Determinants of Human Papillomavirus Coinfections among Montreal University Students: The Influence of Behavioral and Biologic Factors

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-DQB1*06:02, HLA-G*01:01:03, 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.