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Human Papilloma Virus (HPV) Vaccine Efficacy Trial Against Cervical Pre-cancer in Young Adults With GlaxoSmithKline (GSK) Biologicals HPV-16/18

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00122681
Recruitment Status : Completed
First Posted : July 22, 2005
Results First Posted : January 20, 2010
Last Update Posted : August 14, 2017
Sponsor:
Information provided by (Responsible Party):

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition: Infections, Papillomavirus
Interventions: Biological: Cervarix™
Biological: Havrix™-based investigational formulation

  Participant Flow

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
Of the 18729 subjects enrolled in the study, 64 subjects were not vaccinated. Within the 18665 subjects vaccinated, 21 subjects from 1 center were excluded from all analyses because of potential data discrepancies identified at this center. As a result, a total of 18644 subjects are reported as started in the participant flow.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Participant Flow:   Overall Study
    Havrix Group   Cervarix Group
STARTED   9325   9319 
COMPLETED   7811   7798 
NOT COMPLETED   1514   1521 
Adverse Event                20                16 
Lost to Follow-up                1080                1097 
Protocol Violation                7                10 
Withdrawal by Subject                257                251 
Personal reasons                150                147 



  Baseline Characteristics

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
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.
Total Total of all reporting groups

Baseline Measures
   Havrix Group   Cervarix Group   Total 
Overall Participants Analyzed 
[Units: Participants]
 9325   9319   18644 
Age 
[Units: Years]
Mean (Standard Deviation)
 20.0  (3.12)   20.0  (3.10)   20.0  (3.11) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      9325 100.0%      9319 100.0%      18644 100.0% 
Male      0   0.0%      0   0.0%      0   0.0% 


  Outcome Measures

1.  Primary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post-dose 3 ]

Measure Type Primary
Measure Title Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Measure Description

CIN2+ was defined as CIN grades 2 and 3, endocervical adenocarcinoma in situ (AIS) and invasive cervical cancer.

Detection was done in:

  1. DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0).
  2. Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
Time Frame Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post-dose 3  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects who had received 3 doses of study vaccine, who had a normal or low-grade cytology (i.e. negative or Atypical Squamous Cells of Undetermined Significance (ASC-US) or Low-grade Squamous Intraepithelial Lesion (LSIL)) at Month 0.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7767   7814 
Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline) 
[Units: Subjects]
   
HPV-16/18, DNA- & sero- subjects (n= 7312, 7344)   56   4 
HPV-16, DNA- & sero- subjects (n= 6165, 6303)   46   2 
HPV-18, DNA- & sero- subjects (n= 6746, 6794)   15   2 
HPV-16/18, overall (n= 7767, 7814)   65   6 
HPV-16, overall (n= 7276, 7372)   54   4 
HPV-18, overall (n= 7583, 7645)   16   2 


Statistical Analysis 1 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 92.9
95% Confidence Interval 79.9 to 98.3
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ associated with HPV-16 or HPV-18 (by PCR) in HPV DNA negative and seronegative subjects at baseline, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event) expressed.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 95.7
95% Confidence Interval 82.9 to 99.6
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ associated with HPV-16 (by PCR) in HPV DNA negative and seronegative subjects at baseline, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event) expressed.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 86.7
95% Confidence Interval 39.7 to 98.7
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ associated with HPV-18 (by PCR) in HPV DNA negative and seronegative subjects at baseline, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event) expressed.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 90.8
95% Confidence Interval 78.1 to 96.9
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ for HPV-16 or HPV-18 (by PCR) in HPV DNA negative subjects at baseline, regardless of initial serostatus, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event).
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 92.7
95% Confidence Interval 79.3 to 98.2
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ for HPV-16 (by PCR) in HPV DNA negative subjects at baseline, regardless of initial serostatus, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event).
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 6 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 87.6
95% Confidence Interval 44.1 to 98.8
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ for HPV-18 (by PCR) in HPV DNA negative subjects at baseline, regardless of initial serostatus, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event).
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



2.  Primary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)   [ Time Frame: at Month 48 ]

Measure Type Primary
Measure Title Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Measure Description

CIN2+ was defined as CIN grades 2 and 3, endocervical adenocarcinoma in situ (AIS) and invasive cervical cancer.

Detection was done in subjects:

  1. DNA- and sero-: HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
  2. Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
Time Frame at Month 48  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects who had received 3 doses of study vaccine, who had a normal or low-grade cytology (i.e. negative or Atypical Squamous Cells of Undetermined Significance (ASC-US) or Low-grade Squamous Intraepithelial Lesion (LSIL)) at Month 0.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7760   7806 
Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline) 
[Units: Subjects]
   
HPV-16/18, DNA- & sero- subjects (n= 7305, 7338)   97   5 
HPV-16, DNA- & sero- subjects (n= 6160, 6296)   81   2 
HPV-18, DNA- & sero- subjects (n= 6739, 6789)   23   3 
HPV-16/18, overall (n= 7760, 7806)   108   7 
HPV-16, overall (n= 7267, 7364)   91   4 
HPV-18, overall (n= 7577, 7638)   24   3 


Statistical Analysis 1 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 94.9
95% Confidence Interval 87.7 to 98.4
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ associated with HPV-16 or HPV-18 (by PCR) in HPV DNA negative and seronegative subjects at baseline, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event) expressed
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 97.6
95% Confidence Interval 91.0 to 99.7
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ associated with HPV-16 (by PCR) in HPV DNA negative and seronegative subjects at baseline, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event) expressed
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 87.1
95% Confidence Interval 57.2 to 97.5
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ associated with HPV-18 (by PCR) in HPV DNA negative and seronegative subjects at baseline, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event) expressed.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 93.6
95% Confidence Interval 86.3 to 97.5
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ for HPV-16 or HPV-18 (by PCR) in HPV DNA negative subjects at baseline, regardless of initial serostatus, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event).
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 95.7
95% Confidence Interval 88.5 to 98.9
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ for HPV-16 (by PCR) in HPV DNA negative subjects at baseline, regardless of initial serostatus, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event).
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 6 for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
1-Rate Ratio [3] 87.6
95% Confidence Interval 59.2 to 97.6
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Vaccine efficacy against CIN2+ for HPV-18 (by PCR) in HPV DNA negative subjects at baseline, regardless of initial serostatus, using conditional exact method. The VE was defined as follows: VE = 1-Rate Ratio (RR), where RR = incidence rate in HPV Group (vaccine)/ incidence rate in HAV Group (control); Incidence rate = n/T(per 100); n= number of subjects reporting at least one event in each group and T(years) = sum of follow-up period (censored at the first occurrence of an event).
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



3.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

Measure Type Secondary
Measure Title Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
Measure Description

CIN1+ was defined as histopathologically-confirmed lesions including cervical intraepithelial neoplasia of grade 1 (CIN1), grade 2 (CIN2), grade 3 (CIN3), AIS and invasive cervical cancer.

Detection was done in subjects:

  1. DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
  2. Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline
Time Frame Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine and who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7767   7814 
Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen 
[Units: Subjects]
   
HPV-16/18, DNA- & sero- (n= 7312, 7344)   96   8 
HPV-16, DNA- & sero- (n= 6165, 6303)   70   5 
HPV-18, DNA- & sero- (n= 6746, 6794)   31   3 
HPV-16/18, overall (n= 7767, 7814)   111   12 
HPV-16, overall (n= 7276, 7372)   84   9 
HPV-18, overall (n= 7583, 7645)   32   3 

No statistical analysis provided for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen



4.  Secondary:   Number of Subjects Reporting Solicited Local and General Symptoms   [ Time Frame: Within 7 days after any vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Solicited Local and General Symptoms
Measure Description

Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include arthralgia, fatigue, fever (measured in degree celsius (°C) by axillary route), gastrointestinal symptoms, headache, myalgia, rash and urticaria.

