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* Participants are subject who will undergo an elective total hysterectomy procedure for indications of gynecological organ abnormalities, whether benign, pre-cancerous, or malignant other than cervical pathology.
* The 85 percent TCA solution will be applied to participants cervical tissue 24 hours before surgery.

* TCA is an acetic acid analogue solution (CCl3COOH) which is formed from the reaction of acetic acid (CH3COOH) with chlorine (3Cl2).
* High concentrations (85 percent) of this solution can penetrate deeply into the epidermis-dermis layer and cause cells necrosis.
* This solution (1-2 milliliter) will be applied to participants cervical tissue (ectocervix and endocervix) using cotton swab for 1-3 minutes.

85% TCA Solution

Laila Nuranna, Professor

Early detection and treatment of precancerous lesions are the pillars of cervical cancer prevention. Cervical Intraepithelial Neoplasia (CIN) is a precancerous lesion that histologically can be found in one of three stages of development; CIN-I (low grade), CIN-II, or CIN-III (collectively called high grade), depending on the proportion of the depth of the lesion to the thickness of the cervical epithelium. The higher the degree of CIN, the deeper the pre-cancerous lesions are found in the epithelial lining of the cervix. Therefore, from the point of view of precancerous lesions treatment, its effectiveness will be determined by the ability to eradicate all high-grade lesions. In other words, it has an effect that can reach depths beyond the depth of the high grade lesion.

According to a study in the US (1982), as many as 99.7% of CIN-III cases had a lesion depth of less than 4.8 millimeter. Furthermore, a Netherlands study (1990) stated that as many as 99.7% of CIN-III cases had a maximum lesion depth of 3.6 millimeters. While in subjects from developing countries, study from Peru (2018) showed that 93.5% of CIN-III cases have a lesion depth of less than 5 millimeters. Based on the results of these studies, a treatment for CIN can only be said to be effective if it can create a therapeutic effect which can reach depths of 4-5 millimeters in cervix epithelial.

Trichloroacetic acid (TCA) is an acetic acid analogue, which has long been known as a chemical peel and also frequently used to treat genital ward and precancerous skin lesions. The effect of TCA therapy is the destruction of the epithelium forming epithelial necrosis, followed by re-epithelialization of the supporting tissue and stimulation of collagen synthesis within approximately in 24 hours. There are no studies regarding the depth of cervical necrosis that can be achieved by application of this solution to the cervix epithelial.

Primary Objectives:

The purpose of this study is to determine the depth of epithelial necrosis in cervical tissue specimen after 85 percent TCA application on clinically normal cervix.

Procedure:

Patients will receive a single administration of 1-2 milliliter of 85 percent TCA in 24 hours before elective total hysterectomy surgery on indication other than cervical pathology. The 85 percent TCA will be applied topically onto the ectocervix and the endocervix canal with a cotton swab for 1-2 minutes. After surgery, cervical specimen will be fixated in formalin and sent for histopathologic examination.

Depth of Necrosis in Normal Cervical Epithelium After 85% Trichloroacetic Acid (TCA) Application

All Individual Patient Data (IPD) that underlie results in a publication

Based on damage to the cervical epithelium, both squamous (ectocervix), transformation zone, and columnar (endocervix) epithelium. Destruction of base membrane and stromal tissue will also be evaluated. Microscopic evaluation using a micrometer on a 10 times magnification eyepiece. The deepest ablative destruction in epithelial, base membrane, and stromal tissue will be recorded and stated in millimetres.

Measured immediately after application of the 85 percent TCA solution with Visual Analogue Scale (VAS) score. Highest score means worse ouctcome. Minimum score is 0 (No Pain) and maximum score is 10 (worst pain).

Dr Cipto Mangunkusumo General Hospital

Indonesia University

Professor

Antiviral Agents

Local application of the experimental gel or placebo gel.

Philippe SIMON, MD, PhD, Professor

The purpose of this phase-II study is to evaluate the efficacy and safety of an aqueous gel containing an antiviral, administered directly on cervix exhibiting high grade squamous or glandular intraepithelial lesion (CIN 2 and 3) in comparison with a placebo treatment.

