Infections

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Uterine Cervical Neoplasms

Communicable Diseases

All Drugs and Chemicals

Vaccines

300 women between 9-17 yeas of age, receiving 0,2,6 month-schedule experimental HPV vaccines

300 women between 9-17 yeas of age, receiving 0,2,6 month-schedule Placebo.

120 women between 18-26 yeas of age, receiving 0,2,6 month-schedule experimental HPV vaccines

180 women between 27-45 yeas of age, receiving 0,2,6 month-schedule experimental HPV vaccines

120 women between 18-26 yeas of age, receiving 0,2,6 month-schedule Placebo.

180 women between 27-45 yeas of age, receiving 0,2,6 month-schedule Placebo.

Subjects were planned to receive HPV vaccine 0.5ml administered intramuscularly according to a 0, 2, 6 month vaccination schedule

HPV vaccine

Subjects were planned to receive three doses of the placebo control 0.5ml administered intramuscularly according to a 0, 2, 6 month vaccination schedule

Placebo

Rong-cheng Li, MD

Evaluate immunogenicity and safety of recombinant human papillomavirus bivalent ( types 16 and 18 ) vaccine ( Yeast )in different age group. And evaluate persistence of immune response in 9-17years age group. To demonstrate that 9-17years age group was non-inferior to 18-26 years age group and 27-45 years age group in terms of immunogenicity.

This study is a multi-centre, randomized, blinded, placebo controlled study. The study vaccine is recombinant human papillomavirus bivalent (types 16 and 18) vaccine (Yeast), the placebo is aluminium phosphate diluent.

After informed and received the consent of participants/guardians, 1200 healthy females aged 9-45 will be enrolled into three age groups: 9-17, 8-26, 27-45. With the proportion of 1:1, vaccine group and placebo group will receive injection of 0.5ml of vaccine or placebo diluent.

Participants will be injected of vaccine or placebo on a three-dose schedule (0, 2, 6 months). After each inoculation, the immediate reaction will be observed for 30 minutes, and the local and systemic reaction will be systematically observed for 7 days. After the first inoculation, adverse event will be collected until one month after the final inoculation, while serious adverse event will be collected until 6 months after the final inoculation. For every participants, blood samples will be collected before the first inoculation (month 0), one month after the final inoculation (month 7), 6 months after the final inoculation (month 12) to detect the neutralizing antibody of HPV type 16 and 18, and proceed safety and immunogenicity analysis. For participants in 9-14 age group who received the vaccine, neutralizing antibody will also be detected in month 24, 36 and 48 to examine the immune persistency. Meanwhile, some participants will be chosen to study the deviation of gene expression after the vaccination and the association of that with the neutralizing antibody level.

Immunogenicity and Safety of Human Papillomavirus (HPV)-16/18 Vaccine in Healthy Females

Immunogenicity and Safety of Recombinant Human Papillomavirus Bivalent(Type 16 and 18) Vaccine (Yeast) in Healthy Females

Shanghai Zerun Biotechnology Co.,Ltd

Gastrointestinal Agents

Aluminum Hydroxide

Subjects received 3 doses of Cervarix™ vaccine. Cervarix vaccine was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

Subjects received 3 doses of Aluminium Hydroxide \[Al(OH)3\]. Aluminium Hydroxide was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

Subjects were planned to receive three doses of the study vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.

Cervarix

Subjects were planned to receive three doses of the control vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.

Placebo control

GSK Clinical Trials

This is a multicentre study in which women were planned to receive either the Human Papillomavirus Vaccine (HPV) vaccine or control. Under Protocol Amendment 3, study participation will last approximately 48 months and involves a total of eleven scheduled visits. Under Protocol Amendment 4, study participation will last up to 84 months and involves a maximum of seventeen scheduled visits.

The Protocol Posting has been updated due to protocol amendment 5 and in order to comply with the FDA Amendment Act, Sep 2007.