Data are presented across the 3 doses.

Time Frame Within 7 days after any vaccination  

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.
Analysis was performed on a safety subset of the Total vaccinated cohort, which included vaccinated subjects from certain sites. Data are presented for the total subset (total), then stratified subject HPV-16/18 DNA & serostatus at baseline: DNA positive (DNA+) or negative (DNA-), ELISA seropositive (sero+) or seronegative (sero-).

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 3081   3078 
Number of Subjects Reporting Solicited Local and General Symptoms 
[Units: Subjects]
   
Pain, total (n= 3080, 3078)   2403   2787 
Pain, sero+ or DNA+ (n= 827, 830)   622   743 
Pain, sero- & DNA- (n=2219,2211)   1758   2013 
Pain, DNA+ (n= 212, 236)   166   219 
Redness, total (n= 3080, 3078)   851   1349 
Redness, sero+ or DNA+ (n= 827, 830)   211   335 
Redness, sero- & DNA- (n=2219,2211)   630   1005 
Redness, DNA+ (n= 212, 236)   56   96 
Swelling, total (n= 3080, 3078)   609   1293 
Swelling, sero+ or DNA+ (n= 827, 830)   145   325 
Swelling, sero- & DNA- (n=2219,2211)   454   959 
Swelling, DNA+ (n= 212, 236)   27   93 
Arthralgia, total (n=3081, 3078)   551   633 
Arthralgia, sero+ or DNA+ (n= 828, 830)   160   149 
Arthralgia, sero- & DNA- (n=2219,2211)   384   480 
Arthralgia, DNA+ (n= 212, 236)   39   58 
Fatigue, total (n=3081, 3078)   1652   1771 
Fatigue, sero+ or DNA+ (n= 828, 830)   415   443 
Fatigue, sero- & DNA- (n=2219,2211)   1215   1311 
Fatigue, DNA+ (n= 212, 236)   116   123 
Fever ≥ 37.5°C, total (n=3081, 3078)   342   385 
Fever ≥ 37.5°C, sero+ or DNA+ (n= 828, 830)   103   126 
Fever ≥ 37.5°C, sero- & DNA- (n=2219,2211)   236   254 
Fever ≥ 37.5°C, DNA+ (n= 212, 236)   23   37 
Gastro-intestinal symptoms, total (n=3081,3078)   847   856 
Gastro-intestinal,sero+ or DNA+ (n= 828, 830)   241   248 
Gastro-intestinal,sero- & DNA- (n=2219,221   595   601 
Gastro-intestinal symptoms, DNA+ (n= 212, 236)   64   72 
Headache, total (n= 3081, 3078)   1583   1668 
Headache, sero+ or DNA+ (n= 828, 830)   423   425 
Headache, sero- & DNA- (n=2219,2211)   1141   1223 
Headache, DNA+ (n= 212, 236)   112   125 
Myalgia, total (n= 3081, 3078)   1381   1607 
Myalgia, sero+ or DNA+ (n= 828, 830)   347   392 
Myalgia, sero- & DNA- (n=2219, 2211)   1019   1200 
Myalgia, DNA+ (n= 212, 236)   85   119 
Rash, total (n= 3081, 3078)   258   314 
Rash, sero+ or DNA+ (n= 828, 830)   72   91 
Rash, sero- & DNA- (n=2219, 2211)   182   221 
Rash, DNA+ (n= 212, 236)   19   29 
Urticaria, total (n= 3081, 3078)   244   300 
Urticaria, sero+ or DNA+ (n= 828, 830)   73   90 
Urticaria, sero- & DNA- (n=2219, 2211)   169   206 
Urticaria, DNA+ (n= 212, 236)   14   25 

No statistical analysis provided for Number of Subjects Reporting Solicited Local and General Symptoms



5.  Secondary:   Number of Subjects Reporting Unsolicited Adverse Events   [ Time Frame: Within 30 days after any vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Unsolicited Adverse Events
Measure Description Unsolicited adverse event (AE) covers any AE 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 after any vaccination  

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.
Analysis was performed on the Safety Subset of the Total Vaccinated Cohort and stratified according to initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 3187   3184 
Number of Subjects Reporting Unsolicited Adverse Events 
[Units: Subjects]
   
total (n=3187, 3184)   1466   1448 
sero+ DNA+ (n=858, 854)   400   386 
sero- DNA- (n=2289, 2290)   1048   1049 
DNA+ (n=222, 243)   111   122 

No statistical analysis provided for Number of Subjects Reporting Unsolicited Adverse Events



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

Measure Type Secondary
Measure Title Number of Subjects Reporting Serious Adverse Events (SAEs)
Measure Description SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time Frame Throughout the entire study period (Month 0 to Month 48)  

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.
Analysis was performed on the Total Vaccinated Cohort. The data are presented stratified by initial (Month 0) HPV-16/18 DNA status and according to HPV-16 or 18 serostatus (by ELISA).

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 9325   9319 
Number of Subjects Reporting Serious Adverse Events (SAEs) 
[Units: Subjects]
   
Total (n=9325, 9319)   829   835 
Sero + and DNA + (n=2419, 2409)   239   251 
Sero- and DNA- (n=6789, 6804)   587   576 
DNA+ (n=649, 690)   69   82 

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



7.  Secondary:   Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)   [ Time Frame: Throughout the entire study (Month 0 to 48) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)
Measure Description NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.
Time Frame Throughout the entire study (Month 0 to 48)  

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.
Analysis was performed on the Total Vaccinated Cohort and stratified according to initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 9325   9319 
Number of Subjects Reporting New Onset of Chronic Disease (NOCDs) 
[Units: Subjects]
   
Total (n= 9325, 9319)   307   285 
sero+ and DNA+ (n= 2419, 2409)   79   79 
sero- and DNA- (n= 6789, 6804)   225   201 
DNA+ (n= 649, 690)   21   24 

No statistical analysis provided for Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)



8.  Secondary:   Number of Subjects Reporting Medically Significant Conditions   [ Time Frame: Throughout entire study period (Month 0 to Month 48) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Medically Significant Conditions
Measure Description Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time Frame Throughout entire study period (Month 0 to Month 48)  

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.
Analysis was performed on the Total Vaccinated Cohort and stratified according to initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 9325   9319 
Number of Subjects Reporting Medically Significant Conditions 
[Units: Subjects]
   
Total (n=9325, 9319)   3378   3298 
sero+ DNA+ (n= 2419, 2409)   957   958 
sero- DNA- (n= 6789, 6804)   2378   2303 
DNA+ (n= 649, 690)   285   296 

No statistical analysis provided for Number of Subjects Reporting Medically Significant Conditions



9.  Secondary:   Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus   [ Time Frame: Throughout the entire study period (Month 0 to Month 48) ]

Measure Type Secondary
Measure Title Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus
Measure Description Pregnancy outcomes are normal infant, premature infant, abnormal infant, elective termination, therapeutic abortion, ectopic pregnancy, spontaneous abortion, still birth, lost to follow-up, no pregnancy/molar pregnancy, pregnancy ongoing.
Time Frame Throughout the entire study period (Month 0 to Month 48)  

