Self-Collection Screening for Cervical Cancer Prevention

(Merck-3 Trial)

Age: < 65

Sex: Female

Trial Phase: Academic

Sponsor: Indiana University

Disqualifiers: Inability to travel, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to prevent cervical cancer among Kenyan women by increasing screening and vaccination rates. It explores a community-based program that combines testing adult women for high-risk HPV (a virus that can cause cervical cancer) and vaccinating girls against HPV with the HPV Vaccine (also known as Gardasil 9 or Human Papillomavirus 9-valent Vaccine, Recombinant). The trial will evaluate the effectiveness of these methods, particularly for women living with HIV, and gather feedback to improve the program. Women in Kenya who can travel to the Webuye Clinic and girls aged 9 to 14 who can complete the vaccine series are eligible to join. As an unphased trial, this study offers a unique opportunity to contribute to important research that could enhance cervical cancer prevention strategies in the community.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this screening method is safe for cervical cancer prevention?

Research shows that the HPV vaccine, Gardasil 9, is very safe. Used for over 15 years, it has FDA approval. This vaccine protects against nine types of human papillomavirus, which can cause cervical, vaginal, and vulvar cancers.

Studies have found that most people tolerate Gardasil 9 well. Common side effects are usually mild, such as soreness at the injection site, headache, or slight fever. Serious side effects are rare.

Long-term studies confirm that this vaccine provides safe and effective protection against HPV. Thus, the HPV vaccine has undergone thorough testing and is considered safe to use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to screen for cervical cancer using self-collection methods alongside the HPV vaccine. Unlike traditional methods that require a visit to a healthcare provider for a Pap smear, this approach empowers women and girls to collect samples themselves, potentially increasing participation in screening programs. By making the process more accessible and less invasive, it could lead to earlier detection and prevention of cervical cancer, especially in communities with limited access to healthcare facilities. This trial aims to determine how well self-collection works compared to the traditional methods, which could revolutionize how we approach cervical cancer screening worldwide.

What evidence suggests that the HPV Vaccine is effective for preventing cervical cancer?

Studies have shown that the HPV vaccine, which participants in this trial will receive, is highly effective, with success rates nearing 100% in preventing infections from the HPV types covered by the vaccine. This significantly lowers the risk of cervical cancer. Research indicates that the vaccine provides strong and long-lasting protection, especially when administered to girls before age 20. Additionally, the 9-valent HPV vaccine, such as GARDASIL 9, can prevent most cervical cancers and reduce other HPV-related cancers in both males and females. With over 15 years of data, the vaccine remains safe and effective, serving as a powerful tool in the fight against cervical cancer. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

The trial is for Kenyan girls aged 9-14 ready to consent to HPV vaccination and can return for a second dose, and women aged 30-55 able to visit the Webuye Clinic for cervical screening.

Inclusion Criteria

I am a Kenyan girl aged 9 to 14.

I am willing to sign a consent form to be vaccinated.

I can come back for the second dose of the HPV vaccine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Community meetings for enrollment and education

Community Meetings and Self-Collection

Women and girls attend community meetings for education and self-collection of vaginal swabs for HPV testing

Ongoing throughout the study

Multiple community meetings

HPV Vaccination

HPV vaccination is administered to girls aged 9-14 at community meetings

6-12 months for two doses

Community meetings for vaccination

VIA and Cervical Biopsy

Women undergo VIA and cervical biopsy if necessary at the Webuye Clinic

Ongoing throughout the study

Clinic visits for VIA and biopsy

Follow-up

Participants are monitored for recurrence of AGWs and cervical cancer screening

6 months for AGWs, 1-3 years for cervical cancer screening

Clinic visits for follow-up

What Are the Treatments Tested in This Trial?

Interventions

• HPV Vaccine

Trial Overview This program tests self-collection of vaginal swabs in adult women and vaccinates female children against HPV. It aims to improve cervical cancer prevention by overcoming barriers like travel distance, costs, and lack of education.

How Is the Trial Designed?

Group I: All women and girls eligible for the study Experimental Treatment 1 Intervention

All women and girls eligible for the study. There is no control arm.

