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278 Effect of topical imiquimod treatment in the expression of the HPV E7 and human CD28 and CTLA-4 immune molecules in the high-grade cervical lesion
  1. Andrej Cokan1,
  2. Neila Caroline Henrique Da Silva2,
  3. Débora Rayane De Arruda2,
  4. Nathália Lorena Zeferino Araujo2,
  5. Rodrigo Soares Da Silva2,
  6. Christina Alves Peixoto2,
  7. Sheilla Andrade De Oliveira2,
  8. Rajko Kavalar1,
  9. Maja Pakiž1,
  10. Igor But1 and
  11. Norma Lucena Silva2
  1. 1UMC Maribor, Maribor, Slovenia
  2. 2Instituto Aggeu Magalhães-Fiocruz, Recife, Brazil


Introduction/Background Persistent high-risk Human Papillomavirus (HPV) infection and the prolonged existence of cervical lesions are concomitant with heightened E7 oncoprotein expression, disrupting both innate and adaptive immunity. The delicate balance between stimulatory CD28-expressing T cells and inhibitory CTLA-4-expressing T cells plays a pivotal role in orchestrating effective immune responses in the cervical microenvironment. In light of this, our investigation seeks to elucidate whether the application of 5% imiquimod induces modulation in the expression of CD28 and CTLA-4 human molecules in cervical T cells, as well as the viral E7 oncoprotein.

Methodology For this study, 43 women aged 18 to 40 years, diagnosed with cervical HPV infection and histologically confirmed high-grade squamous intraepithelial lesions (HSIL) encompassing CIN2p16+ and CIN3, were enrolled. Participants self-administered a 250 mg cream containing 5% imiquimod thrice weekly over a 16-week period. Biopsies were collected pre- and post-treatment, with treatment success determined by the absence of HSIL post-treatment. Immunohistochemistry was utilized to assess the expression levels of human CD28 and CTLA-4, along with viral E7 molecules.

Results Following imiquimod treatment, a notable reduction in Viral E7 protein levels was observed. Imiquimod exhibited no significant impact on CTLA-4 expression in cervical lesions, irrespective of treatment outcome. The pre-treatment CTLA-4 expression pattern demonstrated similarity in patients with CIN2 or CIN3, with no statistically significant difference. Conversely, CD28 expression increased in CIN3 lesions post-topical imiquimod application, regardless of treatment success (P=0.0304) or failure (P=0.0075). This effect was not evident in CIN2 lesions (P=0.4319). CD28 levels displayed no correlation with CTLA-4 levels (P=0.3242). However, the post-treatment CD28 to CTLA-4 molecule proportion was associated with treatment success (Ratio=1.5; P=0.0494) (figure 1).

Conclusion Imiquimod treatment induces a reduction in viral burden and an elevation in CD28 expression, collectively contributing to the overall treatment success.

Disclosures The authors report no conflicts of interest.

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