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.
Analysis was performed on the Total Vaccinated Cohort and stratified according to initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 2257   2257 
Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus 
[Units: Subjects]
   
total (n=2257, 2257), normal infant   1671   1642 
total, premature birth   66   77 
total, abnormal infant   22   26 
total, elective termination   228   212 
total, therapeutic abortion   1   2 
total, ectopic pregnancy   9   20 
total, spontaneous abortion   195   205 
total, still birth   11   16 
total, lost to follow-up   42   41 
total, no pregnancy, molar pregnancy   1   4 
total, pregnancy ongoing   11   12 
sero- DNA- (n=1553, 1540), normal infant   1164   1159 
sero- DNA-, premature birth   42   37 
sero- DNA-, abnormal infant   15   18 
sero- DNA-, elective termination   162   138 
sero- DNA-, therapeutic abortion   0   1 
sero- DNA-, ectopic pregnancy   7   13 
sero- DNA-, spontaneous abortion   125   134 
sero- DNA -, still birth   8   10 
sero- DNA-, lost to follow-up   21   21 
sero- DNA-, no pregnancy, molar pregnancy   1   3 
sero- DNA-, pregnancy ongoing   8   6 
sero+ DNA+ (n=676, 685), normal infant   486   464 
sero+ DNA+, premature birth   24   39 
sero+ DNA+, abnormal infant   6   8 
sero+ DNA+, elective termination   62   67 
sero+ DNA+, therapeutic abortion   1   1 
sero+ DNA+, ectopic pregnancy   2   7 
sero+ DNA+, spontaneous abortion   68   67 
sero+ DNA+, still birth   3   6 
sero+ DNA+, lost to follow-up   21   19 
sero+ DNA+, no pregnancy, molar pregnancy   0   1 
sero+ DNA+, pregnancy ongoing   3   6 
DNA+(n=162, 199), normal infant   110   131 
DNA+, premature infant   5   19 
DNA+, abnormal infant   0   0 
DNA+, elective termination   21   18 
DNA+, therapeutic abortion   0   1 
DNA+, ectopic pregnancy   0   2 
DNA+, spontaneous abortion   18   21 
DNA+, still birth   0   1 
DNA+, lost to follow-up   7   5 
DNA+, no pregnancy, molar pregnancy   0   0 
DNA+, pregnancy ongoing   1   1 

No statistical analysis provided for Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus



10.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

Measure Type Secondary
Measure Title Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18
Measure Description

Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

Detection was done in subjects:

  1. DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
  2. Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline
Time Frame Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine and who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0. All subjects had at least 5 months of follow-up after Month 12

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7556   7619 
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 
[Units: Subjects]
   
HPV-16/18, DNA- & sero- (n= 7122, 7177)   488   29 
HPV-16, DNA- & sero- (n= 6018, 6163)   337   22 
HPV-18, DNA- & sero- (n= 6567, 6642)   184   7 
HPV-16/18, overall (n= 7556, 7619)   540   37 
HPV-16, overall (n= 7085, 7196)   380   29 
HPV-18, overall (n= 7377, 7457)   195   8 

No statistical analysis provided for Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18



11.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18   [ Time Frame: at Month 48 ]

Measure Type Secondary
Measure Title Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18
Measure Description

Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

Detection was done in subjects:

  1. DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
  2. Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
Time Frame at Month 48  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine, who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0. All subjects had at least 5 months of follow-up after Month 12

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7572   7626 
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 
[Units: Subjects]
   
HPV-16/18, DNA- & sero- (n= 7137, 7182)   588   35 
HPV-16, DNA- & sero- (n= 6029, 6165)   418   24 
HPV-18, DNA- & sero- (n= 6581, 6649)   212   11 
HPV-16/18, overall (n= 7572, 7626)   654   45 
HPV-16, overall (n= 7099, 7202)   473   31 
HPV-18, overall (n= 7394, 7465)   227   14 

No statistical analysis provided for Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18



12.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

Measure Type Secondary
Measure Title Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types
Measure Description

Oncogenic types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Detection was done in subjects who were HPV DNA negative at baseline regardless of initial serostatus.

HRW-HPV= All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV= High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68

Time Frame Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine and who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0. All subjects had at least 5 months of follow-up after Month 12.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7640   7665 
Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types 
[Units: Subjects]
   
HPV-16 (n= 7085, 7196)   380   29 
HPV-18 (n= 7377, 7457)   195   8 
HPV-31 (n= 7398, 7394)   199   45 
HPV-33 (n= 7496, 7527)   100   55 
HPV-35 (n= 7553, 7572)   43   55 
HPV- 39 (n= 7411, 7423)   149   147 
HPV-45 (n= 7540, 7587)   79   19 
HPV-51 (n= 7152, 7188)   354   304 
HPV-52 (n= 7221, 7280)   315   293 
HPV-56 (n= 7435, 7460)   174   182 
HPV-58 (n= 7494, 7512)   101   111 
HPV-59 (n= 7514, 7528)   59   56 
HPV-66 (n= 7358, 7405)   178   168 
HPV-68 (n= 7409, 7441)   134   138 
HRW-HPV (n= 7640, 7665)   1351   1207 
HR-HPV (n= 7640, 7665)   1607   1233 

No statistical analysis provided for Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types



13.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types   [ Time Frame: at Month 48 ]

Measure Type Secondary
Measure Title Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types
Measure Description

Oncogenic types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Detection was done in subjects who were HPV DNA negative at baseline regardless of initial serostatus.

HRW-HPV = All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV = High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68

Time Frame at Month 48  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine and who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0. All subjects had at least 5 months of follow-up after Month 12.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7656   7672 
Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types 
[Units: Subjects]
   
HPV-16 (n= 7099, 7202)   473   31 
HPV-18 (n= 7394, 7465)   227   14 
HPV-31 (n= 7414, 7400)   247   58 
HPV-33 (n= 7513, 7534)   117   65 
HPV-35 (n= 7569, 7579)   56   67 
HPV-39 (n= 7428, 7429)   184   175 
HPV-45 (n= 7556, 7594)   90   24 
HPV-51 (n= 7165, 7190)   416   349 
HPV-52 (n= 7237, 7289)   374   346 
HPV-56 (n= 7451, 7467)   215   226 
HPV-58 (n= 7511, 7518)   122   144 
HPV-59 (n= 7530, 7536)   68   73 
HPV-66 (n= 7375, 7412)   215   211 
HPV-68 (n= 7424, 7450)   169   165 
HRW-HPV (n= 7656, 7672)   1556   1399 
HR-HPV (n= 7656, 7672)   1837   1424 

No statistical analysis provided for Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types



14.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

Measure Type Secondary
Measure Title Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
Measure Description

CIN1+ was defined as histopathologically-confirmed lesions including cervical intraepithelial neoplasia of grade 1 (CIN1), grade 2 (CIN2), grade 3 (CIN3), AIS and invasive cervical cancer.

Detection was done in subjects:

  1. DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
  2. Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline
Time Frame at Month 48  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7760   7806 
Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen 
[Units: Subjects]
   
HPV-16/18, DNA- & sero- (n= 7305, 7338)   165   12 
HPV-16, DNA- & sero- (n= 6160, 6296)   124   6 
HPV-18, DNA- & sero- (n= 6739, 6789)   52   6 
HPV-16/18, overall (n= 7760, 7806)   182   16 
HPV-16, overall (n= 7267, 7364)   140   10 
HPV-18, overall (n= 7577, 7638)   53   6 

No statistical analysis provided for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen



15.  Secondary:   Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

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

Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type (by PCR) over a 12-month interval (evaluations were planned at approximately 6-month intervals).

Detection was done in subjects:

  1. DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
  2. Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline
Time Frame Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine and who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0. All subjects had at least 10 months of follow-up after Month 12

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7404   7466 
Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18 
[Units: Subjects]
   
HPV-16/18, DNA- & sero- (n= 6984, 7035)   227   20 
HPV-16, DNA- & sero- (n= 5903, 6052)   171   17 
HPV-18, DNA- & sero- (n= 6440, 6508)   66   3 
HPV-16/18, overall (n= 7404, 7466)   252   21 
HPV-16, overall (n= 6941, 7057)   192   18 
HPV-18, overall (n= 7231, 7307)   70   3 

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



16.  Secondary:   Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18   [ Time Frame: at Month 48 ]

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

Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type (by PCR) over a 12-month interval (evaluations were planned at approximately 6-month intervals).

