Early Initiation of HPV Vaccination for Human Papillomavirus

Recruiting at 1 trial location

Overseen By Alison Saville, MPH, MSW

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Disqualifiers: Less than 100 patients, 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

3100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether starting the HPV vaccine at ages 9-10, instead of the usual 11-12, will lead to more parents agreeing to vaccinate their children and increase the number of children fully vaccinated before becoming sexually active. The study compares two groups: one where doctors recommend the vaccine at ages 9-10 and another at ages 11-12. Children aged 9-13 who need at least one dose of the HPV vaccine and have visited a participating practice in the Denver or Los Angeles area in the last three years might be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to important research that could influence future vaccination guidelines.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the HPV vaccine, Gardasil 9, is safe for people. The FDA approved Gardasil 9 in 2014. It helps protect against diseases caused by nine types of HPV, including some cancers.

Studies indicate that Gardasil 9 is generally well-tolerated. Most side effects are mild, such as pain at the injection site, headache, or fever. Serious side effects are rare. A wide-ranging safety review confirmed these results over several years of regular use.

Overall, the HPV vaccine has a strong safety record, making it a reliable option for preventing diseases related to HPV. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the early initiation of the HPV vaccine, starting at ages 9-10, compared to the traditional recommendation at ages 11-12. This approach could potentially enhance the vaccine's effectiveness by immunizing children earlier, potentially before any exposure to the virus. By recommending the vaccine at a younger age, the trial aims to improve long-term protection against HPV-related diseases, which could have significant implications for public health strategies.

What evidence suggests that early initiation of the HPV vaccine is effective for increasing vaccination rates?

Research has shown that starting the HPV vaccine at ages 9 or 10, as in one arm of this trial, increases the likelihood of completing the vaccine series by age 13. Another arm of this trial involves starting the vaccine at ages 11 or 12. Early vaccination helps protect against HPV-related diseases before most early sexual activity begins. Over 15 years of research confirm that the HPV vaccine is safe and provides long-lasting protection. Studies have demonstrated that the vaccine is over 99% effective in preventing HPV infections, making it one of the most effective vaccines available worldwide. ^{6 7 8 9 10}

Who Is on the Research Team?

Allison Kempe, MD, MPH

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for medical practices in Metro Denver, Colorado and Metro Los Angeles, California that have a patient base of kids aged 9-13. At least 60% of providers at the practice must agree to participate, and they should not already be recommending HPV vaccination at ages 9-10.

Inclusion Criteria

My practice serves over 100 patients aged 9-13.

You live in certain areas of Colorado or California near Denver or Los Angeles, including some medical clinics.

At least 60% of doctors in the practice have agreed to take part in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Providers recommend HPV vaccine at either 9-10 years or 11-12 years, with standardized training provided to both arms

4 years

Follow-up

Participants are monitored for HPV series completion and age at initiation, with assessments conducted post-intervention

1 year

What Are the Treatments Tested in This Trial?

Interventions

• HPV Vaccine

Trial Overview The study is testing if suggesting the HPV vaccine earlier, at ages 9-10 instead of the usual recommendation at ages 11-12, leads to higher vaccination rates and less parental refusal. The goal is to increase protection against HPV before early sexual activity begins.

How Is the Trial Designed?

Group I: Patients attributed to practices recommending HPV at age 9-10 years of age Experimental Treatment 1 Intervention

Patients attributed to practices routinely recommending HPV vaccine starting at 9-10 years of age.

Group II: Patients attributed to practices recommending HPV at age 11-12 years of age Active Control 1 Intervention

Patients attributed to practices routinely recommending HPV vaccine starting at 11-12 years of age.

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?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

The 9-valent HPV vaccine demonstrated a high efficacy of 92.3% in preventing high-grade cervical, vulvar, and vaginal dysplasia related to HPV types 31, 33, 45, 52, and 58 in a study involving 5,312 participants aged 9-26 years.

The vaccine was well tolerated, with over 99% of recipients developing antibodies for all 9 HPV types, and most adverse events were mild to moderate, supporting its use in vaccination programs in Latin America.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women. Ruiz-Sternberg, ÁM., Moreira, ED., Restrepo, JA., et al.[2021]

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]

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 9-valent HPV vaccine (9vHPV) has been shown to be generally well tolerated in both prior recipients of the quadrivalent HPV vaccine and young men, with a low incidence of serious adverse events (AEs).

The most common AEs were mild injection-site reactions, occurring in over 90% of prior qHPV vaccine recipients and 79% of young men, indicating that the vaccine is safe for use in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of the 9-valent human papillomavirus vaccine: assessment in prior quadrivalent HPV vaccine recipients and in men 16 to 26 years of age. Moreira, ED., Giuliano, AR., de Hoon, J., et al.[2019]

HPV-related cancers, including cervical and head and neck cancers, account for a significant portion of global cancer cases, highlighting the urgent need for effective vaccination strategies, especially since over 80% of people are exposed to HPV by age 50.

While prophylactic vaccines like Gardasil® and Cervarix® have successfully reduced HPV infections in young populations, there are currently no FDA-approved therapeutic vaccines for those already infected, indicating a critical gap in treatment options for HPV-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Vaccines for HPV-Associated Malignancies. Smalley Rumfield, C., Roller, N., Pellom, ST., 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]

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]

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]

Gardasil, a recombinant quadrivalent vaccine, is FDA-approved for girls and women aged 9-26 to prevent diseases caused by HPV types 6, 11, 16, and 18.

The vaccine effectively protects against genital warts and precancerous lesions, significantly reducing the risk of cervical cancer associated with these HPV types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A human papillomavirus vaccine. [2015]

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]

In a study of 645 sexually active young women in New York City, the HPV vaccine significantly reduced the prevalence of vaccine-type HPV infections in the cervix, with odds ratios indicating a strong protective effect against HPV6/11, HPV16, and HPV18 for vaccinated individuals compared to unvaccinated ones.

Despite the vaccine's effectiveness in reducing cervical HPV prevalence, the overall HPV infection rates were high, highlighting the need for ongoing monitoring and follow-up to evaluate the vaccine's protection across different anatomical sites, especially in populations with high exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cervical, anal and oral HPV in an adolescent inner-city health clinic providing free vaccinations. Schlecht, NF., Burk, RD., Nucci-Sack, A., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9980633/

HPV vaccine initiation at 9 or 10 years of age and better series ... Proactive initiation of HPV vaccination at 9–10 years of age was associated with higher rates of series completion by 13 years of age.

2. 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.

3. thelancet.com thelancet.com/journals/lanam/article/PIIS2667-193X(25)00235-2/fulltext

Clinical effectiveness of HPV vaccine by age at vaccination The adjusted VE of >1 dose of HPV vaccine was 54% (95% CI: 8–77%, p = 0·03). When the first dose was given at ≤18 years of age VE was 75% (95% ...

4. acog.org acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/08/human-papillomavirus-vaccination

Human Papillomavirus Vaccination Human papillomavirus vaccines are among the most effective vaccines available worldwide, with unequivocal data demonstrating greater than 99% efficacy.

5. publications.aap.org publications.aap.org/pediatrics/article/152/4/e2022060993/193886/Ten-Year-Follow-up-of-9-Valent-Human

Ten-Year Follow-up of 9-Valent Human Papillomavirus ... Immunogenicity, effectiveness, and safety were demonstrated through 10 years postvaccination. Rates of persistent infection and disease related ...

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

Package Insert - GARDASIL 9 GARDASIL 9, Human Papillomavirus 9-valent Vaccine, Recombinant, is a non-infectious recombinant. 9-valent vaccine prepared from the purified virus-like ...

8. gardasil9.com gardasil9.com/patient-pd/

HPV vaccination can help protect your child ... 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.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8245868/

A Broad Safety Assessment of the 9-Valent Human ... In recent surveys of parents regarding HPV vaccination, safety has been cited as the top concern (2–4). A number of well-designed studies have investigated ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X22013950

Safety of 9-valent human papillomavirus vaccine ... This study was a multiyear post-licensure study to assess HPV9 safety following routine administration.