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CompletedNCT00128661Updated Mar 8, 2019Results posted

Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants

A Phase 3 interventional study of human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine and hepatitis A inactivated virus vaccine in Cervical Cancer and Precancerous Condition, sponsored by GlaxoSmithKline. Completed at 1 site in Costa Rica. Open to female participants aged 18 Years to 25 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-03-08.

Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Prevention

From the registry’s dates

  • Registered 1 year 1 month after the study started (first participant enrolled Jun 2004, registered Aug 2005).
Phase
Phase 3
Study type
Interventional
Enrollment
7,466
Allocation
Randomized
Ages
18 Years to 25 Years
Sex
Female
01

Study summary

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer form forming, growing, or coming back. Vaccines may help the body build an effective immune response against human papillomavirus and may be effective in preventing cervical intraepithelial neoplasia or cervical cancer. It is not yet known whether human papillomavirus vaccine is more effective than hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer.

PURPOSE: This randomized phase III trial is studying human papillomavirus vaccine to see how well it works compared to hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer in younger healthy participants.

Read the detailed description

OBJECTIVES:

Primary

•Demonstrate the efficacy of the candidate vaccine, human papillomavirus 16/18 (HPV 16/18) L1 virus-like particle (VLP)/AS04 vaccine compared with control in preventing grade 2 or 3 cervical intraepithelial neoplasia, adenocarcinoma in situ of the cervix, or invasive cervical cancer (CIN2+) associated with HPV 16 or HPV 18 cervical infection in younger healthy participants who are negative for HPV DNA by polymerase chain reaction (PCR) for the corresponding HPV type at months 0 and 6.

Secondary

  • Determine the duration of protection against HPV 16 or HPV 18 cervical infection in participants treated with the HPV 16/18 L1 VLP/AS04 vaccine.
  • Determine the safety of this vaccine in these participants, regardless of their initial HPV 16/18 DNA status.
  • Evaluate the efficacy of the candidate vaccine, HPV 16/18 L1 VLP/AS04 vaccine compared with control in preventing CIN2+ associated with any oncogenic HPV type cervical infection in participants who are negative for HPV DNA by PCR for the corresponding HPV type at months 0 and 6.
  • Compare the efficacy of the candidate vaccine with control in preventing CIN2+ associated with HPV 16 or HPV 18 cervical infection, detected within the lesional component of the cervical tissue specimen by PCR, in participants who are negative for HPV DNA by PCR for the corresponding HPV type at months 0 and 6 and by enzyme-linked immunosorbent assay (ELISA) at month 0.
  • Compare the efficacy of the candidate vaccine with control in preventing persistent HPV 16 or HPV 18 cervical infection in these participants.
  • Determine the immunogenicity of HPV 16/18 L1 VLP/AS04 vaccine by ELISA and V5/J4 monoclonal antibody inhibition enzyme immunoassay in the first 600 participants randomized to receive HPV 16/18 L1 VLP/AS04 vaccine.

OUTLINE: This is a randomized, controlled, double-blind, parallel-group study. Participants are randomized to 1 of 2 treatment arms.

  • Arm I: Participants receive human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine intramuscularly (IM) once in months 0, 1, and 6.
  • Arm II: Participants receive hepatitis A vaccine (Havrix®) IM once in months 0, 1, and 6.

After completion of study treatment, participants are followed at 6 months and then at least annually for 3 years.

PROJECTED ACCRUAL: Approximately 7,500 participants will be accrued for this study.

02

Conditions studied

  • Cervical Cancer
  • Precancerous Condition

Keywords

  • cervical intraepithelial neoplasia grade 2
  • cervical cancer
  • cervical intraepithelial neoplasia grade 3
03

In context

Uterine Cervical Neoplasms

1,881 studies on the registry are indexed under Uterine Cervical Neoplasms; 567 are open to participants now.

This study's enrollment of 7,466 is above the median of 100 across 1,377 interventional studies indexed under Uterine Cervical Neoplasms.

Browse Uterine Cervical Neoplasms studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 25 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Eligibility criteria

DISEASE CHARACTERISTICS:

•Healthy participants

  • Deemed to be in good general health by history and physical examination

    •Resident of Guanacaste Province of Costa Rica and surrounding areas

  • Must remain a resident for ≥ 6 months after the first study vaccination

PATIENT CHARACTERISTICS:

Age

  • 18 to 25

Performance status

•Not specified

Life expectancy

•Not specified

Hematopoietic

•Not specified

Hepatic

  • No history of chronic hepatitis requiring treatment
  • No acute or chronic clinically significant hepatic function abnormality by physical examination or laboratory findings
  • No known history of hepatitis A infection

Renal

  • No history of kidney disease requiring treatment
  • No acute or chronic clinically significant kidney function abnormality by physical examination or laboratory findings

Cardiovascular

  • No acute or chronic clinically significant cardiovascular function abnormality by physical examination or laboratory findings Pulmonary
  • No acute or chronic clinically significant pulmonary function abnormality by physical examination or laboratory findings Immunology
  • No history of allergic disease
  • No history of autoimmune disorder requiring treatment
  • No history of allergic reaction (e.g., difficulty breathing) to any vaccine
  • No suspected allergy or reaction likely to be exacerbated by a component of the study vaccines (e.g., 2-phenoxyethanol or neomycin)
  • No hypersensitivity to latex
  • No diagnosis or suspicion of any immunodeficient condition by medical history or physical examination Other

