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

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ClinicalTrials.gov Identifier: NCT00128661
Recruitment Status : Completed
First Posted : August 10, 2005
Results First Posted : May 2, 2012
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Cervical Cancer
Precancerous Condition
Interventions Biological: human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine
Biological: hepatitis A inactivated virus vaccine
Enrollment 7466
Recruitment Details  
Pre-assignment Details Solicited symptoms were collected for 3730 and 3740 subjects instead of the 3727 and 3739 subjects who were randomized in the study in the Cervarix and the Havrix groups, respectively. These 4 subjects received both vaccines and were included in the denominator of both arm based on the actual vaccine type administered.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm. Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Period Title: Overall Study
Started 3727 3739
Completed 3453 3481
Not Completed 274 258
Reason Not Completed
Adverse Event             14             11
Lost to Follow-up             10             7
Withdrawal by Subject             243             232
Other             7             8
Arm/Group Title Cervarix Group Havrix Group Total
Hide Arm/Group Description Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm. Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm. Total of all reporting groups
Overall Number of Baseline Participants 3727 3739 7466
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Years Number Analyzed 3727 participants 3739 participants 7466 participants
21.1  (2.3) 21.1  (2.3) 21.1  (2.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3727 participants 3739 participants 7466 participants
Female
3727
 100.0%
3739
 100.0%
7466
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.
Hide Description CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer. Preceding cervical cytology means the last cervical cytology specimen collected before the histopathology specimen was obtained. Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) by polymerase chain reaction (PCR) at Month 0 and Month 6 for the corresponding HPV-type.
Time Frame From Month 6 up to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 2635 2677
Measure Type: Number
Unit of Measure: Events
HPV16 Associated CIN2+ (N=2464;2452) 1 9
HPV18 Associated CIN2+ (N=2567; 2593) 0 2
HPV16 and/or 18 Associated CIN2+ (N=2635;2677) 1 10
2.Secondary Outcome
Title Number of Cervical Infection With HPV16 or HPV18.
Hide Description Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame From Month 6 up to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 2635 2677
Measure Type: Number
Unit of Measure: Events
HPV16 Cervical Infection (N=2464;2452) 50 251
HPV18 Cervical Infection (N=2567;2593) 32 177
HPV16 and/or 18 Cervical Infection (N=2635;2677) 78 387
3.Secondary Outcome
Title Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type
Hide Description Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 detected by polymerase chain reaction (PRC) in the preceding cervical cytology specimen. Note: The assay did not distinguish between HPV types 68 and 73. CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame From Month 6 up to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 2643 2697
Measure Type: Number
Unit of Measure: Events
HPV16 Associated CIN2+ (N=2464;2452) 1 9
HPV18 Associated CIN2+ (N=2567,2593) 0 2
HPV31 Associated CIN2+ (N=2525;2546) 1 6
HPV33 Associated CIN2+ (N=2596;2645) 0 3
HPV35 Associated CIN2+ (N=2593;2631) 0 4
HPV39 Associated CIN2+ (N=2528;2581) 0 0
HPV45 Associated CIN2+ (N=2573;2622) 1 1
HPV51 Associated CIN2+ (N=2453;2539) 1 6
HPV52 Associated CIN2+ (N=2456;2505) 5 10
HPV56 Associated CIN2+ (N=2524;2564) 1 5
HPV58 Associated CIN2+ (N=2551;2595) 2 5
HPV59 Associated CIN2+ (N=2576;2637) 3 3
HPV68 and/or 73 Associated CIN2+ (N=2519;2576) 1 4
Non 16/18 Onco HPV Associated CIN2+ (N=2643;2697) 11 28
Any Oncogenic HPV Associated CIN2+ (N=2643;2697) 11 33
4.Secondary Outcome
Title Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases
Hide Description Persistent incident HPV-16 and /or HPV-18 cervical infection had to fulfil the following criteria: first detection after the 6-month visit, 2 same type HPV positive (by PCR) test results 10+ months apart, and no intervening HPV negative tests for the corresponding type. Persistent HPV16 or HPV18 cervical infection = detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples from all consecutive evaluations over approximately 12 months. Subjects were HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type.
Time Frame From Month 6 up to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 2635 2677
Measure Type: Number
Unit of Measure: Events
Persistent HPV16 Infection (N=2464,2452) 10 71
Persistent HPV18 Infection (N=2567;2593) 0 37
Persistent HPV16 and/or 18 Infection (N=2635;2677) 10 104
5.Secondary Outcome
Title Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.
Hide Description Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs). Seronegative subjects = antibody concentration below 8 ELISA Units per millilitre (EL.U/mL) prior to vaccination. Seropositive subjects=antibody concentration equal to or above 8 EL.U/mL prior to vaccination. Immunogenicity subcohort = subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7)
Time Frame Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 196 157
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
HPV-16 [before vaccination] (N=194;156)
6.7
(5.7 to 7.8)
8.2
(6.7 to 10.0)
HPV-16 [at Month 1] (N=196,157)
646.6
(549.3 to 761.1)
7.9
(6.5 to 9.6)
HPV-16 [at Month 6] (N=195,156)
771.5
(668.3 to 890.7)
8.4
(6.9 to 10.3)
HPV-16 [at Month 7] (N=195,157)
3261
(2959 to 3595)
8.5
(6.9 to 10.3)
HPV-16 [at Month 12] (N=182,146)
2090
(1822 to 2398)
8.3
(6.7 to 10.4)
HPV-16 [at Month 18] (N=25,17)
1045
(776.0 to 1408)
10.4
(4.8 to 22.7)
HPV-16 [at Month 24] (N=175,137)
1486
(1293 to 1709)
8.6
(6.9 to 10.7)
HPV-16 [at Month 30] (N=19,15)
1070
(747.5 to 1532)
11.9
(5.1 to 28.0)
HPV-16 [at Month 36] (N=163,132)
1256
(1080 to 1461)
9.0
(7.4 to 11.0)
HPV-16 [at Month 42] (N=22,18)
1259
(879.4 to 1802)
6.1
(4.0 to 9.4)
HPV-16 [at Month 48] (N=172,131)
1155
(1009 to 1322)
9.5
(7.7 to 11.7)
6.Secondary Outcome
Title Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort
Hide Description Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohortby Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 7 EL.U/mL prior to vaccination. Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).
