Increased incidence of cervical intraepithelial neoplasia in women with systemic lupus erythematosus treated with intravenous cyclophosphamide

Abstract

Objective: To determine if the incidence of cervical intraepithelial neoplasia (CIN) is increased in immunosuppressed women with systemic lupus erythematosus (SLE).

Methods: Women with SLE were consecutively recruited from University of Michigan outpatient rheumatology clinics. Women with abnormal cervical smears at screening were excluded. Cervical smears were obtained at baseline and at 3 and 7 years. Cervical biopsies confirmed cytologic abnormalities (CIN I-III), and were scored by pathologists in blinded fashion. Data were analyzed according to treatment group: (1) prednisone; (2) azathioprine (AZA); (3) intravenous cyclophosphamide (IVCYC); and (4) IVCYC + AZA + prednisone.

Results: Sixty-one of 89 women screened were eligible for enrollment. The overall 3-year incidence of CIN was 9.8%. Stratified by treatment group, the 3-year incidence of CIN was 0/23 (0%) in prednisone treated patients, 0/4 (0%) in AZA treated patients, 2/8 (25%) in IVCYC treated patients, and 4/26 (15%) in CYC + AZA + prednisone treated patients. A dose relationship was observed between cumulative IVCYC exposure and CIN; each increase of 1 g of IVCYC exposure corresponded to a 13% increased risk of CIN (p = 0.04). At 7 years, 45 patients remained under followup and 6 patients had died of unrelated causes. No cases of CIN were observed at 7 years, although there were 2 cases of atypical squamous cells of unknown significance and one case of condyloma.

Conclusion: IVCYC + prednisone therapy for SLE is significantly associated with development of CIN.