Study to Evaluate the Efficacy of the Human Papillomavirus Vaccine in Healthy Adult Women of 26 Years of Age and Older

A Study to Evaluate Safety, Immunogenicity and Efficacy of GSK Biologicals HPV-16/18 L1/AS04 Vaccine Administered Intramuscularly According to a Three-dose Schedule (0, 1, 6 Month) in Healthy Adult Female Subjects Aged 26 Years and Above

IPD is available via the Clinical Study Data Request site (click on the link provided below)

CIN1+ = CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

Persistent HPV infection = detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

* DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and 6 and seronegative/positive (sero-/+) at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA)
* Overall: subjects DNA- at Month 0 and 6 for the corresponding HPV-type, regardless of initial serostatus

CIN1+ = CIN grades 1, 2 and 3, AIS and invasive cervical cancer. Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

* DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0).
* Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

CIN1+ = CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Persistent HPV infection = detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. - DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and 6 and seronegative/positive (sero-/+) at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) - Overall: subjects DNA- at Month 0 and 6 for the corresponding HPV-type, regardless of initial serostatus

CIN1+ = CIN grades 1, 2 and 3, AIS and invasive cervical cancer. Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

Detection was done in:

* DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0).
* Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type(s) PCR in cervical samples at all available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals).

* DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0).
* Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Detection was done in subjects HPV DNA- for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus.

HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18. HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Persistent HPV infection (12-month definition) = detection of the same HPV type(s) by PCR in cervical samples at available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals).

Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

subjects HPV DNA- for the corresponding HPV type at Month 0 6, regardless of initial serostatus.

HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 , 68

CIN2+ was defined as CIN grades 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

Detection was done in:

* DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0).
* Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

Note: Results for seropositive status were not analysed.

CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

Detection was done in:

* DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0).
* Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.

CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

Detection was done on all subjects irrespective of their baseline HPV DNA status.

Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US).

Detection was done in:

* DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0).
* Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

Results for seropositive status were not analysed.

Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Detection was done in subjects who were HPV DNA negative for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus.

HRW-HPV= All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR= High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68

Detection was done on all subjects irrespective of their baseline HPV DNA status.

Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.

Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.

The lesion was assigned to an HPV type found in the lesion if (1) the same HPV type was found in at least 1 of the 2 (closest) preceding cytology samples, or (2) none of the HPV types found in the lesion were found in any of the 2 preceding cytology samples (isolate HPV types)

Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.

HPV-16 assay cut-off value was defined as greater than or equal to 8 ELISA units per millilitre (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 8 EL.U/mL prior to vaccination.

Immuno subset=subjects from selected sites N≥1000, at least 250 per region

Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.

HPV-18 assay cut-off value was defined as greater than or equal to 7 ELISA units per millilitre (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination.

Immuno subset=subjects from selected sites N≥1000, at least 250 per region

GMCs were expressed in ELISA units per milliliter (EL.U/mL).

Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 8 EL.U/mL prior to vaccination.

Immuno subset=subjects from selected sites (N≥1000, at least 250 per region)

GMCs were expressed in ELISA units per milliliter (EL.U/mL).

Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination.

Immuno subset=subjects from selected sites (N≥1000, at least 250 per region)

Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. HPV-16/18 assay cut-off value was defined as greater than or equal to 40 Estimated dose 50% (ED50). Sero- subjects are subjects who had an antibody concentration below 40 ED50 prior to vaccination. Sero+ subjects are subjects who had an antibody concentration equal to or above 50 ED50 prior to vaccination. ED50 = the estimated serum dilution reducing the signal generated by viral infection by 50%

Titers are expressed as geometric mean antibody titers (GMTs).

Seronegative (Sero-) subjects are subjects who had an antibody titer below 40 ED50 prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody titer equal to or above 40 ED50 prior to vaccination.

ED50 = Estimated dose 50%, the estimated serum dilution reducing the signal generated by viral infection by 50%

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 activity. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).

Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = axillary temperature above 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = axillary temperature above 39.0°C.

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. Grade 3 unsolicited AE = an event that prevented normal activity.

A related AE = event assessed by the investigator as causally related to the study vaccination.

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. A related SAE was defined as an event assessed by the investigator as causally related to the study vaccination.

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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.

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

NOCDs include autoimmune disorders, asthma and type I diabetes.

Medically significant conditions were defined as: 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 diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.

Pregnancy outcomes are live infant, premature live infant, elective termination, ectopic pregnancy, 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).

CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

Detection was done on subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

TAA: Type assignment algorithm. The lesion was assigned to an HPV type found in the lesion if

1. the same HPV type was found in at least one of the two (closest) preceding cytology samples, or
2. none of the HPV types found in the lesion were found in any of the two preceding cytology samples (isolate HPV types)

Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. Detection was done in: - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type(s) PCR in cervical samples at all available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals). - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Detection was done in subjects HPV DNA- for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus. HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18. HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. subjects HPV DNA- for the corresponding HPV type at Month 0 6, regardless of initial serostatus. HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 , 68

CIN2+ was defined as CIN grades 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in: - DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline. Note: Results for seropositive status were not analysed.

CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in: - DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA status.

Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US). Detection was done in: - DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline. Results for seropositive status were not analysed.

Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Detection was done in subjects who were HPV DNA negative for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus. HRW-HPV= All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR= High-risk (oncogenic) HPV types: 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 the detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.

Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus. The lesion was assigned to an HPV type found in the lesion if (1) the same HPV type was found in at least 1 of the 2 (closest) preceding cytology samples, or (2) none of the HPV types found in the lesion were found in any of the 2 preceding cytology samples (isolate HPV types)

GlaxoSmithKline

Cervarix Group

Aluminium Hydroxide Group

Total

Age, Continuous

Sex: Female, Male

GSK Response Center

HPV-16/18, DNA- and sero- subjects

HPV-16, DNA- and sero- subjects

HPV-18, DNA- and sero- subjects

HPV-16/18, DNA- and sero+ subjects

HPV-16, DNA- and sero+ subjects

HPV-18, DNA- and sero+ subjects

HPV-16/18, overall

HPV-16, overall

HPV-18, overall

The According-To-Protocol cohort for efficacy included subjects who had a normal or low-grade cytology (negative or atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL)) at Month 0, who received 3 doses. A 15% subset of women enrolled with prior history of HPV infection was excluded.

Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection.

Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).

Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18

Number of Subjects With Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18

HPV-16

HPV-18

HPV-31

HPV-33

HPV-35

HPV-39

HPV-45

HPV-51

HPV-52

HPV-56

HPV-58

HPV-59

HPV-66

HPV-68

HPV-31/45

HPV-31/45/33/52/58

HPV-39/45/59/68

HPV-31/33/35/52/58

HPV-31/45/33/52/58/35/39/51/56/59

HPV-HRW

HPV-HR

Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types Individually or in Combinations.

Number of Subjects With Persistent Infection (12-month Definition) With Oncogenic HPV Types Individually or in Combinations.

Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen

Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen

HPV-16/18

The Total Vaccinated cohort included all subjects with at least one vaccine administration documented.

Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Irrespective of HPV Cervical Infection and Irrespective of Baseline HPV DNA Status

Number of Subjects With Any Cytological Abnormalities Associated With HPV-16 or HPV-18 Cervical Infection

Number of Subjects With Cytological Abnormalities Associated With Oncogenic HPV Types Individually or in Combinations

Number of Subjects With Histopathologically Confirmed Reduction of Local Cervical Therapy

Number of Subjects With First Colposcopy

Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection

Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-confirmed CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).

