Single-Dose HPV Vaccination for the Prevention of Cervical Cancer in Young Adult Women in Costa Rica, The PRISMA ESCUDDO Trial

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 (i.e.: vaccine effectiveness in an intention to treat [ITT] analytical cohort).

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. When looking at these antibodies, the primary focus will be on HPV16/18; antibodies against additional HPV types included in the nonavalent HPV vaccine will also be investigated.

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: Participants are randomized to 1 of 3 arms.

ARM I: Participants receive one dose of recombinant human papillomavirus nonavalent vaccine (Gardasil 9) intramuscularly (IM).

ARM II: Participants receive one dose of recombinant human papillomavirus bivalent vaccine (Cervarix) IM.

ARM III: Participants receive one dose of diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine adsorbed vaccine (Adacel) IM.

After completion of randomization and vaccination, participants are followed for 36 months. At 6 months they receive a phone contact and, thereafter, they participate in cervicovaginal self-sampling every 6 months, annual serology, and oral/anal sampling at selected visits.

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

• EXCLUSION CRITERIA AT ENROLLMENT VISIT: They have been vaccinated against human papillomavirus (HPV).
• EXCLUSION CRITERIA AT ENROLLMENT VISIT: They are allergic to yeast or another vaccine components.
• EXCLUSION CRITERIA AT ENROLLMENT VISIT: They have a diagnosis of an autoimmune, degenerative, or neurological disease without treatment or adequate control; a progressive or severe neurological disease; a genetic immunodeficiency; or any other serious chronic disease without treatment and / or adequate control that, according to the principal investigator or designee, for which vaccination is contraindicated.
• EXCLUSION CRITERIA AT ENROLLMENT VISIT: They have plans to move outside the country in the next six months.
• EXCLUSION CRITERIA AT ENROLLMENT VISIT: They refuse or are unable to self-collect the cervical sample.
• EXCLUSION CRITERIA AT ENROLLMENT VISIT: They are pregnant.
• EXCLUSION CRITERIA AT ENROLLMENT VISIT: They do not have an identification document.
• EXCLUSION CRITERIA AT ENROLLMENT VISIT: The clinician determining eligibility in agreement with the principal investigator considers that there is a reason that precludes participation.
• EXCLUSION CRITERIA AT VACCINATION VISIT: Between the enrollment and vaccine visit, they have been vaccinated against HPV.
• EXCLUSION CRITERIA AT VACCINATION VISIT: Between the enrollment and vaccine visit, they are being evaluated for or have received a diagnosis of: an autoimmune, degenerative, or neurological disease without treatment or adequate control; a progressive or severe neurological disease; a genetic immunodeficiency; or any other serious chronic disease without treatment and/or adequate control, for which vaccination is contraindicated according to the principal investigator or designee.
• EXCLUSION CRITERIA AT VACCINATION VISIT: They have plans to move outside the country in the next six months.
• EXCLUSION CRITERIA AT VACCINATION VISIT: They refuse the urine pregnancy test.
• EXCLUSION CRITERIA AT VACCINATION VISIT: They have a positive urine pregnancy test result.
• EXCLUSION CRITERIA AT VACCINATION VISIT: They are pregnant.
• EXCLUSION CRITERIA AT VACCINATION VISIT: They refuse or are unable to perform the self-collected cervical sample.
• EXCLUSION CRITERIA AT VACCINATION VISIT: The clinician determining eligibility in agreement with the principal investigator considers that there is a reason that precludes participation.