Detection was done in subjects:

  1. DNA- and sero-: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and sero- for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0)
  2. Overall: subjects HPV DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline
Time Frame at Month 48  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine and who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0. All subjects had at least 10 months of follow-up after Month 12.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7461   7517 
Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18 
[Units: Subjects]
   
HPV-16/18, DNA- & sero- (n= 7038, 7082)   354   26 
HPV-16, DNA- & sero- (n= 5949, 6089)   269   19 
HPV-18, DNA- & sero- (n= 6490, 6552)   98   7 
HPV-16/18, overall (n= 7461, 7517)   388   28 
HPV-16, overall (n= 6996, 7103)   300   20 
HPV-18, overall (n= 7288, 7356)   103   8 

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



17.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

Measure Type Secondary
Measure Title Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
Measure Description

Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Detection was done in subjects who were HPV DNA negative at baseline regardless of initial serostatus.

Time Frame Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine and who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7764   7782 
Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen 
[Units: Subjects]
   
HPV-16 (n= 7276, 7372)   84   9 
HPV-18 (n= 7583, 7645)   32   3 
HPV-31 (n= 7599, 7583)   49   6 
HPV-33 (n= 7706, 7720)   34   21 
HPV-35 (n= 7764, 7768)   13   4 
HPV-39 (n= 7614, 7609)   29   18 
HPV-45 (n= 7745, 7782)   12   1 
HPV-51 (n= 7352, 7363)   57   42 
HPV-52 (n= 7414, 7461)   44   29 
HPV-56 (n= 7638, 7646)   26   23 
HPV-58 (n= 7702, 7709)   34   11 
HPV-59 (n=7723, 7720)   12   8 
HPV-66 (n= 7564, 7592)   24   15 
HPV-68 (n= 7614, 7633)   22   11 

No statistical analysis provided for Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen



18.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

Measure Type Secondary
Measure Title Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
Measure Description

Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Detection was done in subjects who were HPV DNA negative at baseline regardless of initial serostatus.

Time Frame at Month 48  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine and who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7757   7774 
Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen 
[Units: Subjects]
   
HPV-16 (n= 7267, 7364)   140   10 
HPV-18 (n= 7577, 7638)   53   6 
HPV-31 (n= 7592, 7575)   79   11 
HPV-33 (n= 7700, 7712)   66   23 
HPV-35 (n= 7757, 7760)   18   7 
HPV-39 (n= 7608, 7602)   48   26 
HPV-45 (n= 7738, 7774)   25   3 
HPV-51 (n= 7341, 7356)   96   61 
HPV-52 (n= 7409, 7455)   81   51 
HPV-56 (n= 7631, 7638)   45   36 
HPV-58 (n= 7696, 7701)   42   25 
HPV-59 (n=7716, 7713)   20   13 
HPV-66 (n= 7559, 7583)   44   30 
HPV-68 (n= 7606, 7626)   43   28 

No statistical analysis provided for Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen



19.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

Measure Type Secondary
Measure Title Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
Measure Description

CIN2+ was defined as histopathologically-confirmed lesions including cervical intraepithelial neoplasia of grade 2 (CIN2), grade 3 (CIN3), AIS and invasive cervical cancer.

Oncogenic types detected included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Detection was done in subjects who were HPV DNA negative at baseline, regardless of initial serostatus.

Time Frame Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine and who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7764   7782 
Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen 
[Units: Subjects]
   
HPV-16 (n= 7276, 7372)   54   4 
HPV-18 (n= 7583, 7645)   16   2 
HPV-31 (n= 7599, 7583)   25   2 
HPV-33 (n= 7706, 7720)   25   12 
HPV-35 (n= 7764, 7768)   6   1 
HPV-39 (n= 7614, 7609)   10   3 
HPV-45 (n= 7745, 7782)   4   0 
HPV-51 (n= 7352, 7363)   27   10 
HPV-52 (n= 7414, 7461)   14   12 
HPV-56 (n= 7638, 7646)   10   4 
HPV-58 (n=7702, 7709)   17   6 
HPV-59 (n= 7723, 7720)   4   1 
HPV-66 (n= 7564, 7592)   10   4 
HPV-68 (n= 7614, 7633)   11   5 

No statistical analysis provided for Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen



20.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

Measure Type Secondary
Measure Title Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
Measure Description

CIN2+ was defined as histopathologically-confirmed lesions including cervical intraepithelial neoplasia of grade 2 (CIN2), grade 3 (CIN3), AIS and invasive cervical cancer.

Oncogenic types detected included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Detection was done in subjects who were HPV DNA negative at baseline, regardless of initial serostatus.

Time Frame at Month 48  

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.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all evaluable subjects, who had received 3 doses of study vaccine and who had a normal or low-grade cytology (i.e. negative or ASC-US or LSIL) at Month 0.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 7757   7774 
Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen 
[Units: Subjects]
   
HPV-16 (n= 7267, 7364)   91   4 
HPV-18 (n= 7577, 7638)   24   3 
HPV-31 (n= 7592, 7575)   40   5 
HPV-33 (n= 7700, 7712)   41   13 
HPV-35 (n= 7757, 7760)   8   3 
HPV-39 (n= 7608, 7602)   16   4 
HPV-45 (n= 7738, 7774)   11   2 
HPV-51 (n= 7341, 7356)   46   21 
HPV-52 (n= 7409, 7455)   33   24 
HPV-56 (n= 7631, 7638)   13   7 
HPV-58 (n=7696, 7701)   21   15 
HPV-59 (n= 7716, 7713)   5   1 
HPV-66 (n= 7559, 7583)   16   7 
HPV-68 (n= 7606, 7626)   15   11 

No statistical analysis provided for Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen



21.  Secondary:   Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18 Antibody Titers by ELISA in the Immunogenicity Subset, According to Initial (Month 0) HPV-16 or HPV-18 Serostatus   [ Time Frame: At Months 6, 7, 12, 24, 36 & 48 ]

Measure Type Secondary
Measure Title Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18 Antibody Titers by ELISA in the Immunogenicity Subset, According to Initial (Month 0) HPV-16 or HPV-18 Serostatus
Measure Description

Cut-off values assessed for seropositivity include 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.

Results are presented for the total group and stratified according to initial (Month 0) HPV-16 or HPV-18 serostatus by ELISA - seronegative (sero-) or seropositive (sero+)

Time Frame At Months 6, 7, 12, 24, 36 & 48  

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 analyses were performed on the ATP cohort for immunogenicity on evaluable subjects for whom immunogenicity data were available.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 898   1036 
Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18 Antibody Titers by ELISA in the Immunogenicity Subset, According to Initial (Month 0) HPV-16 or HPV-18 Serostatus 
[Units: Subjects]
   