Time Frame Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 203 175
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
HPV-18 [before vaccination] (N=200;173)
5.4
(4.8 to 6.1)
6.2
(5.2 to 7.4)
HPV-18 [at Month 1] (N=203;170)
372.7
(322.8 to 430.3)
6.4
(5.4 to 7.6)
HPV-18 [at Month 6] (N=203;175)
532.2
(467.5 to 605.9)
6.7
(5.6 to 7.9)
HPV-18 [at Month 7] (N=202;175)
3276
(3001 to 3576)
6.8
(5.7 to 8.1)
HPV-18 [at Month 12] (N=190;166)
1082
(942.0 to 1242)
7.0
(5.7 to 8.5)
HPV-18 [at Month 18] (N=28;20)
502.4
(339.1 to 744.5)
6.7
(3.8 to 12.1)
HPV-18 [at Month 24] (N=178;150)
633.0
(551.5 to 726.6)
6.9
(5.6 to 8.4)
HPV-18 [at Month 30] (N=17;19)
403.8
(257.8 to 632.5)
6.4
(3.8 to 10.5)
HPV-18 [at Month 36] (N=168;145)
519.7
(449.3 to 601.1)
6.0
(5.0 to 7.2)
HPV-18 [at Month 42] (N=25;19)
582.4
(422.9 to 801.9)
5.5
(3.6 to 8.4)
HPV-18 [at Month 48] (N=179;149)
470.1
(411.2 to 537.4)
6.6
(5.5 to 8.0)
7.Secondary Outcome
Title HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)
Hide Description Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 41 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 41 EL.U/mL prior to vaccination. Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).
Time Frame Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 196 158
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
HPV-16 [before vaccination] (N=196;158)
21.1
(20.5 to 21.8)
21.4
(20.6 to 22.3)
HPV-16 [at Month 1] (N=182;155)
58.5
(48.3 to 70.8)
21.5
(20.7 to 22.3)
HPV-16 [at Month 6] (N=189;156)
80.9
(70.3 to 93.1)
21.5
(20.6 to 22.4)
HPV-16 [at Month 7] (N=193;158)
1047
(926.3 to 1183)
21.4
(20.6 to 22.3)
HPV-16 [at Month 12] (N=175;146)
291.4
(253.7 to 334.8)
22.6
(20.8 to 24.5)
HPV-16 [at Month 18] (N=24;17)
116.6
(83.2 to 163.3)
20.5
(20.5 to 20.5)
HPV-16 [at Month 24] (N=169;138)
184.6
(163.0 to 209.1)
21.4
(20.6 to 22.3)
HPV-16 [at Month 30] (N=18;15)
112.4
(78.7 to 160.6)
20.5
(20.5 to 20.5)
HPV-16 [at Month 36] (N=162;132)
139.7
(122.5 to 159.5)
20.8
(20.2 to 21.3)
HPV-16 [at Month 42] (N=22;18)
126.9
(89.9 to 179.1)
20.5
(20.5 to 20.5)
HPV-16 [at Month 48] (N=168;133)
131.8
(115.5 to 150.5)
21.0
(20.4 to 21.7)
8.Secondary Outcome
Title HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)
Hide Description Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 110 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 110 EL.U/mL prior to vaccination. Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).
Time Frame Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 203 176
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
HPV-18 [before vaccination] (N=203;176)
55.0
(55.0 to 55.0)
55.7
(54.7 to 56.7)
HPV-18 [at Month 1] (N=197;173)
99.1
(88.0 to 111.5)
55.3
(54.7 to 55.8)
HPV-18 [at Month 6] (N=195;175)
111.4
(100.2 to 123.9)
55.4
(54.6 to 56.3)
HPV-18 [at Month 7] (N=198;176)
823.6
(737.7 to 919.5)
55.0
(55.0 to 55.0)
HPV-18 [at Month 12] (N=182;166)
231.1
(203.2 to 262.7)
56.7
(54.7 to 58.8)
HPV-18 [at Month 18] (N=28;20)
121.8
(89.5 to 165.8)
55.0
(55.0 to 55.0)
HPV-18 [at Month 24] (N=170;154)
140.8
(123.8 to 160.2)
55.0
(55.0 to 55.0)
HPV-18 [at Month 30] (N=17;19)
89.5
(67.6 to 118.7)
55.0
(55.0 to 55.0)
HPV-18 [at Month 36] (N=167;145)
107.9
(96.0 to 121.2)
55.0
(55.0 to 55.0)
HPV-18 [at Month 42] (N=25;19)
103.3
(80.3 to 132.9)
55.0
(55.0 to 55.0)
HPV-18 [at Month 48 (N=179;150)
96.9
(87.7 to 107.0)
56.7
(54.0 to 59.6)
9.Secondary Outcome
Title Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
Hide Description Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).
Time Frame Within 60 minutes after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 3730 3740
Measure Type: Number
Unit of Measure: Subjects
Any pain 1627 1610
Grade 3 pain 25 20
Any redness 544 501
Grade 3 redness > 50 mm 0 2
Any swelling 207 201
Grade 3 swelling > 50 mm 0 1
10.Secondary Outcome
Title Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.
Hide Description Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy.Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = oral temperature > 39.0°C.
