HPV in Adolescent Women

描述（由申请人提供）：生殖器感染人乳头瘤病毒（HPV）的高峰后不久，年轻女性成为性活跃。年轻女性中的大多数HPV感染在标准PCR检测中在几个月内变得不可检测，这表明在大多数情况下感染“清除”。然而，缺乏实际病毒清除的证据。如果HPV持续在低水平而不是清除，它可能会重新激活并在以后的生活中被检测到，从而导致临床疾病。低水平的持续性可以解释HPV检测的第二个高峰和老年妇女HPV相关疾病的增加。由于HPV是宫颈癌的病原体，因此了解HPV是否真的在年轻女性中清除，或者HPV是否仍然存在于使用当前方法无法检测的水平，这一点至关重要。因此，我们将描述青春期女性中类型特异性HPV感染、明显清除和病毒再激活（与再感染）的模式。为了实现这些目标，我们将使用高灵敏度的类型特异性巢式PCR检测，以在标准PCR定义的感染明显清除期间潜在地识别HPV持续存在。我们还将确定与标准PCR相比，巢式PCR定义的HPV持续时间。我们还将确定是否明显清除感染的特定HPV类型，后来成为检测是由于再激活或再感染。我们还将进行实验，以确定低水平的持久性是否与HPV整合有关，这是HPV致癌的关键事件。最后，我们将开发生存模型来探索与HPV持续性相关的因素，以确定较长时间的HPV检测是否与特定的性行为相关。 宫颈癌是由人乳头瘤病毒（HPV）感染引起的。我们的研究旨在确定HPV感染是否会在某些女性中持续存在，或者大多数感染是否会在大多数女性中清除。这些信息对于确定为什么一些但不是所有HPV感染的女性会患上癌症很重要。

DESCRIPTION (provided by applicant): Genital infections with human papillomavirus (HPV) peak soon after young women become sexually active. Most HPV infections in young women become undetectable within a few months in standard PCR assays, suggesting that infections "clear" in the majority of cases. However, proof of actual viral clearance is lacking. If HPV persists at low levels rather than clears, it could potentially reactivate and become detectable later in life, and thus contribute to clinical illness. Low level persistence could explain the second peak in HPV detection and the increase in HPV-related disease in older women. Because HPV is the causative agent of cervical cancer, it is critically important to understand whether HPV actually clears in young women, or if HPV remains present at levels undetectable using current methods. We will therefore characterize patterns of type specific HPV infection, apparent clearance, and virus reactivation (vs. re-infection) among adolescent women. To accomplish these goals, we will use type-specific, nested PCR assays of high sensitivity to potentially identify HPV persistence during periods of apparent clearance of infection as defined by standard PCR. We will also determine the duration of HPV persistence defined by nested PCR compared to standard PCR. We will also determine if apparently cleared infection of a specific HPV type that becomes detected later is due to reactivation or re-infection. We will also perform experiments to determine if low-level persistence is associated with HPV integration, a key event in carcinogenesis of HPV. Lastly, we will develop survival models to explore factors associated with HPV persistence to determine if longer periods of HPV detection will be associated with specific sexual behaviors. PUBLIC HEALTH RELEVANCE: Human papillomavirus (HPV) infection is the cause of cervical cancer. Our study is designed to determine if HPV infections can persist in some women, or if most infections actually clear in most women. This information is important in determining why some, but not all women with HPV infection develop cancer.