Cervical Cancer, Precancerous Condition
Conditions
Keywords
cervical intraepithelial neoplasia grade 2, cervical cancer, cervical intraepithelial neoplasia grade 3
Brief summary
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer form forming, growing, or coming back. Vaccines may help the body build an effective immune response against human papillomavirus and may be effective in preventing cervical intraepithelial neoplasia or cervical cancer. It is not yet known whether human papillomavirus vaccine is more effective than hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer. PURPOSE: This randomized phase III trial is studying human papillomavirus vaccine to see how well it works compared to hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer in younger healthy participants.
Detailed description
OBJECTIVES: Primary •Demonstrate the efficacy of the candidate vaccine, human papillomavirus 16/18 (HPV 16/18) L1 virus-like particle (VLP)/AS04 vaccine compared with control in preventing grade 2 or 3 cervical intraepithelial neoplasia, adenocarcinoma in situ of the cervix, or invasive cervical cancer (CIN2+) associated with HPV 16 or HPV 18 cervical infection in younger healthy participants who are negative for HPV DNA by polymerase chain reaction (PCR) for the corresponding HPV type at months 0 and 6. Secondary * Determine the duration of protection against HPV 16 or HPV 18 cervical infection in participants treated with the HPV 16/18 L1 VLP/AS04 vaccine. * Determine the safety of this vaccine in these participants, regardless of their initial HPV 16/18 DNA status. * Evaluate the efficacy of the candidate vaccine, HPV 16/18 L1 VLP/AS04 vaccine compared with control in preventing CIN2+ associated with any oncogenic HPV type cervical infection in participants who are negative for HPV DNA by PCR for the corresponding HPV type at months 0 and 6. * Compare the efficacy of the candidate vaccine with control in preventing CIN2+ associated with HPV 16 or HPV 18 cervical infection, detected within the lesional component of the cervical tissue specimen by PCR, in participants who are negative for HPV DNA by PCR for the corresponding HPV type at months 0 and 6 and by enzyme-linked immunosorbent assay (ELISA) at month 0. * Compare the efficacy of the candidate vaccine with control in preventing persistent HPV 16 or HPV 18 cervical infection in these participants. * Determine the immunogenicity of HPV 16/18 L1 VLP/AS04 vaccine by ELISA and V5/J4 monoclonal antibody inhibition enzyme immunoassay in the first 600 participants randomized to receive HPV 16/18 L1 VLP/AS04 vaccine. OUTLINE: This is a randomized, controlled, double-blind, parallel-group study. Participants are randomized to 1 of 2 treatment arms. * Arm I: Participants receive human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine intramuscularly (IM) once in months 0, 1, and 6. * Arm II: Participants receive hepatitis A vaccine (Havrix®) IM once in months 0, 1, and 6. After completion of study treatment, participants are followed at 6 months and then at least annually for 3 years. PROJECTED ACCRUAL: Approximately 7,500 participants will be accrued for this study.
Interventions
BIOLOGICALhuman papillomavirus 16/18 L1 virus-like particle/AS04 vaccine
Three doses of Cervarix vaccine administered on a 0, 1, 6-month schedule
BIOLOGICALhepatitis A inactivated virus vaccine
Three doses of Havrix vaccine administered on a 0, 1, 6-month schedule
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 25 Years
Healthy volunteers
Yes
Inclusion criteria
DISEASE CHARACTERISTICS: •Healthy participants * Deemed to be in good general health by history and physical examination •Resident of Guanacaste Province of Costa Rica and surrounding areas * Must remain a resident for ≥ 6 months after the first study vaccination PATIENT CHARACTERISTICS: Age * 18 to 25 Performance status •Not specified Life expectancy •Not specified Hematopoietic •Not specified Hepatic * No history of chronic hepatitis requiring treatment * No acute or chronic clinically significant hepatic function abnormality by physical examination or laboratory findings * No known history of hepatitis A infection Renal * No history of kidney disease requiring treatment * No acute or chronic clinically significant kidney function abnormality by physical examination or laboratory findings Cardiovascular * No acute or chronic clinically significant cardiovascular function abnormality by physical examination or laboratory findings Pulmonary * No acute or chronic clinically significant pulmonary function abnormality by physical examination or laboratory findings Immunology * No history of allergic disease * No history of autoimmune disorder requiring treatment * No history of allergic reaction (e.g., difficulty breathing) to any vaccine * No suspected allergy or reaction likely to be exacerbated by a component of the study vaccines (e.g., 2-phenoxyethanol or neomycin) * No hypersensitivity to latex * No diagnosis or suspicion of any immunodeficient condition by medical history or physical examination Other * Not pregnant or nursing ◦No delivery within the past 3 months * Negative pregnancy test * Fertile patients must use effective contraception for 30 days before, during, and for 60 days after completion of study treatment * Able to speak or understand Spanish * Mentally competent * Able to undergo pelvic exam (i.e., no heavy bleeding \[menstruation or otherwise\] or heavy vaginal discharge) * No history of cancer requiring treatment * No history of diabetes requiring treatment * No history of other chronic conditions requiring treatment * No acute or chronic clinically significant neurologic function abnormality by physical examination or laboratory findings * No other acute disease * No fever ≥ 37.5º C PRIOR CONCURRENT THERAPY: Biologic therapy * More than 6 months since prior chronic administration (i.e., \> 14 days) of immune-modulating drugs * More than 90 days since prior immunoglobulins * More than 30 days since