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Introduction Women with systemic lupus erythematosus (SLE) have increased prevalence of precancer cervical squamous intraepithelial lesions (SIL). This study aimed to compare human papillomavirus (HPV) seroprevalence, cervical HPV-DNA detection and HPV-related cervical lesions between SLE and immunocompetent women.Methods In this cross-sectional study, women aged 18–45 years with SLE receiving immunosuppressive or disease-modifying antirheumatic drugs were compared with immunocompetent women, selected from the same hospital in Sao Paulo, Brazil. Eligible participants had no self-reported history of genital warts or any other HPV-related cervical, vaginal or vulvar lesions, nor received prior HPV vaccination. Cervical samples were tested for HPV-DNA using PapilloCheck and for SIL lesions by liquid-based cytology. A multiplex pseudovirion-based serology assay (PsV-Luminex) measured serum antibodies against eight of the HPV types targeted by non-valent (9vHPV) HPV vaccine.Results A total of 122 women with SLE and 132 immunocompetent women (mean age 34.3 and 32.5 years, respectively) were enrolled. Compared with immunocompetent women, SLE participants had higher prevalence of HPV-related cervical lesions (low-grade and high-grade SIL combined, 11.3% vs 2.4%, p=0.009), higher prevalence of at least one cervical HPV type (38.8% vs 20.2%, p=0.003), non-significantly higher prevalence of cervical high-risk HPV types (23.5% vs 14.9% p=0.286) and higher HPV seroprevalence to eight HPV types included in the 9vHPV vaccine (80.4% vs 59.7%, p=0.001).Conclusion Our findings underscore the importance of tailored cervical cancer screening and HPV vaccination of SLE women at young age.