Human Papillomavirus-Related Cervical Carcinoma
Conditions
Brief summary
This phase IV trial tests whether a single dose of the human papillomavirus (HPV) vaccine works in preventing cervical cancer in young women in Costa Rica. Human papilloma viruses, called HPV, are a group of viruses that very frequently cause infection in both men and women, mainly in the genital organs. There are many types of HPV, and some can cause cancer. The World Health Organization recommends a two-dose schedule for adolescents 9-14 and three doses for individuals 15 years old or older. This study examines whether a single dose of HPV vaccine can reduce the frequency with which women between ages 18-30 become infected with HPV.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate one dose of nonavalent human papillomavirus (HPV) vaccination compared to no vaccination in the protection against incident HPV16/18 cervical HPV infections that persist 6-months or more in women aged 18 to 30 years who are cervical HPV16/18 deoxyribonucleic acid (DNA) negative prior to and at the time of vaccination. II. To evaluate one dose of bivalent HPV vaccination compared to no vaccination in the protection against incident HPV16/18 cervical HPV infections that persist 6-months or more in women aged 18 to 30 years who are cervical HPV16/18 DNA negative prior to and at the time of vaccination. SECONDARY OBJECTIVES: I. To quantitate the benefit of one dose of HPV vaccination compared to no vaccination in the protection against incident HPV16/18 cervical HPV infections that persist 6-months or more in women aged 18 to 30 years regardless of cervical HPV DNA status at the time of vaccination. II. To evaluate one dose of HPV vaccination compared to no vaccination in the protection against cervical infections that persist 6-months or more in women aged 18 to 30 years for the following HPV groupings and individual HPV types (analyzed in an ATP cohort and an ITT cohort): IIa. Seven carcinogenic types in the nonavalent HPV vaccine: HPV 16/18/31/33/45/52/58 (analyzed both as an aggregate group and individually); IIb. Non-carcinogenic, genital warts-associated types: HPV 6/11 (analyzed both as an aggregate group and individually). III. To evaluate one dose of HPV vaccination compared to no vaccination in the protection against HPV16/18 anal and oral infections that persist 6-months or more in women aged 18 to 30 years (analyzed in an ATP cohort and an ITT cohort). IV. To evaluate the immunogenicity (absolute levels, proportion of seropositivity, and stability of serum antibodies) of single dose HPV vaccination in women aged 18 to 30 years. ANCILLARY OBJECTIVES: I. To evaluate one dose of HPV vaccination compared to no vaccination in the protection against HPV cervical, anal or oral infection detected at a single timepoint in women aged 18 to 30 years, including but not limited to the following endpoints: Ia. HPV16/18; Ib. HPV 16/18/31/33/45/52/58; and Ic. HPV6/11. II. To estimate the health impact of older-age single-dose HPV vaccination by modeling the number of cervical cancer cases prevented as well as the cost-effectiveness of cervical cancer prevention strategies incorporating vaccination and screening in Costa Rica. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive one dose of recombinant human papillomavirus nonavalent vaccine (Gardasil 9) intramuscularly (IM). ARM II: Patients receive one dose of recombinant human papillomavirus bivalent vaccine (Cervarix) IM. ARM III: Patients receive one dose of diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine adsorbed vaccine (Adacel) IM. After completion of study, patients are followed up at 6 and 12 months, and then every 6 months thereafter.
Interventions
Given IM
OTHERQuestionnaire Administration
Ancillary studies
Given IM
Given IM
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA AT ENROLLMENT: Female. * INCLUSION CRITERIA AT ENROLLMENT: Aged between 18 and 30 years inclusive. * INCLUSION CRITERIA AT ENROLLMENT: Living in the study area. * INCLUSION CRITERIA AT ENROLLMENT: Able to communicate with study personnel. * INCLUSION CRITERIA AT ENROLLMENT: Willing to participate in the study and sign the informed consent. * INCLUSION CRITERIA AT ENROLLMENT: In good health as determined by a medical history (physical exam will be conducted if necessary per the doctor's criterion. * DEFERRAL CRITERIA AT ENROLLMENT VISIT: The enrollment visit will be deferred (i.e., rescheduled for another date) for participants if: the self-collected cervical sample is not able to be collected. * DEFERRAL CRITERIA AT THE VACCINATION VISIT: The vaccination visit will be deferred (i.e., rescheduled for another date) for participants if: * They have an acute disease that precludes vaccination (though vaccines can be administered to potential participants with a minor illness such as diarrhea and mild upper respiratory infection) * They are receiving immunosuppressive treatment, e.g. corticosteroids * They have received any registered vaccine in the last 15 days.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of persistent human papillomavirus (HPV) 16 or 18 infection | 6-month persistence observed during follow-up | Will estimate the rate of incident persistent infections (i.e. the primary endpoint defined above) in each of the three arms of an according to protocol (ATP) cohort and then estimate the two Vaccine Efficacies (VE), comparing each HPV vaccine arm against the control arm. Will require a one-sided p-value of \< 0.0125 for statistical significance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Benefit of one dose of HPV vaccination compared to no vaccination | 6-month persistence observed during follow-up | Will require a one-sided p-value of \< 0.0125 for statistical significance. |
| Incidence of persistent seven carcinogenic types in the nonavalent HPV vaccine | 6-month persistence observed during follow-up | Will evaluate HPV 16/18/31/33/45/52/58 (analyzed both as an aggregate group and individually) and non-carcinogenic, genital warts-associated types: HPV 6/11 (analyzed both as an aggregate group and individually). Will evaluate one dose of HPV vaccination compared to no vaccination in the protection against cervical infections that persist 6-months or more in women aged 18 to 30 years for the following HPV groupings and individual HPV types (analyzed in an ATP cohort and an intent-to-treat \[ITT\] cohort). |
| Protection against HPV16/18 anal and oral infections | 6-month persistence observed during follow-up | Will evaluate one dose of HPV vaccination compared to no vaccination in the protection against HPV16/18 anal and oral infections that persist 6-months or more in women aged 18 to 30 years (analyzed in an ATP cohort and an ITT cohort). |
| Immunogenicity (absolute levels, proportion of seropositivity, and stability of serum antibodies) | Up to 36 months | Will report the Geometric Mean Concentration of the antibodies for each HPV type at the vaccination visit and the 12-, 24-, and 36-month follow-up visits. |
Countries
Costa Rica
Contacts
PRINCIPAL_INVESTIGATORAimee R Kreimer
National Cancer Institute (NCI)
Outcome results
None listed