HPV Vaccine Strategies for Human Papillomavirus

(HPVV Trial)

Overseen By Chunyi Hsu, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Kaiser Permanente

Disqualifiers: Non-pediatric staff, Children over 12, others

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

Compensation: Varies

Number of Visits: Unknown

301201 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify the best methods to encourage HPV vaccinations among children aged 9-12, which can help prevent certain cancers later in life. Researchers are testing three strategies: one tailored to local clinic needs, a standard approach used by health systems, and usual care without research intervention. The focus is on improving how healthcare providers recommend the vaccine (Gardasil 9, Human Papillomavirus Vaccine, Nonavalent). Parents of children aged 9-12 who have visited a pediatric clinic during the study period may be eligible to participate.

As an unphased trial, this study offers a unique opportunity to contribute to important research that could enhance public health strategies for cancer prevention.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether participants need to stop taking their current medications.

What prior data suggests that these implementation strategies are safe for improving HPV vaccination rates?

Research shows that the HPV vaccine, such as Gardasil 9, is generally well-tolerated. Studies have found that some people might experience side effects like soreness at the injection site, tiredness, or muscle aches. These effects are usually mild and resolve on their own.

For the Local Tailoring and Prescribed strategies, which focus on improving vaccine administration, no direct data indicates new risks. These strategies primarily alter how healthcare providers recommend and deliver the vaccine. Previous research suggests these methods are safe and aim to make vaccination easier and more effective.

Overall, while side effects from the HPV vaccine can occur, they are usually not serious. This vaccine has been widely used and is approved for preventing certain types of cancers related to HPV. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the HPV Vaccine Strategies trial because it explores innovative ways to increase HPV vaccination rates among children aged 9-12. Unlike traditional approaches that rely solely on standard medical advice, this trial is testing two unique strategies. The Local Tailoring strategy customizes vaccine promotion to fit the specific needs of each clinic, making it more relatable and effective for different communities. Meanwhile, the Prescribed Strategy provides structured guidelines for healthcare providers, aiming to streamline the vaccination process and ensure consistency. By focusing on these tailored and structured approaches, the trial hopes to find out which method is most effective in boosting vaccination rates, ultimately helping to prevent HPV-related diseases more efficiently.

What evidence suggests that this trial's implementation strategies could be effective for improving HPV vaccination rates?

Research has shown that the HPV vaccine effectively prevents cancers caused by HPV, reducing the types of HPV that lead to these cancers by 90%. In this trial, the Local Tailoring strategy, one of the experimental arms, addresses specific local challenges to enhance vaccine accessibility and acceptance, potentially improving vaccination rates. Another experimental arm, the Prescribed Strategy, employs a set of planned methods to tackle common obstacles, effectively increasing vaccination coverage. Both strategies in this trial aim to vaccinate more teens, thereby lowering their risk of developing HPV-related cancers in the future. ^{1 3 6 7 8}

Who Is on the Research Team?

Erin Hahn, PhD

Principal Investigator

KPSC Department of Research and Evaluation

Chun R Chao, PhD

Principal Investigator

KPSC Department of Research and Evaluation

Are You a Good Fit for This Trial?

This trial is for pediatric clinics, their staff including physicians, nurses, and administrators, as well as parents of children aged 9-12 eligible for the HPV vaccine. It excludes healthcare workers outside pediatrics and parents of children over 12 or without a clinic visit in the study period.

Inclusion Criteria

I am a parent of a child aged 9-12, eligible for the HPV vaccine.

All KPSC pediatric clinics

All providers (physicians, nurses, and medical assistants) and department administrators from the pediatric department

Exclusion Criteria

Providers and administrators who do not work for the pediatric department

My child is older than 12 years and/or hasn't visited the clinic during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Examine baseline associations between patient-, provider-, and clinic-level factors and variations in HPV vaccination rates and provider recommendations

Year 1

Intervention

Conduct a cluster RCT comparing the effectiveness of a 'tailored' multilevel implementation strategy to a 'prescribed' multilevel implementation strategy and to usual care in improving HPV vaccination rates

Year 1 through Year 4

Follow-up

Participants are monitored for the sustainment of study interventions and provider recommendations

12 months after intervention period

What Are the Treatments Tested in This Trial?

Interventions

• Local Tailoring implementation strategy
• Prescribed Strategy

Trial Overview

The trial compares three strategies to improve HPV vaccination rates: a 'local-tailored' strategy addressing local barriers; a 'prescribed' strategy targeting pre-selected barriers; and usual care with no research-led activities.

How Is the Trial Designed?

Group I: Prescribed Strategy Experimental Treatment 1 Intervention

The intervention arm will include 20 clinics randomly assigned to the intervention arm.. All physicians, nurses, department administrator,s and other staff members from the pediatric departments randomized to this arm will be included in the study, as well as parents of HPV vaccine eligible children (9-12 years old) who had one or more visits with their pediatric provider during the data collection period.

Group II: Local Tailoring Experimental Treatment 1 Intervention

The intervention arm will include 20 clinics randomly assigned to the intervention arm. All physicians, nurses, department administrator and other staff members from the pediatric departments randomized to this arm will be included in the study, as well as parents of HPV vaccine eligible children (9-12 years old) who had one or more visits with their pediatric provider during the data collection period.

Group III: Usual Care Active Control 1 Intervention

The intervention arm will include 20 clinics randomly assigned to the usual care arm. All physicians, nurses, department administrators,s and other staff members from the pediatric departments randomized to this arm will be included in the study, as well as parents of HPV vaccine eligible children (9-12 years old) who had one or more visits with their pediatric provider during the data collection period.

Who Is Running the Clinical Trial?

