Occurrence, determinants and dynamics of HPV coinfections in a cohort of Montreal university students
Background: Coinfections with multiple types of human papillomavirus (HPV) are a common occurrence among HPV-infected individuals, but the clinical 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 HPV susceptibility, though this has been rarely studied to date. Purpose: The purpose of this project was to examine the occurrence, determinants and dynamics of HPV coinfections in a cohort of university students in order to explore the relationship(s) between coinfections, lifestyle factors and immunological susceptibility. Methods: This project is based on a secondary analysis of data from the McGill-Concordia Cohort, a longitudinal study of the natural history of HPV infection in 621 female university students in Montreal, Quebec. Participants 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 risk behaviours. Two definitions of coinfections were used: cumulative coinfection over follow-up and concurrent coinfection at each visit. Kaplan-Meier techniques were used to estimate incidence and duration of coinfections and multiple logistic regression was used to identify determinants of coinfections and associations between coinfections and squamous intraepithelial lesions (SIL). Results: More than half of the cohort became infected with HPV and of those, over 60% acquired multiple HPV types over follow-up. Incidence of coinfections was significantly increased among HPV-infected women at enrollment. The most important determinant of coinfection occurrence was number of sexual partners (both lifetime and new), though some genes of the immune response (HLA-DQB1*06:02, HLA-G*01:01:03 and HLA-G*01:01:05) were also significant predictors. Women with coinfections, particularly those with 4+ HPV types, also had longer infection durations and greatly increased odds of SIL. Conclusions: Women with coinfections acquire new HPV types at an increased rate and have greater HPV persistence and occurrence of SIL, which may indicate immunological susceptibility. HPV coinfections mainly occur due to increased sexual activity but a decreased immune response to the virus may also be involved in a subset of women.
Human papillomavirus, coinfections, cohort study, incidence, persistence, risk factors, cervical lesions, immune susceptibility
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