HPV免疫接种计划的高危青少年女性进行队列研究，来解决少数民族年轻女性HPV的健康差异。我们建议延长前瞻性随访（每6个月重复访视一次），以评估长期感染负担，并将样本量增加至略高于1，400例受试者，以提高统计功效。样本量的增加和更长时间的随访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，以评估青少年发育和青少年高危行为的心理社会因素。从这项研究中获得的数据对于了解HPV疫苗接种在疫苗试验中未研究的该组中的“现实世界”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/或口咽HPV感染的潜在影响。

DESCRIPTION (provided by investigator): 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(R), Merck & Co.) targeting HPV16 and HPV18 (high-risk [HR] 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. 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 associations of HPV-related anal and/or oropharyngeal lesions are an important public health concern, yet few vaccine studies in women have evaluated HPV at these sites. Subsequent to the approval and release of GARDASIL, we initiated a prospective cohort study of sexually- active, inner-city, minority 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 750 sexually active teens between the ages of 12-19. Prevalent HPV infection at enrollment was detected in 54% of cervical, 42% of anal and 20% of oral specimens, with vaccine types (HPV 6/11, 16 & 18) present in 7%, 6% and 1% of adolescents, respectively. Adolescents who had three doses were at significantly reduced risk of HPV vaccine types in the cervix compared to those who had no vaccination. With respect to extracervical sites, non-significant reductions were observed for HR-HPV vaccine types in the anal and oral cavities when comparing fully vaccinated to non-vaccinated adolescents. There was considerable incident (4.2 per 100 person years) detection of cervical HPV 16/18 infection not present at enrollment despite vaccination; this observed rate is substantially above that reported in the efficacy trials. We propose to address the health disparities of HPV in minority young women by continuing our cohort study of high-risk adolescent females participating in an HPV immunization program at MSAHC. We propose to extend the prospective follow-up (with repeat visits every 6 months) to evaluate the long-term burden of infection and to increase sample size to just over 1,400 subjects to improve statistical power. The increased sample size and longer follow-up will allow us to determine risk factors for break-through HPV infections, as well as integrate a new aim to evaluate psychosocial elements of adolescent development and high-risk behaviors in teens. Data obtained from this study will be essential to understanding the 'real-world' impact of HPV vaccination in this group not studied in the 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/or oropharyngeal HPV infections.