Abstract

Abstract Background Patients with inflammatory bowel disease (IBD) are at elevated risk of developing anal cancer. However, it remains unclear whether the increased risk manifests from immunosuppressant use or location of the disease (inflammation). We aimed to examine whether the risk of anal cancer in IBD patients is attributable to immunosuppression or the disease’s location by comparing IBD patients with rheumatoid arthritis (RA) and diverticulitis patients, respectively. Methods We conducted a retrospective cohort study using the US Optum® commercial claims database (2008–2018). We estimated the risk of anal cancer in the IBD cohort compared to the RA cohort (to examine risk attributable to immunosuppressant use) and the diverticulitis cohort (to examine risk attributable to similar disease location). Disease cohorts and index dates were identified using a combination of ICD diagnosis codes and prescription drug use. Patients 18 years and older and with a minimum of 12 months of continuous insurance enrollment were included. All three cohorts were mutually exclusive; we excluded persons with HIV/AIDS or organ transplant. We estimated hazard ratios (HRs) using Cox proportional regression, adjusting for age at diagnosis, comorbidity, risk factors for HPV infection (smoking, obesity, genital wart, substance abuse, alcoholism), and prescription drug use. Analyses were stratified by sex. Results The study included 70,314 patients with IBD, 164,991 with RA, and 129,558 with diverticulitis. In men, the adjusted hazard ratio (aHR) of developing anal cancer was 6.78 (95% CI, 3.40–13.55) comparing IBD to RA, and was 2.68 (95% CI, 0.99–7.30) comparing IBD to diverticulitis. Among women, the risk of developing anal cancer was significantly higher in IBD compared to RA (aHR 2.70; 95% CI, 1.36–5.35), but not different compared to diverticulitis (aHR 0.70; 95% CI, 0.20–2.44). The factors associated with a higher risk of anal cancer in both men and women were age at diagnosis, history of genital wart, corticosteroid use, and immunosuppressant use. Conclusion We found a significantly elevated risk of anal cancer in IBD patients than RA patients. However, anal cancer risk was not significantly different when comparing IBD patients to diverticulitis patients. These results indicate that the location of the disease is more strongly associated with anal cancer incidence than the treatment of autoimmune disease.

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