HPV Vaccine is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11

Approved in European Union as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11

Approved in Canada as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11

Approved in Switzerland as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Academic Model Providing Access to Healthcare (AMPATH)

Collaborator

Trials

7

Recruited

10,900+

Published Research Related to This Trial

Self-collection for HPV-based cervical screening can significantly increase participation rates among women, especially in regions where traditional screening methods are culturally challenging due to the requirement of a speculum examination.

Self-collected samples have been shown to have similar sensitivity for detecting cervical pre-cancers as those collected by healthcare practitioners, making it a viable and effective option for improving cervical cancer screening globally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-Collection for Cervical Screening Programs: From Research to Reality. Hawkes, D., Keung, MHT., Huang, Y., et al.[2020]

In a study of 266,647 doses of Gardasil-9® administered in Puglia, Italy, only 22 adverse events following immunization (AEFIs) were reported, resulting in a low reporting rate of 8.25 per 100,000 doses, indicating a favorable safety profile for the vaccine.

Out of the 22 reported AEFIs, only 5 were classified as serious, with 2 leading to hospitalization; however, only 2 serious AEFIs were consistently associated with the vaccine, suggesting that the benefits of Gardasil-9® outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. Di Lorenzo, A., Berardi, P., Martinelli, A., et al.[2022]

A study involving 215,965 individuals who received the nine-valent HPV vaccine (HPV9) found no new safety concerns, confirming its established safety profile from previous research.

While some elevated event categories were noted, such as skin disorders and ill-defined conditions, most were either previously known or had other causes, and no deaths were linked to the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. Hansen, J., Yee, A., Lewis, N., et al.[2023]

In a study involving 12,066 women aged 9 to 26 years who received the HPV vaccines Gardasil® and Cervarix® over three years, 61% reported experiencing mild and transient adverse events after the first dose.

The high rate of reported adverse events is attributed to the study's design, which encouraged participants to document all occurrences, highlighting the importance of ongoing surveillance for vaccine safety, especially for newly marketed vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Human papillomavirus vaccine register]. Spila-Alegiani, S., Da Cas, R., Giambi, C., et al.[2013]

A study involving 429 women aged 30 to 65 showed that mailing self-collection kits for HPV testing resulted in a 64% return rate, with 15% of samples testing positive for HPV, indicating a feasible method to increase screening among those overdue for Pap tests.

Women who tested positive for HPV were more likely to follow up with Pap tests (82%) compared to those who tested negative (51%), suggesting that self-testing can effectively encourage further screening and improve overall cervical health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mailed Human Papillomavirus Self-Collection With Papanicolaou Test Referral for Infrequently Screened Women in the United States. Smith, JS., Des Marais, AC., Deal, AM., et al.[2020]

A comprehensive analysis of adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS) identified 3,112 AEs for Cervarix, 31,606 for Gardasil, and 6,872 for Gardasil 9, highlighting the need for ongoing monitoring of vaccine safety.

The study found 46 unique serious adverse events (SAEs) associated with the HPV vaccines, clustered around behavioral, neurological, immune, nervous, and reproductive systems, indicating that while the vaccines are effective, further research is needed to understand the cause-and-effect relationships of these AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. Zi, W., Yang, Q., Su, J., et al.[2022]

The nine-valent HPV vaccine, Gardasil9, significantly increases the efficacy against cervical cancer from 70% to 90% compared to the quadrivalent vaccine, covering a broader range of HPV types.

Gardasil9 also provides high efficacy (97%) against lesions associated with HPV types 31, 33, 45, 52, and 58, while maintaining similar effectiveness against HPV types 6, 11, 16, and 18 as the quadrivalent vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. Fait, T., Dvořák, V., Pilka, R.[2018]

All three HPV vaccines (bivalent, quadrivalent, and 9vHPV) show high efficacy in preventing infections from specific HPV types and associated high-grade cervical dysplasia in women who have not been previously exposed to HPV.