HPV-16, sero-, pre-vaccination (n= 750, 872)   0   0 
HPV-16, sero-, Month 6 (n= 738, 865)   41   864 
HPV-16, sero-, Month 7 (n= 740, 865)   34   861 
HPV-16, sero-, Month 12 (n= 719, 839)   30   837 
HPV-16, sero-, Month 24 (n= 672, 797)   33   796 
HPV-16, sero-, Month 36 (n= 664, 784)   35   784 
HPV-16, sero-, Month 48 (n= 603, 746)   47   746 
HPV-16, sero+, pre-vaccination (n= 147, 164)   147   164 
HPV-16, sero+, Month 6 (n= 139, 162)   119   161 
HPV-16, sero+, Month 7 (n= 139, 163)   106   162 
HPV-16, sero+, Month 12 (n= 134, 154)   101   154 
HPV-16, sero+, Month 24 (n= 138, 146)   96   146 
HPV-16, sero+, Month 36 (n= 127, 142)   88   142 
HPV-16, sero+, Month 48 (n= 118, 145)   85   145 
HPV-16, total, pre-vaccination (n= 897, 1036)   147   164 
HPV-16, total, Month 6 (n= 877, 1027)   160   1025 
HPV-16, total, Month 7 (n= 879, 1028)   140   1023 
HPV-16, total, Month 12 (n= 853, 993)   131   991 
HPV-16, total, Month 24 (n= 810, 943)   129   942 
HPV-16, total, Month 36 (n= 791, 926)   123   926 
HPV-16, total, Month 48 (n= 721, 891)   132   891 
HPV-18, sero-, pre-vaccination (n= 790,939)   0   0 
HPV-18, sero-, Month 6 (n= 771, 930)   29   927 
HPV-18, sero-, Month 7 (n= 772, 930)   32   925 
HPV-18, sero-, Month 12 (n= 748, 901)   36   901 
HPV-18, sero-, Month 24 (n= 698, 854)   37   853 
HPV-18, sero-, Month 36 (n= 691, 841)   31   841 
HPV-18, sero-, Month 48 (n= 633, 806)   32   804 
HPV-18, sero+, pre-vaccination (n= 108, 97)   108   97 
HPV-18, sero+, Month 6 (n= 105, 97)   90   96 
HPV-18, sero+, Month 7 (n= 105, 97)   90   97 
HPV-18, sero+, Month 12 (n= 106, 92)   89   92 
HPV-18, sero+, Month 24 (n= 102, 89)   84   89 
HPV-18, sero+, Month 36 (n= 98, 86)   73   86 
HPV-18, sero+, Month 48 (n= 91, 86)   70   86 
HPV-18, total, pre-vaccination (n= 898, 1036)   108   97 
HPV-18, total, Month 6 (n= 876, 1027)   119   1023 
HPV-18, total, Month 7 (n= 877, 1027)   122   1022 
HPV-18, total, Month 12 (n= 854, 993)   125   993 
HPV-18, total, Month 24 (n= 800, 943)   121   942 
HPV-18, total, Month 36 (n= 789, 927)   104   927 
HPV-18, total, Month 48 (n= 724, 892)   102   890 

No statistical analysis provided for Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18 Antibody Titers by ELISA in the Immunogenicity Subset, According to Initial (Month 0) HPV-16 or HPV-18 Serostatus



22.  Secondary:   Anti-HPV-16 and Anti-HPV-18 ELISA Titers in the Immunogenicity Subset   [ Time Frame: At Months 6, 7, 12, 24, 36 and 48 ]

Measure Type Secondary
Measure Title Anti-HPV-16 and Anti-HPV-18 ELISA Titers in the Immunogenicity Subset
Measure Description

Titers are given as Geometric Mean Titers (GMTs) expressed as ELISA Units per milliliter (EL.U/mL).

GMTs are presented for the total group and also stratified according to initial (Month 0) HPV-16 or HPV-18 serostatus by ELISA [seronegative (sero-) or seropositive (sero+)].

Time Frame At Months 6, 7, 12, 24, 36 and 48  

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 analyses were performed on the ATP cohort for immunogenicity for whom immunogenicity data were available.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 898   1036 
Anti-HPV-16 and Anti-HPV-18 ELISA Titers in the Immunogenicity Subset 
[Units: EL.U/mL]
Geometric Mean (95% Confidence Interval)
   
Anti-HPV-16, sero-, pre-vaccination (n= 750, 872)   4.0 
 (4.0 to 4.0) 
 4.0 
 (4.0 to 4.0) 
Anti-HPV-16, sero-, Month 6 (n= 738, 865)   4.4 
 (4.2 to 4.5) 
 630.7 
 (591.6 to 672.4) 
Anti-HPV-16, sero-, Month 7 (n= 740, 865)   4.4 
 (4.2 to 4.6) 
 9206.5 
 (8609.4 to 9845.1) 
Anti-HPV-16, sero-, Month 12 (n= 719, 839)   4.3 
 (4.2 to 4.4) 
 3281.1 
 (3064.5 to 3513.0) 
Anti-HPV-16, sero-, Month 24 (n= 672, 797)   4.4 
 (4.2 to 4.5) 
 1592.0 
 (1491.6 to 1699.2) 
Anti-HPV-16, sero-, Month 36 (n= 664, 784)   4.4 
 (4.2 to 4.5) 
 1265.1 
 (1184.8 to 1350.8) 
Anti-HPV-16, sero-, Month 48 (n= 603, 746)   4.6 
 (4.4 to 4.8) 
 1174.3 
 (1096.1 to 1258.0) 
Anti-HPV-16, sero+, pre-vaccination (n= 147, 164)   29.7 
 (25.0 to 35.4) 
 28.9 
 (24.7 to 33.8) 
Anti-HPV-16, sero+, Month 6 (n= 139, 162)   24.4 
 (19.9 to 29.8) 
 1256.9 
 (1030.1 to 1533.7) 
Anti-HPV-16, sero+, Month 7 (n= 139, 163)   21.7 
 (17.4 to 27.0) 
 6423.1 
 (5486.3 to 7520.0) 
Anti-HPV-16, sero+, Month 12 (n= 134, 154)   20.2 
 (16.3 to 25.1) 
 2909.6 
 (2504.3 to 3380.4) 
Anti-HPV-16, sero+, Month 24 (n= 138, 146)   18.7 
 (15.0 to 23.2) 
 1573.2 
 (1356.7 to 1824.2) 
Anti-HPV-16, sero+, Month 36 (n= 127, 142)   17.7 
 (14.0 to 22.2) 
 1244.3 
 (1068.9 to 1448.4) 
Anti-HPV-16, sero+, Month 48 (n= 118, 145)   18.3 
 (14.5 to 23.0) 
 1115.9 
 (959.6 to 1297.7) 
Anti-HPV-16, total, pre-vaccination (n= 897, 1036)   5.6 
 (5.3 to 5.9) 
 5.5 
 (5.2 to 5.8) 
Anti-HPV-16, total, Month 6 (n= 877, 1027)   5.7 
 (5.4 to 6.1) 
 703.2 
 (659.5 to 749.7) 
Anti-HPV-16, total, Month 7 (n= 879, 1028)   5.6 
 (5.3 to 6.0) 
 8695.7 
 (8171.9 to 9253.1) 
Anti-HPV-16, total, Month 12 (n= 853, 993)   5.5 
 (5.2 to 5.8) 
 3220.5 
 (3026.4 to 3427.1) 
Anti-HPV-16, total, Month 24 (n= 810, 943)   5.6 
 (5.3 to 5.9) 
 1589.1 
 (1497.2 to 1686.6) 
Anti-HPV-16, total, Month 36 (n=791, 926)   5.4 
 (5.1 to 5.8) 
 1261.9 
 (1188.3 to 1340.0) 
Anti-HPV-16, total, Month 48 (n=721, 891)   5.7 
 (5.4 to 6.1) 
 1164.6 
 (1093.9 to 1239.8) 
Anti-HPV-18, sero-, pre-vaccination (n=790, 939)   3.5 
 (3.5 to 3.5) 
 3.5 
 (3.5 to 3.5) 
Anti-HPV-18, sero-, Month 6 (n=771, 930)   3.7 
 (3.6 to 3.8) 
 542.7 
 (510.2 to 577.2) 
Anti-HPV-18, sero-, Month 7 (n= 772, 930)   3.8 
 (3.6 to 3.9) 
 4741.3 
 (4452.2 to 5049.1) 
Anti-HPV-18, sero-, Month 12 (n= 748, 901)   3.8 
 (3.7 to 3.9) 
 1521.7 
 (1431.0 to 1618.1) 
Anti-HPV-18, sero-, Month 24 (n= 698, 854)   3.8 
 (3.7 to 3.9) 
 704.4 
 (658.4 to 753.8) 
Anti-HPV-18, sero-, Month 36 (n= 691, 841)   3.7 
 (3.6 to 3.8) 
 534.3 
 (498.9 to 572.1) 
Anti-HPV-18, sero-, Month 48 (n= 633, 806)   3.8 
 (3.7 to 3.9) 
 476.2 
 (443.2 to 511.6) 
Anti-HPV-18, sero+, pre-vaccination (n= 108, 97)   23.4 
 (18.9 to 29.1) 
 24.8 
 (20.1 to 30.6) 
Anti-HPV-18, sero+, Month 6 (n= 105, 97)   19.6 
 (15.2 to 25.4) 
 903.8 
 (714.0 to 1144.2) 
Anti-HPV-18, sero+, Month 7 (n= 105, 97)   20.8 
 (16.2 to 26.8) 
 4135.7 
 (3548.6 to 4819.9) 
Anti-HPV-18, sero+, Month 12 (n= 106, 92)   19.9 
 (15.5 to 25.5) 
 1509.5 
 (1271.3 to 1792.3) 
Anti-HPV-18, sero+, Month 24 (n= 102, 89)   18.9 
 (14.6 to 24.4) 
 745.6 
 (620.1 to 896.6) 
Anti-HPV-18, sero+, Month 36 (n= 98, 86)   16.8 
 (12.8 to 22.1) 
 580.9 
 (475.0 to 710.4) 
Anti-HPV-18, sero+, Month 48 (n= 91, 86)   16.5 
 (12.6 to 21.6) 
 510.6 
 (415.7 to 627.2) 
Anti-HPV-18, total, pre-vaccination (n= 898, 1036)   4.4 
 (4.2 to 4.6) 
 4.2 
 (4.0 to 4.4) 
Anti-HPV-18, total, Month 6 (n= 876, 1027)   4.5 
 (4.3 to 4.8) 
 569.5 
 (536.0 to 605.1) 
Anti-HPV-18, total, Month 7 (n= 877, 1027)   4.6 
 (4.4 to 4.9) 
 4680.5 
 (4413.4 to 4963.7) 
Anti-HPV-18, total, Month 12 (n= 854, 993)   4.6 
 (4.4 to 4.9) 
 1520.5 
 (1435.0 to 1611.2) 
Anti-HPV-18, total, Month 24 (n= 800, 943)   4.7 
 (4.4 to 4.9) 
 708.2 
 (664.6 to 754.8) 
Anti-HPV-18, total, Month 36 (n=789, 927)   4.5 
 (4.3 to 4.8) 
 538.5 
 (504.7 to 574.5) 
Anti-HPV-18, total, Month 48 (n=724, 892)   4.6 
 (4.3 to 4.8) 
 479.4 
 (448.0 to 513.0) 

