Clinical Research Directory

Feasibility Study Comparing Use of One Or Two Probes for Thermal Ablation Among Cervical Cancer Screen Positive Women Living With HIV in C1001P-CS2 Kenya

Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), particularly women living with HIV (WLWH) who have a 6-fold increased risk of cervical cancer compared to women in the general population. Thermal ablation (TA) is recommended by the World Health Organization (WHO) to treat cervical precancerous lesions, although its efficacy can be suboptimal in WLWH. In Kenya, the estimated incidence rate of cervical cancer is 31-33 per 100,000 women per year among women without HIV and approximately 70-100 per 100,000 among WLWH. The proposed study will evaluate the feasibility, acceptability, and safety of a two-probe TA technique (endocervical and ectocervical probes) and whether this approach improves treatment outcomes among WLWH compared to one (ectocervical) probe. This innovation has the potential to significantly enhance cervical cancer prevention efforts in high-burden settings. It will also contribute towards achieving the 90-70-90 goals of the WHO strategy for accelerated elimination of cervical cancer as a public health problem by 2030.

Feasibility Study Comparing One vs Two Probes for Thermal Ablation Among Cervical Cancer Screen Positive WLWH in C1001P-CS9 South Africa

Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), particularly women living with HIV (WLWH) who have a 6-fold increased risk of cervical cancer compared to women in the general population. Thermal ablation (TA) is recommended by the World Health Organization (WHO) to treat cervical precancerous lesions, although its efficacy can be suboptimal in WLWH. The proposed study will evaluate the feasibility, acceptability, and safety of a two-probe TA technique (endocervical and ectocervical probes) and whether this approach improves treatment outcomes among WLWH compared to one (ectocervical) probe. This innovation has the potential to significantly enhance cervical cancer prevention efforts in high-burden settings. It will also contribute towards achieving the 90-70-90 goals of the WHO strategy for accelerated elimination of cervical cancer as a public health problem by 2030.

Feasibility Study Comparing One vs Two Probes for Thermal Ablation Among Cervical Cancer Screen Positive Women Living With HIV in C1001P-CS7 Zimbabwe

Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), particularly women living with HIV (WLWH) who have a 6-fold increased risk of cervical cancer compared to women in the general population. While thermal ablation (TA) is a WHO- recommended treatment for cervical precancerous lesions, its efficacy can be suboptimal in WLWH. We will also conduct a feasibility treatment cohort study of up to 300 Zimbabwean WLWH to provide evidence for a larger treatment effectiveness study. The proposed study will evaluate the feasibility, acceptability, and safety of a two-probe TA technique (endocervical and ectocervical probes) and whether this approach improves treatment outcomes among WLWH compared to one (ectocervical) probe. This innovation has the potential to significantly enhance cervical cancer prevention efforts in high-burden settings and to contribute towards achieving the 90-70-90 goals of the World Health Organization's (WHO) strategy for accelerated elimination of cervical cancer as a public health problem by 2030.

Feasibility Study Comparing One vs Two Probes for TA Among Cervical Cancer Screen Positive WLWH in C1001P-CS5 Rwanda

Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), particularly women living with HIV (WLWH) who have a 6-fold increased risk of cervical cancer compared to women in the general population. Thermal ablation (TA) is recommended by the World Health Organization (WHO) to treat cervical precancerous lesions, although its efficacy can be suboptimal in WLWH. This is even more important at a time when Rwanda has launched a National Cervical Cancer Screening Program (NCCSP) with human papillomavirus (HPV) testing and treatment, mainly using TA with unknown outcomes. Therefore, we will conduct a feasibility study (C1001P-CS5) among 300 Rwandan WLWH to provide evidence needed to launch a future effectiveness study. The proposed study will evaluate the feasibility, acceptability, and safety of a two-probe TA technique (endocervical and ectocervical probes) and whether this approach improves treatment outcomes among WLWH compared to one (ectocervical) probe. This innovation has the potential to significantly enhance cervical cancer prevention efforts in high-burden settings. It will also contribute towards achieving the 90-70-90 goals of the WHO strategy for accelerated elimination of cervical cancer as a public health problem by 2030. Rwanda hopes to achieve this goal early, in 2027 under Mission 2027.

