Natural History of HPV Infections in Mid-adult Women

虽然现在对性活跃的年轻女性的HPV感染的获得和早期自然史了解很多，但对成年中期女性的HPV感染知之甚少。特别是，从新的性伴侣获得新的高危（HR） HPV感染的风险尚不明确，在青春期或青年期获得的HR HPV感染重新激活的频率尚不清楚。此外，与新发感染和再激活感染相关的异常细胞学风险尚不明确。我们将招募1000名年龄在30到50岁之间的女性，她们是华盛顿大学的教职员工或学生，并对她们进行为期两年的半年临床访问。在每次就诊时，执业护士将进行面对面的医疗和性行为访谈（辅以每两周一次的在线性行为日记），并收集宫颈标本进行巴氏涂片检测、HPV基因分型和病毒载量检测。人乳头瘤病毒抗体检测的血清将在登记和离开时收集。妇女还将在每次就诊时自行收集阴道样本进行HPV DNA检测，并选择200名妇女在第6个月至第12个月期间每月进行自我收集。这项纵向研究的具体目的是：1)确定中年妇女新获得和再激活型特异性HR HPV感染的比率和决定因素；2)确定200名妇女（血清学证据表明既往感染且最近没有新的性伴侣）重新激活的概率和决定因素，随后每月阴道自我采集HPV检测6个月；3)比较新获得与再激活型特异性HR HPV感染相关的异常细胞学（未确定意义或更大的非典型鳞状细胞[ASC-US+]）的概率。该项目的研究结果将为临床医生/患者之间的相互作用以及在成年中期妇女人群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.