  • Not pregnant or nursing

    ◦No delivery within the past 3 months

  • Negative pregnancy test
  • Fertile patients must use effective contraception for 30 days before, during, and for 60 days after completion of study treatment
  • Able to speak or understand Spanish
  • Mentally competent
  • Able to undergo pelvic exam (i.e., no heavy bleeding [menstruation or otherwise] or heavy vaginal discharge)
  • No history of cancer requiring treatment
  • No history of diabetes requiring treatment
  • No history of other chronic conditions requiring treatment
  • No acute or chronic clinically significant neurologic function abnormality by physical examination or laboratory findings
  • No other acute disease
  • No fever ≥ 37.5º C

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 6 months since prior chronic administration (i.e., > 14 days) of immune-modulating drugs
  • More than 90 days since prior immunoglobulins
  • More than 30 days since prior and no other concurrent investigational or non-registered vaccines
  • More than 30 days since prior registered vaccines
  • More than 8 days since prior routine meningococcal, hepatitis B, influenza, or diphtheria/tetanus vaccine
  • No prior vaccination against hepatitis A
  • No prior vaccination against human papillomavirus
  • No prior monophosphoryl lipid A or AS04 adjuvant

Chemotherapy

•Not specified

Endocrine therapy

  • More than 6 months since prior chronic administration (i.e., > 14 days) of corticosteroids (e.g., ≥ 0.5 mg/kg/day of prednisone or equivalent)
  • Concurrent inhaled or topical steroids allowed

Radiotherapy

•Not specified

Surgery

•No prior hysterectomy

Other

  • More than 6 months since prior chronic administration (i.e., > 14 days) of immunosuppressants
  • More than 30 days since prior and no other concurrent investigational or non-registered drugs
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
7,466 participants (actual)

Study arms

  • Experimental
    Cervarix Group

    Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

    Biological: human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine

  • Active comparator
    Havrix Group

    Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

    Biological: hepatitis A inactivated virus vaccine

Interventions

  • Biologicalhuman papillomavirus 16/18 L1 virus-like particle/AS04 vaccine

    Three doses of Cervarix vaccine administered on a 0, 1, 6-month schedule

  • Biologicalhepatitis A inactivated virus vaccine

    Three doses of Havrix vaccine administered on a 0, 1, 6-month schedule

06

What researchers measure

Primary outcomes

  1. Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.

    CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer. Preceding cervical cytology means the last cervical cytology specimen collected before the histopathology specimen was obtained. Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) by polymerase chain reaction (PCR) at Month 0 and Month 6 for the corresponding HPV-type.

    Time frame: From Month 6 up to Month 48

Secondary outcomes

  1. Number of Cervical Infection With HPV16 or HPV18.

    Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

    Time frame: From Month 6 up to Month 48

  2. Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type

    Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 detected by polymerase chain reaction (PRC) in the preceding cervical cytology specimen. Note: The assay did not distinguish between HPV types 68 and 73. CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

    Time frame: From Month 6 up to Month 48

  3. Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases

    Persistent incident HPV-16 and /or HPV-18 cervical infection had to fulfil the following criteria: first detection after the 6-month visit, 2 same type HPV positive (by PCR) test results 10+ months apart, and no intervening HPV negative tests for the corresponding type. Persistent HPV16 or HPV18 cervical infection = detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples from all consecutive evaluations over approximately 12 months. Subjects were HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type.

    Time frame: From Month 6 up to Month 48

  4. Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.

    Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs). Seronegative subjects = antibody concentration below 8 ELISA Units per millilitre (EL.U/mL) prior to vaccination. Seropositive subjects=antibody concentration equal to or above 8 EL.U/mL prior to vaccination. Immunogenicity subcohort = subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7)

    Time frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48

  5. Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort

    Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohortby Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 7 EL.U/mL prior to vaccination. Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).

    Time frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48

  6. HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)

    Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 41 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 41 EL.U/mL prior to vaccination. Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).

    Time frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48

  7. HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)

    Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 110 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 110 EL.U/mL prior to vaccination. Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).

    Time frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48

  8. Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.

    Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).

    Time frame: Within 60 minutes after vaccination

  9. Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.

    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy.Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = oral temperature \> 39.0°C.

    Time frame: Within 60 minutes after vaccination

  10. Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.

    Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).

    Time frame: From Day 3 to Day 6 after vaccination

  11. Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.

    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy.Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = oral temperature \> 39.0°C.

    Time frame: From Day 3 to Day 6 after vaccination

  12. Number of Subjects Reporting Serious Adverse Events (SAEs).

    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

    Time frame: During the entire study period (From Month 0 up to Month 48).

  13. Number of Subjects Reporting Unsolicited Adverse Events (AEs).

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

    Time frame: During the entire study period (From Month 0 up to Month 48).

  14. Number of Subjects With All Possible Pregnancy Outcomes

    The range of possible pregnancy outcomes was: Pregnancy loss, Pregnancy resolved alive, and Unresolved pregnancy.

    Time frame: During the entire study period (From Month 0 up to Month 48).

