Association between human papillomavirus infection and sudden sensorineural hearing loss: A nationwide population-based cohort study

BACKGROUND: While the etiology of sudden sensorineural hearing loss (SSNHL) remains unclear, viral infection has been suggested as a possible cause. Human papillomavirus (HPV) might trigger immune-mediated reaction and induce inflammatory cytokines which are injurious to the cochlea. This study aimed to investigate the association between HPV infection and the risk of developing SSNHL using a nationwide population-based data set. METHODS: In this study, we used the population-based National Health Insurance Research Database of Taiwan to enroll 49,247 individuals with HPV infection from January 1st, 2000, to December 31st, 2013, and compared with a control group of 98,494 individuals who had never been diagnosed with HPV infection (at a 1:2 ratio matched by age, sex, index year, and comorbidities) in relation to the risk of subsequent SSNHL. The primary outcome was the time from the index date to the date when the first diagnosis of SSNHL occurred, death, withdrawal from the National Health Insurance Program, or the end of the study. Cox model with frailty was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), relative to comparison group. Sensitivity analyses were performed to validate our findings. FINDINGS: The adjusted hazard ratio (aHR) of developing SSNHL was 1.37 (95% CI, 1.07–1.74) after adjustment for demographic characteristics, comorbidities, and medications. Sensitivity analyses showed consistent positive association. In our sub-group analysis, a significantly higher effect of HPV on SSNHL was noted in the patients with a previous diagnosis of cerebrovascular disease, compared with those without cerebrovascular disease (aHR: 4.59 versus 1.27, p-value for interaction = 0.024). INTERPRETATION: HPV infections are associated with higher risk of subsequent SSNHL in the Taiwanese population. More research is needed to examine the causality and to determine the potential efficacy of specific precautions. FUNDING: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.