Associations between immune-mediated diseases (IMDs) and the risk of HPV-associated diseases: a UK Biobank cohort analysis

Objectives To systematically assess the associations between various immune-mediated diseases (IMDs) and human papillomavirus (HPV)-associated diseases. Design Retrospective cohort study. Setting UK Biobank. Participants A total of 500371 subjects aged 40-69 years were eligible for the analysis, after excluding those with prevalent HPV-associated diseases at baseline and those who had withdrawn their informed consent or lacked information on sex. Exposure Eighty IMDs (involving allergic/atopic diseases, autoimmune diseases, immunodeficiency diseases, etc) were identified in the UK Biobank. Primary and secondary outcome measures The main outcome was the incidence of HPV-associated diseases (including warts and malignancies of the cervix, oropharynx, anus, penis, vulva and vagina). Cox proportional hazards model was used to estimate HRs and 95% CIs with particular adjustment for sexual behaviours. We also conducted subgroup analyses based on benign and malignant status, and anatomical sites of HPV-associated diseases, respectively. Results During a median of 12.0 years of follow-up, 2244 cases out of 500371 subjects developed HPV-associated diseases. Overall, participants with IMDs had a higher risk of HPV-associated diseases than their controls after adjustment for sexual behaviours and other potential confounders (female: HR=1.90, 95%CI=1.66 to 2.17, p<0.001; male: HR=1.66, 95%CI=1.41 to 1.97, p<0.001). Additionally, eight individual IMDs in women (eg, asthma: HR=1.76, 95%CI=1.47 to 2.11, p<0.001) and three in men (eg, chronic nephritic syndrome: HR=6.05, 95%CI=3.32 to 11.04, p<0.001) were associated with increased risk of HPV-associated diseases. Subgroup analyses revealed significant IMD differences between benign and malignant subgroups as well as between oropharyngeal and anogenital subgroups. Conclusion In this large retrospective cohort study, IMDs were significantly associated with an elevated risk of HPV-associated diseases. Besides, gender-specific and region-specific associations were also observed between individual IMDs and HPV-associated diseases.