Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Uterine Cervical Neoplasms

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

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Cervical Intraepithelial Neoplasia

Triage tests for diagnosis of cervical pre-cancer amongHPV positive women

OncoE6

EVA System

Mark H Schiffman, M.D.

Background:

* Cervical cancer is caused by persistent infection of the lining of the cervix with some kinds of human papillomaviruses (HPV). These HPV infections are distantly related to the viruses that cause warts on the skin. Like common wart viruses, most women who have cervical infections with HPV resolve the infections within 2 years without any need for treatment. Cervical infections that do not go away may cause disease that can turn into cancer after many years.
* Only one study has been done in Nigeria to learn how many women have HPV infection. The results of the study differed from most other studies in the world because older women were much more likely to be infected. This study with learn whether the results found in the previous study are true in Irun also, the site of the current study.

Objectives:

* To examine the age distribution of HPV infection and relationship to cancer of the cervix among Nigerian women.
* To understand how different screening methods, including HPV testing, could best reduce the risk of cervical cancer in Nigerian women.

Eligibility:

- Women residing in Irun, Nigeria, who are 15 years of age or older.

Design:

* Participants complete a brief questionnaire related to demographics, household and living conditions and a longer survey with questions related to reproductive history, family history, illnesses, stressful life events and sexual history (U. of Michigan collaboration).
* Participants have a cervical examination, HPV test, Pap test and blood test.
* Women whose tests show they are infected with HPV or have cervical disease will do the following:
* see a doctor and have cervical biopsies of all white abnormal areas (removal of a small tissue sample from the cervix)
* have photographs of the cervix taken
* have a cervical scraping for a new kind of HPV test.
* Some women with normal test results are also asked to see a doctor to check the validity of the testing
* Women with cervical disease receive treatment by a specialist and remain in the program until treatment is successfully completed or a final diagnosis is reached.
* Participants may be contacted for followup up to 5 years after the final diagnosis is made.

BACKGROUND: Cervical cancer, caused by persistent infection with approximately 15-20 genotypes of carcinogenic human papillomavirus (HPV) infection, is the second leading cause of female cancer. Cytology (Pap smears) and the new HPV vaccines are not widely available in poor regions. Immediate treatment of HPV-infected older women by cryotherapy might have greater impact.

Although the same HPV types cause cervical cancer everywhere, and the same stages (infection, persistence vs. clearance, progression to precancer, and invasion) typify cervical carcinogenesis, the patterns of age-specific prevalence of HPV vary widely. These patterns are important for secondary prevention strategies relying on HPV DNA testing.

In many regions, including the US, HPV infections appear as classical sexually-transmitted agents, with peak cervical DNA prevalence at young ages (approximately 20) and low prevalence at older ages. However, in Nigeria, HPV prevalence is high (greater than or equal to 15%) at all ages according to the one study performed in urban Ibadan by Franceschi s group at IARC (n=932 women). This pattern is very uncommon. High prevalence at all ages would preclude use of HPV testing in low-cost strategies, due to poor positive predictive value. One possibly relevant element is the marital structure in Nigeria; a man often has multiple wives.

OBJECTIVES: The major objectives are: 1) To estimate age-specific HPV prevalences in Irun, Nigeria; 2) To investigate epidemiologic risk factors for HPV and cervical intraepithelial neoplasia in this population; 3) To examine the performance of screening options; 4) To assess the correlation of HPV among co-wives, comparing households with multiple wives with those with single wives; and 5) To validate the performance of rapid HPV, an inexpensive HPV test designed for public-sector use in settings like Irun.

ELIGIBILITY: All non-pregnant women aged 15+, without hysterectomy, will be eligible if they can provide written informed consent. Unmarried women less than 21 will be enrolled only with parental consent. Sexually active women will be examined and asked for cervical specimens; self-reported virginal women will be asked for a 10-ml blood sample only.

DESIGN: This is a cross-sectional screening study of 1500 women in Irun, a Nigerian village. Unlike the IARC study, we will incorporate cytology, visual inspection, and colposcopic biopsy of women that test positive by any of the three screening tests. We will determine whether HPV infection at various ages is related to risk of cervical abnormalities. The analyses will include descriptive trend data, multivariable modeling of HPV determinants, and clinical epidemiologic analysis of relative screening test performance in detecting cervical neoplasia.

