Background/Purpose: Human papillomavirus (HPV) is the most common sexually transmitted disease in the US and the main cause of high-grade cervical dysplasia and cervical cancer. Prior studies suggest an increased risk of cervical cancer in women with systemic lupus erythematosus (SLE), however the relationship with immunosuppressive drugs (ISDs) is not well studied. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with SLE receiving hydroxychloroquine (HCQ) to those on ISDs in a nationwide database. We hypothesized that the risk of cervical dysplasia and cervical cancer would be increased among ISD users.

Methods: We utilized US commercial insurance claims data (2001-2012) to conduct a cohort study to examine the incidence rates (IR) of high-grade cervical dysplasia or cervical cancer in women who initiated ISDs or HCQ for SLE. The index date was defined as the dispensing date of the first ISD or HCQ after ≥2 diagnoses of SLE (ICD-9 code 710.0). We required patients to have ≥365 days of continuous enrollment prior to the index date without use of ISDs or HCQ. We assessed baseline covariates during this period. We defined the outcome, high-grade cervical dysplasia or cervical cancer, using a validated claims-based algorithm with a positive predictive value of ≥81%. We also determined the number of gynecologic visits and procedures during follow-up. To control for potential confounders including age, comorbidities, HPV vaccination, corticosteroid use, additional medications, and healthcare utilization, initiators of ISDs were matched to HCQ initiators using propensity scores with a 1:1 ratio.

Results: Among 2,451 propensity score-matched pairs of women with SLE, the median age was 46 years, the mean follow-up was 1.15 (SD 1.38) years, and the overall follow-up was 5,622 person-years. The IR of high-grade cervical dysplasia or cervical cancer per 1,000 person-years was 4.70 in ISD initiators and 1.89 in HCQ initiators (Table). There were 14 cases of high-grade cervical dysplasia or cervical cancer in the ISD group and 5 cases in the HCQ group for a hazard ratio of 2.47 (95% CI: 0.89-6.85). The number of outpatient gynecologic visits (Rate ratio [RR] 0.93, 95% CI: 0.81-1.07) and gynecologic procedures (RR 1.13, 95% CI: 0.98-1.44) was not significantly different between the two groups.

Conclusion: Among women with SLE, initiation of ISDs may be associated with a greater, albeit not statistically significant risk of high-grade cervical dysplasia or cervical cancer compared to HCQ alone. Given the rare nature of cervical cancer and the prolonged latency period, further studies with extended follow-up are needed to confirm this finding.