prior and no other concurrent investigational or non-registered vaccines * More than 30 days since prior registered vaccines * More than 8 days since prior routine meningococcal, hepatitis B, influenza, or diphtheria/tetanus vaccine * No prior vaccination against hepatitis A * No prior vaccination against human papillomavirus * No prior monophosphoryl lipid A or AS04 adjuvant Chemotherapy •Not specified Endocrine therapy * More than 6 months since prior chronic administration (i.e., \> 14 days) of corticosteroids (e.g., ≥ 0.5 mg/kg/day of prednisone or equivalent) * Concurrent inhaled or topical steroids allowed Radiotherapy •Not specified Surgery •No prior hysterectomy Other * More than 6 months since prior chronic administration (i.e., \> 14 days) of immunosuppressants * More than 30 days since prior and no other concurrent investigational or non-registered drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen. | From Month 6 up to Month 48 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Cervical Infection With HPV16 or HPV18. | From Month 6 up to Month 48 | Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type |
| Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | From Month 6 up to Month 48 | 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 |
| Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases | From Month 6 up to Month 48 | 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. |
| Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 | 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) |
| Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 | 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). |
| HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 | 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). |
| Number of Subjects Reporting Serious Adverse Events (SAEs). | During the entire study period (From Month 0 up to Month 48). | 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. |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Within 60 minutes after vaccination | 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). |
| Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Within 60 minutes after vaccination | 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. |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | From Day 3 to Day 6 after vaccination | 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). |
| Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | From Day 3 to Day 6 after vaccination | 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. |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs). | During the entire study period (From Month 0 up to Month 48). | 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. |
| Number of Subjects With All Possible Pregnancy Outcomes | During the entire study period (From Month 0 up to Month 48). | The range of possible pregnancy outcomes was: Pregnancy loss, Pregnancy resolved alive, and Unresolved pregnancy. |
| HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 | 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). |
Countries
Costa Rica
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm. | 3,727 |
| Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm. | 3,739 |
| Total | 7,466 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 11 |
| Overall Study | Lost to Follow-up | 10 | 7 |
| Overall Study | Other | 7 | 8 |
| Overall Study | Withdrawal by Subject | 243 | 232 |
Baseline characteristics
| Characteristic | Cervarix Group | Havrix Group | Total |
|---|---|---|---|
| Age, Continuous Years | 21.1 Years STANDARD_DEVIATION 2.3 | 21.1 Years STANDARD_DEVIATION 2.3 | 21.1 Years STANDARD_DEVIATION 2.3 |
| Sex: Female, Male Female | 3727 Participants | 3739 Participants | 7466 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1,627 / 3,730 | 1,610 / 3,740 |
| serious Total, serious adverse events | 912 / 3,727 | 891 / 3,739 |
Outcome results
Primary
Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen. | HPV16 Associated CIN2+ (N=2464;2452) | 1 Events |
| Cervarix Group | Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen. | HPV18 Associated CIN2+ (N=2567; 2593) | 0 Events |
| Cervarix Group | Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen. | HPV16 and/or 18 Associated CIN2+ (N=2635;2677) | 1 Events |
| Havrix Group | Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen. | HPV16 Associated CIN2+ (N=2464;2452) | 9 Events |
| Havrix Group | Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen. | HPV18 Associated CIN2+ (N=2567; 2593) | 2 Events |
| Havrix Group | Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen. | HPV16 and/or 18 Associated CIN2+ (N=2635;2677) | 10 Events |
Secondary
Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 7] (N=195,157) | 3261 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 24] (N=175,137) | 1486 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 6] (N=195,156) | 771.5 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 30] (N=19,15) | 1070 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 12] (N=182,146) | 2090 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 36] (N=163,132) | 1256 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 1] (N=196,157) | 646.6 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 42] (N=22,18) | 1259 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 18] (N=25,17) | 1045 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 48] (N=172,131) | 1155 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [before vaccination] (N=194;156) | 6.7 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 48] (N=172,131) | 9.5 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [before vaccination] (N=194;156) | 8.2 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 1] (N=196,157) | 7.9 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 6] (N=195,156) | 8.4 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 7] (N=195,157) | 8.5 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 12] (N=182,146) | 8.3 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 18] (N=25,17) | 10.4 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 24] (N=175,137) | 8.6 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 30] (N=19,15) | 11.9 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 36] (N=163,132) | 9.0 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. | HPV-16 [at Month 42] (N=22,18) | 6.1 Titers |
