Natural History of HPV Infections in Mid-adult Women

虽然现在人们对性行为活跃的年轻女性感染HPV的获得性和早期自然病史了解很多，但对中年女性的HPV感染知之甚少。特别是，从新为性伴侣那里感染新的高危(HR)HPV病毒的风险尚未确定，在青春期或年轻成年期获得的高危HPV感染重新激活的频率也未知。此外，与新感染和再激活感染相关的细胞学异常风险尚不确定。我们将招收1000名年龄在30岁到50岁之间的女性，她们是华盛顿大学的教职员工或学生，并跟踪她们进行为期两年的两年一次的临床访问。在每次就诊时，一名护士将进行面对面的医疗和性行为访谈(辅之以两周一次的在线性行为日记)，并收集宫颈样本进行巴氏杆菌检测、HPV基因分型和病毒载量测试。HPV抗体检测的血清将在登记和出境探视时收集。女性还将在每次就诊时自行采集阴道样本进行HPV DNA检测，并将选择200名女性在6个月至12个月就诊期间每月进行自我采集。这项纵向研究的具体目的是1)确定中年女性新获得和重新激活的HPV感染的发生率和决定因素；2)确定200名女性(有血清学证据且最近没有新进性伴侣)在每月进行HPV检测后再次激活的概率和决定因素；以及3)比较细胞学异常(意义不明或更大的非典型鳞状细胞[ASC-US])与新获得和重新激活的特定HPV感染相关的概率。该项目的发现将为临床医生/患者的互动以及在中年成年妇女群体中实施预防性疫苗和宫颈癌筛查指南的制定提供信息。

While much is now known about the acquisition and early natural history of HPV infections in sexually active young women, little is known about HPV infections in mid-adult women. In particular, the risk of acquiring new high-risk (HR) HPV infections from new sex partners is undefined and the frequency of reactivating HR HPV infections that were acquired in adolescence or young adulthood is unknown. Furthermore, the risk of abnormal cytology associated with new versus reactivated infections is undefined. We will enroll 1,000 women between the ages of 30 to 50 who are faculty, staff, or students at the University of Washington andfollow them with bi-annual clinical visits for two years. At each visit, a nurse practitioner will conduct a faceto-face medical and sexual behavior interview (supplemented with bi-weekly online sexual behavior diaries) and collect cervical specimens for Pap testing and for HPV genotyping and viral load testing. Serum for HPV antibody testing will be collected at the enrollment and exit visits. Women will also self-collect vaginal samples for HPV DNA testing at each visit, and a subset of 200 women will be selected to do monthly selfcollections between the month 6 and month 12 visits. The specific aims of this longitudinal study are to 1) define rates and determinants of newly acquired and reactivated type-specific HR HPV infections in midadult women; 2) define the probability and determinants of reactivation in a subset of 200 women (with serologic evidence of prior infection and no recent new sex partners) followed with monthly vaginal selfcollections for HPV testing for 6 months; and 3) compare the probability of abnormal cytology (atypical squamous cells of undetermined significance or greater [ASC-US+]) associated with newly acquired versus re-activated type-specific HR HPV infections. Findings from this project will inform clinician/patient interactions and development of prophylactic vaccine implementation and cervical cancer screening guidelines in populations of mid-adult women.