Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. This Phase IIb study is designed to evaluate the the long-term efficacy, safety and immunogenicity of the 580299 HPV vaccine (CervarixTM) in a Brazilian cohort of women vaccinated in the phase IIb, blinded, primary study 580299/001 (NCT00689741) and having participated in follow-up study 580299/007 (NCT00120848). Only subjects who participated in the primary \& follow-up study will be enrolled in this long-term follow-up study. Subjects were aged 15-25 years at the time of entry into the primary study. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
In this extension study, women who were vaccinated in the primary study, and participated in the follow-up study, will be followed with visits every 6 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
433
Blood sampling at Visit 3, 5 and 7.
Collection of cervical specimen at Visit2, 3, 4, 5, 6 and 7.
Three doses administered intramuscularly at 0, 1 and 6 months.
GSK Investigational Site
Curitiba, Paraná, Brazil
GSK Investigational Site
Porto Alegre, Rio Grande do Sul, Brazil
GSK Investigational Site
São Paulo, São Paulo, Brazil
GSK Investigational Site
Campinas, Brazil
GSK Investigational Site
Fortaleza, Brazil
Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and/or HPV-18
Cervical HPV infection was defined as the first detection of an HPV type in a subject previously negative for that HPV type.
Time frame: Up to year 8
Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and/or HPV-18
Cervical HPV infection was defined as the first detection of an HPV type in a subject previously negative for that HPV type
Time frame: Up to year 9
Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and /or HPV-18
Cervical HPV infection was defined as the first detection of an HPV type in a subject previously negative for that HPV type.
Time frame: Up to year 7
Number of Subjects Presenting Cervical Infections With Any Oncogenic HPV Type
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects Presenting Cervical Infections With Individual Oncogenic Non-vaccine HPV Type
Oncogenic types included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 and/or HPV-18
Persistent cervical HPV infection (6-month definition) was defined as detection of the same HPV type in cervical specimens at 2 consecutive evaluations over a minimum of 5 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Persistent Infection (6-month Definition) With Any Oncogenic HPV Types
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (6-month definition) was defined as detection of the same HPV type in cervical specimens at 2 consecutive evaluations over a minimum of 5 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Persistent Infection (6-month Definition) With Individual Oncogenic Non-vaccine HPV Types
Oncogenic HPV types included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (6-month definition) was defined as detection of the same HPV type in cervical specimens at 2 consecutive evaluations over a minimum of 5 months. Subjects with an event did not report the same event during the earlier studies. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Persistent Infection (12-month Definition) With HPV-16 and/or HPV-18
Persistent cervical HPV infection (12-month definition) was defined as detection of the same HPV type in cervical specimens at all consecutive evaluations over a minimum of 10 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Persistent Infection (12-month Definition) With Any Oncogenic HPV Types
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (12-month definition) was defined as detection of the same HPV type in cervical specimens at all consecutive evaluations over a minimum of 10 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Persistent Infection (12-month Definition) With Individual Oncogenic Non-vaccine HPV Types
Individual oncogenic non-vaccine HPV types include HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (12-month definition) was defined as detection of the same HPV type in cervical specimens at all consecutive evaluations over a minimum of 10 months. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN1+ was defined as CIN (Cervical Intraepithelial Neoplasia) grades 1,2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN1+ was defined as CIN grades 1,2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN1+ was defined as CIN grades 1,2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Oncogenic HPV types assessed included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN2+ was defined as CIN grades 2 and 3, AIS and invasive cervical cancer. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN2+ was defined as CIN grades 2 and 3, AIS and invasive cervical cancer. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN2+ was defined as CIN grades 2 and 3, AIS and invasive cervical cancer. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. and were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With an HPV 16 and/or HPV-18 Cervical Infection
Abnormal cytology included atypical squamus cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), atypical glandular cells (AGC), atypical squamus cells and cannot exclude HSIL (ASC-H). Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With Oncogenic HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC, and ASC-H. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC and ASC-H. Oncogenic HPV types assessed included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With an HPV 16 and/or HPV-18 Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC and ASC-H. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC, and ASC-H. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 8
Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC and ASC-H. Oncogenic HPV types assessed included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 8
Anti-HPV-16 and Anti-HPV-18 Enzyme-linked Immunosorbent Assay (ELISA) Titers in the Immunogenicity Cohort
Titers are given as Geometric Mean Titers (GMTs) expressed as ELISA Units per milliliter (EL.U/mL).