No statistical analysis provided for Anti-HPV-16 and Anti-HPV-18 ELISA Titers in the Immunogenicity Subset



23.  Secondary:   HPV-16 and HPV-18 Seroconversion (V5/J4 Monoclonal Inhibition Test)   [ Time Frame: Month 0, 7, 12 and 24 ]

Measure Type Secondary
Measure Title HPV-16 and HPV-18 Seroconversion (V5/J4 Monoclonal Inhibition Test)
Measure Description

HPV-16 V5 cut-off was defined as greater than or equal to 41 ELU/mL. Only seronegative subjects were analysed. Seronegative subjects are subjects who had an antibody titer of less than 41 ELU/mL before vaccination.

HPV-18 J4 cut-off was defined as greater than or equal to 110 EL.U/mL. Both seropositive and seronegative subjects were included in the analysis. Seropositive subjects were subjects with an antibody titer of greater than or equal to 110 EL.U/mL. Seronegative subjects were subjects with an antibody titer less than 110 EL.U/mL.

Time Frame Month 0, 7, 12 and 24  

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.
Analyses was performed on the Total Vaccinated Cohort on subjects with available results.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 17   17 
HPV-16 and HPV-18 Seroconversion (V5/J4 Monoclonal Inhibition Test) 
[Units: Subjects]
   
pre-vaccination V5 HPV-16 (n= 17,17)   0   0 
Month 7 V5 HPV-16 (n= 17,17)   0   17 
Month 12 V5 HPV-16 (n= 5, 2)   0   2 
Month 24 V5 HPV-16 (n=17, 17)   0   17 
pre-vaccination J4 HPV-18 (n= 17, 17)   0   1 
Month 7 J4 HPV-18 (n= 17,17)   0   17 
Month 12 J4 HPV-18 (n= 5, 2)   1   1 
Month 24 V5 HPV-18 (n=17, 17)   1   11 

No statistical analysis provided for HPV-16 and HPV-18 Seroconversion (V5/J4 Monoclonal Inhibition Test)



24.  Secondary:   HPV-16 and HPV-18 Geometric Mean Titers (GMT) (V5/J4 Monoclonal Inhibition Test)   [ Time Frame: Month 0, 7, 12, 24 ]

Measure Type Secondary
Measure Title HPV-16 and HPV-18 Geometric Mean Titers (GMT) (V5/J4 Monoclonal Inhibition Test)
Measure Description Titers were expressed as GMTs in ELISA units per milliliter (EL.U/mL).
Time Frame Month 0, 7, 12, 24  

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 analyses was performed on the Total Vaccinated cohort on subjects with available results.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 17   17 
HPV-16 and HPV-18 Geometric Mean Titers (GMT) (V5/J4 Monoclonal Inhibition Test) 
[Units: EL.U/mL]
Geometric Mean (95% Confidence Interval)
   
pre-vaccination V5 HPV-16 (n= 17,17)   20.5 
 (20.5 to 20.5) 
 20.5 
 (20.5 to 20.5) 
Month 7 V5 HPV-16 (n= 17,17)   20.5 
 (20.5 to 20.5) 
 816.7 
 (472.5 to 1411.4) 
Month 12 V5 HPV-16 (n= 5, 2)   20.5 
 (20.5 to 20.5) 
 173.5 
 (25.1 to 1199.3) 
Month 24 V5 HPV-16 (n=17, 17)   20.5 
 (20.5 to 20.5) 
 163.3 
 (104.0 to 256.6) 
pre-vaccination J4 HPV-18 (n= 17, 17)   55.0 
 (55.0 to 55.0) 
 57.7 
 (52.1 to 63.8) 
Month 7 J4 HPV-18 (n= 17,17)   55.0 
 (55.0 to 55.0) 
 679.2 
 (423.6 to 1088.9) 
Month 12 J4 HPV-18 (n= 5, 2)   71.0 
 (35.0 to 144.2) 
 83.6 
 (0.4 to 17024.0) 
Month 24 V5 HPV-18 (n=17, 17)   58.1 
 (51.7 to 65.2) 
 139.5 
 (90.5 to 215.1) 

No statistical analysis provided for HPV-16 and HPV-18 Geometric Mean Titers (GMT) (V5/J4 Monoclonal Inhibition Test)



25.  Secondary:   Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)   [ Time Frame: At Month 0, 7, 12, 24, 36 and 48 ]

Measure Type Secondary
Measure Title Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)
Measure Description

Seropositivity was defined as subjects with a titer equal to or greater than 40.

