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 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. III. To evaluate the immunogenicity (absolute levels and stability of serum antibodies) of single dose HPV vaccination in women. IV. For each vaccine separately, to evaluate one dose of HPV vaccination compared to no vaccination in the protection against: IVa. Any new HPV16/18 anal infection that persists 6+ months. IVb. Any new HPV16/18 oral infection that persists 6+ months. IVc. Any new carcinogenic HPV cervical, anal or oral infection detected at a single timepoint and that persists 6+ months. IVd. Any new cervical HPV6/11 infection that persists 6+ months. 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) 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. The 97.5% confidence intervals for the VE will be calculated by inverting appropriate hypotheses tests. |
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. The 97.5% confidence intervals for the VE will be calculated by inverting appropriate hypotheses tests. |
| Health impact of older-age single-dose HPV vaccination | 6-month persistence observed during follow-up | Will require a one-sided p-value of \< 0.0125 for statistical significance. The 97.5% confidence intervals for the VE will be calculated by inverting appropriate hypotheses tests. |
| Immunogenicity (absolute levels and stability of serum antibodies) of single dose HPV vaccination | 6-month persistence observed during follow-up | Will report the Geometric Mean Titer of the antibodies for each HPV type at the five follow-up visits. |
| New HPV16/18 anal infection | 6-month persistence observed during follow-up | Will report the VE against any new carcinogenic HPV type and against HPV 6/11 in the according to ATP cohort using an analysis plan similar to that described for the primary objectives. |
| New HPV16/18 oral infection | 6-month persistence observed during follow-up | Will report the VE against any new carcinogenic HPV type and against HPV 6/11 in the ATP cohort using an analysis plan similar to that described for the primary objectives. |
| Carcinogenic HPV cervical, anal or oral infection detected at a single timepoint | 6-month persistence observed during follow-up | Will report the VE against any new carcinogenic HPV type and against HPV 6/11 in the ATP cohort using an analysis plan similar to that described for the primary objectives. |
| Cervical HPV6/11 infection | 6-month persistence observed during follow-up | Will report the VE against any new carcinogenic HPV type and against HPV 6/11 in the ATP cohort using an analysis plan similar to that described for the primary objectives. |
Countries
Costa Rica
Contacts
PRINCIPAL_INVESTIGATORAimee R Kreimer
National Cancer Institute (NCI)
Outcome results
None listed