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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00128661
First received: August 8, 2005
Last updated: May 24, 2012
Last verified: May 2012
Results First Received: December 15, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions: Cervical Cancer
Precancerous Condition
Interventions: Biological: human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine
Biological: hepatitis A inactivated virus vaccine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Solicited symptoms were collected for 3730 and 3740 subjects instead of the 3727 and 3739 subjects who were randomized in the study in the Cervarix and the Havrix groups, respectively. These 4 sujects received both vaccines and were included in the denominator of both arm based on the actual vaccine type administered.

Reporting Groups
  Description
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.
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.

Participant Flow:   Overall Study
    Cervarix Group     Havrix Group  
STARTED     3727     3739  
COMPLETED     3453     3481  
NOT COMPLETED     274     258  
Adverse Event                 14                 11  
Lost to Follow-up                 10                 7  
Withdrawal by Subject                 243                 232  
Unspecified                 7                 8  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
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.
Total Total of all reporting groups

Baseline Measures
    Cervarix Group     Havrix Group     Total  
Number of Participants  
[units: participants]
  3727     3739     7466  
Age  
[units: Years]
Mean ± Standard Deviation
     
Years     21.1  ± 2.3     21.1  ± 2.3     21.1  ± 2.3  
Gender  
[units: Subjects]
     
Female     3727     3739     7466  
Male     0     0     0  



  Outcome Measures
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1.  Primary:   Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.   [ Time Frame: From Month 6 up to Month 48 ]

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

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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2635     2677  
Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.  
[units: Events]
   
HPV16 Associated CIN2+ (N=2464;2452)     1     9  
HPV18 Associated CIN2+ (N=2567; 2593)     0     2  
HPV16 and/or 18 Associated CIN2+ (N=2635;2677)     1     10  

No statistical analysis provided for Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.



2.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: From Month 6 up to Month 48 ]

Measure Type Secondary
Measure Title Number of Cervical Infection With HPV16 or HPV18.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2635     2677  
Number of Cervical Infection With HPV16 or HPV18.  
[units: Events]
   
HPV16 Cervical Infection (N=2464;2452)     50     251  
HPV18 Cervical Infection (N=2567;2593)     32     177  
HPV16 and/or 18 Cervical Infection (N=2635;2677)     78     387  

No statistical analysis provided for Number of Cervical Infection With HPV16 or HPV18.



3.  Secondary:   Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type   [ Time Frame: From Month 6 up to Month 48 ]

Measure Type Secondary
Measure Title Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type
Measure Description

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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2643     2697  
Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type  
[units: Events]
   
HPV16 Associated CIN2+ (N=2464;2452)     1     9  
HPV18 Associated CIN2+ (N=2567,2593)     0     2  
HPV31 Associated CIN2+ (N=2525;2546)     1     6  
HPV33 Associated CIN2+ (N=2596;2645)     0     3  
HPV35 Associated CIN2+ (N=2593;2631)     0     4  
HPV39 Associated CIN2+ (N=2528;2581)     0     0  
HPV45 Associated CIN2+ (N=2573;2622)     1     1  
HPV51 Associated CIN2+ (N=2453;2539)     1     6  
HPV52 Associated CIN2+ (N=2456;2505)     5     10  
HPV56 Associated CIN2+ (N=2524;2564)     1     5  
HPV58 Associated CIN2+ (N=2551;2595)     2     5  
HPV59 Associated CIN2+ (N=2576;2637)     3     3  
HPV68 and/or 73 Associated CIN2+ (N=2519;2576)     1     4  
Non 16/18 Onco HPV Associated CIN2+ (N=2643;2697)     11     28  
Any Oncogenic HPV Associated CIN2+ (N=2643;2697)     11     33  

No statistical analysis provided for Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type



4.  Secondary:   Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases   [ Time Frame: From Month 6 up to Month 48 ]

Measure Type Secondary
Measure Title Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases
Measure Description

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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2635     2677  
Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases  
[units: Events]
   
Persistent HPV16 Infection (N=2464,2452)     10     71  
Persistent HPV18 Infection (N=2567;2593)     0     37  
Persistent HPV16 and/or 18 Infection (N=2635;2677)     10     104  

No statistical analysis provided for Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases



5.  Secondary:   Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

Measure Type Secondary
Measure Title Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.
Measure Description

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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  196     157  
Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
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 )  

No statistical analysis provided for Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.



