Infections

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Virus Diseases

Papilloma

Warts

Condylomata Acuminata

Communicable Diseases

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Papillomavirus Infections

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Genital Diseases

Urogenital Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Dermatologic Agents

Anesthetics

Vaccines

Immunomodulating Agents

All patients will be subjected to:

* A thorough history taking and proper dermatological examination.
* Skin sampling from anogenital wart lesions: skin sterilization followed by injection of local anesthesia at the base of lesions, then the part of wart above skin surface will be removed using shave biopsy technique.
* DNA extraction of skin samples.
* Conventional PCR for low-risk HPV genotypes (6,11) and RT-PCR for high-risk HPV genotypes.
* Intralesional injection of the quadrivalent HPV vaccine (Gardasil) at a dose of 0.5ml, into the largest wart at 4-week intervals until complete clearance is achieved or for a maximum of three sessions.

• Intralesional injection of the quadrivalent HPV vaccine (Gardasil) at a dose of 0.5ml, into the largest wart at 4-week intervals until complete clearance is achieved or for a maximum of three sessions.

the Quadrivalent Vaccine (Gardasil)

rana ehab, md

This study aims to investigate the relationship between HPV genotypes and treatment outcomes of intralesional immunotherapy of anogenital warts with the quadrivalent vaccine (Gardasil).

Human papillomavirus (HPV), a member of the Papillomaviridae family, is a small, icosahedral, non-enveloped virus with a circular double-stranded DNA genome. Sexually transmitted HPV, which mainly infects mucosal and keratinized epithelium, has a cytopathic effect on the epithelium. Genital mucosal HPV infection is persistent and multifocal and can be subclinical (Alacam \& Bakir, 2021). Infection with HPV causes a large proportion of cervical, vaginal, vulvar, anal, and penile cancers, as well as genital warts (Choi, 2019).

Anogenital warts are common benign dermatological conditions caused by different HPV genotypes, with serotypes 6, 11, 16, and 18 being the most causative types (Santos-López et al., 2015). Their prevalence varies according to geographical locations. Data is not yet available on the HPV burden in the general population of Egypt (Elazab et al., 2021). In October 2014, a very important multicenter observational study in Egypt concluded that the prevalence of HPV among Egyptian women aged 18 years or more is about 10.4%, with the highest prevalence of HPV infection being observed among women aged 45-54 years (Shaltout et al., 2014).

Different modalities are available for the treatment of warts, such as topical podophyllin, imiquimod, podophyllotoxin, or trichloroacetic acid, surgical excision, electrosurgery, cryosurgery, laser surgery, and intralesional immunotherapy (Gill, 2021; Nofal et al., 2022). Available treatments are time-consuming, painful, and can leave scars or hypopigmentation. Furthermore, recurrence rates after any treatment range from 6% to 100% (Ciccarese et al., 2019). As a result, there has been a demand for safer modalities to treat recalcitrant warts. Immunotherapy presents an alternative approach to the management of warts as it provides ease of application, but even distant lesions get resolved with application to a single lesion. Immunotherapy has been performed with imiquimod, BCG vaccine, HPV vaccines, and auto implantation therapy (Gill, 2021).

Three HPV vaccines are licensed as protective measures against the development of genital warts, cervical cancer, and other anogenital cancers. They include the bivalent vaccine targeting serotypes 16/18 (Cervarix), the quadrivalent vaccine targeting serotypes 6/11/16/18 (Gardasil), and the nonavalent vaccine targeting serotypes 6/11/16/18/31/33/45/52/58 (Gardasil-9) (Vaccine Information Statement \| HPV \| VIS \| CDC, 2021). There is a strong immune response against the HPV vaccine that not only causes the clearance of local wart lesions but also causes the clearance of distant lesions. The vaccine is designed to elicit neutralizing antibody responses which prevent initial infection with HPV, but in warts it mainly acts by mounting cell-mediated and humoral responses which help in the clearance of warts. The quadrivalent HPV vaccine contains inactive L1 proteins from four different strains: 6, 11, 16, and 18; synthesized in the yeast Saccharomyces cerevisiae (Gill, 2021).

