Smith Michaela A, Tellier Pierre-Paul, Roger Michel, Coutlée Francois, Franco Eduardo L, Richardson Harriet
Authors' Affiliations: Department of Public Health Sciences, Queen's University, Kingston, Ontario; Departments of Family Medicine, Oncology, and Epidemiology, Biostatistics, and Occupational Health, McGill University; and Département de Microbiologie, Infectiologie, et Immunologie, Université de Montréal and Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):812-22. doi: 10.1158/1055-9965.EPI-13-1255. Epub 2014 Feb 25.
Human papillomavirus (HPV) coinfections are common among HPV-infected individuals, but the significance and etiology of these infections remain unclear. Though current evidence suggests that women with coinfections have increased HPV exposure (i.e., more sexual partners), it is also hypothesized that these women may represent a subgroup with increased biologic susceptibility. This study sought to examine determinants of coinfections in a cohort of young women, examining both behavioral and biologic factors related to HPV acquisition over time.
Female university students (n = 537) in Montreal, Canada, were followed for 2 years at 6-month intervals. At each visit, cervical specimens were collected for cytology and HPV testing, and women completed a questionnaire about lifestyle and behavior. HLA alleles were typed from purified DNA collected from cervical specimens. Two definitions of coinfections were used: cumulative coinfection over follow-up and concurrent coinfection at each visit. Multiple logistic regression was used to determine predictors of both cumulative and concurrent coinfections using baseline and time-dependent covariates.
The most consistent determinant of coinfection occurrence was number of sexual partners, though several genes of the immune response (HLA-DQB106:02, HLA-G01:01:03, and HLA-G*01:01:05) were also identified as significant predictors of cumulative coinfections.
HPV coinfections mainly occur due to increased sexual activity, but biologic susceptibility may also be involved in a subset of women. Immunologic factors may put women at greater risk of coinfections over the long term, but short-term risk is almost exclusively driven by modifiable sexual behaviors.
Additional research should continue to further identify immunologic biomarkers of HPV susceptibility.
人乳头瘤病毒（HPV）合并感染在HPV感染个体中很常见，但这些感染的意义和病因仍不清楚。尽管目前的证据表明合并感染的女性有更高的HPV暴露风险（即更多性伴侣），但也有人推测这些女性可能代表了生物易感性增加的一个亚组。本研究旨在调查一组年轻女性中合并感染的决定因素，同时研究与HPV感染相关的行为和生物学因素随时间的变化情况。
对加拿大蒙特利尔的537名女大学生进行为期2年的随访，每6个月进行一次。每次随访时，收集宫颈标本进行细胞学和HPV检测，女性完成一份关于生活方式和行为的问卷。从宫颈标本中提取的纯化DNA进行HLA等位基因分型。使用了两种合并感染的定义：随访期间的累积合并感染和每次随访时的同时合并感染。采用多元逻辑回归分析，利用基线和随时间变化的协变量确定累积合并感染和同时合并感染的预测因素。
合并感染发生的最一致决定因素是性伴侣数量，不过免疫反应的几个基因（HLA-DQB106:02、HLA-G01:01:03和HLA-G*01:01:05）也被确定为累积合并感染的重要预测因素。
HPV合并感染主要是由于性活动增加，但生物易感性也可能在一部分女性中起作用。免疫因素可能使女性长期面临更高的合并感染风险，但短期风险几乎完全由可改变的性行为驱动。
进一步的研究应继续深入确定HPV易感性的免疫生物标志物。