6.  Secondary:   Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

Measure Type Secondary
Measure Title Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort
Measure Description

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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  203     175  
Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
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 )  

No statistical analysis provided for Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort



7.  Secondary:   HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

Measure Type Secondary
Measure Title HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)
Measure Description

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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  196     158  
HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
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 )  

No statistical analysis provided for HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)



8.  Secondary:   HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

Measure Type Secondary
Measure Title HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)
Measure Description

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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  203     176  
HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
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 )  

No statistical analysis provided for HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)



9.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.   [ Time Frame: Within 60 minutes after vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  3730     3740  
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.  
[units: Subjects]
   
Any pain     1627     1610  
Grade 3 pain     25     20  
Any redness     544     501  
Grade 3 redness > 50 mm     0     2  
Any swelling     207     201  
Grade 3 swelling > 50 mm     0     1  

No statistical analysis provided for Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.



10.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.   [ Time Frame: Within 60 minutes after vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  3730     3740  
Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.  
[units: Subjects]
   
Any fatigue     512     502  
Grade 3 fatigue     6     5  
Any myalgia     257     232  
Grade 3 myalgia     0     1  
Any arthralgia     58     64  
Grade 3 arthralgia     0     1  
Any gastrointestinal     191     171  
Grade 3 gastrointestinal     0     0  
Any headache     714     718  
Grade 3 headache     2     0  
Any rash     15     17  
Grade 3 rash     0     0  
Any urticaria     19     21  
Grade 3 urticaria     0     0  
Fever (oral) >= 37.5°C     472     477  
Fever (oral) > 39.0°C     0     0  

No statistical analysis provided for Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.



11.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.   [ Time Frame: From Day 3 to Day 6 after vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  380     376  
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.  
[units: Subjects]
   
Any pain     202     74  
Grade 3 pain     0     0  
Any redness     6     1  
Grade 3 redness     1     0  
Any swelling     23     1  
Grade 3 swelling     7     0  

No statistical analysis provided for Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.



12.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.   [ Time Frame: From Day 3 to Day 6 after vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  380     376  
Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.  
[units: Subjects]
   
Any pain     214     189  
Grade 3 pain     2     0  
Any myalgia     250     211  
Grade 3 myalgia     1     0  
Any arthralgia     44     32  
Grade 3 arthralgia     0     0  
Any gastrointestinal     157     119  
Grade 3 gastrointestinal     0     1  
Any headache     247     242  
Grade 3 headache     1     2  
Any rash     31     26  
Grade 3 rash     0     0  
Any urticaria     3     1  
Grade 3 urticaria     0     0  
Fever (oral) >= 37.5°C     43     37  
Fever (oral) > 39.0°C     0     0  

No statistical analysis provided for Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.



13.  Secondary:   Number of Subjects Reporting Serious Adverse Events (SAEs).   [ Time Frame: During the entire study period (From Month 0 up to Month 48). ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Serious Adverse Events (SAEs).
Measure Description 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).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  3727     3739  
Number of Subjects Reporting Serious Adverse Events (SAEs).  
[units: Subjects]
  912     891  

No statistical analysis provided for Number of Subjects Reporting Serious Adverse Events (SAEs).



14.  Secondary:   Number of Subjects Reporting Unsolicited Adverse Events (AEs).   [ Time Frame: During the entire study period (From Month 0 up to Month 48). ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Unsolicited Adverse Events (AEs).
Measure Description 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).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  3727     3739  
Number of Subjects Reporting Unsolicited Adverse Events (AEs).  
[units: Subjects]
  3228     3254  

No statistical analysis provided for Number of Subjects Reporting Unsolicited Adverse Events (AEs).