Human Papilloma Virus Genotypes and Treatment Outcomes of Intralesional Immunotherapy of Anogenital Warts

The response will be considered complete if there is disappearance of the warts, partial if the warts regressed in size by 50-99% and no response if there is 0-49% decrease in wart size.

Zagazig University

lecturer of dermatology

Anti-Inflammatory Agents

Antineoplastic Agents

Antirheumatic Agents

Analgesics

Anti-Infective Agents

Curcumin

Interferons

Interferon-gamma

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Enzyme Inhibitors

Participants received a dosage of 200mg capsules with active ingredient /Nanocurcumin per day after breakfast, for 8 weeks.

Participants received a dosage of 200mg capsules without Nanocurcumin per day after breakfast, for 8 weeks

Curcumin oral capsule in nano-sized particle.

Curcumin Oral Capsule

Trichloroacetic acid

Blood sample collection

Cotton swab for collecting sample from AGW lesions.

Cotton swab

Hernayati Hutabarat

The goal of this clinical trial is to demonstrate the adjuvant administration of oral nanocurcumin in 90% TCA therapy that increases the proportion of clinical improvement in patients with Anogenital Warts (AGW), mediated by NFĸB, IFN-γ, and FOXP3+Treg. Specific objectives of this clinical trial include:

* To prove that the oral administration of nanocurcumin decreases the levels of IFN-γ, FOXP3+Treg, and NFĸB in lesions of AGW patients, and
* To demonstrate that the reduction in IFN-γ, FOXP3+Treg, and NFĸB levels in lesions is associated with the proportion of clinical improvement in AGW patients undergoing TCA 90% therapy with adjuvant of oral nanocurcumin.

The main questions it aims to answer are:

* Does adjuvant oral nanocurcumin administration in 90% TCA therapy increase the proportion of clinical improvement in patients with AGW compared to controls (90% TCA therapy alone)?
* Is there a greater decrease in IFN-γ, FOXP3+Treg, and NFĸB levels in lesions of patients with AGW given adjuvant oral nanocurcumin compared to controls?
* Is the decrease in IFN-γ, FOXP3+TReg, and NFĸB levels in lesions of patients with AGW, with adjunctive oral nanocurcumin administration in 90% TCA therapy, associated with the degree of clinical improvement in patients with AGW?

Participants will be divided into 2 groups. The first one was given capsules without active ingredients/nanocurcumin (control group), and the second one was given capsules with nanocurcumin (experimental group), both group received a dosage of 200mg capsules per day after breakfast, for 8 weeks. The researchers conducted a comparison between those 2 groups to assess whether the adjuvant administration of oral nanocurcumin in 90% TCA therapy enhances the proportion of clinical improvement in patients with AGW.

The study is expected to enhance various aspects, including education, healthcare services, and research development aspects. This research aims to improve the understanding of the efficacy of oral nanocurcumin administration in patients with AGW and its implications on clinical aspects and its biomarkers (IFN-γ, Treg FOXP3+, and NF-kB levels) in AGW lesions. Therefore, it is anticipated to enhance the clinical improvement of the patients, potentially reducing the transmission rate of the disease. Furthermore, this study serves as a foundation for the development of future therapies for patients with AGW, opening avenues for further research endeavors, and exploring traditional medicine as a medical therapy with a robust evidence base.

Subjects were obtained from multiple centers in Indonesia, predominantly in Jakarta and nearby the area, such as, from the Dermatology \& Venereology outpatient clinic at Dr Cipto Mangunkusumo hospital, HIV and STI Clinics at Tambora Health Center (CINTTA Clinic), Penjaringan Health Center, Kalideres Health Center, Taman Sari Health Center, Cengkareng Health Center, and several foundations that provide care for HIV and STI patients. The acetic acid testing was conducted to confirm the diagnosis of AGW.

