Phase 3
N=1,240
Single Dose of Cervarix Vaccine in Girls or Three Doses of Gardasil Vaccine in Women for the Prevention of Human Papillomavirus Infection, the PRIMAVERA-ESCUDDO Trial
Human Papillomavirus-Related Cervical Carcinoma
Bottom Line
View on ClinicalTrials.gov: NCT03728881 ↗Enrolled (actual)
1,240
Serious AEs
2.1%
Results posted
Jul 2025
Primary outcome: Primary: Number Seropositive for HPV16 at 36 Months — 538; 366 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant Vaccine (Biological); Recombinant Human Papillomavirus Bivalent Vaccine (Biological)
- Age
- Pediatric, Adult · 9+ yrs
- Sex
- Female
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number Seropositive for HPV16 at 36 Months |
538; 366 | — |
| PRIMARY Immunogenicity for HPV16 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2 and 6 Months, in 18-25 Year Old Women, 36 Months After Initial Vaccination |
21.4; 42.9 | — |
| PRIMARY Number Seropositive for HPV18 at 36 Months |
517; 358 | — |
| PRIMARY Immunogenicity for HPV18 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2, and 6 Months, in 18-25 Year Old Women, 36 Months After Initial Vaccination |
8.0; 7.2 | — |
| PRIMARY Number Seropositive for HPV16 at 24 Months |
546; 371 | — |
| PRIMARY Immunogenicity for HPV16 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2, and 6 Months, in 18-25 Year Old Women, 24 Months After Initial Vaccination |
20.6; 48.8 | — |
| PRIMARY Number Seropositive for HPV18 at 24 Months |
521; 367 | — |
| PRIMARY Immunogenicity for HPV18 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2, and 6 Months, in 18-25 Year Old Women, 24 Months After Initial Vaccination |
7.9; 8.8 | — |
| SECONDARY Comparison of Proportions With Seroconversion Based on HPV16 Antibody Levels Assessed at 36 Months |
538; 366 | =1.0 |
| SECONDARY Comparison of Proportions With Seroconversion Based on HPV18 Antibody Levels Assessed at 36 Months |
517; 358 | =0.006 sig |
| SECONDARY Comparison of Proportions With Seroconversion Based HPV16 Antibody Levels at 24 Months |
547; 371 | =1.0 |
| SECONDARY Comparison of Proportions With Seroconversion Based on HPV18 Antibody Levels Assessed at 24 Months |
521; 367 | =0.48 |
| SECONDARY Comparison of Distribution of HPV16 Antibodies Levels Assessed at 36 Months |
4.39; 9.834; 7.613; 17.245; 11.148; 23.906 | — |
| SECONDARY Comparison of Distribution of HPV18 Antibodies Levels Assessed at 36 Months |
1.511; 1.272; 2.748; 2.163; 4.067; 3.518 | — |
| SECONDARY Comparison of Distribution of HPV16 Antibodies Levels Assessed at 24 Months |
4.170; 11.071; 7.226; 19.538; 10.966; 27.914 | — |
| SECONDARY Comparison of Distribution of HPV18 Antibodies Levels Assessed at 24 Months |
1.568; 1.563; 2.757; 2.993; 4.259; 4.118 | — |
| SECONDARY Number Seropositive for HPV16 at 36 Months, Excluding 9-10 Year Olds |
461; 366 | — |
| SECONDARY Comparison of GMCs for HPV16 Antibodies Assessed at 36 Months, Excluding 9-10-year-old Girls |
20.8; 42.8 | — |
| SECONDARY Comparison of Seroconversion Proportions for HPV16 Antibodies Assessed at 36 Months, Excluding 9-10-year-old Girls |
461; 366 | 1.0 |
| SECONDARY Number Seropositive for HPV18 at 36 Months, Excluding 9-10 Year Olds |
441; 358 | — |
| SECONDARY Comparison of GMCs for HPV18 Antibodies, Assessed at 36 Months, Excluding 9-10-year-old Girls |
7.9; 7.2 | — |
| SECONDARY Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 36 Months, Excluding 9-10-year-old Girls |
441; 358 | =0.0006 sig |
| SECONDARY Number Seropositive for HPV16 at 24 Months, Excluding 9-10 Year Olds |
463; 371 | — |
| SECONDARY Comparison of GMCs for HPV16 Assessed at 24 Months, Excluding 9-10-year-old Girls |
20.0; 48.8 | — |
| SECONDARY Comparison of Seroconversion Proportions for HPV16 Assessed at 24 Months, Excluding 9-10-year-old Girls |
463; 371 | =1.0 |
| SECONDARY Number Seropositive for HPV18 at 24 Months, Excluding 9-10 Year Olds |
440; 367 | — |
| SECONDARY Comparison of GMCs for HPV18 Antibodies, Assessed at 24 Months, Excluding 9-10-year-old Girls |
7.6; 8.8 | — |
| SECONDARY Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 24 Months, Excluding 9-10-year-old Girls |
440; 367 | =0.478 |
| SECONDARY Number Seropositive for HPV16 Antibodies, Assessed at 1 Month After Vaccination, in Younger and Older Girls |
99; 461 | — |
| SECONDARY Comparison of GMCs for HPV16 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls |
83.4; 62.6 | — |
| SECONDARY Comparison of Seroconversion Proportions for HPV16 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls |
99; 461 | — |
| SECONDARY Number Seropositive for HPV18 Antibodies, Assessed at 1 Month After Vaccination, in Younger and Older Girls |
100; 446 | — |
| SECONDARY Comparison of GMCs for HPV18 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls |
32.8; 25.4 | — |
| SECONDARY Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls |
100; 446 | — |
| SECONDARY Number Seropositive for HPV16 Antibodies, Assessed at 12 Months After Vaccination, in Younger and Older Girls |
85; 462 | — |
| SECONDARY Comparison of GMCs for HPV16 Antibodies, Assessed at 12 Months After Vaccination in Younger and Older Girls |
25.0; 17.0 | — |
| SECONDARY Comparison of Seroconversion Proportions for HPV16 Antibodies, Assessed at 12 Months After Vaccination in Younger and Older Girls |
85; 462 | =1.0 |
| SECONDARY Number Seropositive for HPV18 Antibodies, Assessed at 12 Months After Vaccination, in Younger and Older Girls |
84; 440 | — |
| SECONDARY Comparison of GMCs for HPV18 Antibodies, Assessed at 12 Months After Vaccination in Younger and Older Girls |
10.6; 7.5 | — |
| SECONDARY Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 12 Months After Vaccination, in Younger and Older Girls |
84; 440 | =0.368 |
| SECONDARY Number Seropositive for HPV16 at 36 Months, By Enrollment Age Group |
203; 335; 226; 140 | — |
| SECONDARY Comparison of GMCs for HPV16 Antibodies Assessed at 36 Months, by Enrollment Age Group |
21.7; 21.2; 47.1; 36.7 | =0.079 |
| SECONDARY Comparison of Seroconversion Proportions for HPV16, Assessed at 36 Months, by Enrollment Age Group |
203; 335; 226; 140 | =1.0000 |
| SECONDARY Number Seropositive for HPV18 at 36 Months, By Enrollment Age Group |
199; 318; 201; 157 | — |
| SECONDARY Comparison of GMCs for HPV18 Antibodies, Assessed at 36 Months, by Enrollment Age Group |
8.1; 7.9; 8.0; 6.4 | =0.14 |
| SECONDARY Comparison of Seroconversion Proportions for HPV18, Assessed at 36 Months, by Enrollment Age Group |
199; 318; 201; 157 | =0.001 sig |
| SECONDARY Number Seropositive for HPV16 at 24 Months, By Enrollment Age Group |
211; 335; 229; 142 | — |
| SECONDARY Comparison of GMCs for HPV16 Antibodies Assessed at 24 Months, by Enrollment Age Group |
22.0; 19.8; 53.2; 42.0 | =0.028 sig |
| SECONDARY Comparison of Seroconversion Proportions for HPV16, Assessed at 24 Months, by Enrollment Age Group |
211; 335; 229; 142 | =1.000 |
| SECONDARY Number Seropositive for HPV18 at 24 Months, By Enrollment Age Group |
205; 316; 208; 159 | — |
| SECONDARY Comparison of GMCs for HPV18 Antibodies, Assessed at 24 Months, by Enrollment Age Group |
8.4; 7.6; 9.9; 7.6 | =0.24 |
| SECONDARY Comparison of Seroconversion Proportions for HPV18, Assessed at 24 Months, by Enrollment Age Group |
205; 316; 208; 159 | =0.216 |
| SECONDARY Number Seropositive for HPV16, Assessed at 36 Months, by Enrollment Month Group |
195; 145; 343; 221 | — |
| SECONDARY Comparison of GMCs for HPV16 Antibodies Assessed at 36 Months, by Enrollment Month Group |
21.6; 41.6; 21.3; 43.6 | =0.73 |
| SECONDARY Comparison of Seroconversion Proportions for HPV16, Assessed at 36 Months, by Enrollment Month |
195; 145; 343; 221 | =1.000 |
| SECONDARY Number Seropositive for HPV18, Assessed at 36 Months, by Enrollment Month Group |
182; 149; 335; 209 | — |
| SECONDARY Comparison of GMCs for HPV18 Antibodies, Assessed at 36 Months, by Enrollment Month Group |
7.9; 6.3; 8.1; 8.0 | =0.15 |
| SECONDARY Comparison of Seroconversion Proportions for HPV18, Assessed at 36 Months, by Enrollment Month |
182; 149; 335; 209 | =0.253 |
| SECONDARY Number Seropositive for HPV16, Assessed at 24 Months, by Enrollment Month |
196; 147; 350; 224 | — |
| SECONDARY Comparison of GMCs for HPV16 Antibodies Assessed at 24 Months, by Enrollment Month Group |
20.4; 47.9; 20.7; 49.2 | =0.95 |
| SECONDARY Comparison of Seroconversion Proportions for HPV16, Assessed at 24 Months, by Enrollment Month |
196; 147; 350; 224 | =1.000 |
| SECONDARY Number Seropositive for HPV18, Assessed at 24 Months, by Enrollment Month Group |
182; 154; 339; 213 | — |
| SECONDARY Comparison of GMCs for HPV18 Antibodies Assessed at 24 Months, by Enrollment Month Group |
7.4; 8.2; 8.2; 9.3 | =0.88 |
| SECONDARY Comparison of Seroconversion Proportions for HPV18, Assessed at 24 Months, by Enrollment Month |