Human Papillomavirus Epidemiology in Nigeria

Epidemiologic and Molecular Features of Cervical Cancer in Nigeria - Project Itoju (Care)

National Cancer Institute (NCI)

Infections

Symptoms and General Pathology

Digestive System Diseases

Communicable Diseases

Hepatitis A

Hepatitis

Persistent Infection

Hepatitis E

Carcinoma

Carcinoma in Situ

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

All Drugs and Chemicals

Gastrointestinal Agents

Vaccines

Aluminum Hydroxide

Aluminum sulfate

Immunologic Factors

This dosage contains 40μg HPV 16 virus-like particle antigen and 20μg HPV 18 virus-like particle antigen adsorbed in alum-adjuvant

commercialized HEV vaccine which contains 30μg HEV antigen adsorbed in alum-adjuvant

HPV Vaccine

HEV vaccine

Jun Zhang, Master

Youlin Qiao, Ph.D

Ting Wu, Ph. D

This is a Phase III clinical trial of the novel recombinant HPV 16/18 bivalent vaccine manufactured by Xiamen Innovax Biotech CO., LTD. The primary objective of this study is to demonstrate the efficacy of the vaccine against relevant outcomes in healthy women above 18 years old at enrolment. The secondary objectives are to evaluate the safety, immunogenicity and immuno-persistence of the vaccine. Meanwhile, this study tries to compare the difference of safety and immunogenicity among different lots. Approximately 6000 study subjects will be enrolled and randomly stratified into 2 groups and receive human papillomavirus (HPV) vaccine(three different lots) or commercialized hepatitis E vaccine(Hecolin) according to a 0-1-6 month schedule.

Efficacy and Immunogenicity Study of Recombinant Human Papillomavirus Bivalent（Type 16/18 ）Vaccine

A Phase III Multicenter, Randomized, Double-Blind, Placebo(Hepatitis E Vaccine)Controlled Study to Evaluate the Efficacy, Immunogenicity and Safety of a Recombinant(E.Coli)Human Papillomavirus Bivalent Vaccine in Healthy Women

Histopathologically confirmed CIN2+ and/or VIN2+ and/or VaIN2+ associated with oncogenic HPV types (e.g. HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) detected within the lesional component of the tissue specimen (by PCR).

Xiamen Innovax Biotech Co., Ltd

Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.

Ministry of Science and Technology of the People´s Republic of China

Xiamen University

professor

Participants in this arm have received 3 doses of HPV 16/18 bivalent vaccine that contains 40μg HPV 16 virus-like particle antigen and 20μg HPV 18 virus-like particle antigen adsorbed in alum-adjuvant.

Participants in this arm have received 3 doses of HEV vaccine that contains 30μg HEV virus-like particle antigen adsorbed in alum-adjuvant.

The bivalent HPV-16/18 vaccine was a mixture of two aluminum hydroxide adjuvant-absorbed recombinant L1 VLPs of HPV-16 and HPV-18 expressed in E. coli. A 0.5 ml dose of the bivalent HPV test vaccine comprised 40 μg of HPV-16 and 20 μg of HPV-18 L1 VLPs absorbed with 208 μg of aluminum adjuvant

Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine (Escherichia coli)

Chao Zhao, Doctor

Ting Wu, Ph. D.

The primary objective of this study is to evaluate the durability of protection of Recombinant Human Papillomavirus Bivalent (Types 16,18) Vaccine administered in females aged 18-45 years.

This is a follow-up study that is based on phase III clinical study of a recombinant human papillomavirus 16/18 bivalent vaccine in females aged 18-45 years (Unique Protocol ID: HPV-PRO-003, Identifiers: NCT01735006). The investigators will recruit people who have participated in phase III clinical study on Hebei Province before and to evaluate the durability of protection of the bivalent HPV vaccine on 90m and 114m after dose 1.

The Durability of Protection Study of a Recombinant HPV 16/18 Bivalent Vaccine in Female

The Durability of Protection Study of A Bivalent Human Papillomavirus (Type 16, 18) Recombinant Vaccine (E.Coli) in Healthy Women Aged 18 to 45 Years

To observe the number of Subjects With Histopathologically-confirmed CIN2+ and/or VIN2+ and/or VaIN2+ Associated With HPV-16 and/or -18 Cervical Infection on 90m and 114m after dose 1

To detect the HPV16 and HPV18 DNA on the gynecological specimens ( Cervical exfoliated cell specimens and biopsy specimens) collected from the subjects

Jun Zhang

Professor

Papillomavirus Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Anti-Infective Agents

Antineoplastic Agents

Vitamins

Acetic Acid

Retinol acetate

Door-to-door recruitment of women for self-collected HPV testing

Community health meeting recruitment of women for self-collected HPV testing

Self-collection cervical cancer screening, STI screening, and education on HIV by a community health worker. Women who test positive for high-risk HPV types will be referred to a designated health centre for VIA follow-up and treatment if indicated.