15.  Secondary:   Number of Subjects With All Possible Pregnancy Outcomes   [ Time Frame: During the entire study period (From Month 0 up to Month 48). ]

Measure Type Secondary
Measure Title Number of Subjects With All Possible Pregnancy Outcomes
Measure Description 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).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed on the Total Vaccinated Cohort, on all pregnant subjects.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2123     2129  
Number of Subjects With All Possible Pregnancy Outcomes  
[units: subjects]
   
Pregnancy loss     317     294  
Pregnancy resolved alive     1756     1766  
Unresolved pregnancy     50     69  

No statistical analysis provided for Number of Subjects With All Possible Pregnancy Outcomes



16.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: During the first year of follow-up period ]

Measure Type Secondary
Measure Title Number of Cervical Infection With HPV16 or HPV18.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2380     2420  
Number of Cervical Infection With HPV16 or HPV18.  
[units: Events]
   
HPV16 Cervical Infection (N=2242;2232)     21     37  
HPV18 Cervical Infection (N=2330;2347)     7     29  
HPV16 and/or 18 Cervical Infection (N=2380;2420)     27     64  

No statistical analysis provided for Number of Cervical Infection With HPV16 or HPV18.



17.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: During the second year of follow-up period ]

Measure Type Secondary
Measure Title Number of Cervical Infection With HPV16 or HPV18.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2313     2349  
Number of Cervical Infection With HPV16 or HPV18.  
[units: Events]
   
HPV16 Cervical Infection (N=2170;2176)     10     77  
HPV18 Cervical Infection (N=2269;2307)     9     47  
HPV16 and/or 18 Cervical Infection (N=2313;2349)     18     117  

No statistical analysis provided for Number of Cervical Infection With HPV16 or HPV18.



18.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: During the third year of follow-up period ]

Measure Type Secondary
Measure Title Number of Cervical Infection With HPV16 or HPV18.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2232     2196  
Number of Cervical Infection With HPV16 or HPV18.  
[units: Events]
   
HPV16 Cervical Infection (N=2097;2026)     6     60  
HPV18 Cervical Infection (N=2200;2196)     6     44  
HPV16 and/or 18 Cervical Infection (N=2236;2166)     11     88  

No statistical analysis provided for Number of Cervical Infection With HPV16 or HPV18.



19.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: From the fourth year follow-up period ]

Measure Type Secondary
Measure Title Number of Cervical Infection With HPV16 or HPV18.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2421     2325  
Number of Cervical Infection With HPV16 or HPV18.  
[units: Events]
   
HPV16 Cervical Infection (N=2277;2139)     13     77  
HPV18 Cervical Infection (N=2389;2325)     10     57  
HPV16 and/or 18 Cervical Infection (N=2421;2261)     22     118  

No statistical analysis provided for Number of Cervical Infection With HPV16 or HPV18.



20.  Secondary:   Number of Subjects Reporting Unsolicited Adverse Events (AEs).   [ Time Frame: within 30 days (Days 0-29) after vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Unsolicited Adverse Events (AEs).
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
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.
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.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  3727     3739  
Number of Subjects Reporting Unsolicited Adverse Events (AEs).  
[units: Subjects]
  1638     1536  

No statistical analysis provided for Number of Subjects Reporting Unsolicited Adverse Events (AEs).




  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame Solicited AEs: within 60 minutes after vaccination for all subjects; From Day 3 to Day 6 post-vaccination in the subset. 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
Additional Description Solicited AEs were collected and tabulated for all subjects and for a 10% random subset of participants.

Reporting Groups
  Description
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.
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.