Effect of Web-Based Education on Attitudes and Beliefs About HPV Testing

Cervical cancer is a highly preventable public health issue that significantly impacts women's quality of life. Although effective screening programs such as Human Papilloma Virus (HPV) testing and Pap-smears are widely available, women's participation in these early detection services often remains limited. The primary barriers to screening attendance include insufficient education, lack of information, negative beliefs, psychosocial or cultural factors, and misconceptions regarding gynecological examinations. To improve screening uptake, health interventions must focus not only on increasing knowledge but also on promoting correct beliefs and positive attitudes toward testing. Web-based health education serves as an effective method to overcome barriers such as cost, transportation difficulties, and geographical limitations, allowing wider access to healthcare guidance. This study aims to evaluate the effects of a specialized web-based educational intervention on women's attitudes and beliefs regarding the HPV test. The research is designed as a randomized controlled trial with a pre-test and post-test design. Participants will be assigned to either an intervention group or a control group. The intervention group will receive structured health education through a dedicated web platform, while the control group will receive routine standard follow-up. Data will be gathered using a specific attitude and belief scale before and after the application to measure the intervention's impact.

A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers

Background: Often, metastatic human papillomavirus (HPV) associated cancers cannot be cured. They also do not respond well to treatment. Some forms of colon cancer also have poor responses to treatment. Researchers want to see if a new drug treatment can help people with these types of cancers. Objective: To find a safe dose of entinostat in combination with PDS01ADC and bintrafusp alfa and to see if this treatment will cause tumors to shrink. Eligibility: Adults ages 18 and older who have cervical, oropharyngeal, anal, vulvar, vaginal, penile, squamous cell rectal, or another cancer that may be associated with HPV infection or microsatellite stable small bowel or colorectal cancer. Design: Participants will be screened with a medical history and physical exam. Their ability to do daily activities will be assessed. They may have imaging scans of the brain and/or chest, abdomen, and pelvis. They may have nuclear bone scans. They will have an electrocardiogram to test heart function. They will have blood and urine tests. They may have a tumor biopsy. Participants with skin lesions may have them photographed. Some screening tests will be repeated during the study. Treatment will be done in 28-day cycles. Participants will get bintrafusp alfa through an intravenous catheter every 2 weeks. They will get PDS01ADC as an injection under the skin every 4 weeks. They will take entinostat by mouth once a week. They will complete a medicine diary. Participants will get treatment for 2 years. They will have 1-2 follow-up visits in the 30 days after treatment ends. Then they will be contacted every 6 months to check on their health....

The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise

Background: * Infections caused by viruses are common causes of illnesses: the common cold, many ear infections, sore throats, chicken pox, and the flu are caused by different viruses. Usually, these illnesses last only few days or, at most, a few weeks. Some virus infections like influenza are cleared from the body, and others such as the chicken pox virus remain in the body in an inactive state. However, some people may become quite ill when they are infected with a particular virus, possibly because part of their immune system does not respond properly to fight the virus. * Researchers have discovered some reasons why a person may not be able to clear an infection caused by a virus. Some persons have changes in the genes that involve the immune system that result in the inability to properly control infection with a particular virus. Identifying changes in genes that involve the immune system should help scientists better understand how the immune system works to protect people from infection and may help develop new therapies. Objectives: * To study possible immune defects that may be linked to a particular severe viral infection. * To determine if identified immune defects are genetic in origin. Eligibility: * Individuals of any age who have or have had a diagnosis of a virus infection that physicians consider to be unusually severe, prolonged, or difficult to treat. * Relatives of the participants with a severe viral infection may also participate in the study. We will use their blood and/or skin specimens to try to determine if identified immune defects are hereditary. Design: * Prior to the study, the participant's doctor will give researchers the details of the infection, along with medical records for review. Eligible participants will be invited to the NIH Clinical Center for a full evaluation as an outpatient or inpatient. * At the Clinical Center, participants will be treated with the best available therapy for the particular viral infection, and researchers will monitor how the infection responds to the treatment. * Researchers will take intermittent blood samples and conduct other tests (such as skin biopsies) to evaluate the immune system. - During and after the illness, researchers will conduct follow-up visits to determine the course of infection and response to therapy.

Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL

Problem description: Yearly, approximately 45000 women develop vulvar cancer worldwide. It is estimated that about 30% of all vulvar carcinomas are HPV related. As with other HPV related (pre)malignancies, the incidence has been rising over the past 20 years. The peak incidence of premalignant lesions of the vulva, also called Vulvar High Grade Squamous Intraepithelial Lesion (vHSIL), lies between 35 and 40 years of age. Multiple treatments are available, including surgery, laser vaporization, and topical imiquimod, with comparable success rate. Despite treatment, at least 30% of women will develop a recurrence within 2 years, with a much higher lifetime risk of recurrence. This results in multiple treatments with sometimes disfiguring effects and associated negative psychosocial and psychosexual impact. Woman with vulvar HSIL have a lifelong increased risk of vulvar cancer, and approximately 10% of women with (treated) vulvar HSIL will develop vulvar cancer within 10 years of first diagnosis. The risk of malignancy is significantly higher in women with recurrent disease, compared to women without recurrence. Solution / research direction, To date, a successful strategy for reduction of recurrences of HSIL has not been established. The available positive evidence on the use of concurrent HPV vaccination in the treatment of vulvar HSIL is rising, yet insufficient to guide clinical practice. There is limited data that prophylactic HPV vaccination after treatment of vulvar HSIL reduces the chance of recurrence, therefore leading to a reduction in repeated (surgical) interventions. There are no randomised controlled studies supporting this data. Aim The aim of current project is to determine the effectiveness of nonavalent HPV vaccination versus placebo in preventing recurrence in women treated for vulvar HSIL. Plan of investigation This is a randomised, double blinded, placebo controlled trial in women treated for vulvar HSIL. Adult female patients, diagnosed with vulvar HSIL planned for treatment and no prior HPV vaccination will be included. Randomisation will be in a 1:1 ratio to additional nonavalent HPV vaccination versus additional placebo vaccination. Expected outcome. Based on previous non-randomised studies, a significant reduction in recurrences, improvement of quality of life and a reduction of economic burden of the disease is expected.

Assessment of Patients' Quality of Sexual Life After Anal Cancer Treatment

The purpose of this this study, to evaluate the quality of sexual life of patients treated for anal cancer treated by radiotherapy, during their treatment, then 3 months after treatment and, finally, 2 years after treatment. cancer diagnosis.

Prognostic Biomarkers for Patients With Human Papillomavirus (HPV) Positive Oropharyngeal Squamous Cell Carcinoma

The purpose of this research study is to investigate the relationship between vascular habitats and treatment response AND to investigate the potential utility of dynamic contrast enhanced (DCE)-MRI derived parameters in predicting treatment response. This data can be used to assist in the development of a clinical decision support (CDS) tool for risk categorization and individualized decision-making. While "low-risk" patients could benefit from de-escalated radiation therapy, "high-risk" patients could receive early initiation of targeted therapies, or immunotherapies.

HPV Vaccine Reduced Dose

This study aims to answer the question: does 1-dose HPV vaccination generate the same immune responses compared to 2- or 3-dose HPV vaccination? This will be done by studying the immune response in blood, lymph nodes, and bone marrow. Human papillomaviruses (HPV) cause cancers (cervical, anal, oropharyngeal, vulvar, vaginal, and penile), and the current HPV vaccine is highly effective at preventing disease by HPV types that cause 90% of cancer cases. While this vaccine generates high levels of antibodies that last for \> 10 years, understanding of how this occurs is limited, and studying this immune response will help design new and better vaccines. The study population consists of healthy adult (age 18-45) participants who have not previously received an HPV vaccine, do not have antibodies against certain types of HPV, do not have a history of HPV infection or disease (such as genital warts, abnormal pap test, or HPV DNA test), and do not have contraindications to study procedures. Populations of increased concern are not being enrolled.