  15. Number of Cervical Infection With HPV16 or HPV18.

    Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

    Time frame: During the first year of follow-up period

  16. Number of Cervical Infection With HPV16 or HPV18.

    Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

    Time frame: During the second year of follow-up period

  17. Number of Cervical Infection With HPV16 or HPV18.

    Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

    Time frame: During the third year of follow-up period

  18. Number of Cervical Infection With HPV16 or HPV18.

    Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

    Time frame: From the fourth year follow-up period

  19. Number of Subjects Reporting Unsolicited Adverse Events (AEs).

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

    Time frame: within 30 days (Days 0-29) after vaccination

07

Results

Posted May 2, 2012
Limitations and caveats
The following analysis "occurence of histopathologically confirmed CIN2+ cases associated with HPV16 or HPV18 infection was not performed, in accordance with the Statistical Analysis Plan submitted to the FDA.

Participant flow

Participant flow — Overall Study
MilestoneCervarix GroupHavrix Group
Started37273739
Completed34533481
Not completed274258
Withdrew: Adverse event1411
Withdrew: Lost to follow-up107
Withdrew: Withdrawal by subject243232
Withdrew: Other78

Outcome measures

PrimaryNumber of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.

CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer. Preceding cervical cytology means the last cervical cytology specimen collected before the histopathology specimen was obtained. Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) by polymerase chain reaction (PCR) at Month 0 and Month 6 for the corresponding HPV-type.

Time frame:
From Month 6 up to Month 48
Reported as:
Number · Events
Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.
EventsCervarix GroupHavrix Group
HPV16 Associated CIN2+ (N=2464;2452)19
HPV18 Associated CIN2+ (N=2567; 2593)02
HPV16 and/or 18 Associated CIN2+ (N=2635;2677)110
SecondaryNumber of Cervical Infection With HPV16 or HPV18.

Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

Time frame:
From Month 6 up to Month 48
Reported as:
Number · Events
Number of Cervical Infection With HPV16 or HPV18.
EventsCervarix GroupHavrix Group
HPV16 Cervical Infection (N=2464;2452)50251
HPV18 Cervical Infection (N=2567;2593)32177
HPV16 and/or 18 Cervical Infection (N=2635;2677)78387
SecondaryNumber of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type

Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 detected by polymerase chain reaction (PRC) in the preceding cervical cytology specimen. Note: The assay did not distinguish between HPV types 68 and 73. CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

Time frame:
From Month 6 up to Month 48
Reported as:
Number · Events
Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type
EventsCervarix GroupHavrix Group
HPV16 Associated CIN2+ (N=2464;2452)19
HPV18 Associated CIN2+ (N=2567,2593)02
HPV31 Associated CIN2+ (N=2525;2546)16
HPV33 Associated CIN2+ (N=2596;2645)03
HPV35 Associated CIN2+ (N=2593;2631)04
HPV39 Associated CIN2+ (N=2528;2581)00
HPV45 Associated CIN2+ (N=2573;2622)11
HPV51 Associated CIN2+ (N=2453;2539)16
HPV52 Associated CIN2+ (N=2456;2505)510
HPV56 Associated CIN2+ (N=2524;2564)15
HPV58 Associated CIN2+ (N=2551;2595)25
HPV59 Associated CIN2+ (N=2576;2637)33
HPV68 and/or 73 Associated CIN2+ (N=2519;2576)14
Non 16/18 Onco HPV Associated CIN2+ (N=2643;2697)1128
Any Oncogenic HPV Associated CIN2+ (N=2643;2697)1133
SecondaryNumber of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases

Persistent incident HPV-16 and /or HPV-18 cervical infection had to fulfil the following criteria: first detection after the 6-month visit, 2 same type HPV positive (by PCR) test results 10+ months apart, and no intervening HPV negative tests for the corresponding type. Persistent HPV16 or HPV18 cervical infection = detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples from all consecutive evaluations over approximately 12 months. Subjects were HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type.

Time frame:
From Month 6 up to Month 48
Reported as:
Number · Events
Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases
EventsCervarix GroupHavrix Group
Persistent HPV16 Infection (N=2464,2452)1071
Persistent HPV18 Infection (N=2567;2593)037
Persistent HPV16 and/or 18 Infection (N=2635;2677)10104
SecondaryGeometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.

Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs). Seronegative subjects = antibody concentration below 8 ELISA Units per millilitre (EL.U/mL) prior to vaccination. Seropositive subjects=antibody concentration equal to or above 8 EL.U/mL prior to vaccination. Immunogenicity subcohort = subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7)

Time frame:
Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48
Reported as:
Geometric mean · Titers
Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.
TitersCervarix GroupHavrix Group
HPV-16 [before vaccination] (N=194;156)6.7 (5.7 to 7.8)8.2 (6.7 to 10.0)
HPV-16 [at Month 1] (N=196,157)646.6 (549.3 to 761.1)7.9 (6.5 to 9.6)
HPV-16 [at Month 6] (N=195,156)771.5 (668.3 to 890.7)8.4 (6.9 to 10.3)
HPV-16 [at Month 7] (N=195,157)3261 (2959 to 3595)8.5 (6.9 to 10.3)
HPV-16 [at Month 12] (N=182,146)2090 (1822 to 2398)8.3 (6.7 to 10.4)
HPV-16 [at Month 18] (N=25,17)1045 (776.0 to 1408)10.4 (4.8 to 22.7)
HPV-16 [at Month 24] (N=175,137)1486 (1293 to 1709)8.6 (6.9 to 10.7)
HPV-16 [at Month 30] (N=19,15)1070 (747.5 to 1532)11.9 (5.1 to 28.0)
HPV-16 [at Month 36] (N=163,132)1256 (1080 to 1461)9.0 (7.4 to 11.0)
HPV-16 [at Month 42] (N=22,18)1259 (879.4 to 1802)6.1 (4.0 to 9.4)
HPV-16 [at Month 48] (N=172,131)1155 (1009 to 1322)9.5 (7.7 to 11.7)
SecondaryGeometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort

Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohortby Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 7 EL.U/mL prior to vaccination. Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).