Serious Adverse Events
    Cervarix Group     Havrix Group  
Total, serious adverse events      
# participants affected / at risk     912/3727 (24.47%)     891/3739 (23.83%)  
Blood and lymphatic system disorders      
Anaemia of pregnancy *    
# participants affected / at risk     24/3727 (0.64%)     22/3739 (0.59%)  
Lymphadenitis *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Blood disorder *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Anaemia *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Anaemia haemolytic autoimmune *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Haemorrhagic anaemia *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Haemorrhagic disorder *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Thrombocytopenia *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Cardiac disorders      
Cardiovascular disorder *    
# participants affected / at risk     5/3727 (0.13%)     0/3739 (0.00%)  
Acute myocardial infarction *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Congestive cardiomyopathy *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Congenital, familial and genetic disorders      
Congenital flat feet *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Multiple congenital abnormalities *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Endocrine disorders      
Hyperthyroidism *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Eye disorders      
Eye degenerative disorder *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Retinal disorder *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Strabismus *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Ulcerative keratitis *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Gastrointestinal disorders      
Gastrointestinal disorder *    
# participants affected / at risk     9/3727 (0.24%)     9/3739 (0.24%)  
Pancreatitis acute *    
# participants affected / at risk     6/3727 (0.16%)     5/3739 (0.13%)  
Abdominal pain *    
# participants affected / at risk     6/3727 (0.16%)     3/3739 (0.08%)  
Irritable bowel syndrome *    
# participants affected / at risk     1/3727 (0.03%)     4/3739 (0.11%)  
Colitis ulcerative *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Appendix disorder *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Constipation *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Gastrointestinal inflammation *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Abdominal mass *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Abdominal pain lower *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Abdominal pain upper *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Crohn’s disease *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Duodenal ulcer haemorrhage *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Femoral hernia *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Gastritis *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Gastrointestinal haemorrhage *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Ileus paralytic *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Intestinal obstruction *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Pancreatitis chronic *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Peritoneal adhesions *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Peritoneal disorder *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Tooth ankylosis *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Tooth development disorder *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Tooth malformation *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
General disorders      
Pyrexia *    
# participants affected / at risk     5/3727 (0.13%)     1/3739 (0.03%)  
Eye complication associated with device *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Gait disturbance *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Hepatobiliary disorders      
Cholecystitis *    
# participants affected / at risk     26/3727 (0.70%)     19/3739 (0.51%)  
Cholelithiasis *    
# participants affected / at risk     22/3727 (0.59%)     9/3739 (0.24%)  
Liver disorder *    
# participants affected / at risk     0/3727 (0.00%)     3/3739 (0.08%)  
Bile duct stone *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Biliary cirrhosis *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Biliary tract disorder *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Immune system disorders      
Anaphylactic shock *    
# participants affected / at risk     0/3727 (0.00%)     2/3739 (0.05%)  
Rhesus incompatibility *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Infections and infestations      
Dengue fever *    
# participants affected / at risk     38/3727 (1.02%)     48/3739 (1.28%)  
Urinary tract infection *    
# participants affected / at risk     25/3727 (0.67%)     24/3739 (0.64%)  
Appendicitis *    
# participants affected / at risk     17/3727 (0.46%)     18/3739 (0.48%)  
Postoperative wound infection *    
# participants affected / at risk     12/3727 (0.32%)     12/3739 (0.32%)  
Postpartum sepsis *    
# participants affected / at risk     12/3727 (0.32%)     8/3739 (0.21%)  
Subcutaneous abscess *    
# participants affected / at risk     5/3727 (0.13%)     5/3739 (0.13%)  
Infectious peritonitis *    
# participants affected / at risk     6/3727 (0.16%)     2/3739 (0.05%)  
Pelvic inflammatory disease *    
# participants affected / at risk     3/3727 (0.08%)     3/3739 (0.08%)  
Cellulitis *    
# participants affected / at risk     1/3727 (0.03%)     4/3739 (0.11%)  
Salpingitis *    
# participants affected / at risk     3/3727 (0.08%)     2/3739 (0.05%)  
Staphylococcal infection *    
# participants affected / at risk     3/3727 (0.08%)     2/3739 (0.05%)  
Bronchopneumonia *    
# participants affected / at risk     1/3727 (0.03%)     3/3739 (0.08%)  
Viral infection *    
