cervical high squamous intraepithelial lesion (cHSIL) / CIN cervical premalignancy
Conditions
Interventions
Imiquimod
Sponsors
Catharina Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Primary cHSIL lesions (e.g. CIN3 or CIN 2), histologically confirmed by diagnostic biopsy NB: In case of CIN 2,
Exclusion criteria
Exclusion criteria: - Concomitant diagnoses of VAIN (vaginal intraepithelial neoplasia e.g. vaginal HSIL) - PAP 4 cytology as indication for the baseline colposcopy at study entrance - Adenocarcinoma in situ (AIS) diagnosis - Previous imiquimod therapy for cHSIL - previous cervical malignancy - current malignant disease - immunodeficiency (including HIV/AIDS and immunosuppressive medication) - pregnancy - legal incapability - insufficient knowledge of the Dutch language
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Confirm the relationship between a complete clinical response to imiquimod and the increased stromal infiltration of CD4+ T cells, CD11c+ cells and/or M1-like macrophages as well as the decreased infiltration with FoxP3+ Tregs in primary cHSIL. • Validate the association of a *hot signature*, defined as the sum of the numbers of stromal CD4+/CD11c+/M1+ cells per square millimeter minus the number of stromal FoxP3+ cells per square millimeter, with a complete response to imiquimod treatment in primary cHSIL. • Determine the sensitivity and specificity of the *hot signature* in patients with primary cHSIL lesions to estimate the predictive value for therapy efficacy upon imiquimod treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Explore the *hot signature* as a predictive biomarker for therapy efficacy to imiquimod treatment in patients with residual/recurrent cHSIL (rrcHSIL). • Explore the *hot signature* as a predictive biomarker for spontaneous regression of cHSIL (e.g. CIN2). • Determine treatment efficacy, HPV clearance, therapy adherence and reported side effects upon imiquimod therapy. • Evaluate maintenance of lesion regression after imiquimod treatment by determination of recurrent cHSIL or progression to cervical cancer and time to recurrence/progression. • Explore and evaluate other potential more specific predictive (immune) biomarkers in cHSIL which are easily accessible and readily implemented for clinical prognosis, including dedicated gene expression profiles by Nanostring and gene methylation assays. • Develop a simplified pathological scoring system by explorative development of a simplified dual immunohistochemistry protocol to identify the hot signature and exploration of the predictive value of this *immunoscore* in cHSIL. • Validate the *hot signature* defined as epithelial or stromal CD4+/CD11c+/CD68+ cells via single immunohistochemistry per square millimeter with a complete response to imiquimod treatment in primary cHSIL • Determine the vaginal microbiome in cHSIL patients treated with imiquimod or not treated to explore the potential interaction of the vaginal microbiome and composition of immune infiltrates and the relation to imiquimod treatment and relation to spontaneous regression. | — |
Countries
Netherlands
Contacts
Public ContactEMG van Esch
Catharina Ziekenhuis
Outcome results
None listed