Assessing Durable Antibody Response to HPV Vaccination

This is a single center, longitudinal cohort study in which subjects will receive 9-valent HPV vaccine according to package insert (i.e., one dose of 9-valent HPV vaccine on day (D) 0 followed by a second dose 2 months later and a third dose 6 months later). Immune responses in the blood, saliva, bone marrow, and lymph nodes will be assessed in subjects receiving the HPV vaccine. Blood samples for immunologic testing will be collected at screening (from D-60 to D-45), on D0 (before vaccination), D1 (optional visit), D7±1, D14±5, D30±5, D60±5 (Visit 8, before vaccination), Visit 8 +1 day (optional visit), Visit 8 + 7±1 days, Visit 8 + 14±5 days, Visit 8 + 30±5 days, D180±5 (Visit 13, before vaccination), Visit 13 + 7±1 days, Visit 13 + 14±5 days, Visit 13 + 30±5 days, D365±14, D730±14, D1095±14, D1460±14, D1825±30. Saliva samples for antibody testing will be collected on D0 (before vaccination), D30, D60 (before vaccination), Visit 8 + 30±5 days, D180 (before vaccination), Visit 13 + 30±5 days, D365, and D730. Axillary lymph node sampling by fine needle aspiration will be done 3 times per group. Group 1 will have lymph node sampling done D-30 to D0, D14, and D30. Group 2 will have lymph node sampling done D60, Visit 8 + 14±5 days, and Visit 8 + 30±5 days. Group 3 will have lymph node sampling D180, Visit 13 + 14±5 days, and Visit 13 + 30±5 days. Bone marrow sampling will be done for all groups at D730±14 and D1825±30.

My Self-Sampling for HPV Awareness, Results, and Empowerment

The overall objective of this study is to conduct formative research and pilot test the provider-level and patient-level components of the My Self-Sampling for HPV Awareness, Results, and Empowerment (MySHARE+) intervention. MySHARE+ aims to harness the power of technology and apply a multilevel approach to promote the adoption of cervical cancer screening (HPV self-sampling; Pap triage adherence) among under/never-screened women living with HIV (WLH). The specific aims are to 1) identify facilitators and barriers to implementing a healthcare provider prompt in a primary care setting and 2) conduct a pilot randomized controlled trial (RCT) to examine the feasibility, acceptability, and preliminary efficacy of a mHealth educational intervention in promoting cervical cancer awareness and HPV self-sampling among WLH. Under aim 1: Providers of healthcare and/or social services to WLH will complete an online survey to identify barriers to implementing a healthcare provider prompt in a primary care setting and participate in semi-structured interviews to provide feedback on drafted prompts. Prompts will be piloted at one local clinic to improve patient-provider communication about cervical cancer screening, followed with semi-structured interviews with providers involved. Under aim 2: Participants will be enrolled in a text messaging intervention and sent an HPV self-sampling test kit to return via mail. Participants in the intervention group will receive the full mHealth intervention while the control group will receive more generic text messages and reminders over the course of the study.

Prevención en Sus Manos: Feasibility of a Novel Community-Based Strategy to Improve Access to Cervical Cancer Screening

Cervical cancer is a disease that is preventable through vaccination against the virus that causes it, human papillomavirus (HPV), and through screening and treatment of cervical disease before it becomes cancet.

mSaada: A Mobile Health Tool

In the R21 phase of this project, investigators will: (1) work with key stakeholders and local and international developers to finalize the mSaada platform, building on the existing prototype to add patient and specimen tracking functionality; and (2) carry out a pilot to identify the patient, provider and health system factors necessary to design a trial to evaluate mSaada effectiveness in assisting community health volunteer-led home-based HPV screening, and implementation factors. Investigators will carry out a six-month pilot of mSaada with community units in two health facilities providing HPV-based screening, and use performance metrics including system usage rates, workflow observations and qualitative data to guide the planning of a to determine effectiveness. In the R33 phase of the project, investigators plan to: (1) conduct an 18-month c-RCT across 12 health facilities to determine the impact of mSaada on cervical cancer screening uptake, treatment acquisition and cervical cancer knowledge levels among women in the community; and (2) measure the requisite implementation factors for mSaada effectiveness, sustainability, and scale-up. The rigorous study design will allow us to determine the clinical impact of mSaada, ensure the local and regional infrastructure has the capacity necessary for sustainability and develop strategies for widespread implementation and scale-up. Collaboration with key stakeholders from the Kenya Ministry of Health will facilitate the development of a long-term sustainability plan as the country moves toward HPV-based cervical cancer screening. Investigators anticipate the mSaada platform will play a pivotal role in facilitating the introduction of HPV-based screening programs that can reach women in settings with limited health care infrastructure.

Comparative Self-collection for Cervical Cancer Screening Pivotal Study

To evaluate whether individuals drawn from the intended use population can successfully interpret and follow the IFU for the Mia by XytoTest self-collection device and perform a vaginal sample collection yielding sufficient cellular material for primary hrHPV screening. To assess the clinical performance of Mia self-collected vaginal specimens by evaluating agreement with paired clinician-collected cervical specimens for the detection of high-risk HPV, when both specimen types are analyzed using the cobas HPV Test (Roche Molecular Systems). Residual samples may be used to determine adequacy for additional assays that require vaginal and/or cervical specimens (such as mRNA E6 and E7 Biomarker Test, dual stain cytology).