# participants affected / at risk     1/3727 (0.03%)     3/3739 (0.08%)  
Amniotic cavity infection *    
# participants affected / at risk     1/3727 (0.03%)     2/3739 (0.05%)  
Bartholin’s abscess *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Bronchitis *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Sexually transmitted disease *    
# participants affected / at risk     1/3727 (0.03%)     2/3739 (0.05%)  
HIV infection *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Otitis externa *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Parametritis *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Pneumonia *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Tooth abscess *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Vaginal infection *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Anal abscess *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Breast abscess *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Candida sepsis *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Chronic sinusitis *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Genital herpes *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Genitourinary tract infection *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Malaria *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Mastitis postpartum *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Meningitis viral *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Otitis media *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Pilonidal cyst *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Pneumonia viral *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Post procedural infection *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Pyoderma *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Skin infection *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Syphilis *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Varicella *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Vulval abscess *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Injury, poisoning and procedural complications      
Multiple injuries *    
# participants affected / at risk     3/3727 (0.08%)     10/3739 (0.27%)  
Injury *    
# participants affected / at risk     2/3727 (0.05%)     5/3739 (0.13%)  
Postoperative wound complication *    
# participants affected / at risk     4/3727 (0.11%)     3/3739 (0.08%)  
Concussion *    
# participants affected / at risk     2/3727 (0.05%)     3/3739 (0.08%)  
Lower limb fracture *    
# participants affected / at risk     2/3727 (0.05%)     2/3739 (0.05%)  
Open wound *    
# participants affected / at risk     3/3727 (0.08%)     1/3739 (0.03%)  
Humerus fracture *    
# participants affected / at risk     3/3727 (0.08%)     0/3739 (0.00%)  
Toxicity to various agents *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Lumbar vertebral fracture *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Multiple fractures *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Post procedural complication *    
# participants affected / at risk     0/3727 (0.00%)     2/3739 (0.05%)  
Road traffic accident *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Thermal burn *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Ulna fracture *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Venom poisoning *    
# participants affected / at risk     0/3727 (0.00%)     2/3739 (0.05%)  
Chemical poisoning *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Contusion *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Facial bones fracture *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Femoral neck fracture *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Foot fracture *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Foreign body *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Jaw fracture *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Muscle injury *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Muscle strain *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Radius fracture *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Tendon injury *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Tibia fracture *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Investigations      
Medical observation *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Metabolism and nutrition disorders      
Gestational diabetes *    
# participants affected / at risk     5/3727 (0.13%)     6/3739 (0.16%)  
Type 2 diabetes mellitus *    
# participants affected / at risk     3/3727 (0.08%)     1/3739 (0.03%)  
Diabetic ketoacidosis *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Hypokalaemia *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Musculoskeletal and connective tissue disorders      
Rheumatoid arthritis *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Systemic lupus erythematosus *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Back pain *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Intervertebral disc displacement *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Musculoskeletal pain *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Myalgia *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Tenosynovitis *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Benign ovarian tumour *    
# participants affected / at risk     11/3727 (0.30%)     7/3739 (0.19%)  
Thyroid cancer *    
# participants affected / at risk     1/3727 (0.03%)     3/3739 (0.08%)  
Ovarian cancer *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Uterine leiomyoma *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Benign hydatidiform mole *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Colon neoplasm *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Nasal sinus cancer *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Non-Hodgkin’s lymphoma *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Placental neoplasm *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Vulval neoplasm *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Nervous system disorders      