Subjects with an antibody titer smaller than 40 prior to vaccination were seronegative prior to vaccination and subjects with a titer equal to or greater than 40 were seropositive prior to vaccination.

Time Frame At Month 0, 7, 12, 24, 36 and 48  

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 analyses were performed on the ATP cohort for immunogenicity which included subjects for whom immunogenicity data were available.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 47   48 
Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA) 
[Units: Subjects]
   
pre-vaccination HPV-16 (n= 44, 46)   0   0 
Month 7 HPV-16 (n= 44, 46)   0   46 
Month 12 HPV-16 (n= 43, 45)   0   45 
Month 24 HPV-16 (n= 40, 46)   0   46 
Month 36 HPV-16 (n= 33, 41)   0   41 
Month 48 HPV-16 (n= 33, 41)   0   40 
pre-vaccination HPV-18 (n= 47, 48)   0   0 
Month 7 HPV-18 (n= 44, 46)   0   46 
Month 12 HPV-18 (n= 43, 45)   0   44 
Month 24 HPV-18 (n= 40, 46)   0   46 
Month 36 HPV-18 (n= 33, 41)   0   41 
Month 48 HPV-18 (n= 33, 41)   2   39 

No statistical analysis provided for Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)



26.  Secondary:   Titers for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)   [ Time Frame: At month 0, 7, 12, 24, 36 and 48 ]

Measure Type Secondary
Measure Title Titers for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)
Measure Description Titers were expressed as GMTs.
Time Frame At month 0, 7, 12, 24, 36 and 48  

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 analyses were performed on the ATP cohort for immunogenicity for whom immunogenicity data were available.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed 
[Units: Participants]
 47   48 
Titers for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA) 
[Units: Titer]
Geometric Mean (95% Confidence Interval)
   
pre-vaccination HPV-16 (n= 44, 46)   20.0 
 (20.0 to 20.0) 
 20.0 
 (20.0 to 20.0) 
Month 7 HPV-16 (n= 44, 46)   20.0 
 (20.0 to 20.0) 
 27364.8 
 (19780.1 to 37857.9) 
Month 12 HPV-16 (n= 43, 45)   20.0 
 (20.0 to 20.0) 
 8385.9 
 (5857.3 to 12006.0) 
Month 24 HPV-16 (n= 40, 46)   20.0 
 (20.0 to 20.0) 
 3647.4 
 (2586.5 to 5143.4) 
Month 36 HPV-16 (n= 33, 41)   20.0 
 (20.0 to 20.0) 
 2245.1 
 (1616.6 to 3117.9) 
Month 48 HPV-16 (n= 33, 41)   20.0 
 (20.0 to 20.0) 
 1931.1 
 (1294.4 to 2880.8) 
pre-vaccination HPV-18 (n= 47, 48)   20.0 
 (20.0 to 20.0) 
 20.0 
 (20.0 to 20.0) 
Month 7 HPV-18 (n= 44, 46)   20.0 
 (20.0 to 20.0) 
 9052.7 
 (6851.8 to 11960.5) 
Month 12 HPV-18 (n= 43, 45)   20.0 
 (20.0 to 20.0) 
 1889.9 
 (1316.0 to 2714.1) 
Month 24 HPV-18 (n= 40, 46)   20.0 
 (20.0 to 20.0) 
 1695.6 
 (1200.7 to 2394.4) 
Month 36 HPV-18 (n= 33, 41)   20.0 
 (20.0 to 20.0) 
 1326.9 
 (948.0 to 1857.3) 
Month 48 HPV-18 (n= 33, 41)   23.8 
 (18.6 to 30.4) 
 1078.1 
 (714.9 to 1625.6) 

No statistical analysis provided for Titers for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)



27.  Secondary:   Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 6-month Persistent Infection   [ Time Frame: At Month 7 ]

Measure Type Secondary
Measure Title Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 6-month Persistent Infection
Measure Description GMT for anti-HPV-16 antibodies by ELISA in subjects with breakthrough persistent infections 6-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections. Due to the lack of seronegative subjects at Month 7, the hazard ratio (and Confidence Interval) was not calculated.
Time Frame At Month 7  

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 based on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available, only on subjects HPV-16 DNA negative and seronegative at baseline.

Reporting Groups
  Description
Cervarix Group Without HPV-16 6-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6 and who did not present 6-Month persistent infection with HPV-16.
Cervarix Group With HPV-16 6-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6, who presented 6-Month persistent infection with HPV-16.

Measured Values
   Cervarix Group Without HPV-16 6-Month Persistent Infection   Cervarix Group With HPV-16 6-Month Persistent Infection 
Participants Analyzed 
[Units: Participants]
 1123   45 
Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 6-month Persistent Infection 
[Units: EL.U/mL]
Geometric Mean (95% Confidence Interval)
 7667.34 
 (7212.13 to 8151.29) 
 6986.30 
 (5692.83 to 8573.66) 


Statistical Analysis 1 for Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 6-month Persistent Infection
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Chi-squared
P Value [4] 0.3910
Hazard Ratio (HR) [5] 0.798
95% Confidence Interval 0.476 to 1.337
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Hazard ratio of anti-HPV-16 GMTs at Month 7 (by ELISA) in subjects without 6-month persistent infection compared to subjects with 6-month persistent infection
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



28.  Secondary:   Number of Seroconverted Subjects for Anti-HPV-16 Without and With 6-month Persistent Infection.   [ Time Frame: At Month 7 ]

Measure Type Secondary
Measure Title Number of Seroconverted Subjects for Anti-HPV-16 Without and With 6-month Persistent Infection.
Measure Description Seroconversion rates for anti-HPV-16 antibodies by ELISA in subjects with breakthrough persistent infections 6-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections. Due to the lack of seronegative subjects at Month 7, the hazard ratio (and Confidence interval) was not calculated.
Time Frame At Month 7  

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 based on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available, only on subjects HPV-16 DNA negative and seronegative at baseline.

Reporting Groups
  Description
Cervarix Group Without HPV-16 6-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6 and who did not present 6-Month persistent infection with HPV-16.
Cervarix Group With HPV-16 6-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6, who presented 6-Month persistent infection with HPV-16.

Measured Values
   Cervarix Group Without HPV-16 6-Month Persistent Infection   Cervarix Group With HPV-16 6-Month Persistent Infection 
Participants Analyzed 
[Units: Participants]
 1123   45 
Number of Seroconverted Subjects for Anti-HPV-16 Without and With 6-month Persistent Infection. 
[Units: Subjects]
 1118   45 

No statistical analysis provided for Number of Seroconverted Subjects for Anti-HPV-16 Without and With 6-month Persistent Infection.



29.  Secondary:   Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 12-month Persistent Infection   [ Time Frame: At Month 7 ]

Measure Type Secondary
Measure Title Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 12-month Persistent Infection
Measure Description GMTs for anti-HPV-16 antibodies by ELISA in subjects with breakthrough persistent infections 12-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections.
Time Frame At Month 7  

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 based on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available, only on subjects HPV-16 DNA negative and seronegative at baseline.

Reporting Groups
  Description
Cervarix Group Without HPV-16 12-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6, without 12 Month persistent infection with HPV-16.
Cervarix Group With HPV-16 12-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6, with 12 Month persistent infection with HPV-16.