Time frame:
Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48
Reported as:
Geometric mean · Titers
Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort
TitersCervarix GroupHavrix Group
HPV-18 [before vaccination] (N=200;173)5.4 (4.8 to 6.1)6.2 (5.2 to 7.4)
HPV-18 [at Month 1] (N=203;170)372.7 (322.8 to 430.3)6.4 (5.4 to 7.6)
HPV-18 [at Month 6] (N=203;175)532.2 (467.5 to 605.9)6.7 (5.6 to 7.9)
HPV-18 [at Month 7] (N=202;175)3276 (3001 to 3576)6.8 (5.7 to 8.1)
HPV-18 [at Month 12] (N=190;166)1082 (942.0 to 1242)7.0 (5.7 to 8.5)
HPV-18 [at Month 18] (N=28;20)502.4 (339.1 to 744.5)6.7 (3.8 to 12.1)
HPV-18 [at Month 24] (N=178;150)633.0 (551.5 to 726.6)6.9 (5.6 to 8.4)
HPV-18 [at Month 30] (N=17;19)403.8 (257.8 to 632.5)6.4 (3.8 to 10.5)
HPV-18 [at Month 36] (N=168;145)519.7 (449.3 to 601.1)6.0 (5.0 to 7.2)
HPV-18 [at Month 42] (N=25;19)582.4 (422.9 to 801.9)5.5 (3.6 to 8.4)
HPV-18 [at Month 48] (N=179;149)470.1 (411.2 to 537.4)6.6 (5.5 to 8.0)
SecondaryHPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)

Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 41 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 41 EL.U/mL prior to vaccination. Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).

Time frame:
Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48
Reported as:
Geometric mean · Titers
HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)
TitersCervarix GroupHavrix Group
HPV-16 [before vaccination] (N=196;158)21.1 (20.5 to 21.8)21.4 (20.6 to 22.3)
HPV-16 [at Month 1] (N=182;155)58.5 (48.3 to 70.8)21.5 (20.7 to 22.3)
HPV-16 [at Month 6] (N=189;156)80.9 (70.3 to 93.1)21.5 (20.6 to 22.4)
HPV-16 [at Month 7] (N=193;158)1047 (926.3 to 1183)21.4 (20.6 to 22.3)
HPV-16 [at Month 12] (N=175;146)291.4 (253.7 to 334.8)22.6 (20.8 to 24.5)
HPV-16 [at Month 18] (N=24;17)116.6 (83.2 to 163.3)20.5 (20.5 to 20.5)
HPV-16 [at Month 24] (N=169;138)184.6 (163.0 to 209.1)21.4 (20.6 to 22.3)
HPV-16 [at Month 30] (N=18;15)112.4 (78.7 to 160.6)20.5 (20.5 to 20.5)
HPV-16 [at Month 36] (N=162;132)139.7 (122.5 to 159.5)20.8 (20.2 to 21.3)
HPV-16 [at Month 42] (N=22;18)126.9 (89.9 to 179.1)20.5 (20.5 to 20.5)
HPV-16 [at Month 48] (N=168;133)131.8 (115.5 to 150.5)21.0 (20.4 to 21.7)
SecondaryHPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)

Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 110 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 110 EL.U/mL prior to vaccination. Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).

Time frame:
Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48
Reported as:
Geometric mean · Titers
HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)
TitersCervarix GroupHavrix Group
HPV-18 [before vaccination] (N=203;176)55.0 (55.0 to 55.0)55.7 (54.7 to 56.7)
HPV-18 [at Month 1] (N=197;173)99.1 (88.0 to 111.5)55.3 (54.7 to 55.8)
HPV-18 [at Month 6] (N=195;175)111.4 (100.2 to 123.9)55.4 (54.6 to 56.3)
HPV-18 [at Month 7] (N=198;176)823.6 (737.7 to 919.5)55.0 (55.0 to 55.0)
HPV-18 [at Month 12] (N=182;166)231.1 (203.2 to 262.7)56.7 (54.7 to 58.8)
HPV-18 [at Month 18] (N=28;20)121.8 (89.5 to 165.8)55.0 (55.0 to 55.0)
HPV-18 [at Month 24] (N=170;154)140.8 (123.8 to 160.2)55.0 (55.0 to 55.0)
HPV-18 [at Month 30] (N=17;19)89.5 (67.6 to 118.7)55.0 (55.0 to 55.0)
HPV-18 [at Month 36] (N=167;145)107.9 (96.0 to 121.2)55.0 (55.0 to 55.0)
HPV-18 [at Month 42] (N=25;19)103.3 (80.3 to 132.9)55.0 (55.0 to 55.0)
HPV-18 [at Month 48 (N=179;150)96.9 (87.7 to 107.0)56.7 (54.0 to 59.6)
SecondaryNumber of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.

Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).

Time frame:
Within 60 minutes after vaccination
Reported as:
Number · Subjects
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
SubjectsCervarix GroupHavrix Group
Any pain16271610
Grade 3 pain2520
Any redness544501
Grade 3 redness > 50 mm02
Any swelling207201
Grade 3 swelling > 50 mm01
SecondaryNumber of Subjects Reporting Any and Grade 3 Solicited General Symptoms.

Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy.Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = oral temperature \> 39.0°C.

Time frame:
Within 60 minutes after vaccination
Reported as:
Number · Subjects
Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.
SubjectsCervarix GroupHavrix Group
Any fatigue512502
Grade 3 fatigue65
Any myalgia257232
Grade 3 myalgia01
Any arthralgia5864
Grade 3 arthralgia01
Any gastrointestinal191171
Grade 3 gastrointestinal00
Any headache714718
Grade 3 headache20
Any rash1517
Grade 3 rash00
Any urticaria1921
Grade 3 urticaria00
Fever (oral) >= 37.5°C472477
Fever (oral) > 39.0°C00
SecondaryNumber of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.

Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).

Time frame:
From Day 3 to Day 6 after vaccination
Reported as:
Number · Subjects
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.
SubjectsCervarix GroupHavrix Group
Any pain20274
Grade 3 pain00
Any redness61
Grade 3 redness10
Any swelling231
Grade 3 swelling70
SecondaryNumber of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.

Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy.Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = oral temperature \> 39.0°C.

Time frame:
From Day 3 to Day 6 after vaccination
Reported as:
Number · Subjects
Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.
SubjectsCervarix GroupHavrix Group
Any pain214189
Grade 3 pain20
Any myalgia250211
Grade 3 myalgia10
Any arthralgia4432
Grade 3 arthralgia00
Any gastrointestinal157119
Grade 3 gastrointestinal01
Any headache247242
Grade 3 headache12
Any rash3126
Grade 3 rash00
Any urticaria31
Grade 3 urticaria00
Fever (oral) >= 37.5°C4337
Fever (oral) > 39.0°C00
SecondaryNumber of Subjects Reporting Serious Adverse Events (SAEs).

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

Time frame:
During the entire study period (From Month 0 up to Month 48).
Reported as:
Number · Subjects
Number of Subjects Reporting Serious Adverse Events (SAEs).
SubjectsCervarix GroupHavrix Group
Number of Subjects Reporting Serious Adverse Events (SAEs).912891
SecondaryNumber of Subjects Reporting Unsolicited Adverse Events (AEs).

An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

Time frame:
During the entire study period (From Month 0 up to Month 48).
Reported as:
Number · Subjects
Number of Subjects Reporting Unsolicited Adverse Events (AEs).
SubjectsCervarix GroupHavrix Group
Number of Subjects Reporting Unsolicited Adverse Events (AEs).32283254
SecondaryNumber of Subjects With All Possible Pregnancy Outcomes

The range of possible pregnancy outcomes was: Pregnancy loss, Pregnancy resolved alive, and Unresolved pregnancy.

Time frame:
During the entire study period (From Month 0 up to Month 48).
Reported as:
Number · subjects
Number of Subjects With All Possible Pregnancy Outcomes
subjectsCervarix GroupHavrix Group
Pregnancy loss317294
Pregnancy resolved alive17561766
Unresolved pregnancy5069
SecondaryNumber of Cervical Infection With HPV16 or HPV18.

Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

Time frame:
During the first year of follow-up period
Reported as:
Number · Events
Number of Cervical Infection With HPV16 or HPV18.
EventsCervarix GroupHavrix Group
HPV16 Cervical Infection (N=2242;2232)2137
HPV18 Cervical Infection (N=2330;2347)729
HPV16 and/or 18 Cervical Infection (N=2380;2420)2764
SecondaryNumber of Cervical Infection With HPV16 or HPV18.

Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

Time frame:
During the second year of follow-up period
Reported as:
Number · Events
Number of Cervical Infection With HPV16 or HPV18.
EventsCervarix GroupHavrix Group
HPV16 Cervical Infection (N=2170;2176)1077
HPV18 Cervical Infection (N=2269;2307)947
HPV16 and/or 18 Cervical Infection (N=2313;2349)18117
SecondaryNumber of Cervical Infection With HPV16 or HPV18.

Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

Time frame:
During the third year of follow-up period
Reported as:
Number · Events
Number of Cervical Infection With HPV16 or HPV18.
EventsCervarix GroupHavrix Group
HPV16 Cervical Infection (N=2097;2026)660
HPV18 Cervical Infection (N=2200;2196)644
HPV16 and/or 18 Cervical Infection (N=2236;2166)1188
SecondaryNumber of Cervical Infection With HPV16 or HPV18.

Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

Time frame:
From the fourth year follow-up period
Reported as:
Number · Events
Number of Cervical Infection With HPV16 or HPV18.
EventsCervarix GroupHavrix Group
HPV16 Cervical Infection (N=2277;2139)1377
HPV18 Cervical Infection (N=2389;2325)1057
HPV16 and/or 18 Cervical Infection (N=2421;2261)22118
SecondaryNumber of Subjects Reporting Unsolicited Adverse Events (AEs).

