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subjects received 3 doses of Cervarix™ vaccine in primary vaccination study NCT00316693.

subjects received 3 doses of Aimmugen ™ vaccine in primary vaccination study NCT00316693.

LBC samples will be collected at Months 36 and 48 for cytology and HPV DNA testing (by PCR)

Liquid-based cytology (LBC) sampling

Blood samples will be collected at Months 36 and 48 for antibody determination

Blood sampling

GSK Clinical Trials

This extension study is conducted to assess the efficacy of the GSK 580299 vaccine against cervical intraepithelial neoplasia (CIN) lesions, cervical cancer and cytological abnormalities associated with human papillomavirus (HPV)-16 and/or HPV-18 or other oncogenic HPV types for an additional two years. All subjects who participated in the primary vaccination study NCT00316693 and who confirmed their interest in participating in a long term follow up study will therefore be invited to be followed for up to 48 months after administration of the first dose of vaccine. In addition, safety and persistence of the humoral immune response will be evaluated in this study.

This protocol posting deals with objectives \& outcome measures of the extension phase at Months 36 and 48. The objectives \& outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00316693).

Extension Study of the Efficacy of the GSK 580299 Vaccine in Japanese Women Vaccinated in the Primary NCT00316693 Study

Long-term Extension Study of the Efficacy of the 580299 Vaccine in the Prevention of HPV-16 and/or HPV-18 Associated Cervical Intraepithelial Neoplasia (CIN) in Japanese Women Vaccinated in the Primary Vaccination Study NCT00316693

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Low-grade cervical lesions and higher lesions are defined as CIN1+, i.e. CIN grade 1 (CIN1), CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer (ICC).

Detection of vaccine oncogenic Human papillomavirus (HPV) types 16 or 18 was made by polymerase chain reaction (PCR).

For single type: Subjects Deoxyribonucleic acid (DNA) negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type.

For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.

Cytologically confirmed abnormalities and lesions (ASC-US+) are defined as atypical squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), atypical squamous cell-cannot exclude HSIL (ASC-H) and atypical glandular cells (AGC).

For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type.

For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.

Cytologically confirmed abnormalities and lesions (ASC-US+) are defined as ASC-US, LSIL, HSIL, ASC-H and AGC.

HR= High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Low-grade cervical lesions and higher lesions are defined as CIN1+, i.e. CIN1, CIN2, CIN3, AIS or ICC.

HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type.

For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.

HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Persistent infection (12-month definition): detection of at least 2 positive HPV DNA PCR assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an approximate interval of 12 months (\>300 days).

For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type.

For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.

Persistent infection: subjects with at least 2 positive samples (difference \> than 300 days) and no negative samples in between.

HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Assay cut-off values assessed were 8 Enzyme-linked Immunosorbent Assay (ELISA) units per millilitre (EL.U/mL) for HPV-16 antibodies and 7 ELISA units per millilitre (EL.U/mL) for HPV-18 antibodies in the Cervarix Group.

Titers were expressed as Geometric Mean Titers (GMTs). Geometric mean titres were assessed by ELISA in the Cervarix Group.

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.

NOCDs included autoimmune diseases, diabetes mellitus.

MSCs were defined as adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common disease.

Pregnancy outcomes are live infant, elective termination, ectopic pregnancy, stillbirth, spontaneous abortion, lost to follow-up and pregnancy ongoing. For each category it was specified if the infant presents congenital anomaly (CA) or no apparent congenital anomaly (No ACA).

GlaxoSmithKline

The analysis was performed on all subjects from the Total Vaccinated cohort who came for the current follow-up study and for whom data were available. Other adverse events (solicited and unsolicited) were not assessed and not reported during this study.

Cervarix Group

Aimmugen Group

Total

Japanase women aged 20 to 25 years at the time of first vaccination in the primary study NCT00316693

Age, Continuous

Sex: Female, Male

GSK Response Center

CIN1+ HPV-16/18 (N=332;335)

CIN1+ HPV-16 (N=286;289)

CIN1+ HPV-18 (N=294;291)

The analysis was performed in subjects who were seronegative at baseline and negative for human papillomavirus (HPV) desoxyribonucleic acid (DNA) at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered and for whom data concerning efficacy outcome measures were available in this follow-up study.

Number of Subjects Reporting Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Cases Associated With HPV16 and/or HPV18 Detected Within the Lesional Component of the Cervical Tissue Specimen.

ASC-US+ HPV-16/18 (N=332;335)

ASC-US+ HPV-16 (N=286;289)

ASC-US+ HPV-18 (N=294;291)

The analysis was performed in subjects who were seronegative at baseline and negative for HPV DNA at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered and for whom data concerning efficacy outcome measures were available in this follow-up study.

Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18.

The analysis was performed in subjects who were DNA negative at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered, regardless of their initial serostatus and for whom data concerning efficacy outcome measures were available in this current follow-up study.

Number of Subjects Reporting Cytologically Confirmed Abnormalities and Lesions Concurrently Associated With Any Oncogenic HPV Types.

Number of Subjects Reporting CIN1+ Associated With Any Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen.

Incident infection HPV-16/18 (N=332;335)

Incident infection HPV-16 (N=286;289)

Incident infection HPV-18 (N=294;291)

Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18.

The analysis was performed in subjects who were negative for HPV DNA at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered, regardless of their initial serostatus and for whom data concerning efficacy outcome measures were available in this current follow-up study.

Number of Subjects Reporting Incident Cervical Infection With Any Oncogenic HPV Types.

Persistent infection HPV-16/18 (N=257;241)

Persistent infection HPV-16 (N=225;206)

Persistent infection HPV-18 (N=227;209)

Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18.

Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With Any Oncogenic HPV-types.

HPV-16 >=8 EL.U/mL [at Month 0] (N=282)

HPV-16 >=8 EL.U/mL [at Month 12] (N=291)

HPV-18 >=7 EL.U/mL [at Month 0] (N=281)

HPV-18 >=7 EL.U/mL [at Month 12] (N=290)

The According-To-Protocol cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available in this current follow-up study for antibodies against at least one study vaccine antigen component.

Number of Subjects With HPV-16 and HPV-18 Antibodies Titers Equal to or Above the Assay Cut-off Values.

HPV-16 [Month 0] (N=282)

HPV-16 [Month 12] (N=291)

HPV-18 [Month 0] (N=281)

HPV-18 [Month 12] (N=290)

The According-To-Protocol cohort for immunogenicity M48 EXT- NCT00316693 included all evaluable subjects for whom data concerning immunogenicity outcome measures were available in this current follow-up study for antibodies against at least one study vaccine antigen component.

HPV-16 and HPV-18 Antibody Titers

The analysis was performed on all subjects from the Total Vaccinated cohort who came for the current follow-up study and for whom data were available.

Spots Global Cancer Trial Database for including new onset of autoimmune disease [noad])