182; 154; 339; 213 | =0.629 |
| SECONDARY Number Seropositive for HPV16, Assessed at 36 Months, by Enrollment District |
249; 169; 289; 197 | — |
| SECONDARY Comparison of GMCs for HPV16 Antibodies, Assessed at 36 Months, by Enrollment District |
21.5; 41.0; 21.4; 44.6 | =0.46 |
| SECONDARY Comparison of Seroconversion Proportions for HPV16, Assessed at 36 Months, by Enrollment District |
99.6; 100.0; 100.0; 100.0 | =1.000 |
| SECONDARY Number Seropositive for HPV18, Assessed at 36 Months, by Enrollment District |
240; 157; 277; 201 | — |
| SECONDARY Comparison of GMCs for HPV18 Antibodies, Assessed at 36 Months, by Enrollment District |
8.5; 6.7; 7.7; 7.7 | =0.095 |
| SECONDARY Comparison of Seroconversion Proportions for HPV18, Assessed at 36 Months, by Enrollment District |
240; 157; 277; 201 | =0.327 |
| SECONDARY Number Seropositive for HPV16, Assessed at 24 Months, by Enrollment District |
253; 171; 293; 200 | — |
| SECONDARY Comparison of GMCs for HPV16 Antibodies, Assessed at 24 Months, by Enrollment District |
21.0; 46.3; 20.3; 51.1 | =0.30 |
| SECONDARY Comparison of Seroconversion Proportions for HPV16, Assessed at 24 Months, by Enrollment District |
253; 171; 293; 200 | =1.000 |
| SECONDARY Number Seropositive for HPV18, Assessed at 24 Months, by Enrollment District |
242; 161; 279; 206 | — |
| SECONDARY Comparison of GMCs for HPV18 Antibodies, Assessed at 24 Months, by Enrollment District |
8.4; 8.2; 7.6; 9.4 | =0.10 |
| SECONDARY Comparison of Seroconversion Proportions for HPV18, Assessed at 24 Months, by Enrollment District |
242; 161; 279; 206 | =1.000 |
Summary
This phase IIIb trial compares a single dose of the Cervarix vaccine in girls to 3 doses of the Gardasil vaccine in young women for the prevention of human papillomavirus (HPV) infection. Cervarix is a vaccine used to prevent cervical cancer caused by HPV types 16 and 18. Gardasil is vaccine used to prevent cervical, vulvar, and vaginal cancer caused by HPV types 16 and 18 and genital warts caused by HPV types 6 and 11. Giving only one dose of the Cervarix vaccine in girls may work the same as 3 doses of the Gardasil vaccine in young women in preventing HPV infection and ultimately, cervical and other HPV-related cancers. Currently, many women around the world cannot get HPV vaccines because they are too expensive. If this trial can show one dose given to young girls is enough to prevent cancer, more girls might be able to get the vaccine.
Eligibility Criteria
Inclusion Criteria
- Aged between:
- 9 and 14 years inclusive for Cervarix group
- 18 and 25 years inclusive for Gardasil group
- Living in the study area without plans to move outside the country in the next six months
- Able to communicate with study personnel
- Able and willing to provide a blood sample
- Willing to permit export of blood samples to the United States
- Willing to participate in the study and:
- If Cervarix group and less than 12 years old, receive study information and be supported in study participation by at least one of parent (or guardian), who is willing to sign the informed consent document
- If Cervarix group and 12 years old or older, sign the informed assent and be supported in study participation by at least one parent (or guardian), who is willing to sign the informed consent document
- If Gardasil group, sign the informed consent
- In good health as determined by a medical history (physical exam will be conducted if necessary per the doctor's criterion)
Exclusion 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)
- They are allergic to one of the vaccine components, including yeast (if Gardasil group)
- They have received immunoglobulins within 90 days preceding enrollment/vaccination visit
- They are unwilling to provide a blood sample
- Unwilling to permit export of blood samples to the United States
- They have a positive urine pregnancy test result
- They are pregnant
- They are planning to become pregnant
- The clinician determining eligibility in agreement with the principal investigator considers that there is a reason that precludes participation
- They have been vaccinated against HPV
- The participant or her parent/legal guardian, as applicable, does not have an identification document
Data sourced from ClinicalTrials.gov (NCT03728881). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.