Will chronic prednisone (corticosteroid) and Benlysta (belimumab) for Systemic Lupus Erythematosus (SLE) prevent resolution of vaginal Human Papillomavirus (HPV) infection?

Chronic Prednisone and Benlysta May Impair Resolution of Vaginal HPV Infection in SLE Patients

Patients with SLE taking chronic prednisone and belimumab (Benlysta) are likely to have impaired clearance of vaginal HPV infection due to immunosuppression, which increases the risk of persistent HPV infection and development of cervical dysplasia. 1

Mechanism of Impaired HPV Clearance in SLE

SLE patients have inherently dysregulated immune responses that affect their ability to clear HPV infections:

• The dysregulation of innate and adaptive immune responses in SLE patients impairs viral clearance 1
• This leads to persistent carriage of HPV and higher prevalence of multiple HPV types, including high-risk subtypes 1
• Immunosuppressive medications further compromise the immune system's ability to eliminate the virus

Impact of Specific Medications

Prednisone

• Studies have shown lower immunogenicity of HPV vaccine with reduced seroconversion rates in patients taking prednisolone 1
• Cumulative doses of prednisolone correlate inversely with anti-HPV antibody titers 2
• Higher cumulative doses of prednisolone are associated with sero-reversion of anti-HPV antibodies 2

Belimumab (Benlysta)

• Belimumab is a monoclonal antibody that inhibits B lymphocyte stimulator, affecting B-cell differentiation and survival 3, 4
• While belimumab has demonstrated efficacy in controlling SLE disease activity 5, 6, its mechanism of action further compromises immune function
• By targeting B-cell function, belimumab may impair the humoral immune response needed to clear HPV infection

Clinical Implications

Increased Risk of HPV-Related Complications

• SLE patients have higher rates of developing abnormal Pap smears and precancerous cervical intraepithelial lesions than healthy women 1
• A systematic review of 27 studies noted an increased rate of cervical cancer in SLE patients 1
• Long-term HPV infection combined with multiple HPV types predisposes SLE patients to cervical dysplasia 1

Management Considerations

1. More frequent cervical cancer screening:

   • Due to higher risk of persistent HPV and cervical dysplasia, more vigilant screening may be necessary

2. Treatment of genital warts:

   • If genital warts are present, treatment options include:
     • Cryotherapy with liquid nitrogen 7
     • Trichloroacetic acid (TCA) 80-90% 7
     • Surgical removal for large or treatment-resistant warts 7

3. HPV vaccination:

   • HPV vaccines have proven safe and immunogenic in patients with SLE 1
   • Vaccination should be strongly encouraged in SLE patients due to elevated risks associated with HPV infection 1
   • Optimal timing would be before initiation of immunosuppressive therapy to ensure higher immunogenicity 1

Important Caveats

• The effect of immunosuppressive medications on HPV clearance may vary among individuals
• There is some incongruity among different studies regarding the influence of immunosuppressive agents on cervical dysplasia 1
• The majority of studies found no association between immunosuppressive drugs and increased frequency of cervical dysplasia, while a few studies pointed to increased risk following cyclophosphamide exposure 1
• Even with appropriate treatment of visible genital warts, recurrence rates are high (at least 25% within 3 months) with all treatment modalities 1
• If left untreated, genital warts may resolve spontaneously in 20-30% of patients within 3 months, even in immunocompetent individuals 1

Given the evidence, patients with SLE on chronic prednisone and belimumab should be monitored more closely for persistent HPV infection and its complications, with a lower threshold for intervention and more frequent cervical cancer screening.