Modulation of sHLA-G, PD-1, and PD-L1 Expression in Cervical Lesions Following Imiquimod Treatment and Its Association with Treatment Success

Simple Summary This study investigates the therapeutic potential of imiquimod (IMQ), a synthetic toll-like receptor 7 agonist, for treating cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV) infection. Given the risks associated with conventional surgical treatments, IMQ non-invasive application makes it an attractive alternative. This study specifically explores the correlation between IMQ treatment and the expression levels of immune checkpoint molecules PD-1, PD-L1, and sHLA-G in cervical lesions. The results suggest that baseline sHLA-G levels may predict treatment outcomes, while PD-L1 expression before treatment correlates with success. Understanding these immunomodulatory effects sheds light on IMQ potential as a conservative treatment for high-risk cervical lesions.Abstract (1) Background: Cervical intraepithelial neoplasia (CIN) is a precancerous condition linked to human papillomavirus (HPV) infection, often necessitating surgical interventions carrying the risk of subsequent preterm births. This study explores the potential of imiquimod (IMQ), as a non-invasive alternative treatment. The focus is on understanding IMQ impact on immune checkpoint molecules, particularly PD-1, PD-L1, and sHLA-G, which play pivotal roles in shaping immune responses and cancer progression. (2) Methods: Forty-three patients diagnosed with a high-risk squamous intraepithelial lesion (HSIL, p16-positive) self-applied 5% IMQ encapsulated in sachets containing 250 g of cream into the vaginal cavity three times a week for 16 weeks. The impact of IMQ therapy on cervical lesion regression was assessed through immunohistochemistry (IHC), examining changes in sHLA-G, PD-L1, and PD-1 levels. The antiviral activity of IMQ was evaluated through HPV-E7 immunofluorescence. Ethical considerations were adhered to, and the research methods were based on a previously approved clinical trial (clinicaltrials.gov Identifier: NCT04859361). (3) Results: IMQ treatment demonstrated efficacy, leading to lesion regression. sHLA-G levels in CIN before starting IMQ application were associated with unsuccessful treatment (p = 0.0036). IMQ did not significantly alter the expression of PD-1. We observed a decrease in PD-L1 levels in those who were successfully treated (p = 0.0509) and a reduction in HPV burden. (4) Conclusions: IMQ exhibits promise as a non-invasive treatment for CIN, emphasising its potential to modulate the immune microenvironment. Baseline sHLA-G levels emerge as potential predictors of treatment response. Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions.