Dados do Trabalho

Título

Enhancing Predictive Insights: Immunophenotyping, Microbiome and Clinical Outcome in Imiquimod-treated Patients with High-Grade Cervical Intraepithelial Lesions

Introdução

The primary approach to prevent cervical cancer involves surgically removing high-grade intraepithelial lesions (NIC 2/3), which can compromise woman's fertility. To provide a safer alternative, non-excisional therapies have been explored, including the use of Imiquimod. This treatment exhibits antiviral and antitumor properties. Moreover, researchers are increasingly investigating the impact of the local microbiome on tumor development and its role in immune modulation.

Objetivo

To determine the immunophenotypic profile of cervicovaginal cells and lavage to evaluate the local immune response, as well as characterize the microbiological profile of women diagnosed with NIC 3 lesions and investigate potential correlations with the treatment employing Imiquimod.

Métodos

This randomized clinical trial includes three groups: Group 1: HPV-positive NIC 3 patients who will receive 16 doses of imiquimod, applied twice a week for 8 weeks, followed by Excision of the Transformation Zone (ETZ); Group 2: HPV-positive NIC 3 patients undergoing standard ETZ at the outpatient clinic; Group 3: healthy patients with negative high-risk cytology and HPV. Cervicovaginal lavage samples will be collected at different time points to correlate cellular response profiles to Imiquimod or standard EZT treatment with baseline levels in healthy patients. The cervicovaginal lavage samples will be used for cell immunophenotypic analysis using flow cytometry technology, immune mediators´ quantification using Cytometric Bead Array technology, and microbiome evaluation through MiniION nanopore sequencing.

Resultados

This study aims to yield valuable data that could offer patients diagnosed with high-grade cervical lesions a less invasive treatment option, thereby reducing the risk of potential complications associated with ablative treatment of the transformation zone of the cervix. Additionally, we endeavor to explore alternative treatment strategies to mitigate the impact of NIC 3 on women's fertility, potentially avoiding fertility impairments caused by surgical procedures. Alongside these objectives, our research endeavors to identify distinctive molecular signatures within the cervicovaginal microenvironment and comprehensively characterize the local microbiome.

Conclusões

Our study strives to attain a more comprehensive immunophenotypic and microbiological characterization of NIC 3 patients eligible for Imiquimod treatment, with the ultimate goal of minimizing the need for ablative surgical procedures on the cervix. By doing so, we aspire to mitigate potential fertility issues and reduce gestational risks in women of childbearing age who require treatment for NIC 3.

Palavras-chave

HPV, Micorbiome, Imiquimod.

Financiador do resumo

Barretos Cancer Hospital (Edital: N.013/2021), CAPES, FQM

Área

Estudo Clínico - Tumores Ginecológicos