An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

Time frame:
within 30 days (Days 0-29) after vaccination
Reported as:
Number · Subjects
Number of Subjects Reporting Unsolicited Adverse Events (AEs).
SubjectsCervarix GroupHavrix Group
Number of Subjects Reporting Unsolicited Adverse Events (AEs).16381536

Adverse events

Collected over Solicited AEs: within 60 minutes after vaccination for all participants [please refer to Participant Flow Pre-assignment Details for population description]; From Day 3 to Day 6 post-vaccination for a 10% random subset of participants. SAEs: From Month 0 up to Month 48. Unsolicited AEs: From Month 0 up to Month 48 and Within 30 days (Days 0-29) after vaccination. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cervarix Group—912/3,727 (24.5%)1,627/3,730 (43.6%)
Havrix Group—891/3,739 (23.8%)1,610/3,740 (43%)
Most frequent serious events
Showing 10 of 266
Most frequent serious events
EventCervarix GroupHavrix Group
Abortion spontaneous incompletePregnancy, puerperium and perinatal conditions134/3727108/3739
False labourPregnancy, puerperium and perinatal conditions66/372788/3739
Abortion spontaneous completePregnancy, puerperium and perinatal conditions64/372764/3739
Foetal distress syndromePregnancy, puerperium and perinatal conditions57/372764/3739
Abortion missedPregnancy, puerperium and perinatal conditions59/372763/3739
Caesarean sectionSurgical and medical procedures56/372759/3739
Uterine hypotonusPregnancy, puerperium and perinatal conditions54/372754/3739
Gestational hypertensionPregnancy, puerperium and perinatal conditions39/372753/3739
Dengue feverInfections and infestations38/372748/3739
Cephalo-pelvic disproportionPregnancy, puerperium and perinatal conditions33/372745/3739
Most frequent other events
Showing 10 of 30
Most frequent other events
EventCervarix GroupHavrix Group
MyalgiaGeneral disorders250/380211/376
HeadacheGeneral disorders247/380242/376
FatigueGeneral disorders214/380189/376
PainGeneral disorders202/38074/376
PainGeneral disorders1627/37301610/3740
GastrointestinalGeneral disorders157/380119/376
Menstruation irregularReproductive system and breast disorders1021/37271011/3739
InfluenzaInfections and infestations903/3727950/3739
Vaginal infectionInfections and infestations709/3727763/3739
HeadacheGeneral disorders714/3730718/3740

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Cervarix GroupHavrix GroupTotal
Years21.1 ± 2.321.1 ± 2.321.1 ± 2.3
Sex: Female, Male
Sex: Female, Male(Participants)Cervarix GroupHavrix GroupTotal
Female372737397466
Male000
08