Secondary
Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 7] (N=202;175) | 3276 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 24] (N=178;150) | 633.0 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 6] (N=203;175) | 532.2 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 30] (N=17;19) | 403.8 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 12] (N=190;166) | 1082 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 36] (N=168;145) | 519.7 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 1] (N=203;170) | 372.7 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 42] (N=25;19) | 582.4 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 18] (N=28;20) | 502.4 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 48] (N=179;149) | 470.1 Titers |
| Cervarix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [before vaccination] (N=200;173) | 5.4 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 48] (N=179;149) | 6.6 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [before vaccination] (N=200;173) | 6.2 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 1] (N=203;170) | 6.4 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 6] (N=203;175) | 6.7 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 7] (N=202;175) | 6.8 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 12] (N=190;166) | 7.0 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 18] (N=28;20) | 6.7 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 24] (N=178;150) | 6.9 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 30] (N=17;19) | 6.4 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 36] (N=168;145) | 6.0 Titers |
| Havrix Group | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort | HPV-18 [at Month 42] (N=25;19) | 5.5 Titers |
Secondary
HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 7] (N=193;158) | 1047 Titers |
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 24] (N=169;138) | 184.6 Titers |
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 6] (N=189;156) | 80.9 Titers |
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 30] (N=18;15) | 112.4 Titers |
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 12] (N=175;146) | 291.4 Titers |
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 36] (N=162;132) | 139.7 Titers |
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 1] (N=182;155) | 58.5 Titers |
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 42] (N=22;18) | 126.9 Titers |
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 18] (N=24;17) | 116.6 Titers |
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 48] (N=168;133) | 131.8 Titers |
| Cervarix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [before vaccination] (N=196;158) | 21.1 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 48] (N=168;133) | 21.0 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [before vaccination] (N=196;158) | 21.4 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 1] (N=182;155) | 21.5 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 6] (N=189;156) | 21.5 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 7] (N=193;158) | 21.4 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 12] (N=175;146) | 22.6 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 18] (N=24;17) | 20.5 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 24] (N=169;138) | 21.4 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 30] (N=18;15) | 20.5 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 36] (N=162;132) | 20.8 Titers |
| Havrix Group | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) | HPV-16 [at Month 42] (N=22;18) | 20.5 Titers |
Secondary
HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 48 (N=179;150) | 96.9 Titers |
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 6] (N=195;175) | 111.4 Titers |
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 42] (N=25;19) | 103.3 Titers |
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 7] (N=198;176) | 823.6 Titers |
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [before vaccination] (N=203;176) | 55.0 Titers |
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 12] (N=182;166) | 231.1 Titers |
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 36] (N=167;145) | 107.9 Titers |
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 18] (N=28;20) | 121.8 Titers |
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 1] (N=197;173) | 99.1 Titers |
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 24] (N=170;154) | 140.8 Titers |
| Cervarix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 30] (N=17;19) | 89.5 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 24] (N=170;154) | 55.0 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 30] (N=17;19) | 55.0 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 36] (N=167;145) | 55.0 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 42] (N=25;19) | 55.0 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 48 (N=179;150) | 56.7 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [before vaccination] (N=203;176) | 55.7 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 1] (N=197;173) | 55.3 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 6] (N=195;175) | 55.4 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 7] (N=198;176) | 55.0 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 12] (N=182;166) | 56.7 Titers |
| Havrix Group | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) | HPV-18 [at Month 18] (N=28;20) | 55.0 Titers |
Secondary
Number of Cervical Infection With HPV16 or HPV18.