Time Frame Within 60 minutes after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 3730 3740
Measure Type: Number
Unit of Measure: Subjects
Any fatigue 512 502
Grade 3 fatigue 6 5
Any myalgia 257 232
Grade 3 myalgia 0 1
Any arthralgia 58 64
Grade 3 arthralgia 0 1
Any gastrointestinal 191 171
Grade 3 gastrointestinal 0 0
Any headache 714 718
Grade 3 headache 2 0
Any rash 15 17
Grade 3 rash 0 0
Any urticaria 19 21
Grade 3 urticaria 0 0
Fever (oral) >= 37.5°C 472 477
Fever (oral) > 39.0°C 0 0
11.Secondary Outcome
Title Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.
Hide Description Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).
Time Frame From Day 3 to Day 6 after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 380 376
Measure Type: Number
Unit of Measure: Subjects
Any pain 202 74
Grade 3 pain 0 0
Any redness 6 1
Grade 3 redness 1 0
Any swelling 23 1
Grade 3 swelling 7 0
12.Secondary Outcome
Title Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.
Hide Description Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy.Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = oral temperature > 39.0°C.
Time Frame From Day 3 to Day 6 after vaccination
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Hide Analysis Population Description
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 380 376
Measure Type: Number
Unit of Measure: Subjects
Any pain 214 189
Grade 3 pain 2 0
Any myalgia 250 211
Grade 3 myalgia 1 0
Any arthralgia 44 32
Grade 3 arthralgia 0 0
Any gastrointestinal 157 119
Grade 3 gastrointestinal 0 1
Any headache 247 242
Grade 3 headache 1 2
Any rash 31 26
Grade 3 rash 0 0
Any urticaria 3 1
Grade 3 urticaria 0 0
Fever (oral) >= 37.5°C 43 37
Fever (oral) > 39.0°C 0 0
13.Secondary Outcome
Title Number of Subjects Reporting Serious Adverse Events (SAEs).
Hide Description SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.
Time Frame During the entire study period (From Month 0 up to Month 48).
Hide Outcome Measure Data
Hide Analysis Population Description
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 3727 3739
Measure Type: Number
Unit of Measure: Subjects
912 891
14.Secondary Outcome
Title Number of Subjects Reporting Unsolicited Adverse Events (AEs).
Hide Description An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time Frame During the entire study period (From Month 0 up to Month 48).
Hide Outcome Measure Data
Hide Analysis Population Description
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 3727 3739
Measure Type: Number
Unit of Measure: Subjects
3228 3254
15.Secondary Outcome
Title Number of Subjects With All Possible Pregnancy Outcomes
Hide Description The range of possible pregnancy outcomes was: Pregnancy loss, Pregnancy resolved alive, and Unresolved pregnancy.
Time Frame During the entire study period (From Month 0 up to Month 48).
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Hide Analysis Population Description
The analysis was performed on the Total Vaccinated Cohort, on all pregnant subjects.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 2123 2129
Measure Type: Number
Unit of Measure: subjects
Pregnancy loss 317 294
Pregnancy resolved alive 1756 1766
Unresolved pregnancy 50 69
16.Secondary Outcome
Title Number of Cervical Infection With HPV16 or HPV18.
Hide Description Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame During the first year of follow-up period
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Hide Analysis Population Description
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 2380 2420
Measure Type: Number
Unit of Measure: Events
HPV16 Cervical Infection (N=2242;2232) 21 37
HPV18 Cervical Infection (N=2330;2347) 7 29
HPV16 and/or 18 Cervical Infection (N=2380;2420) 27 64
17.Secondary Outcome
Title Number of Cervical Infection With HPV16 or HPV18.
Hide Description Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame During the second year of follow-up period
Hide Outcome Measure Data
Hide Analysis Population Description
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 2313 2349
Measure Type: Number
Unit of Measure: Events
HPV16 Cervical Infection (N=2170;2176) 10 77
HPV18 Cervical Infection (N=2269;2307) 9 47
HPV16 and/or 18 Cervical Infection (N=2313;2349) 18 117
18.Secondary Outcome
Title Number of Cervical Infection With HPV16 or HPV18.
Hide Description Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame During the third year of follow-up period
Hide Outcome Measure Data
Hide Analysis Population Description
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 2232 2196
Measure Type: Number
Unit of Measure: Events
HPV16 Cervical Infection (N=2097;2026) 6 60
HPV18 Cervical Infection (N=2200;2196) 6 44
HPV16 and/or 18 Cervical Infection (N=2236;2166) 11 88
19.Secondary Outcome
Title Number of Cervical Infection With HPV16 or HPV18.
Hide Description Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame From the fourth year follow-up period
Hide Outcome Measure Data
Hide Analysis Population Description
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 2421 2325
Measure Type: Number
Unit of Measure: Events
HPV16 Cervical Infection (N=2277;2139) 13 77
HPV18 Cervical Infection (N=2389;2325) 10 57
HPV16 and/or 18 Cervical Infection (N=2421;2261) 22 118
20.Secondary Outcome
Title Number of Subjects Reporting Unsolicited Adverse Events (AEs).
Hide Description An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time Frame within 30 days (Days 0-29) after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description:
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Overall Number of Participants Analyzed 3727 3739
Measure Type: Number
Unit of Measure: Subjects
1638 1536
Time Frame Solicited AEs: within 60 minutes after vaccination for all participants [please refer to Participant Flow Pre-assignment Details for population description]; From Day 3 to Day 6 post-vaccination for a 10% random subset of participants. SAEs: From Month 0 up to Month 48. Unsolicited AEs: From Month 0 up to Month 48 and Within 30 days (Days 0-29) after vaccination
Adverse Event Reporting Description For this study, the Total Number (#) of Participants Affected by Other (non-serious) Adverse Events (AEs) was analyzed separately for expected AEs and for unexpected AEs. A consolidated analysis of all expected and unexpected AEs was not technically possible to be performed and the relevant data are no longer available. Therefore, the Total #Participants Affected in Other Adverse Events Table is currently populated by the highest value of #Participants affected within other AE’s table.