Human Papilloma Virus (HPV) infections induce cervical intraepithelial neoplasia (CIN) of cervix. To reduce incidence of invasive tumor associated with high grade CIN lesions, the standard treatment is the conisation of cervix (surgical act). A local treatment with antiviral would preserve the cervix of young subjects and reduce obstetrical morbidity induced by the conisation.

This clinical study is aimed at:

* to evaluate the efficacy of a gel with antiviral directly applied on the cervix exhibiting high grade CIN lesions (CIN2/3): conisation is still indicated?
* to evaluate the safety and tolerance after local application.

Safety and Efficacy Study of Antiviral Local Application to Treat High Grade Cervical Intraepithelial Lesions (CIN2/3)

A Randomized, Double-blind, Multi-centre, Placebo Controlled Phase II Clinical Study to Evaluate the Efficacy, Tolerance and Safety of an Aqueous Gel Containing an Antiviral, Directly Applied on the Cervix Exhibiting High Grade Intraepithelial Lesion.

Efficacy will be measured by histological and cytological criteria at week 12 (disappearance of CIN 2+) in correlation with viral status (positive or negative) before and after treatment.

The recurrence rate will be assessed at week 28, by the same histological and cytological criteria in correlation with the viral status (positive or negative) before and after treatment.

Safety will be measured by record of adverse events, changes in clinical biology test results; local tolerance will be measured by patient questioning and gynecological examination of vagina and cervix.

The viral load and genotypes of HPVhr will be determined before treatment, during follow-up and at the end of the study, by using a quantitative analysis.

Colposcopic description of lesion will be done before, during and after treatment of the lesion, during follow up and at the end of the study.

Mithra Pharmaceuticals

Maud Jost

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Cidofovir

Enzyme Inhibitors

topical gel applied once a week for 3 weeks

Cidofovir gel

Michel Bossens, MD, PhD

Human Papilloma Virus (HPV) infections induce cervical intraepithelial neoplasia (CIN) of cervix. To reduce incidence of invasive tumor associated with high grade CIN lesions, the standard treatment is the conisation of cervix (surgical act). A local treatment with the antiviral and anti-proliferative cidofovir would preserve the cervix of young subjects and reduce obstetrical morbidity induced by the conisation.

This clinical study is aimed at :

1. evaluating the tolerance and safety of a cidofovir gel directly applied on the cervix exhibiting high grade CIN lesions;
2. evaluating the pharmacokinetic (PK) profile of cidofovir after local application.

Safety and Tolerability of Cidofovir Gel Applied on Cervix Squamous Lesions

A Phase I Clinical Study to Evaluate the Tolerance and Safety of an Aqueous Gel Containing 2% (w/w) of Cidofovir, Directly Applied on the Cervix Exhibiting High Grade Squamous Intraepithelial Lesion(s) (CIN 2 and 3)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Depth of Necrosis in Normal Cervical Epithelium After 85% Trichloroacetic Acid (TCA) Application	NCT04911075	Cervix; Intraep...	85% TCA Solutio...	18 Years - 65 Years	Indonesia University
Safety and Efficacy Study of Antiviral Local Application to Treat High Grade Cervical Intraepithelial Lesions (CIN2/3)	NCT01303328	Uterine Cervica... Cervix Intraepi...	C1	18 Years - 50 Years	Mithra Pharmaceuticals
Depth of Necrosis in Normal Cervical Epithelium After 85% Trichloroacetic Acid (TCA) Application	NCT04911075	Cervix; Intraep...	85% TCA Solutio...	18 Years - 65 Years	Indonesia University
Safety and Tolerability of Cidofovir Gel Applied on Cervix Squamous Lesions	NCT00989443	Uterine Cervica... Cervix Intraepi...	Cidofovir gel	18 Years - 50 Years	Mithra Pharmaceuticals
Safety and Tolerability of Cidofovir Gel Applied on Cervix Squamous Lesions	NCT00989443	Uterine Cervica... Cervix Intraepi...	Cidofovir gel	18 Years - 50 Years	Mithra Pharmaceuticals
Safety and Efficacy Study of Antiviral Local Application to Treat High Grade Cervical Intraepithelial Lesions (CIN2/3)	NCT01303328	Uterine Cervica... Cervix Intraepi...	C1	18 Years - 50 Years	Mithra Pharmaceuticals

Spots Global Cancer Trial Database for cervix intraepithelial neoplasia