Migraine *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Convulsion *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Nervous system disorder *    
# participants affected / at risk     0/3727 (0.00%)     2/3739 (0.05%)  
Tension headache *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Autonomic nervous system imbalance *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Complicated migraine *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Epilepsy *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Headache *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Hydrocephalus *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Intracranial hypotension *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Vascular headache *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Pregnancy, puerperium and perinatal conditions      
Abortion spontaneous incomplete *    
# participants affected / at risk     134/3727 (3.60%)     108/3739 (2.89%)  
False labour *    
# participants affected / at risk     66/3727 (1.77%)     88/3739 (2.35%)  
Abortion spontaneous complete *    
# participants affected / at risk     64/3727 (1.72%)     64/3739 (1.71%)  
Abortion missed *    
# participants affected / at risk     59/3727 (1.58%)     63/3739 (1.68%)  
Foetal distress syndrome *    
# participants affected / at risk     57/3727 (1.53%)     64/3739 (1.71%)  
Uterine hypotonus *    
# participants affected / at risk     54/3727 (1.45%)     54/3739 (1.44%)  
Gestational hypertension *    
# participants affected / at risk     39/3727 (1.05%)     53/3739 (1.42%)  
Abortion threatened *    
# participants affected / at risk     42/3727 (1.13%)     37/3739 (0.99%)  
Cephalo-pelvic disproportion *    
# participants affected / at risk     33/3727 (0.89%)     45/3739 (1.20%)  
Breech presentation *    
# participants affected / at risk     40/3727 (1.07%)     33/3739 (0.88%)  
Pre-eclampsia *    
# participants affected / at risk     18/3727 (0.48%)     23/3739 (0.62%)  
Failed induction of labour *    
# participants affected / at risk     19/3727 (0.51%)     20/3739 (0.53%)  
Complication of pregnancy *    
# participants affected / at risk     18/3727 (0.48%)     19/3739 (0.51%)  
Intra-uterine death *    
# participants affected / at risk     16/3727 (0.43%)     18/3739 (0.48%)  
Foetal growth restriction *    
# participants affected / at risk     18/3727 (0.48%)     14/3739 (0.37%)  
Premature rupture of membranes *    
# participants affected / at risk     11/3727 (0.30%)     19/3739 (0.51%)  
Obstructed labour *    
# participants affected / at risk     13/3727 (0.35%)     15/3739 (0.40%)  
Abnormal product of conception *    
# participants affected / at risk     14/3727 (0.38%)     11/3739 (0.29%)  
Ectopic pregnancy *    
# participants affected / at risk     9/3727 (0.24%)     14/3739 (0.37%)  
Postpartum haemorrhage *    
# participants affected / at risk     13/3727 (0.35%)     7/3739 (0.19%)  
Oligohydramnios *    
# participants affected / at risk     11/3727 (0.30%)     8/3739 (0.21%)  
Premature separation of placenta *    
# participants affected / at risk     5/3727 (0.13%)     10/3739 (0.27%)  
Hyperemesis gravidarum *    
# participants affected / at risk     6/3727 (0.16%)     8/3739 (0.21%)  
Multiple pregnancy *    
# participants affected / at risk     8/3727 (0.21%)     2/3739 (0.05%)  
Placenta praevia haemorrhage *    
# participants affected / at risk     6/3727 (0.16%)     4/3739 (0.11%)  
Foetal disorder *    
# participants affected / at risk     7/3727 (0.19%)     2/3739 (0.05%)  
Large for dates baby *    
# participants affected / at risk     4/3727 (0.11%)     4/3739 (0.11%)  
Premature delivery *    
# participants affected / at risk     5/3727 (0.13%)     2/3739 (0.05%)  
Premature labour *    
# participants affected / at risk     2/3727 (0.05%)     4/3739 (0.11%)  
Transverse presentation *    
# participants affected / at risk     3/3727 (0.08%)     3/3739 (0.08%)  
Abortion incomplete *    
# participants affected / at risk     4/3727 (0.11%)     1/3739 (0.03%)  
Umbilical cord abnormality *    
# participants affected / at risk     3/3727 (0.08%)     2/3739 (0.05%)  
Eclampsia *    
# participants affected / at risk     1/3727 (0.03%)     3/3739 (0.08%)  
Retained placenta or membranes *    
# participants affected / at risk     4/3727 (0.11%)     0/3739 (0.00%)  
Abortion complicated *    
# participants affected / at risk     3/3727 (0.08%)     0/3739 (0.00%)  
Foetal malpresentation *    
# participants affected / at risk     0/3727 (0.00%)     3/3739 (0.08%)  
Placenta praevia *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Polyhydramnios *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Traumatic delivery *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Umbilical cord prolapse *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Abortion incomplete complicated *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Abortion spontaneous incomplete complicated *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Foetal malposition *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Intrapartum haemorrhage *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Pelvic haematoma obstetric *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Placental disorder *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Post abortion haemorrhage *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Postpartum disorder *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Previous caesarean section *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Prolonged labour *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Prolonged pregnancy *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Twin pregnancy *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Uterine inversion *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Psychiatric disorders      