 
Arm/Group Title Cervarix Group Havrix Group
Hide Arm/Group Description Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm. Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
All-Cause Mortality
Cervarix Group Havrix Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cervarix Group Havrix Group
Affected / at Risk (%) Affected / at Risk (%)
Total   912/3727 (24.47%)   891/3739 (23.83%) 
Blood and lymphatic system disorders     
Anaemia of pregnancy *  24/3727 (0.64%)  22/3739 (0.59%) 
Lymphadenitis *  2/3727 (0.05%)  1/3739 (0.03%) 
Blood disorder *  1/3727 (0.03%)  1/3739 (0.03%) 
Anaemia *  0/3727 (0.00%)  1/3739 (0.03%) 
Anaemia haemolytic autoimmune *  1/3727 (0.03%)  0/3739 (0.00%) 
Haemorrhagic anaemia *  1/3727 (0.03%)  0/3739 (0.00%) 
Haemorrhagic disorder *  0/3727 (0.00%)  1/3739 (0.03%) 
Thrombocytopenia *  0/3727 (0.00%)  1/3739 (0.03%) 
Cardiac disorders     
Cardiovascular disorder *  5/3727 (0.13%)  0/3739 (0.00%) 
Acute myocardial infarction *  1/3727 (0.03%)  0/3739 (0.00%) 
Congestive cardiomyopathy *  1/3727 (0.03%)  0/3739 (0.00%) 
Congenital, familial and genetic disorders     
Congenital flat feet *  0/3727 (0.00%)  1/3739 (0.03%) 
Multiple congenital abnormalities *  1/3727 (0.03%)  0/3739 (0.00%) 
Endocrine disorders     
Hyperthyroidism *  2/3727 (0.05%)  1/3739 (0.03%) 
Eye disorders     
Eye degenerative disorder *  1/3727 (0.03%)  0/3739 (0.00%) 
Retinal disorder *  0/3727 (0.00%)  1/3739 (0.03%) 
Strabismus *  1/3727 (0.03%)  0/3739 (0.00%) 
Ulcerative keratitis *  1/3727 (0.03%)  0/3739 (0.00%) 
Gastrointestinal disorders     
Gastrointestinal disorder *  9/3727 (0.24%)  9/3739 (0.24%) 
Pancreatitis acute *  6/3727 (0.16%)  5/3739 (0.13%) 
Abdominal pain *  6/3727 (0.16%)  3/3739 (0.08%) 
Irritable bowel syndrome *  1/3727 (0.03%)  4/3739 (0.11%) 
Colitis ulcerative *  2/3727 (0.05%)  1/3739 (0.03%) 
Appendix disorder *  2/3727 (0.05%)  0/3739 (0.00%) 
Constipation *  1/3727 (0.03%)  1/3739 (0.03%) 
Gastrointestinal inflammation *  1/3727 (0.03%)  1/3739 (0.03%) 
Abdominal mass *  0/3727 (0.00%)  1/3739 (0.03%) 
Abdominal pain lower *  1/3727 (0.03%)  0/3739 (0.00%) 
Abdominal pain upper *  0/3727 (0.00%)  1/3739 (0.03%) 
Crohn’s disease *  1/3727 (0.03%)  0/3739 (0.00%) 
Duodenal ulcer haemorrhage *  1/3727 (0.03%)  0/3739 (0.00%) 
Femoral hernia *  0/3727 (0.00%)  1/3739 (0.03%) 
Gastritis *  1/3727 (0.03%)  0/3739 (0.00%) 
Gastrointestinal haemorrhage *  0/3727 (0.00%)  1/3739 (0.03%) 
Ileus paralytic *  1/3727 (0.03%)  0/3739 (0.00%) 
Intestinal obstruction *  0/3727 (0.00%)  1/3739 (0.03%) 
Pancreatitis chronic *  1/3727 (0.03%)  0/3739 (0.00%) 
Peritoneal adhesions *  1/3727 (0.03%)  0/3739 (0.00%) 
Peritoneal disorder *  0/3727 (0.00%)  1/3739 (0.03%) 
Tooth ankylosis *  1/3727 (0.03%)  0/3739 (0.00%) 
Tooth development disorder *  1/3727 (0.03%)  0/3739 (0.00%) 
Tooth malformation *  1/3727 (0.03%)  0/3739 (0.00%) 
General disorders     
Pyrexia *  5/3727 (0.13%)  1/3739 (0.03%) 
Eye complication associated with device *  1/3727 (0.03%)  0/3739 (0.00%) 
Gait disturbance *  0/3727 (0.00%)  1/3739 (0.03%) 
Hepatobiliary disorders     
Cholecystitis *  26/3727 (0.70%)  19/3739 (0.51%) 
Cholelithiasis *  22/3727 (0.59%)  9/3739 (0.24%) 
Liver disorder *  0/3727 (0.00%)  3/3739 (0.08%) 
Bile duct stone *  1/3727 (0.03%)  0/3739 (0.00%) 
Biliary cirrhosis *  1/3727 (0.03%)  0/3739 (0.00%) 
Biliary tract disorder *  1/3727 (0.03%)  0/3739 (0.00%) 
Immune system disorders     
Anaphylactic shock *  0/3727 (0.00%)  2/3739 (0.05%) 
Rhesus incompatibility *  0/3727 (0.00%)  1/3739 (0.03%) 
Infections and infestations     
Dengue fever *  38/3727 (1.02%)  48/3739 (1.28%) 
Urinary tract infection *  25/3727 (0.67%)  24/3739 (0.64%) 
Appendicitis *  17/3727 (0.46%)  18/3739 (0.48%) 
Postoperative wound infection *  12/3727 (0.32%)  12/3739 (0.32%) 
Postpartum sepsis *  12/3727 (0.32%)  8/3739 (0.21%) 
