Patients with systemic lupus erythematosus (SLE) seem to experience an increased prevalence of oncogenic virus infections. The aim of the present study was to investigate whether SLE patients have an increased risk of virus-associated malignancies, defined as malignancies potentially caused by virus infection. A hospital-based cohort of 576 SLE patients was linked to the Danish Cancer Registry. The cohort was followed up for malignancies from the date of SLE diagnosis, and standardized incidence ratios (SIRs) were calculated for various forms of cancer. The median duration of followup was 13.2 years. Compared to the general population, the patients experienced an increased overall risk of cancer (SIR 1.6 [95% confidence interval (95% CI)] 1.2-2.0). We observed an increased risk of virus-associated cancers combined (SIR 2.9 [95% CI 2.0-4.1]). Among human papillomavirus (HPV)-associated malignant and premalignant conditions, high risk was found for anal cancer (SIR 26.9 [95% CI 8.7-83.4]), vaginal/vulvar cancer (SIR 9.1 [95% CI 2.3-36.5]), epithelial dysplasia/carcinoma in situ of the uterine cervix (SIR 1.8 [95% CI 1.2-2.7]), and nonmelanoma skin cancer (SIR 2.0 [95% CI 1.2-3.6]). Increased SIRs were also found for other potentially virus-induced cancer types (liver cancer SIR 9.9 [95% CI 2.5-39.8], bladder cancer SIR 3.6 [95% CI 1.4-9.7], and non-Hodgkin's lymphoma SIR 5.0 [95% CI 1.9-13.3]). The patients in this SLE cohort experienced an increased risk of HPV-associated tumors and other potentially virus-induced cancers during long-term followup. Our findings call for clinical alertness to oncogenic virus infections in SLE patients. Copyright © 2011 by the American College of Rheumatology.