Intentional self-injury *    
# participants affected / at risk     20/3727 (0.54%)     17/3739 (0.45%)  
Depression *    
# participants affected / at risk     5/3727 (0.13%)     3/3739 (0.08%)  
Mental disorder *    
# participants affected / at risk     5/3727 (0.13%)     3/3739 (0.08%)  
Post-traumatic stress disorder *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Acute psychosis *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Drug dependence *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Emotional disorder *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Psychotic disorder *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Renal and urinary disorders      
Calculus urinary *    
# participants affected / at risk     1/3727 (0.03%)     2/3739 (0.05%)  
Tubulointerstitial nephritis *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Nephrolithiasis *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Proteinuria *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Calculus ureteric *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Haematuria *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Reproductive system and breast disorders      
Ovarian cyst *    
# participants affected / at risk     5/3727 (0.13%)     6/3739 (0.16%)  
Uterine haemorrhage *    
# participants affected / at risk     5/3727 (0.13%)     5/3739 (0.13%)  
Menometrorrhagia *    
# participants affected / at risk     5/3727 (0.13%)     2/3739 (0.05%)  
Vaginal haemorrhage *    
# participants affected / at risk     3/3727 (0.08%)     4/3739 (0.11%)  
Breast inflammation *    
# participants affected / at risk     2/3727 (0.05%)     2/3739 (0.05%)  
Endometriosis *    
# participants affected / at risk     2/3727 (0.05%)     2/3739 (0.05%)  
Pelvic pain *    
# participants affected / at risk     1/3727 (0.03%)     3/3739 (0.08%)  
Perineal pain *    
# participants affected / at risk     1/3727 (0.03%)     3/3739 (0.08%)  
Genital disorder female *    
# participants affected / at risk     1/3727 (0.03%)     2/3739 (0.05%)  
Menstruation irregular *    
# participants affected / at risk     1/3727 (0.03%)     2/3739 (0.05%)  
Bartholin’s cyst *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Cervix disorder *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Uterine polyp *    
# participants affected / at risk     1/3727 (0.03%)     1/3739 (0.03%)  
Amenorrhoea *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Breast disorder *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Breast enlargement *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Cervical dysplasia *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Haematocolpos *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Haematosalpinx *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Ovarian torsion *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Ovulation pain *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Polycystic ovaries *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Polymenorrhagia *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Respiratory disorder *    
# participants affected / at risk     5/3727 (0.13%)     2/3739 (0.05%)  
Asthma *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Status asthmaticus *    
# participants affected / at risk     2/3727 (0.05%)     0/3739 (0.00%)  
Bronchitis chronic *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Dyspnoea *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Neonatal respiratory failure *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Pleural effusion *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Skin and subcutaneous tissue disorders      
Urticaria *    
# participants affected / at risk     0/3727 (0.00%)     2/3739 (0.05%)  
Granuloma skin *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Skin disorder *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Toxic skin eruption *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Social circumstances      
Physical assault *    
# participants affected / at risk     3/3727 (0.08%)     0/3739 (0.00%)  
Sexual abuse *    
# participants affected / at risk     1/3727 (0.03%)     0/3739 (0.00%)  
Surgical and medical procedures      
Caesarean section *    
# participants affected / at risk     56/3727 (1.50%)     59/3739 (1.58%)  
Therapeutic procedure *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Vascular disorders      
Hypertension *    
# participants affected / at risk     5/3727 (0.13%)     6/3739 (0.16%)  
Essential hypertension *    
# participants affected / at risk     4/3727 (0.11%)     1/3739 (0.03%)  
Circulatory collapse *    
# participants affected / at risk     2/3727 (0.05%)     1/3739 (0.03%)  
Phlebitis *    
# participants affected / at risk     0/3727 (0.00%)     2/3739 (0.05%)  
Varicose vein *    
# participants affected / at risk     0/3727 (0.00%)     2/3739 (0.05%)  
Embolism venous *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
Varicophlebitis *    
# participants affected / at risk     0/3727 (0.00%)     1/3739 (0.03%)  
* Events were collected by non-systematic assessment




  Other Adverse Events


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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.  


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:
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;29:2011-4. PMC3046309

Publications automatically indexed to this study:


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00128661     History of Changes
Obsolete Identifiers: NCT00344357
Other Study ID Numbers: CDR0000441189, NCI-04-C-N191, NCI-590299/009, GSK-590299/009
Study First Received: August 8, 2005
Results First Received: December 15, 2011
Last Updated: May 24, 2012
Health Authority: United States: Food and Drug Administration