Comparing One or Two Doses of the Human Papillomavirus Vaccine for the Prevention of Human Papillomavirus Infection, ESCUDDO Study

This phase IV trial investigates whether one dose of a human papillomavirus vaccine works as well as two doses in preventing human papillomavirus (HPV) infection. Certain types of HPV cause almost all cases of cervical cancer. Vaccines that protect against infection with these types of human papillomavirus may reduce the risk of cervical cancer. Both Gardasil-9 and Cervarix protect against HPV 16 and 18, which cause 70% of all cervical cancers. However, HPV vaccination rates are too low, especially in countries with very high rates of cervical cancer. HPV vaccines are expensive-many countries cannot afford them-more than one dose is needed, and giving multiple doses is difficult. Researchers want to find out if one dose prevents HPV infection. If it does, more people might get the vaccine.

Sex

Female

Minimum age

12 Years

Maximum age

21 Years

Inclusion Criteria:

* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Female
* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Aged between 12 and 16 years inclusive
* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Living in the study area without plans to move outside the country in the next six months
* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Able to communicate with study personnel
* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Willing to participate in the study and sign the informed assent
* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Supported in study participation by at least one of their parents (or guardians), who is willing to sign the informed consent document
* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: In good health as determined by a medical history (physical exam will be conducted if necessary per the doctor's criterion)
* INITIAL SURVEY ELIGIBILITY CRITERIA: Same as trial participants except for the age range, which is between 17 and 20 years old inclusive
* END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: Same as trial and initial survey participants except for the age range, which will be closely matched to the current ages of trial participants when they are attending their E54 visits, and thus is expected to be approximately between 16 and 21 years old inclusive

Exclusion Criteria:

* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: 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 (NOTE: Potential participants with these conditions can be included after consultation with the external medical advisor of the study or with an appropriate specialist
* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: They are allergic to one of the vaccine components, yeast, or latex
* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: The clinician determining the eligibility in agreement with principal investigator considers that there is a reason that precludes participation
* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: They have been vaccinated against HPV
* RANDOMIZED TRIAL ELIGIBILITY CRITERIA: The girl or her parent/legal guardian does not have an identification document
* INITIAL SURVEY ELIGIBILITY CRITERIA: Same as trial participants
* END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: They have a positive or equivocal urine pregnancy test result
* END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: They are pregnant
* END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: investigator considers that there is a reason that precludes participation
* END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: They have been vaccinated against HPV
* END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: They or their parent/legal guardian, as applicable, does not have an identification document

• DERIVEDKreimer AR, Porras C, Liu D, Hildesheim A, Carvajal LJ, Ocampo R, Romero B, Gail MH, Cortes B, Sierra MS, Coronado K, Sampson J, Coto C, Dagnall CL, Mora D, Kemp TJ, Zuniga M, Pinto LA, Barrientos G, Schussler J, Estrada Y, Montero C, Avila C, Ruggieri D, Cyr JT, Chanock S, Lowy DR, Schiller JT, Herrero R. Noninferiority of One HPV Vaccine Dose to Two Doses. N Engl J Med. 2025 Dec 18;393(24):2421-2433. doi: 10.1056/NEJMoa2506765. Epub 2025 Dec 3. PMID 41337735
• DERIVEDBergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2. PMID 41276263
• DERIVEDPorras C, Sampson JN, Herrero R, Gail MH, Cortes B, Hildesheim A, Cyr J, Romero B, Schiller JT, Montero C, Pinto LA, Schussler J, Coronado K, Sierra MS, Kim JJ, Torres CM, Carvajal L, Wagner S, Campos NG, Ocampo R, Kemp TJ, Zuniga M, Lowy DR, Avila C, Chanock S, Castrillo A, Estrada Y, Barrientos G, Monge C, Oconitrillo MY, Kreimer AR. Rationale and design of a double-blind randomized non-inferiority clinical trial to evaluate one or two doses of vaccine against human papillomavirus including an epidemiologic survey to estimate vaccine efficacy: The Costa Rica ESCUDDO trial. Vaccine. 2022 Jan 3;40(1):76-88. doi: 10.1016/j.vaccine.2021.11.041. Epub 2021 Nov 29. PMID 34857420
• DERIVEDTeppler H, Bautista O; Thomas Group; Flores S, McCauley J, Luxembourg A. Design of a Phase III immunogenicity and safety study evaluating two-dose regimens of 9-valent human papillomavirus (9vHPV) vaccine with extended dosing intervals. Contemp Clin Trials. 2021 Jun;105:106403. doi: 10.1016/j.cct.2021.106403. Epub 2021 Apr 12. PMID 33857679
• DERIVEDKreimer AR, Cernuschi T, Rees H, Saslow D, Porras C, Schiller J. Prioritisation of the human papillomavirus vaccine in a time of constrained supply. Lancet Child Adolesc Health. 2020 May;4(5):349-351. doi: 10.1016/S2352-4642(20)30038-9. Epub 2020 Feb 17. No abstract available.