Subcutaneous abscess *  5/3727 (0.13%)  5/3739 (0.13%) 
Infectious peritonitis *  6/3727 (0.16%)  2/3739 (0.05%) 
Pelvic inflammatory disease *  3/3727 (0.08%)  3/3739 (0.08%) 
Cellulitis *  1/3727 (0.03%)  4/3739 (0.11%) 
Salpingitis *  3/3727 (0.08%)  2/3739 (0.05%) 
Staphylococcal infection *  3/3727 (0.08%)  2/3739 (0.05%) 
Bronchopneumonia *  1/3727 (0.03%)  3/3739 (0.08%) 
Viral infection *  1/3727 (0.03%)  3/3739 (0.08%) 
Amniotic cavity infection *  1/3727 (0.03%)  2/3739 (0.05%) 
Bartholin’s abscess *  2/3727 (0.05%)  1/3739 (0.03%) 
Bronchitis *  2/3727 (0.05%)  1/3739 (0.03%) 
Sexually transmitted disease *  1/3727 (0.03%)  2/3739 (0.05%) 
HIV infection *  1/3727 (0.03%)  1/3739 (0.03%) 
Otitis externa *  2/3727 (0.05%)  0/3739 (0.00%) 
Parametritis *  1/3727 (0.03%)  1/3739 (0.03%) 
Pneumonia *  2/3727 (0.05%)  0/3739 (0.00%) 
Tooth abscess *  2/3727 (0.05%)  0/3739 (0.00%) 
Vaginal infection *  1/3727 (0.03%)  1/3739 (0.03%) 
Anal abscess *  1/3727 (0.03%)  0/3739 (0.00%) 
Breast abscess *  1/3727 (0.03%)  0/3739 (0.00%) 
Candida sepsis *  1/3727 (0.03%)  0/3739 (0.00%) 
Chronic sinusitis *  1/3727 (0.03%)  0/3739 (0.00%) 
Genital herpes *  1/3727 (0.03%)  0/3739 (0.00%) 
Genitourinary tract infection *  0/3727 (0.00%)  1/3739 (0.03%) 
Malaria *  1/3727 (0.03%)  0/3739 (0.00%) 
Mastitis postpartum *  0/3727 (0.00%)  1/3739 (0.03%) 
Meningitis viral *  1/3727 (0.03%)  0/3739 (0.00%) 
Otitis media *  0/3727 (0.00%)  1/3739 (0.03%) 
Pilonidal cyst *  1/3727 (0.03%)  0/3739 (0.00%) 
Pneumonia viral *  1/3727 (0.03%)  0/3739 (0.00%) 
Post procedural infection *  0/3727 (0.00%)  1/3739 (0.03%) 
Pyoderma *  1/3727 (0.03%)  0/3739 (0.00%) 
Skin infection *  0/3727 (0.00%)  1/3739 (0.03%) 
Syphilis *  0/3727 (0.00%)  1/3739 (0.03%) 
Varicella *  0/3727 (0.00%)  1/3739 (0.03%) 
Vulval abscess *  1/3727 (0.03%)  0/3739 (0.00%) 
Injury, poisoning and procedural complications     
Multiple injuries *  3/3727 (0.08%)  10/3739 (0.27%) 
Injury *  2/3727 (0.05%)  5/3739 (0.13%) 
Postoperative wound complication *  4/3727 (0.11%)  3/3739 (0.08%) 
Concussion *  2/3727 (0.05%)  3/3739 (0.08%) 
Lower limb fracture *  2/3727 (0.05%)  2/3739 (0.05%) 
Open wound *  3/3727 (0.08%)  1/3739 (0.03%) 
Humerus fracture *  3/3727 (0.08%)  0/3739 (0.00%) 
Toxicity to various agents *  2/3727 (0.05%)  1/3739 (0.03%) 
Lumbar vertebral fracture *  1/3727 (0.03%)  1/3739 (0.03%) 
Multiple fractures *  2/3727 (0.05%)  0/3739 (0.00%) 
Post procedural complication *  0/3727 (0.00%)  2/3739 (0.05%) 
Road traffic accident *  1/3727 (0.03%)  1/3739 (0.03%) 
Thermal burn *  2/3727 (0.05%)  0/3739 (0.00%) 
Ulna fracture *  1/3727 (0.03%)  1/3739 (0.03%) 
Venom poisoning *  0/3727 (0.00%)  2/3739 (0.05%) 
Chemical poisoning *  0/3727 (0.00%)  1/3739 (0.03%) 
Contusion *  1/3727 (0.03%)  0/3739 (0.00%) 
Facial bones fracture *  0/3727 (0.00%)  1/3739 (0.03%) 
Femoral neck fracture *  1/3727 (0.03%)  0/3739 (0.00%) 
Foot fracture *  1/3727 (0.03%)  0/3739 (0.00%) 
Foreign body *  1/3727 (0.03%)  0/3739 (0.00%) 
Jaw fracture *  1/3727 (0.03%)  0/3739 (0.00%) 
Muscle injury *  0/3727 (0.00%)  1/3739 (0.03%) 
Muscle strain *  0/3727 (0.00%)  1/3739 (0.03%) 
Radius fracture *  1/3727 (0.03%)  0/3739 (0.00%) 
Tendon injury *  0/3727 (0.00%)  1/3739 (0.03%) 
Tibia fracture *  0/3727 (0.00%)  1/3739 (0.03%) 
Investigations     
Medical observation *  1/3727 (0.03%)  0/3739 (0.00%) 
Metabolism and nutrition disorders     
Gestational diabetes *  5/3727 (0.13%)  6/3739 (0.16%) 
Type 2 diabetes mellitus *  3/3727 (0.08%)  1/3739 (0.03%) 
Diabetic ketoacidosis *  0/3727 (0.00%)  1/3739 (0.03%) 
Hypokalaemia *  0/3727 (0.00%)  1/3739 (0.03%) 
Musculoskeletal and connective tissue disorders     
Rheumatoid arthritis *  1/3727 (0.03%)  1/3739 (0.03%) 
Systemic lupus erythematosus *  2/3727 (0.05%)  0/3739 (0.00%) 
Back pain *  1/3727 (0.03%)  0/3739 (0.00%) 
