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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00122681
First received: July 20, 2005
Last updated: July 11, 2013
Last verified: February 2012
Results First Received: November 30, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Human Papillomavirus (HPV) Infection
Cervical Neoplasia
Interventions: Biological: Cervarix™
Biological: Havrix™-based investigational formulation

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

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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  
Number of Participants  
[units: participants]
  9325     9319     18644  
Age  
[units: years]
Mean ± Standard Deviation
  20.0  ± 3.12     20.0  ± 3.10     20.0  ± 3.11  
Gender  
[units: subjects]
     
Female     9325     9319     18644  
Male     0     0     0  



  Outcome Measures
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1.  Primary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection   [ 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
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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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  
[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  

No statistical analysis provided for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection



2.  Primary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection   [ 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
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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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  
[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  

No statistical analysis provided for Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection



3.  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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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



4.  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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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



5.  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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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)



6.  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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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)



7.  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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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



8.  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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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



9.  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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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



10.  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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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



11.  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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of Participants Analyzed  
[units: participants]
  7553     7587  
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



12.  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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of Participants Analyzed  
[units: participants]
  7569     7594  
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



13.  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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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  
Number of 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



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  
Safety Issue No  

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

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

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

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

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

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

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

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

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

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

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

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

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The 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  
Number of 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)




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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