Text and Talk: A Multi-level Intervention to Increase Provider HPV Vaccine Recommendation Effectiveness

This study will test the effectiveness of two interventions (parent-targeted text messages and a brief clinician-targeted training) at increasing HPV vaccination among 11- to 12-year-olds living in Florida.

Evaluation of the Q-Pad hrHPV Test System for Identifying Precancer

The EQUIP Study is testing whether high-risk human papillomavirus (hrHPV), the virus that causes most cervical cancers, can be accurately detected from menstrual blood collected at home. People who have been referred for colposcopy after an abnormal Pap or hrHPV test will use the Q-Pad Kit during their period to collect menstrual samples on a special menstrual pad and mail them to a central laboratory for hrHPV testing. The same participants will have a standard cervical sample collected for routine hrHPV testing and will undergo colposcopy as part of their usual care. By comparing hrHPV results from menstrual samples with results from cervical samples and biopsy findings, the study will evaluate how well the Q-Pad hrHPV Test System detects cervical precancer and will also assess how easy and acceptable it is for participants to use this at-home collection method.

Digital Interventions to Increase HPV Vaccination Intentions Among Nigerian Caregivers

This study evaluates whether different types of digital health communication can increase parents' intention to vaccinate their daughters against human papillomavirus (HPV) in Nigeria. HPV vaccination is recommended for girls aged 9-14 years and helps prevent cervical cancer, yet vaccination rates remain low. Parents of eligible, unvaccinated girls will be randomly assigned to receive one of several types of digital content delivered online. These include: (1) a short chatbot conversation based on motivational interviewing principles, (2) an interactive game designed to help parents recognize and resist common forms of vaccine misinformation, (3) a set of short edutainment videos about HPV vaccination, (4) standard informational infographics about HPV vaccination from a national public health agency, or (5) unrelated health content about menstruation. The main outcome is parents' self-reported intention to vaccinate their daughter against HPV, measured immediately and one week after exposure to the assigned content. Additional outcomes include HPV-related knowledge, perceptions of vaccine safety, willingness to recommend the vaccine to others, and self-reported vaccine uptake at 1-week and 6 month follow-up. The results will help inform scalable communication strategies to improve HPV vaccination uptake in low- and middle-income settings.

The HPV 9-10 Trial: Early Initiation of HPV Vaccination

Every year, thousands of Americans die from cancers related to human papillomavirus (HPV). The vast majority of those deaths could be prevented with a safe and effective vaccine, yet many parents choose not have their children vaccinated when it is recommended at age 11 or 12. In this study, we will examine in a randomized trial whether earlier initiation of the vaccine at age 9-10 years will result in less parental refusal and higher rates of full vaccination at younger ages, before early sexual activity begins.

A Clinical Trial to Investigate the Safety and Efficacy of Papillex® on Abnormal Cervical Cells Caused by HPV.

The goal of this clinical trial is to investigate the safety and efficacy of Papillex® on the regression of abnormal cervical cells caused by HPV in women with a cervical intraepithelial neoplasia (CIN) 1 or 2 diagnosis. The main question it aims to answer is: Is there a difference in the proportion of participants with a regression in CIN based on histology or cytology from baseline at day 180 between Papillex® and placebo? Participants will be asked to consume Papillex® or placebo for 180 days, complete questionnaires, a PAP smear, HPV test, and colonoscopy (where applicable).

Post-treatment Surveillance in HPV+ Oropharyngeal SCC

In this research study the investigators are examining a blood test to detect HPV DNA in the blood that can possibly detect cancer recurrence earlier than with standard surveillance measures.

Playing Game to Learn About Children's Vaccine Project

This proposed study aims to conduct timely research that promotes vaccine confidence and vaccination of one strongly recommended vaccine with suboptimal uptake rates: Human papillomavirus (HPV) in vulnerable and underserved youth aged 11-14.

Acceptability of the HPV Vaccine and Anal HPV in Transgender Women and Men Who Have Sex With Men: A Pilot Study

Protocol Title: "Acceptability of the Human Papillomavirus (HPV) Vaccine and Anal HPV in Transgender Women (TGW) and Men Who Have Sex with Men (MSM): A Pilot Study.