Study locations

1 site
  • Proyecto Epidemiologico Guanacaste
    Liberia, Costa Rica
09

References and documents

Publications

  • Kreimer AR, Rodriguez AC, Hildesheim A, Herrero R, Porras C, Schiffman M, Gonzalez P, Solomon D, Jimenez S, Schiller JT, Lowy DR, Quint W, Sherman ME, Schussler J, Wacholder S; CVT Vaccine Group. Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine. J Natl Cancer Inst. 2011 Oct 5;103(19):1444-51. doi: 10.1093/jnci/djr319. Epub 2011 Sep 9. PubMed 21908768 ↗
  • Kemp TJ, Hildesheim A, Safaeian M, Dauner JG, Pan Y, Porras C, Schiller JT, Lowy DR, Herrero R, Pinto LA. HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection. Vaccine. 2011 Mar 3;29(11):2011-4. doi: 10.1016/j.vaccine.2011.01.001. Epub 2011 Jan 15. PubMed 21241731 ↗
  • Sierra MS, Tsang SH, Porras C, Herrero R, Sampson JN, Cortes B, Schussler J, Wagner S, Carvajal L, Quint W, Kreimer AR, Hu S, Rodriguez AC, Romero B, Hildesheim A; Costa Rica HPV Vaccine Trial (CVT) Group. Analysis of cervical HPV infections among unvaccinated young adult women to inform vaccine strategies in this age group: the Costa Rica HPV Vaccine Trial. Sex Transm Infect. 2022 Jul 16;99(3):180-6. doi: 10.1136/sextrans-2022-055434. Online ahead of print. PubMed 35842229 ↗
  • Shing JZ, Hu S, Herrero R, Hildesheim A, Porras C, Sampson JN, Schussler J, Schiller JT, Lowy DR, Sierra MS, Carvajal L, Kreimer AR; Costa Rica HPV Vaccine Trial Group. Precancerous cervical lesions caused by non-vaccine-preventable HPV types after vaccination with the bivalent AS04-adjuvanted HPV vaccine: an analysis of the long-term follow-up study from the randomised Costa Rica HPV Vaccine Trial. Lancet Oncol. 2022 Jul;23(7):940-949. doi: 10.1016/S1470-2045(22)00291-1. Epub 2022 Jun 13. PubMed 35709811 ↗
  • Usyk M, Schlecht NF, Pickering S, Williams L, Sollecito CC, Gradissimo A, Porras C, Safaeian M, Pinto L, Herrero R, Strickler HD, Viswanathan S, Nucci-Sack A, Diaz A; Costa Rica HPV Vaccine Trial (CVT) Group; Burk RD. molBV reveals immune landscape of bacterial vaginosis and predicts human papillomavirus infection natural history. Nat Commun. 2022 Jan 11;13(1):233. doi: 10.1038/s41467-021-27628-3. PubMed 35017496 ↗
  • Usyk M, Zolnik CP, Castle PE, Porras C, Herrero R, Gradissimo A, Gonzalez P, Safaeian M, Schiffman M, Burk RD; Costa Rica HPV Vaccine Trial (CVT) Group. Cervicovaginal microbiome and natural history of HPV in a longitudinal study. PLoS Pathog. 2020 Mar 26;16(3):e1008376. doi: 10.1371/journal.ppat.1008376. eCollection 2020 Mar. PubMed 32214382 ↗
  • Safaeian M, Castellsague X, Hildesheim A, Wacholder S, Schiffman MH, Bozonnat MC, Baril L, Rosillon D; Costa Rica HPV Vaccine Trial and the PATRICIA study groups. Risk of HPV-16/18 Infections and Associated Cervical Abnormalities in Women Seropositive for Naturally Acquired Antibodies: Pooled Analysis Based on Control Arms of Two Large Clinical Trials. J Infect Dis. 2018 Jun 5;218(1):84-94. doi: 10.1093/infdis/jiy112. PubMed 29718393 ↗
  • Hildesheim A, Gonzalez P, Kreimer AR, Wacholder S, Schussler J, Rodriguez AC, Porras C, Schiffman M, Sidawy M, Schiller JT, Lowy DR, Herrero R; Costa Rica HPV Vaccine Trial (CVT) Group. Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment. Am J Obstet Gynecol. 2016 Aug;215(2):212.e1-212.e15. doi: 10.1016/j.ajog.2016.02.021. Epub 2016 Feb 16. PubMed 26892991 ↗
  • Beachler DC, Kreimer AR, Schiffman M, Herrero R, Wacholder S, Rodriguez AC, Lowy DR, Porras C, Schiller JT, Quint W, Jimenez S, Safaeian M, Struijk L, Schussler J, Hildesheim A, Gonzalez P; Costa Rica HPV Vaccine Trial (CVT) Group. Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection. J Natl Cancer Inst. 2015 Oct 14;108(1):djv302. doi: 10.1093/jnci/djv302. Print 2016 Jan. PubMed 26467666 ↗
  • Panagiotou OA, Befano BL, Gonzalez P, Rodriguez AC, Herrero R, Schiller JT, Kreimer AR, Schiffman M, Hildesheim A, Wilcox AJ, Wacholder S; Costa Rica HPV Vaccine Trial (CVT) Group (see end of manuscript for full list of investigators). Effect of bivalent human papillomavirus vaccination on pregnancy outcomes: long term observational follow-up in the Costa Rica HPV Vaccine Trial. BMJ. 2015 Sep 7;351:h4358. doi: 10.1136/bmj.h4358. PubMed 26346155 ↗
  • Kreimer AR, Struyf F, Del Rosario-Raymundo MR, Hildesheim A, Skinner SR, Wacholder S, Garland SM, Herrero R, David MP, Wheeler CM; Costa Rica Vaccine Trial Study Group Authors; Gonzalez P, Jimenez S, Lowy DR, Pinto LA, Porras C, Rodriguez AC, Safaeian M, Schiffman M, Schiller JT, Schussler J, Sherman ME; PATRICIA Study Group Authors; Bosch FX, Castellsague X, Chatterjee A, Chow SN, Descamps D, Diaz-Mitoma F, Dubin G, Germar MJ, Harper DM, Lewis DJ, Limson G, Naud P, Peters K, Poppe WA, Ramjattan B, Romanowski B, Salmeron J, Schwarz TF, Teixeira JC, Tjalma WA; HPV PATRICIA Principal Investigators/Co-Principal Investigator Collaborators; GSK Vaccines Clinical Study Support Group. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials. Lancet Oncol. 2015 Jul;16(7):775-86. doi: 10.1016/S1470-2045(15)00047-9. Epub 2015 Jun 9. PubMed 26071347 ↗
  • Gonzalez P, Hildesheim A, Herrero R, Katki H, Wacholder S, Porras C, Safaeian M, Jimenez S, Darragh TM, Cortes B, Befano B, Schiffman M, Carvajal L, Palefsky J, Schiller J, Ocampo R, Schussler J, Lowy D, Guillen D, Stoler MH, Quint W, Morales J, Avila C, Rodriguez AC, Kreimer AR; Costa Rica HPV Vaccine Trial (CVT) Group. Rationale and design of a long term follow-up study of women who did and did not receive HPV 16/18 vaccination in Guanacaste, Costa Rica. Vaccine. 2015 Apr 27;33(18):2141-51. doi: 10.1016/j.vaccine.2015.03.015. Epub 2015 Mar 18. PubMed 25796338 ↗