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV18 Cervical Infection (N=2269;2307) | 9 Events |
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 and/or 18 Cervical Infection (N=2313;2349) | 18 Events |
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 Cervical Infection (N=2170;2176) | 10 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV18 Cervical Infection (N=2269;2307) | 47 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 Cervical Infection (N=2170;2176) | 77 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 and/or 18 Cervical Infection (N=2313;2349) | 117 Events |
Secondary
Number of Cervical Infection With HPV16 or HPV18.
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 Cervical Infection (N=2464;2452) | 50 Events |
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV18 Cervical Infection (N=2567;2593) | 32 Events |
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 and/or 18 Cervical Infection (N=2635;2677) | 78 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 Cervical Infection (N=2464;2452) | 251 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV18 Cervical Infection (N=2567;2593) | 177 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 and/or 18 Cervical Infection (N=2635;2677) | 387 Events |
Secondary
Number of Cervical Infection With HPV16 or HPV18.
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 Cervical Infection (N=2277;2139) | 13 Events |
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV18 Cervical Infection (N=2389;2325) | 10 Events |
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 and/or 18 Cervical Infection (N=2421;2261) | 22 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 Cervical Infection (N=2277;2139) | 77 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV18 Cervical Infection (N=2389;2325) | 57 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 and/or 18 Cervical Infection (N=2421;2261) | 118 Events |
Secondary
Number of Cervical Infection With HPV16 or HPV18.
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 Cervical Infection (N=2097;2026) | 6 Events |
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV18 Cervical Infection (N=2200;2196) | 6 Events |
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 and/or 18 Cervical Infection (N=2236;2166) | 11 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 Cervical Infection (N=2097;2026) | 60 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV18 Cervical Infection (N=2200;2196) | 44 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 and/or 18 Cervical Infection (N=2236;2166) | 88 Events |
Secondary
Number of Cervical Infection With HPV16 or HPV18.
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 Cervical Infection (N=2242;2232) | 21 Events |
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV18 Cervical Infection (N=2330;2347) | 7 Events |
| Cervarix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 and/or 18 Cervical Infection (N=2380;2420) | 27 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 Cervical Infection (N=2242;2232) | 37 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV18 Cervical Infection (N=2330;2347) | 29 Events |
| Havrix Group | Number of Cervical Infection With HPV16 or HPV18. | HPV16 and/or 18 Cervical Infection (N=2380;2420) | 64 Events |
Secondary
Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV35 Associated CIN2+ (N=2593;2631) | 0 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV52 Associated CIN2+ (N=2456;2505) | 5 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV18 Associated CIN2+ (N=2567,2593) | 0 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV56 Associated CIN2+ (N=2524;2564) | 1 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV39 Associated CIN2+ (N=2528;2581) | 0 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV58 Associated CIN2+ (N=2551;2595) | 2 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV33 Associated CIN2+ (N=2596;2645) | 0 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV59 Associated CIN2+ (N=2576;2637) | 3 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV45 Associated CIN2+ (N=2573;2622) | 1 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV68 and/or 73 Associated CIN2+ (N=2519;2576) | 1 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV31 Associated CIN2+ (N=2525;2546) | 1 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | Non 16/18 Onco HPV Associated CIN2+ (N=2643;2697) | 11 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV51 Associated CIN2+ (N=2453;2539) | 1 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | Any Oncogenic HPV Associated CIN2+ (N=2643;2697) | 11 Events |
| Cervarix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV16 Associated CIN2+ (N=2464;2452) | 1 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | Any Oncogenic HPV Associated CIN2+ (N=2643;2697) | 33 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV16 Associated CIN2+ (N=2464;2452) | 9 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV18 Associated CIN2+ (N=2567,2593) | 2 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV31 Associated CIN2+ (N=2525;2546) | 6 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV33 Associated CIN2+ (N=2596;2645) | 3 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV35 Associated CIN2+ (N=2593;2631) | 4 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV39 Associated CIN2+ (N=2528;2581) | 0 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV45 Associated CIN2+ (N=2573;2622) | 1 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV51 Associated CIN2+ (N=2453;2539) | 6 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV52 Associated CIN2+ (N=2456;2505) | 10 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV56 Associated CIN2+ (N=2524;2564) | 5 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV58 Associated CIN2+ (N=2551;2595) | 5 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV59 Associated CIN2+ (N=2576;2637) | 3 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | HPV68 and/or 73 Associated CIN2+ (N=2519;2576) | 4 Events |
| Havrix Group | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type | Non 16/18 Onco HPV Associated CIN2+ (N=2643;2697) | 28 Events |
Secondary
Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases | Persistent HPV16 Infection (N=2464,2452) | 10 Events |
| Cervarix Group | Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases | Persistent HPV18 Infection (N=2567;2593) | 0 Events |
| Cervarix Group | Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases | Persistent HPV16 and/or 18 Infection (N=2635;2677) | 10 Events |
| Havrix Group | Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases | Persistent HPV16 Infection (N=2464,2452) | 71 Events |
| Havrix Group | Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases | Persistent HPV18 Infection (N=2567;2593) | 37 Events |
| Havrix Group | Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases | Persistent HPV16 and/or 18 Infection (N=2635;2677) | 104 Events |
Secondary
Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.