Measured Values
   Cervarix Group Without HPV-16 12-Month Persistent Infection   Cervarix Group With HPV-16 12-Month Persistent Infection 
Participants Analyzed 
[Units: Participants]
 1120   37 
Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 12-month Persistent Infection 
[Units: EL.U/mL]
Geometric Mean (95% Confidence Interval)
 7683.56 
 (7229.22 to 8166.44) 
 6839.71 
 (5362.44 to 8723.96) 


Statistical Analysis 1 for Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 12-month Persistent Infection
Groups [1] Cervarix Group Without HPV-16 12-Month Persistent Infection
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Chi-squared
P Value [4] 0.3796
Hazard Ratio (HR) [5] 0.778
95% Confidence Interval 0.444 to 1.362
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Hazard ratio of anti-HPV-16 GMTs at Month 7 (by ELISA) in subjects without 12-month persistent infection compared to subjects with 12-month persistent infection.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



30.  Secondary:   Number of Seroconverted Subjects for Anti-HPV-16 Without and With 12-month Persistent Infection   [ Time Frame: At Month 7 ]

Measure Type Secondary
Measure Title Number of Seroconverted Subjects for Anti-HPV-16 Without and With 12-month Persistent Infection
Measure Description Seroconversion rates for anti-HPV-16 antibodies by ELISA in subjects with breakthrough persistent infections 12-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections. Due to the lack of seronegative subjects at Month 7, the hazard ratio (and Confidence Interval) was not calculated.
Time Frame At Month 7  

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 based on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available, only on subjects HPV-16 DNA negative and seronegative at baseline.

Reporting Groups
  Description
Cervarix Group Without HPV-16 12-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6, without 12 Month persistent infection with HPV-16.
Cervarix Group With HPV-16 12-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6, with 12 Month persistent infection with HPV-16.

Measured Values
   Cervarix Group Without HPV-16 12-Month Persistent Infection   Cervarix Group With HPV-16 12-Month Persistent Infection 
Participants Analyzed 
[Units: Participants]
 1120   37 
Number of Seroconverted Subjects for Anti-HPV-16 Without and With 12-month Persistent Infection 
[Units: Subjects]
 1115   37 

No statistical analysis provided for Number of Seroconverted Subjects for Anti-HPV-16 Without and With 12-month Persistent Infection



31.  Secondary:   Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 6-month Persistent Infection   [ Time Frame: At Month 7 ]

Measure Type Secondary
Measure Title Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 6-month Persistent Infection
Measure Description GMTs for anti-HPV-18 antibodies by ELISA in subjects with breakthrough persistent infections 6-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections.
Time Frame At Month 7  

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 based on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available, only on subjects HPV-18 DNA negative and seronegative at baseline.

Reporting Groups
  Description
Cervarix Group Without HPV-18 6-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6 and who did not present 6-Month persistent infection with HPV-18.
Cervarix Group With HPV-18 6-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6, who presented 6-Month persistent infection with HPV-18.

Measured Values
   Cervarix Group Without HPV-18 6-Month Persistent Infection   Cervarix Group With HPV-18 6-Month Persistent Infection 
Participants Analyzed 
[Units: Participants]
 1248   28 
Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 6-month Persistent Infection 
[Units: EL.U/mL]
Geometric Mean (95% Confidence Interval)
 3963.50 
 (3750.71 to 4188.37) 
 2945.69 
 (2271.74 to 3819.58) 


Statistical Analysis 1 for Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 6-month Persistent Infection
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Chi-squared
P Value [4] 0.1035
Hazard Ratio (HR) [5] 0.610
95% Confidence Interval 0.337 to 1.106
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Hazard ratio of anti-HPV-18 GMTs at Month 7 (by ELISA) in subjects without 6-month persistent infection compared to subjects with 6-month persistent infection.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



32.  Secondary:   Number of Seroconverted Subjects for Anti-HPV-18 Without and With 6-month Persistent Infection.   [ Time Frame: At Month 7 ]

Measure Type Secondary
Measure Title Number of Seroconverted Subjects for Anti-HPV-18 Without and With 6-month Persistent Infection.
Measure Description Seroconversion rates for anti-HPV-18 antibodies by ELISA in subjects with breakthrough persistent infections 6-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections. Due to the lack of seronegative subjects at Month 7, the hazard ratio (and Confidence Interval) was not calculated.
Time Frame At Month 7  

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 based on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available, only on subjects HPV-18 DNA negative and seronegative at baseline.

Reporting Groups
  Description
Cervarix Group Without HPV-18 6-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6 and who did not present 6-Month persistent infection with HPV-18.
Cervarix Group With HPV-18 6-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6, who presented 6-Month persistent infection with HPV-18.

Measured Values
   Cervarix Group Without HPV-18 6-Month Persistent Infection   Cervarix Group With HPV-18 6-Month Persistent Infection 
Participants Analyzed 
[Units: Participants]
 1248   28 
Number of Seroconverted Subjects for Anti-HPV-18 Without and With 6-month Persistent Infection. 
[Units: Subjects]
 1242   28 

No statistical analysis provided for Number of Seroconverted Subjects for Anti-HPV-18 Without and With 6-month Persistent Infection.



33.  Secondary:   Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 12-month Persistent Infection   [ Time Frame: At Month 7 ]

Measure Type Secondary
Measure Title Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 12-month Persistent Infection
Measure Description GMTs for anti-HPV-18 antibodies by ELISA in subjects with breakthrough persistent infections 12-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections.
Time Frame At Month 7  

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 based on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available, only on subjects HPV-18 DNA negative and seronegative at baseline.

Reporting Groups
  Description
Cervarix Group Without HPV-18 12-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6 and who did not present 12-Month persistent infection with HPV-18.
Cervarix Group With HPV-18 12-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6, who presented 12-Month persistent infection with HPV-18.

Measured Values
   Cervarix Group Without HPV-18 12-Month Persistent Infection   Cervarix Group With HPV-18 12-Month Persistent Infection 
Participants Analyzed 
[Units: Participants]
 1243   21 
Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 12-month Persistent Infection 
[Units: EL.U/mL]
Geometric Mean (95% Confidence Interval)
 3965.67 
 (3753.09 to 4190.29) 
 3063.23 
 (2261.65 to 4148.91) 


Statistical Analysis 1 for Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 12-month Persistent Infection
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Chi-squared
P Value [4] 0.2111
Hazard Ratio (HR) [5] 0.635
95% Confidence Interval 0.312 to 1.293
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Hazard ratio of anti-HPV-18 GMTs at Month 7 (by ELISA) in subjects without 12-month persistent infection compared to subjects with 12-month persistent infection.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



34.  Secondary:   Number of Seroconverted Subjects for Anti-HPV-18 Without and With 12-month Persistent Infection   [ Time Frame: At Month 7 ]

Measure Type Secondary
Measure Title Number of Seroconverted Subjects for Anti-HPV-18 Without and With 12-month Persistent Infection
Measure Description Seroconversion rates for anti-HPV-18 antibodies by ELISA in subjects with breakthrough persistent infections 12-month definition, were compared to those in a matched set of subjects without breakthrough persistent infections. Due to the lack of seronegative subjects at Month 7, the hazard ratio (and Confidence Interval) was not calculated.
Time Frame At Month 7  

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 based on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available, only on subjects HPV-18 DNA negative and seronegative at baseline.

Reporting Groups
  Description
Cervarix Group Without HPV-18 12-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6 and who did not present 12-Month persistent infection with HPV-18.
Cervarix Group With HPV-18 12-Month Persistent Infection Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6, who presented 12-Month persistent infection with HPV-18.

Measured Values
   Cervarix Group Without HPV-18 12-Month Persistent Infection   Cervarix Group With HPV-18 12-Month Persistent Infection 
Participants Analyzed 
[Units: Participants]
 1243   21 
Number of Seroconverted Subjects for Anti-HPV-18 Without and With 12-month Persistent Infection 
[Units: Subjects]
 1237   21 

No statistical analysis provided for Number of Seroconverted Subjects for Anti-HPV-18 Without and With 12-month Persistent Infection




  Serious Adverse Events


  Other Adverse Events


  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
No text entered.


  More Information