Role of estrous cycle and contraceptives in anogenital papillomavirus infection

动情周期和避孕药在肛门生殖器乳头瘤病毒感染中的作用

• 批准号: 9016827
• 负责人: NEIL D CHRISTENSEN
• 金额: $ 23.21万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9016827
• 关键词: Address; Anus; Cervarix; Cervix Uteri; Clinical Research; Contraceptive Agents; Contraceptive Usage; Coupled; Data; Development; Diestrus; Disease; Disease Progression; Dysplasia; Economics; Estrogen Receptors; Estrous Cycle; Estrus; Female; Gardasil; Genital system; Goals; Histology; Hormonal; Human Papilloma Virus Vaccine; Human Papillomavirus; Human papilloma virus infection; Individual; Infection; Intervention; Irrigation; Life Cycle Stages; Light; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Menstrual cycle; Modeling; Monitor; Mucous Membrane; Mus; Nude Mice; Papillomavirus; Papillomavirus Infections; Pathology; Predisposition; Production; Progesterone Receptors; Public Health; Role; Sampling; Sexually Transmitted Diseases; Site; Staging; Testing; Therapeutic; Therapeutic Effect; Tissues; Vaccines; Vagina; Viral; Virus; Virus Diseases; Virus Shedding; Woman; Work; base; effective therapy; hormonal contraception; innovation; male; mouse model; pre-clinical; prophylactic; public health relevance; research study; social; uptake

 DESCRIPTION (provided by applicant): Human papillomavirus (HPV) infection is the most common sexually transmitted disease and claims more than 270,000 women's lives from cervical cancer annually. Two protective HPV vaccines hold promise to substantially reduce HPV related cancers in the coming years. However, these vaccines offer no protection against pre-existing infections. In addition, the uptake of these vaccines is very low worldwide due to social and economic barriers. Therefore, HPV associated diseases and cancers will continue to be a public health problem until an effective therapeutic treatment is available. Although both males and females are exposed to HPV infections, more severe pathology is found in females, especially at ano-genital sites. The long term goal of this proposal is to gain a better understanding of the role of the menstrual cycle and hormonal contraceptives in papillomavirus infection and persistence. We propose to study papillomavirus infections at ano-genital sites using the newly discovered mouse papillomavirus (MmuPV1), which induces mild to high grade dysplasia at different ano-genital sites. We hypothesize that the changes in the ano-genital mucosal microenvironment during the menstrual cycle influence papillomavirus susceptibility and persistence in females. To test our primary hypotheses, we propose the following two specific aims. Specific Aim 1: To define the role of the estrous cycle in viral susceptibility at vaginal and anal mucosa. We hypothesize that different stages of the estrous cycle show differential susceptibility to viral infection at ano-genital sites. We will synchronize female mic at either the estrus or diestrus stage and infect them at both vaginal and anal sites. Viral production will be analyzed by Q-PCR from lavage samples. The resulting data will determine whether these stages of the estrous cycle are more or less susceptible to viral infection at vaginal and/or anal sites. Specific Aim 2: To determine the role of contraceptives on viral infection and persistence at vaginal and anal mucosa. We hypothesize that hormonal contraceptive usage increases viral infection and persistence. We will test two of the most commonly prescribed hormonally-based contraceptives and a non-hormonal contraceptive in this study. Lavage samples from virally infected vagina and anus will be collected for viral copy number quantification and histological analysis. Together, these studies promise to reveal new information about papillomavirus infections at female ano-genital sites. In particular, they should shed light on the role of the menstrual cycle and the influence of contraceptives on the disease. The proposed work will provide new evidence to guide individuals in making informed decisions about their contraceptive usage.

 描述(申请人提供)：人类乳头瘤病毒(HPV)感染是最常见的性传播疾病，每年有超过27万名妇女死于宫颈癌。两种保护性HPV疫苗有望在未来几年大幅减少HPV相关癌症。然而，这些疫苗对先前存在的感染没有提供保护。此外，由于社会和经济障碍，这些疫苗在世界范围内的使用量非常低。因此，在获得有效的治疗方法之前，HPV相关疾病和癌症将继续是一个公共卫生问题。虽然男性和女性都暴露于HPV感染，但女性的病理更严重，特别是在无生殖器部位。这项建议的长期目标是更好地了解月经周期和荷尔蒙避孕药在乳头瘤病毒感染和持久性中的作用。我们建议使用新发现的小鼠乳头瘤病毒(MmuPV1)来研究非生殖器部位的乳头状瘤病毒感染，该病毒可在不同的非生殖器部位引起轻度到高度的不典型增生。我们假设月经周期中无生殖器粘膜微环境的变化会影响女性对乳头状瘤病毒的易感性和持久性。为了检验我们的主要假设，我们提出了以下两个具体目标。具体目标1：明确动情周期在阴道和肛门粘膜病毒易感性中的作用。我们假设发情周期的不同阶段表现出对非生殖器部位病毒感染的不同易感性。我们将在发情期或间情期同步雌性麦克风，并在阴道和肛门感染它们。病毒产量将通过Q-PCR从灌洗液样本中进行分析。由此得出的数据将决定发情周期的这些阶段在阴道和/或肛门部位是否更容易受到病毒感染。具体目的2：确定避孕药对阴道和肛门粘膜病毒感染和持久性的作用。我们假设荷尔蒙避孕药的使用会增加病毒感染和持久性。在这项研究中，我们将测试两种最常用的激素避孕药和一种非激素避孕药。将从受病毒感染的阴道和肛门收集灌洗液样本进行病毒拷贝数量化和组织学分析。总而言之，这些研究有望揭示女性生殖器外部位乳头瘤病毒感染的新信息。特别是，他们应该 阐明月经周期的作用和避孕药对疾病的影响。这项拟议的工作将提供新的证据，指导个人就其避孕措施的使用做出明智的决定。