Clinical trial NCT06129253: Global Burden Estimation of Human Papillomavirus (GLOBE-HPV)
Official title: Global Burden Estimation of Human Papillomavirus (GLOBE-HPV)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: HPV Infection
Keywords: HPV Positivity
HPV Infection
High Risk (HR) HPV
Cervical Cancer
Lead sponsor: International Vaccine Institute
Sponsor class: OTHER
Collaborators: name: London School of Hygiene and Tropical Medicine
name: Karolinska Institutet
name: Centers for Disease Control and Prevention
First posted: 2023-11-13
Enrollment: 29750
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: The study will enroll girls and women aged 9-50 years old, with equal distribution across the following age strata: 9-14, 15-20, 21-30, and 31-50 years.

Brief summary: This study is a multi-country and multi-site project to estimate the point-prevalence of high-risk (HR) HPV genotype infections among representative samples of girls and women aged 9-50 years, and among specific sub-populations to estimate the incidence of persistent HPV infection among sexually active young women. The data to fulfill the objectives will be collected through a series of Cross-Sectional Surveys (CSS) and Longitudinal Studies (LS) in all 8 countries 3 South Asian countries including Bangladesh, Pakistan, Nepal and 5 sub-Saharan African countries including Sierra Leone, Tanzania, Ghana, Zambia and DR Congo. Qualitative sub-studies (QS) will be conducted in selected countries and populations following the CSS to further understand and unpack risk factors for HPV infection as well as to explore how gender-related dynamics including perceptions of gender norms and stigma, influence HPV burden and/or create barriers that shape girls/women access to and uptake of HPV prevention, screening, and treatment services. Specific study protocols and corresponding ethical applications for the qualitative sub-studies will be developed separately.

Detailed description: The study will incorporate a harmonized protocol among the 8 countries to estimate point-prevalence of high-risk HPV (HR HPV) in low socio-economic populations and, among specific sub-populations, the incidence of persistent HPV infection. Due to differences in study settings, study population, targeted age-group, and eligibility criteria, country-specific protocols will be developed to complement the multi-country master protocol. In the master protocol, general principles on study design and methodology will be described, while the country-specific protocol will elaborate in more detail on methodology in each country related to subject identification, the enrolment process, and laboratory analysis. A standardized survey questionnaire, with some minor country-specific adaptations, and laboratory assays will be implemented throughout the participating countries in order to generate comparable data.

Two separate approaches will be implemented to estimate prevalence and incidence respectively in each participating country. First, cross-sectional surveys (CSS) will be conducted in both urban and rural areas of selected countries in order to estimate the point prevalence of HPV infection in sub-Saharan Africa and South Asia. The CSS will enrol girls and women aged 9-50 years, with equal sample size from four age-strata: 9-14, 15-20, 21- 30, 31-50. For specific populations, age-strata will be modified to include 12-35 years olds considering the target population characteristics and local context. Multi-stage cluster random sampling or another applicable sampling strategy will be applied to ensure representativeness. Urine samples will be collected for HPV testing, along with data on demographics, socioeconomic status, sexual and reproductive history, attitudes towards and awareness and uptake of cervical cancer screening and HPV vaccination, and potential risk factors for HPV infection and cervical cancer. Additional data will be collected on knowledge of HPV, and attitudes, uptake and use of vaccines, using standardized questionnaires and case report forms.

Second, Longitudinal studies (LS) will estimate the incidence of persistent HPV infection in sexually active girls and young women in geographically defined communities and special populations. Depending on the country setting, the LS will enroll sexually active girls and women who are aged between 15-35 years and follow them up to 24 months. Participants will be tested every 6 months for 24 months to determine incident persistent HR HPV infection. In selected countries, urine and self-collected vaginal swabs (SCVS) will be collected at the first visit to determine the comparability of HPV genotyping results from both sample types. For all the other visits, only SCVS will be collected. Data on demographics, socioeconomic status, sexual and reproductive history, cervical screening, HPV vaccination, and other potential risk factors will be collected using standardized questionnaires.