Intervertebral disc displacement *  0/3727 (0.00%)  1/3739 (0.03%) 
Musculoskeletal pain *  1/3727 (0.03%)  0/3739 (0.00%) 
Myalgia *  0/3727 (0.00%)  1/3739 (0.03%) 
Tenosynovitis *  0/3727 (0.00%)  1/3739 (0.03%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign ovarian tumour *  11/3727 (0.30%)  7/3739 (0.19%) 
Thyroid cancer *  1/3727 (0.03%)  3/3739 (0.08%) 
Ovarian cancer *  2/3727 (0.05%)  1/3739 (0.03%) 
Uterine leiomyoma *  2/3727 (0.05%)  1/3739 (0.03%) 
Benign hydatidiform mole *  1/3727 (0.03%)  1/3739 (0.03%) 
Colon neoplasm *  0/3727 (0.00%)  1/3739 (0.03%) 
Nasal sinus cancer *  1/3727 (0.03%)  0/3739 (0.00%) 
Non-Hodgkin’s lymphoma *  0/3727 (0.00%)  1/3739 (0.03%) 
Placental neoplasm *  0/3727 (0.00%)  1/3739 (0.03%) 
Vulval neoplasm *  0/3727 (0.00%)  1/3739 (0.03%) 
Nervous system disorders     
Migraine *  2/3727 (0.05%)  1/3739 (0.03%) 
Convulsion *  1/3727 (0.03%)  1/3739 (0.03%) 
Nervous system disorder *  0/3727 (0.00%)  2/3739 (0.05%) 
Tension headache *  1/3727 (0.03%)  1/3739 (0.03%) 
Autonomic nervous system imbalance *  1/3727 (0.03%)  0/3739 (0.00%) 
Complicated migraine *  0/3727 (0.00%)  1/3739 (0.03%) 
Epilepsy *  0/3727 (0.00%)  1/3739 (0.03%) 
Headache *  0/3727 (0.00%)  1/3739 (0.03%) 
Hydrocephalus *  0/3727 (0.00%)  1/3739 (0.03%) 
Intracranial hypotension *  1/3727 (0.03%)  0/3739 (0.00%) 
Vascular headache *  1/3727 (0.03%)  0/3739 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous incomplete *  134/3727 (3.60%)  108/3739 (2.89%) 
False labour *  66/3727 (1.77%)  88/3739 (2.35%) 
Abortion spontaneous complete *  64/3727 (1.72%)  64/3739 (1.71%) 
Abortion missed *  59/3727 (1.58%)  63/3739 (1.68%) 
Foetal distress syndrome *  57/3727 (1.53%)  64/3739 (1.71%) 
Uterine hypotonus *  54/3727 (1.45%)  54/3739 (1.44%) 
Gestational hypertension *  39/3727 (1.05%)  53/3739 (1.42%) 
Abortion threatened *  42/3727 (1.13%)  37/3739 (0.99%) 
Cephalo-pelvic disproportion *  33/3727 (0.89%)  45/3739 (1.20%) 
Breech presentation *  40/3727 (1.07%)  33/3739 (0.88%) 
Pre-eclampsia *  18/3727 (0.48%)  23/3739 (0.62%) 
Failed induction of labour *  19/3727 (0.51%)  20/3739 (0.53%) 
Complication of pregnancy *  18/3727 (0.48%)  19/3739 (0.51%) 
Intra-uterine death *  16/3727 (0.43%)  18/3739 (0.48%) 
Foetal growth restriction *  18/3727 (0.48%)  14/3739 (0.37%) 
Premature rupture of membranes *  11/3727 (0.30%)  19/3739 (0.51%) 
Obstructed labour *  13/3727 (0.35%)  15/3739 (0.40%) 
Abnormal product of conception *  14/3727 (0.38%)  11/3739 (0.29%) 
Ectopic pregnancy *  9/3727 (0.24%)  14/3739 (0.37%) 
Postpartum haemorrhage *  13/3727 (0.35%)  7/3739 (0.19%) 
Oligohydramnios *  11/3727 (0.30%)  8/3739 (0.21%) 
Premature separation of placenta *  5/3727 (0.13%)  10/3739 (0.27%) 
Hyperemesis gravidarum *  6/3727 (0.16%)  8/3739 (0.21%) 
Multiple pregnancy *  8/3727 (0.21%)  2/3739 (0.05%) 
Placenta praevia haemorrhage *  6/3727 (0.16%)  4/3739 (0.11%) 
Foetal disorder *  7/3727 (0.19%)  2/3739 (0.05%) 
Large for dates baby *  4/3727 (0.11%)  4/3739 (0.11%) 
Premature delivery *  5/3727 (0.13%)  2/3739 (0.05%) 
Premature labour *  2/3727 (0.05%)  4/3739 (0.11%) 
Transverse presentation *  3/3727 (0.08%)  3/3739 (0.08%) 
Abortion incomplete *  4/3727 (0.11%)  1/3739 (0.03%) 
Umbilical cord abnormality *  3/3727 (0.08%)  2/3739 (0.05%) 
Eclampsia *  1/3727 (0.03%)  3/3739 (0.08%) 
Retained placenta or membranes *  4/3727 (0.11%)  0/3739 (0.00%) 
Abortion complicated *  3/3727 (0.08%)  0/3739 (0.00%) 
Foetal malpresentation *  0/3727 (0.00%)  3/3739 (0.08%) 
Placenta praevia *  2/3727 (0.05%)  1/3739 (0.03%) 
Polyhydramnios *  1/3727 (0.03%)  1/3739 (0.03%) 
Traumatic delivery *  1/3727 (0.03%)  1/3739 (0.03%) 
Umbilical cord prolapse *  2/3727 (0.05%)  0/3739 (0.00%) 
Abortion incomplete complicated *  0/3727 (0.00%)  1/3739 (0.03%) 
Abortion spontaneous incomplete complicated *  0/3727 (0.00%)  1/3739 (0.03%) 
