Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Squamous Intraepithelial Lesions of the Cervix

Carcinoma

Carcinoma, Squamous Cell

Carcinoma in Situ

Uterine Cervical Dysplasia

Precancerous Conditions

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Cervical Intraepithelial Neoplasia

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Imiquimod

Immunomodulating Agents

Immunologic Factors

Adjuvants, Immunologic

Interferons

36 patients diagnosed with CIN 3 who will be undergone 16 applications of 5g imiquimod twice a week and then Loop Electrosurgical Excision Procedure will procedure (60 days). Pathological analysis will evaluate the lesion histologically after immunomodulatory treatment. The individual's immunological response will also be evaluated during applications and after surgical intervention.

30 patients diagnosed with CIN 3 who will be undergone Loop Electrosurgical Excision Procedure (60 days). Pathological analysis will evaluate the lesion histologically after treatment (LEEP). The individual's immunological response will also be evaluated after surgical intervention.

Immunological markers will be evaluated in a healthy population that had negative screening tests for cervical lesions to compare to the population in the injury and intervention groups.

Experimental group will be treated with 16 applications of imiquimod and subsequently LEEP.

Active comparator group will be treated with LEEP.

Loop Electrosurgical Excision Procedure

The goal of this clinical trial is to identify the immunophenotypic profile of the local immune response, the cervicovaginal microenvironment and the microbiological profile of women with CIN 3 treated with imiquimod. Participants will be divided in 3 groups: CIN 3 who will use 16 doses of imiquimod in the uterine cervix, applied twice a week and will be treated with LEEP procedure; 2) patients with CIN 3 who will undergo standard treatment with LEEP procedure; 3) patients with negative cytology and HPV (human papillomavirus) test. Blood and cervicovaginal lavage collections will be performed at different times, for comparisons between cellular response profiles to imiquimod during treatment and baseline levels in healthy patients.

INTRODUCTION: High-grade intraepithelial lesions (CIN 2/3) are considered precursor lesions of cervical cancer, and its treatment involves destructive or excisional methods. Some studies have proven the efficacy of the immunomodulator imiquimod as a topical treatment for CIN 2/3 lesions. Imiquimod activates the innate immune response through dendritic cells, monocytes and macrophages, in addition to modulating the response pattern of T lymphocytes. Thus, the characterization of the immune response in the treatment with imiquimod in lesions caused by oncogenic HPV, may benefit women in a way that it is possible to measure the response of each patient, improving the understanding of its mechanism of action, directly impacting the efficacy and adverse events. caused by the drug. OBJECTIVES: To identify the immunophenotypic profile of the local immune response, the cervicovaginal microenvironment and the microbiological profile of women with CIN 3 treated with imiquimod. MATERIALS AND METHODS: It will be included 90 patients, 60 with high-risk HPV, diagnosed with CIN 3 and 30 patients with negative cytology and HPV. Patients will be divided into 3 groups: 1) patients with CIN 3 who will use 16 doses of imiquimod in the uterine cervix, applied twice a week; 2) patients with CIN 3 who will undergo standard treatment with Transformation Zone Excision (EZT); 3) patients with negative cytology and HPV. Blood and cervicovaginal lavage will be collected for immunophenotypic analysis (flow cytometry), quantification of immunological mediators (Cytometric Bead Array) and evaluation of the microbiome (MiniION). The results obtained will be correlated with the clinical and pathological data of the patients.

Clinical Outcome and Biomarkers for Predicting Immunological Response in Patients Treated With Imiquimod

Immunophenotyping, Microbiome, Clinical Outcome and Biomarkers for Predicting Immunological Response in Patients With High-grade Cervical Intraepithelial Lesions Treated With Imiquimod

Analysis of the vaginal microbiota and its correlation with the immunological response to imiquimod in CIN 3 lesions

A satisfactory immunological response is expected after the application of the immunomodulator imiquimod twice a week for 8 weeks in patients with CIN 3, with the objective of histological regression of the high squamous intraepithelial lesion (HSIL), which will be confirmed histologically after performing the gold standard LEEP treatment, which will be made available to all patients with CIN 3 included in the study

Detection of the immunological response measured from vaginal and plasma collection during applications of the immunomodulatory drug (pg/,L)

Fundação de Amparo à Pesquisa do Estado de São Paulo

Farmoquimica S.A.

Hospital de Cancer de Barretos - Fundacao Pio XII

Barretos Cancer Hospital

Symptoms and General Pathology

Gland and Hormone Related Diseases

Syndrome

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Gonadal Disorders

Endocrine System Diseases

* Hormonal screening
* Vaginal swab
* Fecal sample
* Blood samples
* Food Frequency Questionnaire

Venous blood samples and vaginal swab will be obtained on the same day.

Venous blood sample, vaginal swab

Xu Shan Gao, drs.

Sam Schoenmakers, Dr. drs.

Xu Shan Gao, Drs

Joop S.E. Laven, Prof. dr.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects up to 10% of the reproductive-aged women worldwide. The etiology is still unknown and treatment therefore remains symptomatic. Studies indicate a possible role of the gut microbiome in the pathology of PCOS. PCOS women have a disturbed gut microbiome, with certain species associated with the PCOS characteristics:hyperandrogenism, ovarian dysfunction, obesity, glucose intolerance and insulin resistance. Although differences have been found in gut microbiome composition between PCOS and healthy women, the literature is inconclusive regarding the difference in gut microbiome biodiversity. Studies examining the vaginal microbiome in PCOS women show consistent results with specific species in the vaginal microbiome. However, there are only few studies on the vaginal microbiome in PCOS women and no studies have yet investigated the correlation between sex-specific hormones and PCOS characteristics. More research is needed to understand the function of the microbiome in the pathophysiology of PCOS, so that this can offer perspectives in future therapies.

Gut- and Vaginal Microbiome Composition in Association With PCOS

Changes in the Gut- and Vaginal Microbiome Composition in Association With PCOS Clinical Phenotypes.

Bacterial composition in the gut is analysed using 16S rRNA gene sequencing

Bacterial composition in the vagina is analysed using 16S rRNA gene sequencing

Relative abundance of bacterial communities

Expression of metabolic indicators (metabolomics)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Outcome and Biomarkers for Predicting Immunological Response in Patients Treated With Imiquimod	NCT06356012	HSIL, High-Grad... Vaginal Microbi... Biomarkers	Imiquimod Loop Electrosur...	25 Years - 45 Years	Barretos Cancer Hospital
Gut- and Vaginal Microbiome Composition in Association With PCOS	NCT05706922	Polycystic Ovar...	Venous blood sa...	18 Years - 45 Years	Erasmus Medical Center
Gut- and Vaginal Microbiome Composition in Association With PCOS	NCT05706922	Polycystic Ovar...	Venous blood sa...	18 Years - 45 Years	Erasmus Medical Center

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