Kaiser Permanente

Lead Sponsor

Trials

563

Recruited

27,400,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Both Gardasil and Cervarix vaccines have been proven safe and highly effective in preventing infections and lesions from HPV types 16 and 18, which are responsible for 70% of cervical cancers globally.

The main challenge now is to establish effective vaccination strategies, including determining the best age for vaccination and improving vaccine acceptance, especially in low-resource settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus vaccine update. Ames, A., Gravitt, P.[2020]

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]

The HPV vaccination quality improvement (QI) program successfully trained 95% of participating physicians, demonstrating effective implementation of training and feedback strategies in a large health care system.

While the overall increase in HPV vaccination coverage was modest (8.6% in the QI arm vs. 6.4% in the control), a significant improvement of 3.3 percentage points was observed when excluding data from physicians with poor reporting, indicating potential for greater impact with refined implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementing Evidence-Based Strategies to Improve HPV Vaccine Delivery. Gilkey, MB., Parks, MJ., Margolis, MA., et al.[2020]

A single dose of the nonavalent HPV vaccine, Gardasil9, was shown to induce stable and high antibody responses for HPV16 and HPV18 in 201 healthy children over a 24-month period, suggesting it could simplify vaccination logistics.

The study demonstrated that antibody levels remained significantly elevated after the initial dose, with a notable boost observed after a delayed booster at 30 months, indicating the potential for long-lasting immunity with fewer doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HPV16/18 Antibody Responses After a Single Dose of Nonavalent HPV Vaccine. Zeng, Y., Moscicki, AB., Woo, H., et al.[2023]

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]

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 22,486 girls aged 11 to 17 showed that a combined intervention targeting both clinicians and families significantly increased HPV vaccination rates by 9, 8, and 13 percentage points for doses 1, 2, and 3, respectively.

The clinician-focused approach was particularly effective for starting the HPV vaccination series, while the family-focused approach helped in completing the series, highlighting the importance of a dual strategy for optimal vaccination outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of decision support for families, clinicians, or both on HPV vaccine receipt. Fiks, AG., Grundmeier, RW., Mayne, S., et al.[2022]

A program to educate patients and provide financial assistance significantly increased HPV vaccination rates among patients with recurrent respiratory papillomatosis (RRP) from 9.7% to 43.8%.

Vaccinated patients experienced longer intersurgical intervals (from 3.5 months to 12.8 months) and fewer surgical procedures per year (from 2.7 to 0.81), indicating that HPV vaccination can reduce the disease burden associated with RRP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of Routine HPV Vaccination in the Management of Recurrent Respiratory Papillomatosis. Yiu, Y., Fayson, S., Smith, H., et al.[2019]

Vaccinating 12-year-old girls with the quadrivalent HPV vaccine is predicted to significantly reduce the incidence of anogenital warts by 72.1% and cervical intraepithelial neoplasia lesions (CIN2 and -3) by 46.1% over 70 years, while the bivalent vaccine shows no reduction in AGWs but a 51.0% reduction in CIN2 and -3.

Switching from bivalent or quadrivalent vaccines to a nonavalent vaccine could further enhance protection, potentially reducing AGW episodes by an additional 66.7% and CIN2 and -3 cases by an additional 9.3%, indicating a greater long-term effectiveness against precancerous lesions and cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population-level impact of the bivalent, quadrivalent, and nonavalent human papillomavirus vaccines: a model-based analysis. Van de Velde, N., Boily, MC., Drolet, M., et al.[2022]

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]

This trial will evaluate two ECHO-delivered interventions aimed at increasing HPV vaccination rates among adolescents aged 11-14 in 36 primary care clinics, focusing on the effectiveness of provider training and parent recall notices.

The study aims to demonstrate that these interventions can improve HPV vaccination uptake, ultimately helping to prevent HPV-related cancers by addressing communication needs for both healthcare providers and parents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing the adoption of evidence-based communication practices for HPV vaccination in primary care clinics: The HPV ECHO study protocol for a cluster randomized controlled trial. Calo, WA., Shah, PD., Fogel, BN., et al.[2023]

The Gardasil vaccine significantly increased the intersurgical interval (ISI) by an average of 3.1 months in patients with recurrent respiratory papillomatosis (RRP), indicating a positive effect on disease management.

40% of patients achieved complete remission and 25% experienced partial remission, with males showing a greater response compared to females, suggesting that the vaccine can effectively modulate the severity of RRP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant therapy in the treatment of recurrent respiratory papilloma. Young, DL., Moore, MM., Halstead, LA.[2015]

In a study of 167 HIV-infected women, the prevalence of high-risk HPV types was found to be significantly higher in the anus (90%) compared to the cervix (83%), indicating a need for targeted screening and prevention in this population.

The nonavalent HPV vaccine, which targets both high-risk and low-risk HPV types, is supported by the findings as 9v HR-HPV types were prevalent (67% in the anus and 51% in the cervix), highlighting its potential effectiveness in reducing HPV-related disease in HIV-infected women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and Incidence of Anal and Cervical High-Risk Human Papillomavirus (HPV) Types Covered by Current HPV Vaccines Among HIV-Infected Women in the SUN Study. Kojic, EM., Conley, L., Bush, T., et al.[2019]

In a study involving 1,042 participants aged 10 to 17, the concomitant administration of Gardasil, Menactra, and Adacel was found to produce immune responses that were noninferior to those from nonconcomitant administration, indicating that the vaccines can be given together without compromising their effectiveness.

The study demonstrated that the concomitant administration was generally well-tolerated, with no participants withdrawing due to adverse events, suggesting a safe approach to vaccination that could improve compliance by reducing the number of clinic visits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and immunogenicity of gardasil given concomitantly with Menactra and Adacel. Reisinger, KS., Block, SL., Collins-Ogle, M., et al.[2015]

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