Lesions meeting the research criteria (a minimum of 3 lesions, and the diameter of at least one lesion is between 5 mm to under 50 mm) continued to be treated with 90% TCA solution. If participants had giant AGW lesions, they were referred to the Surgery outpatient clinic at Dr Cipto Mangunkusumo hospital for further management. Participants underwent 8 weekly visits.

Sample collection and drug administration protocol included: sample collection using wet cotton swabs swiped on the lesion for biomarkers (IFN-γ, FOXP3+TReg, and NFĸB) examination, as well as blood collection for HIV and CD4+ examination at week 1, 4, and 8, application of 90% TCA solution + nanocurcumin/control capsule administration at every visit for 8 weeks, along with control and clinical evaluation / side effect assessment. If lesions were no longer visible and the acetic acid test was negative by week 8, the lesions were considered healed and no further application of 90% TCA solution was conducted, but biomarkers examination continued. If lesions were still visible, application would continue until lesions were healed, with treatment continued at a center accessible to the patient. Participants who tested positive for HIV were referred to the HIV outpatient clinic for appropriate treatment.

Additional details related to the drug administration and sample collection protocol included:

* Participants were provided with information sheets on how to consume the medication and instructed on its usage and were required to fill out a Medication Diary every time they took the medication, experienced lapses, or developed any complaints.
* In case of non-compliance or lapses, patients were asked to write down and report to the contact number listed in the Diary.
* To reduce discomfort, the skin swabbing process was performed carefully and with sufficient time. Each patient was provided with Gentamicin cream to take home, in case of unwanted infections occurring at home, and were instructed to report to the researcher for further management.
* In case of side effects such as allergic reactions, nausea, vomiting, abdominal pain, or severe headaches, patients were instructed to report and discontinue medication consumption. They were provided with medication to alleviate symptoms and considered dropouts.
* Medications were provided for side effects including mild allergic reactions. For severe allergic reactions, participants were advised to immediately go to the nearest Emergency Department for management and the researcher would accompany them.
* The education provided to the participants included the following: scheduled follow-up visits every 7 days after therapy, postponement of sexual intercourse or the use protection (condoms), Counseling regarding the possibility of HIV and other STI transmission risks for themselves and their sexual partners, recommendation for pap smear examinations every 3 years for women aged 21 years and older, and Informing the sexual partners of the participants about the possibility of transmission even in the absence of visible lesions and encouraging them to undergo examinations.

The Effect of Oral Nanocurcumin as an Adjuvant Therapy for Anogenital Warts: Evaluation of Clinical Improvement, NFĸB, IFN-γ, and FOXP3+TReg From Lesions Tissue

The Effect of Oral Nanocurcumin as an Adjuvant Therapy for Anogenital Warts: Evaluation of Clinical Improvement, Nuclear Factor Kappa-Light-Chain-Enchancer of Activated B Cells, Interferon-γ, and FOXP3+ Regulatory T Cell From Lesions Tissue

The percentage reduction in the volume of AGW lesions in visit 8 compared to the initial volume.

* Decrease of IFN-γ level in lesions of AGW patients
* reduction in IFN-γ level in lesions is associated with the proportion of clinical improvement in AGW patients

* Decreases of FOXP3+Treg level in lesions of AGW patients
* reduction in FOXP3+Treg level in lesions is associated with the proportion of clinical improvement in AGW patients

* Decreases of NFĸB level in lesions of AGW patients
* reduction in NFĸB level in lesions is associated with the proportion of clinical improvement in AGW patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Human Papilloma Virus Genotypes and Treatment Outcomes of Intralesional Immunotherapy of Anogenital Warts	NCT05761002	Human Papilloma... Anogenital Wart	the Quadrivalen...	20 Years - 60 Years	Zagazig University
The Effect of Oral Nanocurcumin as an Adjuvant Therapy for Anogenital Warts: Evaluation of Clinical Improvement, NFĸB, IFN-γ, and FOXP3+TReg From Lesions Tissue	NCT06281353	Anogenital Wart	Curcumin Oral C... Trichloroacetic... Blood sample co... Cotton swab	18 Years - 60 Years	Indonesia University

Spots Global Cancer Trial Database for anogenital wart