Risk of cervical cancer in women with autoimmune diseases, in relation with their use of immunosuppressants and screening: Population-based cohort study

Severely immunosuppressed individuals have a strongly increased risk of cervical cancer. In patients with autoimmune diseases (AID), who have defects in their immune system and receive immunosuppressants, the risk of cervical cancer is less clear. We conducted a cohort study, using Danish nationwide population-based registers including information on AID diagnoses, immunosuppressant intake, cervical screening participation, and cervical cancer incidence. Standardized incidence ratios (SIR) were computed to compare the risk of cervical cancer in AID patients to that of the general population. Hazard ratios (HR) from time-dependent Cox models stratified by AID were used to explore the effect of the most frequently used immunosuppressants, taking into account potential dose-response relationships and lag times between drug exposure and cervical cancer development. Cervical screening coverage of patients with AIDs was compared to the general population. Among 341,758 patients with AIDs, the risk of cervical cancer was not higher than in the general population (SIR = 1.0, 95% CI: 0.9-1.1, based on 720 cases). The intake of immunosuppressants was generally not associated with the risk, apart from azathioprine. The crude HR comparing the period of exposure versus non-exposure to azathioprine was 1.4 (95% CI: 0.9-2.1). Furthermore, the risk was substantially increased in patients who received a high cumulative dose of azathioprine (HR = 2.2, 95% CI = 1.2-3.9), and appeared to be highest when considering that the immunosuppressant exposure would take 5 years to trigger cervical cancer. Patients with AIDs had similarly high screening rates as the general population. Although most patients with AIDs do not have an increased risk of cervical cancer, those taking substantial amounts of azathioprine might need more stringent cervical screening measures.