While the bivalent and quadrivalent vaccines have demonstrated early clinical effectiveness in reducing HPV 16 and 18 prevalence, the overall benefits of HPV vaccination in reducing cervical cancer are still largely theoretical, highlighting the need for large-scale studies to confirm long-term effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of 2-, 4- and 9-valent HPV vaccines on morbidity and mortality from cervical cancer. Luckett, R., Feldman, S.[2018]

The nonavalent HPV vaccine (9vHPV) has shown increased efficacy compared to the quadrivalent HPV vaccine (4vHPV), with an estimated 90% prevention rate for cervical cancer and up to 80% for precancerous cervical lesions in women aged 16-26 years.

The 9vHPV vaccine may provide broader protection against various HPV-related diseases in both males and females, but its future adoption will depend on factors like cost-effectiveness and ongoing safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the benefits and potential issues of the nonavalent HPV vaccine. Mariani, L., Preti, M., Cristoforoni, P., et al.[2017]

The nonavalent HPV vaccine (9vHPV) has shown over 90% efficacy in preventing cervical, vulvar, and vaginal precancers caused by HPV types 16, 18, and five additional cancer-causing types (31, 33, 45, 52, 58) in Phase III clinical studies.

9vHPV has the potential to prevent up to 93% of cervical cancer cases and has demonstrated lasting antibody responses for at least five years, indicating its long-term effectiveness in reducing the burden of HPV-related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human papillomavirus nonavalent vaccine in the prevention of cancers caused by human papillomavirus. Toh, ZQ., Kosasih, J., Russell, FM., et al.[2020]

The 9-valent HPV vaccine (Gardasil 9®) significantly increases protection against cervical cancer by covering 9 oncogenic HPV types, raising potential protection from about 70% to 90%, based on clinical trials involving young women.

Clinical trials demonstrated that the 9vHPV vaccine has a comparable safety profile and immunogenicity to the original 4-valent vaccine, with a 2-dose regimen showing similar effectiveness in younger boys and girls compared to the standard 3-dose regimen for older women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine. Zhang, Z., Zhang, J., Xia, N., et al.[2019]

Citations

1. cdc.gov cdc.gov/hpv/hcp/vaccination-considerations/safety-and-effectiveness-data.html

HPV Vaccine Safety and Effectiveness Data More than 15 years of monitoring and research have accumulated reassuring evidence that HPV vaccination provides safe, effective, and long-lasting protection.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4865336/

Update on the new 9-valent vaccine for human ... The vaccine has the potential to prevent most cervical cancers and further reduce the incidences of other HPV-associated cancers in males and females.

3. cdc.gov cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html

HPV Vaccine Efficacy All HPV vaccines have been found to have high efficacy (close to 100%) for prevention of HPV vaccine type-related persistent infection, cervical ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8486335/

Real-World Effectiveness of Human Papillomavirus ... HPV vaccine effectiveness against cervical cancer at the population level is high among girls vaccinated younger than age 20 years.

5. merckvaccines.com merckvaccines.com/gardasil9/efficacy/

Efficacy of GARDASIL®9 (Human Papillomavirus 9-valent ... GARDASIL 9 is a vaccine indicated in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head ...

6. cdc.gov cdc.gov/vaccine-safety/vaccines/hpv.html

Human Papillomavirus (HPV) Vaccine Safety Gardasil 9 (human papillomavirus 9-valent vaccine, recombinant; 9vHPV) was approved by FDA for use in 2014. The safety of Gardasil 9 was studied in clinical ...

7. gardasil9.com gardasil9.com/

GARDASIL®9 (Human Papillomavirus 9-valent Vaccine ... GARDASIL 9 helps protect individuals ages 9 to 45 against the following diseases caused by 9 types of HPV: cervical, vaginal, and vulvar cancers in females.

8. fda.gov fda.gov/media/90064/download

Package Insert - GARDASIL 9 GARDASIL 9 has not been demonstrated to provide protection against disease caused by: • HPV types not covered by the vaccine [see Description (11)],. • HPV ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4964727/

Quadrivalent HPV vaccine safety review and safety monitoring ... The 9vHPV targets five additional cancer-causing HPV types: HPV 31, 33, 45, 52, and 58. The Food and Drug Administration (FDA) licensed 4vHPV for females age 9– ...