Foetal malposition *  1/3727 (0.03%)  0/3739 (0.00%) 
Intrapartum haemorrhage *  1/3727 (0.03%)  0/3739 (0.00%) 
Pelvic haematoma obstetric *  0/3727 (0.00%)  1/3739 (0.03%) 
Placental disorder *  1/3727 (0.03%)  0/3739 (0.00%) 
Post abortion haemorrhage *  0/3727 (0.00%)  1/3739 (0.03%) 
Postpartum disorder *  0/3727 (0.00%)  1/3739 (0.03%) 
Previous caesarean section *  1/3727 (0.03%)  0/3739 (0.00%) 
Prolonged labour *  0/3727 (0.00%)  1/3739 (0.03%) 
Prolonged pregnancy *  1/3727 (0.03%)  0/3739 (0.00%) 
Twin pregnancy *  0/3727 (0.00%)  1/3739 (0.03%) 
Uterine inversion *  1/3727 (0.03%)  0/3739 (0.00%) 
Psychiatric disorders     
Intentional self-injury *  20/3727 (0.54%)  17/3739 (0.45%) 
Depression *  5/3727 (0.13%)  3/3739 (0.08%) 
Mental disorder *  5/3727 (0.13%)  3/3739 (0.08%) 
Post-traumatic stress disorder *  1/3727 (0.03%)  1/3739 (0.03%) 
Acute psychosis *  1/3727 (0.03%)  0/3739 (0.00%) 
Drug dependence *  0/3727 (0.00%)  1/3739 (0.03%) 
Emotional disorder *  1/3727 (0.03%)  0/3739 (0.00%) 
Psychotic disorder *  1/3727 (0.03%)  0/3739 (0.00%) 
Renal and urinary disorders     
Calculus urinary *  1/3727 (0.03%)  2/3739 (0.05%) 
Tubulointerstitial nephritis *  2/3727 (0.05%)  1/3739 (0.03%) 
Nephrolithiasis *  2/3727 (0.05%)  0/3739 (0.00%) 
Proteinuria *  2/3727 (0.05%)  0/3739 (0.00%) 
Calculus ureteric *  1/3727 (0.03%)  0/3739 (0.00%) 
Haematuria *  1/3727 (0.03%)  0/3739 (0.00%) 
Reproductive system and breast disorders     
Ovarian cyst *  5/3727 (0.13%)  6/3739 (0.16%) 
Uterine haemorrhage *  5/3727 (0.13%)  5/3739 (0.13%) 
Menometrorrhagia *  5/3727 (0.13%)  2/3739 (0.05%) 
Vaginal haemorrhage *  3/3727 (0.08%)  4/3739 (0.11%) 
Breast inflammation *  2/3727 (0.05%)  2/3739 (0.05%) 
Endometriosis *  2/3727 (0.05%)  2/3739 (0.05%) 
Pelvic pain *  1/3727 (0.03%)  3/3739 (0.08%) 
Perineal pain *  1/3727 (0.03%)  3/3739 (0.08%) 
Genital disorder female *  1/3727 (0.03%)  2/3739 (0.05%) 
Menstruation irregular *  1/3727 (0.03%)  2/3739 (0.05%) 
Bartholin’s cyst *  1/3727 (0.03%)  1/3739 (0.03%) 
Cervix disorder *  2/3727 (0.05%)  0/3739 (0.00%) 
Uterine polyp *  1/3727 (0.03%)  1/3739 (0.03%) 
Amenorrhoea *  1/3727 (0.03%)  0/3739 (0.00%) 
Breast disorder *  1/3727 (0.03%)  0/3739 (0.00%) 
Breast enlargement *  1/3727 (0.03%)  0/3739 (0.00%) 
Cervical dysplasia *  0/3727 (0.00%)  1/3739 (0.03%) 
Haematocolpos *  0/3727 (0.00%)  1/3739 (0.03%) 
Haematosalpinx *  1/3727 (0.03%)  0/3739 (0.00%) 
Ovarian torsion *  0/3727 (0.00%)  1/3739 (0.03%) 
Ovulation pain *  0/3727 (0.00%)  1/3739 (0.03%) 
Polycystic ovaries *  0/3727 (0.00%)  1/3739 (0.03%) 
Polymenorrhagia *  1/3727 (0.03%)  0/3739 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory disorder *  5/3727 (0.13%)  2/3739 (0.05%) 
Asthma *  2/3727 (0.05%)  0/3739 (0.00%) 
Status asthmaticus *  2/3727 (0.05%)  0/3739 (0.00%) 
Bronchitis chronic *  1/3727 (0.03%)  0/3739 (0.00%) 
Dyspnoea *  1/3727 (0.03%)  0/3739 (0.00%) 
Neonatal respiratory failure *  0/3727 (0.00%)  1/3739 (0.03%) 
Pleural effusion *  1/3727 (0.03%)  0/3739 (0.00%) 
Skin and subcutaneous tissue disorders     
Urticaria *  0/3727 (0.00%)  2/3739 (0.05%) 
Granuloma skin *  0/3727 (0.00%)  1/3739 (0.03%) 
Skin disorder *  0/3727 (0.00%)  1/3739 (0.03%) 
Toxic skin eruption *  0/3727 (0.00%)  1/3739 (0.03%) 
Social circumstances     
Physical assault *  3/3727 (0.08%)  0/3739 (0.00%) 
Sexual abuse *  1/3727 (0.03%)  0/3739 (0.00%) 
Surgical and medical procedures     
Caesarean section *  56/3727 (1.50%)  59/3739 (1.58%) 
Therapeutic procedure *  0/3727 (0.00%)  1/3739 (0.03%) 
Vascular disorders     
Hypertension *  5/3727 (0.13%)  6/3739 (0.16%) 
Essential hypertension *  4/3727 (0.11%)  1/3739 (0.03%) 
Circulatory collapse *  2/3727 (0.05%)  1/3739 (0.03%) 
Phlebitis *  0/3727 (0.00%)  2/3739 (0.05%) 
Varicose vein *  0/3727 (0.00%)  2/3739 (0.05%) 
Embolism venous *  0/3727 (0.00%)  1/3739 (0.03%) 