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
Population: The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any fatigue | 512 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 fatigue | 6 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any myalgia | 257 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 myalgia | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any arthralgia | 58 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 arthralgia | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any gastrointestinal | 191 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 gastrointestinal | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any headache | 714 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 headache | 2 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any rash | 15 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 rash | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any urticaria | 19 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 urticaria | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Fever (oral) >= 37.5°C | 472 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Fever (oral) > 39.0°C | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Fever (oral) > 39.0°C | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any fatigue | 502 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any headache | 718 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 fatigue | 5 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any urticaria | 21 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any myalgia | 232 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 headache | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 myalgia | 1 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Fever (oral) >= 37.5°C | 477 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any arthralgia | 64 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any rash | 17 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 arthralgia | 1 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 urticaria | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Any gastrointestinal | 171 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 rash | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Grade 3 gastrointestinal | 0 Subjects |
Secondary
Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.
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
Population: The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any pain | 214 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 pain | 2 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any myalgia | 250 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 myalgia | 1 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any arthralgia | 44 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 arthralgia | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any gastrointestinal | 157 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 gastrointestinal | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any headache | 247 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 headache | 1 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any rash | 31 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 rash | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any urticaria | 3 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 urticaria | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Fever (oral) >= 37.5°C | 43 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Fever (oral) > 39.0°C | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Fever (oral) > 39.0°C | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any pain | 189 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any headache | 242 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 pain | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any urticaria | 1 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any myalgia | 211 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 headache | 2 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 myalgia | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Fever (oral) >= 37.5°C | 37 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any arthralgia | 32 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any rash | 26 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 arthralgia | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 urticaria | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Any gastrointestinal | 119 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 rash | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. | Grade 3 gastrointestinal | 1 Subjects |
Secondary
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
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
Population: The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any pain | 1627 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 pain | 25 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any redness | 544 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 redness > 50 mm | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any swelling | 207 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 swelling > 50 mm | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any swelling | 201 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any pain | 1610 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 redness > 50 mm | 2 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 pain | 20 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 swelling > 50 mm | 1 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any redness | 501 Subjects |
Secondary
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.
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
Population: The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Any pain | 202 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Grade 3 pain | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Any redness | 6 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Grade 3 redness | 1 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Any swelling | 23 Subjects |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Grade 3 swelling | 7 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Any swelling | 1 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Any pain | 74 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Grade 3 redness | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Grade 3 pain | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Grade 3 swelling | 0 Subjects |
| Havrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. | Any redness | 1 Subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs).
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).
Population: The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Serious Adverse Events (SAEs). | 912 Subjects |
| Havrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs). | 891 Subjects |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AEs).
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).
Population: The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs). | 3228 Subjects |
| Havrix Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs). | 3254 Subjects |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AEs).
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
Population: The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs). | 1638 Subjects |
| Havrix Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs). | 1536 Subjects |
Secondary
Number of Subjects With All Possible Pregnancy Outcomes
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).
Population: The analysis was performed on the Total Vaccinated Cohort, on all pregnant subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects With All Possible Pregnancy Outcomes | Pregnancy loss | 317 subjects |
| Cervarix Group | Number of Subjects With All Possible Pregnancy Outcomes | Pregnancy resolved alive | 1756 subjects |
| Cervarix Group | Number of Subjects With All Possible Pregnancy Outcomes | Unresolved pregnancy | 50 subjects |
| Havrix Group | Number of Subjects With All Possible Pregnancy Outcomes | Pregnancy loss | 294 subjects |
| Havrix Group | Number of Subjects With All Possible Pregnancy Outcomes | Pregnancy resolved alive | 1766 subjects |
| Havrix Group | Number of Subjects With All Possible Pregnancy Outcomes | Unresolved pregnancy | 69 subjects |