Female Human Papillomavirus Infection Associated with Increased Risk of Infertility: A Nationwide Population-Based Cohort Study
Li-Chuan Hsu, Kuan‐Hao Tsui, James Cheng‐Chung Wei, Hei‐Tung Yip, Yao‐Min Hung, Renin Chang
Abstract
OBJECTIVE: This study investigated whether women with a history of human papillomavirus (HPV) infection have an increased risk of infertility. MATERIAL AND METHODS: All patients with an HPV infection (n = 11,198) in Taiwan's National Health Insurance Research Database (2000-2012) were propensity score matched with control subjects (n = 11,198) without an HPV infection by age, sex, index year, and relevant co-morbidities. Both groups were tracked until a diagnosis of infertility was recorded. The Chi-square test was used to analyze the distribution of demographic characteristics in the HPV group and non-HPV group. A Cox proportional hazards regression was used to estimate the hazard ratios (HRs) for the development of infertility, adjusting for age, sex, and co-morbidities. The Kaplan-Meier method was used to plot the cumulative incidence curves. We also performed negative controls to test for possible unmeasured confounding. RESULTS: The HPV cohort had a higher risk of infertility. The adjusted HR (aHR) was found to be 1.39 (95% CI = 1.19-1.63) after adjusting for demographic characteristics and relevant co-morbidities. In the age subgroup analysis, patients with an HPV infection had an increased risk of infertility compared to the non-HPV cohort in the group aged 26 to 35 years (aHR, 1.53; 95% CI = 1.24-1.88). As we used propensity score matching to treat measurable confounders and negative controls to access unmeasured confounders, the findings of the study are robust. CONCLUSIONS: Among females of reproductive age, HPV infection is a potential risk factor that predisposes individuals to subsequent infertility.