Varicophlebitis *  0/3727 (0.00%)  1/3739 (0.03%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cervarix Group Havrix Group
Affected / at Risk (%) Affected / at Risk (%)
Total   1627/3730 (43.62%)   1610/3740 (43.05%) 
Gastrointestinal disorders     
Gastrointestinal inflammation * [1]  263/3727 (7.06%)  249/3739 (6.66%) 
General disorders     
Pain  [2]  1627/3730 (43.62%)  1610/3740 (43.05%) 
Redness  [2]  544/3730 (14.58%)  501/3740 (13.40%) 
Swelling  [2]  207/3730 (5.55%)  201/3740 (5.37%) 
Fatigue  [2]  512/3730 (13.73%)  502/3740 (13.42%) 
Myalgia  [2]  257/3730 (6.89%)  232/3740 (6.20%) 
Gastrointestinal  [2]  191/3730 (5.12%)  171/3740 (4.57%) 
Headache  [2]  714/3730 (19.14%)  718/3740 (19.20%) 
Fever  [2]  472/3730 (12.65%)  477/3740 (12.75%) 
Pain  [3]  202/380 (53.16%)  74/376 (19.68%) 
Swelling  [3]  23/380 (6.05%)  1/376 (0.27%) 
Fatigue  [3]  214/380 (56.32%)  189/376 (50.27%) 
Myalgia  [3]  250/380 (65.79%)  211/376 (56.12%) 
Arthralgia  [3]  44/380 (11.58%)  32/376 (8.51%) 
Gastrointestinal  [3]  157/380 (41.32%)  119/376 (31.65%) 
Headache  [3]  247/380 (65.00%)  242/376 (64.36%) 
Rash  [3]  31/380 (8.16%)  26/376 (6.91%) 
Fever  [3]  43/380 (11.32%)  37/376 (9.84%) 
Infections and infestations     
Influenza * [4]  263/3727 (7.06%)  293/3739 (7.84%) 
Influenza * [1]  903/3727 (24.23%)  950/3739 (25.41%) 
Vaginal infection * [1]  709/3727 (19.02%)  763/3739 (20.41%) 
Vulvovaginal candidiasis * [1]  714/3727 (19.16%)  678/3739 (18.13%) 
Urinary tract infection * [1]  555/3727 (14.89%)  565/3739 (15.11%) 
Upper respiratory tract infection * [1]  324/3727 (8.69%)  327/3739 (8.75%) 
Dengue fever * [1]  174/3727 (4.67%)  190/3739 (5.08%) 
Musculoskeletal and connective tissue disorders     
Myalgia * [4]  355/3727 (9.53%)  166/3739 (4.44%) 
Myalgia * [1]  386/3727 (10.36%)  189/3739 (5.05%) 
Nervous system disorders     
Headache * [4]  218/3727 (5.85%)  214/3739 (5.72%) 
Headache * [1]  324/3727 (8.69%)  315/3739 (8.42%) 
Reproductive system and breast disorders     
Menstruation irregular * [1]  1021/3727 (27.39%)  1011/3739 (27.04%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
From Month 0 up to Month 48
[2]
Within 60 minutes after vaccination.
[3]
From Day 3 to Day 6 post-vaccination, in a 10% random subset of participants.
[4]
Within 30 days (Days 0-29) after vaccination
The following analysis "occurence of histopathologically confirmed CIN2+ cases associated with HPV16 or HPV18 infection was not performed, in accordance with the Statistical Analysis Plan submitted to the FDA.
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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Kreimer AR, Struyf F, Del Rosario-Raymundo MR, Hildesheim A, Skinner SR, Wacholder S, Garland SM, Herrero R, David MP, Wheeler CM; Costa Rica Vaccine Trial Study Group Authors, González P, Jiménez S, Lowy DR, Pinto LA, Porras C, Rodriguez AC, Safaeian M, Schiffman M, Schiller JT, Schussler J, Sherman ME; PATRICIA Study Group Authors, Bosch FX, Castellsague X, Chatterjee A, Chow SN, Descamps D, Diaz-Mitoma F, Dubin G, Germar MJ, Harper DM, Lewis DJ, Limson G, Naud P, Peters K, Poppe WA, Ramjattan B, Romanowski B, Salmeron J, Schwarz TF, Teixeira JC, Tjalma WA; HPV PATRICIA Principal Investigators/Co-Principal Investigator Collaborators; GSK Vaccines Clinical Study Support Group. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials. Lancet Oncol. 2015 Jul;16(7):775-86. doi: 10.1016/S1470-2045(15)00047-9. Epub 2015 Jun 9.
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00128661     History of Changes
Obsolete Identifiers: NCT00344357
Other Study ID Numbers: CDR0000441189
NCI-04-C-N191
NCI-590299/009
GSK-590299/009 ( Other Identifier: GSK Bio )
First Submitted: August 8, 2005
First Posted: August 10, 2005
Results First Submitted: December 15, 2011
Results First Posted: May 2, 2012
Last Update Posted: March 8, 2019