Background/Purpose: An impaired clearance of cervical human papillomavirus (HPV) related to inadequate immune responses may result in persistent infection and increase the risk to develop cervical dysplasia in patients with systemic lupus erythematosus (SLE). We aim to identify risk factors for HPV infection and clearance in patients with SLE.

Methods: All SLE patients have been included in the ongoingPAPILUP study (National center for rare immune-mediated inflammatory diseases, Internal Medicine Department, Bichat Hospital, Paris, France) that aimed to improve HPV-related cervical cancer screening (CCS) in SLE patients. All SLE patients aged 30 to 65 who had HPV-related CCS between September 2021 and July 2022 were screened. The frequency of High-Risk (HR)-HPV was assessed in SLE patients in comparison to healthy and HIV-positive controls screened during the same period. The risk factors for persistent infection and clearance of HR-HPV in SLE patients were analyzed.

Results: Overall, 65 of the 107 SLE patients involved in the PAPILUP study were analyzed. The median age at CCS was 45 [39-51]. CCS was up to date in only 36 (55.4%) patients and only one patient (1.5%) had received HPV vaccine. The median SLE disease duration was 12 years [6-21] with a median SLEDAI score of 2 [0-4] at study time. Thirty-one (47.7%) patients had an history of lupus nephritis. Thirty-four (52.3%), 62 (95.4%) and 21 (32.3%) were currently receiving glucocorticoids, hydroxychloroquine and immunosuppressive drugs, respectively. HR-HPV were detected in 19 (29.2%) SLE patients. The frequency of HR-HPV did not differ between SLE patients and healthy controls (119 subjects, median age 43 [37-50], 21.8% of HR-HPV infection, p= 0.291). However the frequencies of multiple HR-HPV (at least 2 coexisting types )and abnormal cervical cytology (ACC, i.e cervical cytology samples enriched with atypical squamous cells, low-grade or high-grade squamous intraepithelial lesions) tended to be higher in SLE patients as compared to healthy controls (15.4% of multiple HR-HPV in SLE vs 6.7 % in healthy p=0.059; 16.9% of ACC in SLE vs 9.2% in healthy, p=0.125). Of note, the frequency of multiple HR-HPV (15.4% vs 11.5%, p=0.407) and ACC (16.9% vs 11.5%, p=0.255) in SLE patients were in the same range as those in HIV-positive patients (n=192, median age 46 [41-53]). Using multivariable logistic regression model, the only significant risk factor for HR-HPV identified in SLE patients was the duration of the lupus disease (OR 16.1 [1.7-156], p=0.017) . A second HPV screening was performed 12.9 [10.2-14.1] months after the first one in 14 (73.7%) of the 19 HPV+SLE patients. A persistent HR-HPV infection was observed in 11 cases (78.6%). Of note, HR-HPV cleared in 2 of 4 (50%) patients who had never received steroids and immunosuppressive (IS) drugs but in only 1 of 10 (10%, p=0.099) who received long term steroids (median exposure length 9 [5.5-17.7] years) and IS drugs (median exposure length 6 [3.6-10] years).

Conclusion: Multiple HR-HPV and abnormal cervical cytology are frequent in SLE patients comparable to that of HIV-positive patients. The duration of SLE disease increases the risk for HR-HPV regardless of age. Long lasting immunosuppression induced by treatment might impede HPV clearance.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-factors-for-human-papillomavirus-cervical-infection-and-clearance-in-patients-with-systemic-lupus-erythematosus-the-papilup-study/