Self-collected HPV testing for cervical cancer screening

Gina Ogilvie, MD

Sheona Mitchell-Foster, MD

Carolyn Nakisige, MD

The purpose of this pragmatic cluster randomized control trial is to test the effectiveness of cervical cancer screening follow-up completion using two implementation approaches for self-collected HPV testing in a rural, low-resource setting: 1) community health workers recruiting women door-to-door and 2) community health workers recruiting women at community health meetings.

This study will also help to further understand how current patient referral systems are working between health facilities, patient and provider preferences for integrated care and health system related barriers to integrated cervical cancer screening.

Hypothesis: More women will receive screening via the community health meeting but the engagement to care (i.e., visual inspection with acetic acid-our main outcome) will be greater in the door-to-door arm.

A cluster randomized control trial will be conducted with the objective of understanding differences in the effectiveness of cervical cancer screening models using self-collected HPV testing on engagement in care. In 31 villages, women will be recruited for self-collected cervical cancer and sexually transmitted infection (STI) screening by: 1) Community health worker recruitment for self-collection (door-to-door), 2) community health meetings. Visual inspection with acetic acid (VIA), cryotherapy and thermocoagulation will be offered in local health facilities for all women who test positive for high-risk (HR)-HPV types. Women needing advanced cancer care will be referred to the Uganda Cancer Institute in Kampala.

The unit of randomization (2 arms) will be villages and the analysis will also account for clustering within this unit or randomization. All participants will receive an integrated package of cervical cancer screening and education and will participate in a survey at baseline. Samples will be tested using GeneXpert (XpertHPV) point of care testing at the Kigandalo health facility for HPV and high risk HPV (HR-HPV). Intervention arms will be implemented in phases by year to avoid temporal contamination.

Pragmatic cluster randomized control trial

Integrated Cervical Cancer Screening in Mayuge District Uganda (ASPIRE Mayuge)

Integrated Cervical Cancer Screening in Mayuge District Uganda (ASPIRE Mayuge): A Pragmatic Cluster Randomized Control Trial

Data will be available on request through study investigators.

Measured using years of lives saved compared between each study arm and the ICER

Evaluating reach, fidelity, barriers and facilitators of implementation in each arm from the community and health system perspective using mixed methods

Assess men's knowledge level of HPV and cervical cancer and determine which factors impact the supportiveness towards a partner seeking screening.

Proportion of total screened women who complete VIA follow-up and treatment after testing positive for high-risk HPV type

Total number of women who test positive for HPV out of the total number of samples obtained

Total number of women who test positive for STIs out of total number of women who test positive for HPV; total number of women who test negative for STIs out of total number of women who test positive for HPV; total number of women who test positive for STIs out of total number of women who test negative for HPV; total number of women who test negative for STIs out of total number of women who test negative for HPV

Association (adjusted OR) estimated between HPV and HIV; other STIs

Semi-structured focus group discussions with women who did and did not attend follow-up screening in each study arm.

Mediation analysis using counterfactual approach to assess mediating effect of patient reported experience, knowledge change and co-infection status with other STIs on engagement in care after positive HR-HPV test

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Human Papillomavirus Epidemiology in Nigeria	NCT00804466	Human Papilloma... Cervical Intrae... Human Papilloma... Uterine Cervica...	OncoE6 EVA System	30 Years - 49 Years	National Institutes of Health Clinical Center (CC)
Efficacy and Immunogenicity Study of Recombinant Human Papillomavirus Bivalent（Type 16/18 ）Vaccine	NCT01735006	Cervical Intrae... Cervical Cancer Vaginal Intraep... Vulvar Intraepi... Persistent Infe...	HPV Vaccine HEV vaccine	18 Years - 45 Years	Xiamen University
The Durability of Protection Study of a Recombinant HPV 16/18 Bivalent Vaccine in Female	NCT04969445	Cervical Intrae... Cervical Cancer Vaginal Intraep... Vulvar Intraepi... Persistent Infe...	Recombinant Hum...	26 Years - 54 Years	Xiamen University
Integrated Cervical Cancer Screening in Mayuge District Uganda (ASPIRE Mayuge)	NCT04000503	Human Papilloma... Human Papilloma... Papillomavirus ... Cervical Cancer Pre-Cancerous D...	Self-collected ...	25 Years - 49 Years	University of British Columbia

Spots Global Cancer Trial Database for human papillomavirus 18