Time frame: At Months 77-101
Anti-HPV-16 and Anti-HPV-18 Pseudovirion-based Neutralization Assay (PBNA) Titers in the Immunogenicity Subset
Data are expressed as Geometric Mean Titers (GMTs). The titer is the serum dilution giving a 50 percent reduction of the signal compared to a control without serum
Time frame: At Months 77-101
Number of Subjects With New Onset Chronic Diseases (NOCD) up to Year 7
NOCDs include for example asthma, type I diabetes, allergies, ...
Time frame: Up to year 7
Number of Subjects With NOCD up to Year 8
NOCDs included for example asthma, type I diabetes, allergies, ... NOCDs which were not unblinded at the subject level at the time of the analysis are not presented and will be disclosed as soon as they become available.
Time frame: Up to year 8
Number of Subjects With New Onset Autoimmune Disease (NOAD) up to Year 7
Time frame: Up to year 7
Number of Subjects With NOAD up to Year 8
The values of NOADs are not yet corresponding to the values in each group. The cases are still blinded. They will be disclosed as soon as the results will be available.
Time frame: Up to year 8
Number of Subjects With Medically Significant Conditions up to Year 7
Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. Medically significant conditions which were not unblinded at the time of the analysis are not presented yet.
Time frame: Up to year 7
Number of Subjects With Medically Significant Conditions up to Year 8
Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. Medically significant conditions which were not unblinded at the time of the analysis are not presented yet.
Time frame: up to year 8
Number of Subjects With Serious Adverse Events (SAEs) up to Year 7
SAEs assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject
Time frame: Up to year 7
Number of Subjects With SAEs up to Year 8
SAEs assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject
Time frame: up to year 8
Number of Subjects Presenting Cervical Infections With Any Oncogenic HPV Type.
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects Presenting Cervical Infections With Individual Oncogenic Non-vaccine HPV Type
Oncogenic types included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 and/or HPV-18
Persistent cervical HPV infection (6-month definition) was defined as detection of the same HPV type in cervical specimens at 2 consecutive evaluations over a minimum of 5 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study
Time frame: Up to year 9
Number of Subjects With Persistent Infection (6-month Definition) With Any Oncogenic HPV Type
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (6-month definition) was defined as detection of the same HPV type in cervical specimens at 2 consecutive evaluations over a minimum of 5 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Persistent Infection (6-month Definition) With Individual Oncogenic Non-vaccine HPV Types
Oncogenic HPV types included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (6-month definition) was defined as detection of the same HPV type in cervical specimens at 2 consecutive evaluations over a minimum of 5 months. Subjects with an event did not report the same event during the earlier studies. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Persistent Infection (12-month Definition) With HPV-16 and/or HPV-18
Persistent cervical HPV infection (12-month definition) was defined as detection of the same HPV type in cervical specimens at all consecutive evaluations over a minimum of 10 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study
Time frame: Up to year 9
Number of Subjects With Persistent Infection (12-month Definition) With Any Oncogenic HPV Types
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (12-month definition) was defined as detection of the same HPV type in cervical specimens at all consecutive evaluations over a minimum of 10 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Persistent Infection (12-month Definition) With Individual Oncogenic Non-vaccine HPV Types
Individual oncogenic non-vaccine HPV types include HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (12-month definition) was defined as detection of the same HPV type in cervical specimens at all consecutive evaluations over a minimum of 10 months. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study
Time frame: Up to year 9
Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
Cervical Intraepithelial Neoplasia (CIN1)+ was defined as CIN grades 1,2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN1+ was defined as CIN grades 1,2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN1+ was defined as CIN grades 1,2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Oncogenic HPV types assessed included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN2+ was defined as CIN grades 2 and 3, AIS and invasive cervical cancer. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN2+ was defined as CIN grades 2 and 3, AIS and invasive cervical cancer. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN2+ was defined as CIN grades 2 and 3, AIS and invasive cervical cancer. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undertermined Significance (ASC-US) Associated With an HPV 16 and/or HPV-18 Cervical Infection
Abnormal cytology included atypical squamus cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), atypical glandular cells (AGC), atypical squamus cells and cannot exclude HSIL (ASC-H). Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study
Time frame: Up to year 9
Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undertermined Significance (ASC-US) Associated With Oncogenic HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC, and ASC-H. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undertermined Significance (ASC-US) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC and ASC-H. Oncogenic HPV types assessed included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study
Time frame: Up to year 9
Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With an HPV 16 and/or HPV-18 Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC and ASC-H. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC, and ASC-H. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 9
Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC and ASC-H. Oncogenic HPV types assessed included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 9
Anti-HPV-16 and Anti-HPV-18 Enzyme-linked Immunosorbent Assay (ELISA) Titers in the Immunogenicity Cohort
Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked immunosorbent assay (ELISA) Units per milliliter (EL.U/mL). The cut-off-vales assessed were \>= 8 or 7 EL. U/mL for anti-HPV-16 and 18, respectively.
