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:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00122681

First received: July 20, 2005

Last updated: February 23, 2012

Last verified: February 2012

History of Changes

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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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: 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). 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: 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) 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: 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) 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: 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) 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: 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) 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:

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: 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) 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

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: 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) 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: 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) 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:

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

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:

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

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)

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

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.

Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

Publications:

Romanowski B et al. Clinical benefit of the AS04-adjuvanted human papillomavirus 16/18 vaccine against CIN2+ related to the 5 most common oncogenic HPV types: PATRICIA trial. Abstract presented at IDSA. Philadelphia, USA, 29 October-1 November, 2009.

Naud P et al. Cross-protective efficacy of the ASO4-adjuvanted HPV-16/18 vaccine against oncogenic HPV-31, -33 and - 45. Abstract presented at European Research Organization on Genital Infection and Neoplasia 2010 (EUROGIN). Monte Carlo, Monaco, 17-20 February 2010.

Skinner R. S et al. Cross-protective efficacy of Cervarix™ against oncogenic HPV types beyond HPV-16/18. Abstract presented at International Papillomavirus Conference and Clinical Workshop (IPvC). Malmo, Sweden, 8-14 May 2009.

Kitchener H et al. Cross-protective efficacy of the AS04-adjuvanted HPV-16/18 vaccine in oncogenic HPV infection-naïve women: results from a double-blind, randomised, Phase III trial (PATRICIA). Abstract presented at the 16th International Meeting of European Society of Gynaecological Oncology. Belgrade, Serbia, 11-14 October 2009.

Paavonen J, Naud P, Salmerón J, Wheeler CM, Chow SN, Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR, Hedrick J, Jaisamrarn U, Limson G, Garland S, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Jenkins D, Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G; HPV PATRICIA Study Group; Greenacre M. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009 Jul 25;374(9686):301-14. Epub 2009 Jul 6.

Descamps D et al. (2009) Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: A pooled analysis of 11 clinical trials. Hum Vaccin. 5(5):51-59.

Wacholder S et al. (2010) Risk of miscarriage with bivalent vaccine against human papillomavirus (HPV) types 16 and 18: pooled analysis of two randomised controlled trials. BMJ. 340:c712

Szarewski A et al. Cross-protective efficacy of CervarixTM against oncogenic types beyond HPV-16/18 : analysis of the According-to-Protocol (ATP) cohort in a double blind, randomized controlled Phase III efficacy trial. Abstract presented at FIGO 2009 - 19th World Congress of Gynecology & Obstetrics. Cape Town, South Africa, 4-9 October, 2009.

Paavonen J, Jenkins D, Bosch FX, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter DL, Kitchener HC, Castellsague X, de Carvalho NS, Skinner SR, Harper DM, Hedrick JA, Jaisamrarn U, Limson GA, Dionne M, Quint W, Spiessens B, Peeters P, Struyf F, Wieting SL, Lehtinen MO, Dubin G; HPV PATRICIA study group. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet. 2007 Jun 30;369(9580):2161-70.

Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, Dubin G, Breuer T. Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008 Dec 2;26(51):6630-8.

Wheeler C et al. Cross-protective efficacy of the AS04-adjuvanted human papillomavirus (HPV)-16/18 vaccine against cervical intraepithelial neoplasia 2+ in a Phase III, double-blind, randomised trial (PATRICIA). Abstract presented at the 16th International Meeting of European Society of Gynaecological Oncology. Belgrade, Serbia, 11-14 October 2009.

Chow SN et al. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against abnormal cytology and reduction in colposcopy referrals and cervical excisions in an HPV-negative population. Abstract presented at the 16th International Meeting of European Society of Gynaecological Oncology. Belgrade, Serbia, 11-14 October 2009.

Poppe W et al. Vaccine efficacy in women with evidence of prior HPV-16/18 infection and incomplete protection by natural immunity: analysis from a Phase III, double blind, randomised trial of the AS04-adjuvanted HPV-16/18 vaccine. Abstract presented at the 16th International Meeting of European Society of Gynaecological Oncology. Belgrade, Serbia, 11-14 October 2009.

Tjalma W et al. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against abnormal cytology and low-grade histopathological lesions in an oncogenic HPV-naïve population. Abstract presented at the 16th International Meeting of European Society of Gynaecological Oncology. Belgrade, Serbia, 11-14 October 2009.

Publications automatically indexed to this study:

Roset Bahmanyar E, Paavonen J, Naud P, Salmerón J, Chow SN, Apter D, Kitchener H, Castellsagué X, Teixeira JC, Skinner SR, Jaisamrarn U, Limson GA, Garland SM, Szarewski A, Romanowski B, Aoki F, Schwarz TF, Poppe WA, De Carvalho NS, Harper DM, Bosch FX, Raillard A, Descamps D, Struyf F, Lehtinen M, Dubin G; HPV PATRICIA Study Group. Prevalence and risk factors for cervical HPV infection and abnormalities in young adult women at enrolment in the multinational PATRICIA trial. Gynecol Oncol. 2012 Dec;127(3):440-50. doi: 10.1016/j.ygyno.2012.08.033. Epub 2012 Aug 30.

Lehtinen M, Paavonen J, Wheeler CM, Jaisamrarn U, Garland SM, Castellsagué X, Skinner SR, Apter D, Naud P, Salmerón J, Chow SN, Kitchener H, Teixeira JC, Hedrick J, Limson G, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, De Carvalho NS, Germar MJ, Peters K, Mindel A, De Sutter P, Bosch FX, David MP, Descamps D, Struyf F, Dubin G; HPV PATRICIA Study Group. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012 Jan;13(1):89-99. Epub 2011 Nov 8.

Wheeler CM, Castellsagué X, Garland SM, Szarewski A, Paavonen J, Naud P, Salmerón J, Chow SN, Apter D, Kitchener H, Teixeira JC, Skinner SR, Jaisamrarn U, Limson G, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Harper DM, Huh W, Hardt K, Zahaf T, Descamps D, Struyf F, Dubin G, Lehtinen M; HPV PATRICIA Study Group. Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012 Jan;13(1):100-10. Epub 2011 Nov 8.

Szarewski A, Poppe WA, Skinner SR, Wheeler CM, Paavonen J, Naud P, Salmeron J, Chow SN, Apter D, Kitchener H, Castellsagué X, Teixeira JC, Hedrick J, Jaisamrarn U, Limson G, Garland S, Romanowski B, Aoki FY, Schwarz TF, Bosch FX, Harper DM, Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G; HPV PATRICIA Study Group. Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18. Int J Cancer. 2012 Jul 1;131(1):106-16. doi: 10.1002/ijc.26362. Epub 2011 Oct 23.

Wacholder S, Chen BE, Wilcox A, Macones G, Gonzalez P, Befano B, Hildesheim A, Rodríguez AC, Solomon D, Herrero R, Schiffman M; CVT group. Risk of miscarriage with bivalent vaccine against human papillomavirus (HPV) types 16 and 18: pooled analysis of two randomised controlled trials. BMJ. 2010 Mar 2;340:c712.

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00122681 History of Changes
Other Study ID Numbers:	580299/008
Study First Received:	July 20, 2005
Results First Received:	November 30, 2009
Last Updated:	February 23, 2012
Health Authority:	United States: Food and Drug Administration

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