Minkyo Song 1, Eric A Engels 1, Megan A Clarke 1, Aimée R Kreimer 1, Meredith S Shiels 1
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Correspondence to: Minkyo Song, M.D., Ph.D.
Background: In the U.S., anal squamous cell carcinoma (SCC) rates have rapidly increased, particularly among older women. As immunosuppression is associated with increased risk, autoimmune conditions may be associated with greater risk of anal SCC.
Methods: We conducted a population-based case-control study using Surveillance, Epidemiology, and End Results-Medicare (2000-2017). Anal SCC cases (N = 4,505) were matched to 200,000 cancer-free controls. Using multivariable logistic regression, we calculated odds ratios (OR) and 95% confidence intervals (95%CI) for associations between 47 autoimmune conditions diagnosed before selection, identified via Medicare claims and anal SCC. The Bonferroni threshold was used to correct for multiple comparisons. Population attributable fractions (PAF) were calculated for conditions nominally associated with anal SCC.
Results: 18% of cases and 15% of controls had a diagnosed autoimmune condition. Any autoimmune condition was associated with an increased risk of anal SCC (OR 1.11, 95%CI 1.02-1.21; PAF = 1.8%). Anal SCC was associated with systemic lupus erythematosus (OR 1.79, 95%CI 1.32-2.42; PAF = 0.4%) and nominally associated (p < 0.05) with sarcoidosis (2.09, 1.30-3.37; 0.2%), and psoriasis (1.28, 1.06-1.56; 0.5%). Stratified by sex, only women showed significant associations for systemic lupus erythematosus (OR 1.97, 95%CI 1.46-2.68). Significant interaction was observed by sex for psoriasis (men vs women: OR 1.68, 95%CI 1.03-4.28 vs OR 1.12, 95%CI 0.88-1.43) and polymyalgia rheumatica (0.33, 0.12-0.89 vs 0.99, 0.75-1.30).
Conclusion: Systemic lupus erythematosus, sarcoidosis, and psoriasis were associated with a moderately increased risk of anal SCC. Given these conditions' rarity and moderate associations with anal SCC, autoimmune diseases cannot explain the rising trend in anal SCC.