Time frame: At Month 77 until year 9 (Month 113)
Anti-HPV-16 and Anti-HPV-18 Pseudovirion-based Neutralization Assay (PBNA) Titers in the Immunogenicity Subset
Data are expressed as Geometric Mean Titers (GMTs). The titer is the serum dilution giving a 50 percent reduction of the signal compared to a control without serum
Time frame: At Month 77 until year 9 (Month 113)
Number of Subjects With New Onset Chronic Diseases (NOCD) up to Year 9
NOCDs include for example asthma, type I diabetes, allergies, ...
Time frame: Up to year 9
Number of Subjects With New Onset Autoimmune Disease (NOAD) up to Year 9.
Time frame: Up to year 9
Number of Subjects With Medically Signifant Conditions up to Year 9
Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time frame: Up to year 9
Number of Subjects With Serious Adverse Events (SAEs) up to Year 9.
SAEs assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject
Time frame: up to year 9
Number of Subjects Presenting Cervical Infections With Any Oncogenic HPV Type.
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects Presenting Cervical Infections With Individual Oncogenic Non-vaccine HPV Type.
Oncogenic types included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 and/or HPV-18
Persistent cervical HPV infection (6-month definition) was defined as detection of the same HPV type in cervical specimens at 2 consecutive evaluations over a minimum of 5 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study
Time frame: Up to year 7
Number of Subjects With Persistent Infection (6-month Definition) With Any Oncogenic HPV Type
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (6-month definition) was defined as detection of the same HPV type in cervical specimens at 2 consecutive evaluations over a minimum of 5 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Persistent Infection (6-month Definition) With Individual Oncogenic Non-vaccine HPV Types
Oncogenic HPV types included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (6-month definition) was defined as detection of the same HPV type in cervical specimens at 2 consecutive evaluations over a minimum of 5 months. Subjects with an event did not report the same event during the earlier studies. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Persistent Infection (12-month Definition) With HPV-16 and/or HPV-18
Persistent cervical HPV infection (12-month definition) was defined as detection of the same HPV type in cervical specimens at all consecutive evaluations over a minimum of 10 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Persistent Infection (12-month Definition) With Any Oncogenic HPV Type
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (12-month definition) was defined as detection of the same HPV type in cervical specimens at all consecutive evaluations over a minimum of 10 months. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had a normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Persistent Infection (12-month Definition) With Individual Oncogenic Non-vaccine HPV Types
Individual oncogenic non-vaccine HPV types include HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Persistent cervical HPV infection (12-month definition) was defined as detection of the same HPV type in cervical specimens at all consecutive evaluations over a minimum of 10 months. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN1+ was defined as CIN grades 1,2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN1+ was defined as CIN grades 1,2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN1+ was defined as CIN grades 1,2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Oncogenic HPV types assessed included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN2+ was defined as CIN grades 2 and 3, AIS and invasive cervical cancer. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN2+ was defined as CIN grades 2 and 3, AIS and invasive cervical cancer. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
CIN2+ was defined as CIN grades 2 and 3, AIS and invasive cervical cancer. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With an HPV 16 and/or HPV-18 Cervical Infection
Abnormal cytology included atypical squamus cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), atypical glandular cells (AGC), atypical squamus cells and cannot exclude HSIL (ASC-H). Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With Oncogenic HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC, and ASC-H. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC and ASC-H. Oncogenic HPV types assessed included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With an HPV 16 and/or HPV-18 Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC and ASC-H. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC, and ASC-H. Oncogenic HPV types assessed included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies. Subjects were DNA negative for the 14 oncogenic HPV types and had normal cytology at baseline in the primary study. Subjects with an event were DNA negative for the corresponding HPV type at Month 6 in the primary study.
Time frame: Up to year 7
Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
Abnormal cytology included ASC-US, LSIL, HSIL, AGC and ASC-H. Oncogenic HPV types assessed included HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Subjects with an event did not report the same event in the earlier studies and were DNA negative for the corresponding HPV type at month 6 in the primary study.
Time frame: Up to year 7
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