Furthermore, the qualitative sub-studies in five selected countries (Bangladesh, Nepal, Pakistan, Sierra Leone, DR Congo) will follow and draw on findings from the CSS, focusing on girls and women of different age strata as well as community members (including boys and men) and key informants in the health care system in each study site. Qualitative study methods will vary depending on the site and CSS findings, but will include both individual in- depth interviews (IDIs) (up to \~ 30 individuals per site), key informant interviews as well as multiple focus group discussions (FGDs) with \~6-8 participants/group. Detailed qualitative study methodology will be developed separately as another study protocol and adapted according to the procedures for each site.

Eligibility criteria: Inclusion Criteria:

1. 9 to 50 years old (for urban and rural CSSs) at the time of enrollment.
2. Resident in the selected community for at least the past 3 months (with the exception of pastoralists, refugees, and commercial sex workers).
3. Able to understand the purpose of the study and study procedures.
4. If aged 18 years or older or legally considered an emancipated minor, able and willing to provide consent to participate in the study including sample collection.
5. If aged \<18 years (and not considered an emancipated minor), supported in their participation by a parent or guardian who is able and willing to provide consent, and
6. If aged \<18 years (and not considered an emancipated minor), able and willing to provide assent to participate in the study.

Exclusion Criteria:

1. Decline consent to participate any activity of the study.
2. A medical condition or other reason, not directly related to HPV infection or HPV-related diseases, in the opinion of the investigator, precludes enrolment in the study.

Primary outcomes:
measure: To estimate the prevalence (single time point detection) of HPV 16 and/or 18 infection among a representative sample of girls and women aged 9-50y in a range of settings.
timeFrame: Q4 2023 to Q4 2024
measure: To estimate the incidence of ≥6-month persistent HPV 16 and/or 18 infection (defined as two sequential type-specific positives with an interval of 6 months) in selected populations over 2 years.
timeFrame: Q4 2023 to Q4 2026
Secondary outcomes:
measure: To estimate the prevalence of high risk (HR) HPV infection among a representative sample of girls and women aged 9-50 years in a range of settings, and to evaluate potential risk factors for HPV infection.
timeFrame: Q4 2023 to Q4 2024
measure: To estimate the incidence of ≥6-month persistent HR HPV infection in selected populations over 2 years.
timeFrame: Q4 2023 to Q4 2026
measure: Descriptive statistics of the knowledge, attitudes, and beliefs regarding HPV vaccination, cervical cancer screening and treatment.
timeFrame: Q1 2024 to Q4 2025
measure: Descriptive statistics of the perceptions of gender norms and stigma, and gender-related dynamics that may influence HPV burden and/or create barriers that influence girls/women's access to and uptake of HPV prevention, screening, and treatment services
timeFrame: Q1 2024 to Q4 2025
measure: Sensitivity, specificity, Accuracy, ROC, Cohen's kappa coefficient of HPV genotyping results obtained from urine and self-collected vaginal swabs (SCVS).
timeFrame: Q1 2024 to Q4 2024
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Diarrhoeal Disease Research, Bangladesh (icddr,b)
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Institut National pour la Recherche Biomedicale (INRB)
city: Ho
country: Ghana
facility: University of Health and Allied Sciences (UHAS)
state: Volta
city: Dhulikhel
country: Nepal
facility: Dhulikhel Hospital Kathmandu University Hospital (DHKUH)
city: Karachi
country: Pakistan
facility: Aga Khan University (AKU)
city: Freetown
country: Sierra Leone
facility: College of Medicine and Allied Health Sciences (COMAHS)
city: Mwanza
country: Tanzania
facility: Mwanza Intervention Trial Unit (MITU)
city: Lusaka
country: Zambia
facility: ZAMBART
Study officials:
affiliation: Associate Research Scientist
name: Alexandra Hill
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor of Clinical Epidemiology & International Health
name: Deborah Watson-Jones
role: PRINCIPAL_INVESTIGATOR
References: