Immunosuppression did not affect the probability of abnormal anal cytology among patients with inflammatory bowel disease (IBD), according to a prospective, single-center, cross-sectional study of 270 adults published in the November issue of Clinical Gastroenterology and Hepatology.
“Although our study suggested that immunosuppression may not play a role in the risk of dysplasia, a question remains as to whether it contributes to malignant transformation in patients with dysplasia. More research needs to be performed to identify the utility of wider anal dysplasia screening programs in high-risk populations, and the role of HPV vaccine in prevention,” Dr. Shamita Shah of Stanford (Calif.) University and her associates wrote in Clinical Gastroenterology and Hepatology.
Immunosuppression is a cornerstone of IBD management. Because immunosuppressive medications inhibit cell-mediated immunity, patients are at increased risk of opportunistic infections and neoplasias, the researchers noted. One study reported a greater risk of cervical dysplasia among immunosuppressed women with IBD, but the risk of anal dysplasia and cancer in IBD has not been well studied, they said (Clinical Gasteroenterol Hepatol. 2015. doi: 10.1016/j.cgh.2015.05.031).
To examine associations between anal dysplasia and IBD, human papillomavirus infection, and immunosuppression, the researchers analyzed anal Pap tests from 100 IBD patients who were immunosuppressed, 94 IBD patients who were not immunosuppressed, and 76 healthy controls. They identified 19 cases of atypical squamous cells of undetermined significance (ASCUS). The prevalence of ASCUS was somewhat higher among IBD patients (8.8%) than controls (2.6%; P = 0.1), but did not vary based on immunosuppression status or HPV infection. High-risk HPV occurred in 2% of the entire cohort, including 11% of patients with ASCUS and 1.5% of patients with normal Pap cytology (P = .01). High-resolution anoscopy of six patients with ASCUS revealed two cases of condylomatous disease, but no biopsy-positive dysplasia, the investigators reported.
Patients with Crohn’s disease had a significantly higher prevalence of ASCUS than other study participants (P = .02), but patients with ulcerative colitis or unspecified IBD did not, said the researchers. Having had Crohn’s disease for at least 10 years was associated with a fivefold increase in the odds of ASCUS in the multivariate analysis (95% confidence interval, 1.9-13.6), and female sex was also a risk factor (odds ratio, 3.3; P = .047). Notably, women with long-standing Crohn’s disease were almost five times more likely to have abnormal anal Pap cytology than other subjects (P = .0038), the investigators said. “One proposed mechanism for this was a reduction in human defensins in Crohn’s disease patients,” they added. Defensins – antiviral proteins that are found in immune cells – are known to inhibit cutaneous and mucosal HPV, and can be decreased in patients with Crohn’s disease for several reasons, they said. “Although more research is needed in this area, the hindered ability for an IBD patient to defend against viral illness may be responsible for their susceptibility to HPV-related cervical and anal neoplasias.”
Hologic donated the anal Pap tests used in the study. The researchers disclosed no conflicts of interest.