  • Lang Kuhs KA, Porras C, Schiller JT, Rodriguez AC, Schiffman M, Gonzalez P, Wacholder S, Ghosh A, Li Y, Lowy DR, Kreimer AR, Poncelet S, Schussler J, Quint W, van Doorn LJ, Sherman ME, Sidawy M, Herrero R, Hildesheim A, Safaeian M; Costa Rica Vaccine Trial Group. Effect of different human papillomavirus serological and DNA criteria on vaccine efficacy estimates. Am J Epidemiol. 2014 Sep 15;180(6):599-607. doi: 10.1093/aje/kwu168. Epub 2014 Aug 19. PubMed 25139208 ↗
  • Hildesheim A, Wacholder S, Catteau G, Struyf F, Dubin G, Herrero R; CVT Group. Efficacy of the HPV-16/18 vaccine: final according to protocol results from the blinded phase of the randomized Costa Rica HPV-16/18 vaccine trial. Vaccine. 2014 Sep 3;32(39):5087-97. doi: 10.1016/j.vaccine.2014.06.038. Epub 2014 Jul 10. PubMed 25018097 ↗
  • Lang Kuhs KA, Gonzalez P, Rodriguez AC, van Doorn LJ, Schiffman M, Struijk L, Chen S, Quint W, Lowy DR, Porras C, DelVecchio C, Jimenez S, Safaeian M, Schiller JT, Wacholder S, Herrero R, Hildesheim A, Kreimer AR; Costa Rica Vaccine Trial Group. Reduced prevalence of vulvar HPV16/18 infection among women who received the HPV16/18 bivalent vaccine: a nested analysis within the Costa Rica Vaccine Trial. J Infect Dis. 2014 Dec 15;210(12):1890-9. doi: 10.1093/infdis/jiu357. Epub 2014 Jun 23. PubMed 24958910 ↗
  • Lang Kuhs KA, Gonzalez P, Struijk L, Castro F, Hildesheim A, van Doorn LJ, Rodriguez AC, Schiffman M, Quint W, Lowy DR, Porras C, Delvecchio C, Katki HA, Jimenez S, Safaeian M, Schiller J, Solomon D, Wacholder S, Herrero R, Kreimer AR; Costa Rica Vaccine Trial Group. Prevalence of and risk factors for oral human papillomavirus among young women in Costa Rica. J Infect Dis. 2013 Nov 15;208(10):1643-52. doi: 10.1093/infdis/jit369. Epub 2013 Sep 6. PubMed 24014882 ↗
  • Herrero R, Quint W, Hildesheim A, Gonzalez P, Struijk L, Katki HA, Porras C, Schiffman M, Rodriguez AC, Solomon D, Jimenez S, Schiller JT, Lowy DR, van Doorn LJ, Wacholder S, Kreimer AR; CVT Vaccine Group. Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica. PLoS One. 2013 Jul 17;8(7):e68329. doi: 10.1371/journal.pone.0068329. Print 2013. PubMed 23873171 ↗
  • Clarke M, Schiffman M, Wacholder S, Rodriguez AC, Hildesheim A, Quint W; Costa Rican Vaccine Trial Group. A prospective study of absolute risk and determinants of human papillomavirus incidence among young women in Costa Rica. BMC Infect Dis. 2013 Jul 8;13:308. doi: 10.1186/1471-2334-13-308. PubMed 23834901 ↗
  • Castro FA, Quint W, Gonzalez P, Katki HA, Herrero R, van Doorn LJ, Schiffman M, Struijk L, Rodriguez AC, DelVecchio C, Lowy DR, Porras C, Jimenez S, Schiller J, Solomon D, Wacholder S, Hildesheim A, Kreimer AR; Costa Rica Vaccine Trial Group. Prevalence of and risk factors for anal human papillomavirus infection among young healthy women in Costa Rica. J Infect Dis. 2012 Oct 1;206(7):1103-10. doi: 10.1093/infdis/jis458. Epub 2012 Jul 30. PubMed 22850119 ↗
  • Kreimer AR, Gonzalez P, Katki HA, Porras C, Schiffman M, Rodriguez AC, Solomon D, Jimenez S, Schiller JT, Lowy DR, van Doorn LJ, Struijk L, Quint W, Chen S, Wacholder S, Hildesheim A, Herrero R; CVT Vaccine Group. Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the Costa Rica Vaccine Trial. Lancet Oncol. 2011 Sep;12(9):862-70. doi: 10.1016/S1470-2045(11)70213-3. Epub 2011 Aug 22. Erratum In: Lancet Oncol. 2011 Nov;12(12):1096. PubMed 21865087 ↗
  • Wacholder S, Chen BE, Wilcox A, Macones G, Gonzalez P, Befano B, Hildesheim A, Rodriguez AC, Solomon D, Herrero R, Schiffman M; CVT group. Risk of miscarriage with bivalent vaccine against human papillomavirus (HPV) types 16 and 18: pooled analysis of two randomised controlled trials. BMJ. 2010 Mar 2;340:c712. doi: 10.1136/bmj.c712. PubMed 20197322 ↗
  • Dessy FJ, Giannini SL, Bougelet CA, Kemp TJ, David MP, Poncelet SM, Pinto LA, Wettendorff MA. Correlation between direct ELISA, single epitope-based inhibition ELISA and pseudovirion-based neutralization assay for measuring anti-HPV-16 and anti-HPV-18 antibody response after vaccination with the AS04-adjuvanted HPV-16/18 cervical cancer vaccine. Hum Vaccin. 2008 Nov-Dec;4(6):425-34. doi: 10.4161/hv.4.6.6912. Epub 2008 Nov 11. PubMed 18948732 ↗
  • Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, Schiller JT, Gonzalez P, Dubin G, Porras C, Jimenez SE, Lowy DR; Costa Rican HPV Vaccine Trial Group. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial. JAMA. 2007 Aug 15;298(7):743-53. doi: 10.1001/jama.298.7.743. PubMed 17699008 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 8, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00128661
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Aug 10, 2005
Start date
Jun 30, 2004
Primary completion
Dec 31, 2010
Completion
Dec 31, 2010
Results posted
May 2, 2012
Last update
Mar 8, 2019

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline
View the source record on ClinicalTrials.gov ↗

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Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Uterine Cervical Neoplasms→

Other studies from this sponsor

GlaxoSmithKline

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