Sero- before vaccination

Sero- at Month 7

Sero- at Month 12

Sero- at Month 18

Sero- at Month 24

Sero- at Month 36

Sero- at Month 48

Sero- at Month 60

Sero- at Month 72

Sero- at Month 84

Sero+ before vaccination

Sero+ at Month 7

Sero+ at Month 12

Sero+ at Month 24

Sero+ at Month 18

Sero+ at Month 36

Sero+ at Month 48

Sero+ at Month 60

Sero+ at Month 72

Sero+ at Month 84

The According-To-Protocol cohort for immunogenicity included subjects for whom immunogenicity data were available and for whom assay results were available for antibodies against at least 1 study vaccine antigen component after vaccination. The 15% subset of women enrolled with prior history of HPV disease/infection was included.

Number of Seroconverted Subjects Against HPV-16 in the Immunogenicity Subset.

Sero- at month 84

Number of Seroconverted Subjects Against HPV-18 in the Immunogenicity Subset.

Sero-before vaccination

Sero+ at month 12

Sero+ at month 36

Geometric Mean Concentrations (GMCs) Against HPV-16 Antibody in the Immunogenicity Subset.

Geometric Mean Concentrations (GMCs) Against HPV-18 Antibody in the Immunogenicity Subset.

HPV-16 sero- [pre-vaccination]

HPV-16 sero- [at Month 7]

HPV-16 sero- [at Month 12]

HPV-16 sero- [at Month 18]

HPV-16 sero- [at Month 24]

HPV-16 sero- [at Month 48]

HPV-16 sero- [at Month 84]

HPV-16 sero+ [pre-vaccination]

HPV-16 sero+ [at Month 7]

HPV-16 sero+ [at Month 12]

HPV-16 sero+ [at Month 18]

HPV-16 sero+ [at Month 24]

HPV-16 sero+ [at Month 48]

HPV-16 sero+ [at Month 84]

HPV-18 sero- [pre-vaccination]

HPV-18 sero- [at Month 7]

HPV-18 sero- [at Month 12]

HPV-18 sero- [at Month 18]

HPV-18 sero- [at Month 24]

HPV-18 sero- [at Month 48]

HPV-18 sero- [at Month 84]

HPV-18 sero+ [pre-vaccination]

HPV-18 sero+ [at Month 7]

HPV-18 sero+ [at Month 12]

HPV-18 sero+ [at Month 18]

HPV-18 sero+ [at Month 24]

HPV-18 sero+ [at Month 48]

HPV-18 sero+ [at Month 84]

Number of Seroconverted Subjects Against HPV-16 and HPV-18 Viral Neutralization in a Selected Subset of Subjects.

Geometric Mean Titers (GMTs) Against HPV-16 and HPV-18 Viral Neutralization Antibodies in a Selected Subset of Subjects.

Any pain

Grade 3 pain

Any redness

Grade 3 redness

The Total Vaccinated cohort included all subjects with at least one vaccine administration documented and symptom sheets completed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immunogenicity and Safety of Human Papillomavirus (HPV)-16/18 Vaccine in Healthy Females	NCT02740790	Human Papilloma...	HPV vaccine Placebo	9 Years - 45 Years	Shanghai Zerun Biotechnology Co.,Ltd
Immunogenicity and Safety of Human Papillomavirus (HPV)-16/18 Vaccine in Healthy Females	NCT02740790	Human Papilloma...	HPV vaccine Placebo	9 Years - 45 Years	Shanghai Zerun Biotechnology Co.,Ltd
Study to Evaluate the Efficacy of the Human Papillomavirus Vaccine in Healthy Adult Women of 26 Years of Age and Older	NCT00294047	Infections, Pap... Papillomavirus ...	Cervarix Placebo control	26 Years -	GlaxoSmithKline
Efficacy, Immunogenicity and Safety of GSK Biologicals' HPV GSK 580299 Vaccine in Healthy Chinese Female Subjects	NCT00779766	Infections, Pap...	HPV GSK 580299 ... Placebo control	18 Years - 25 Years	GlaxoSmithKline
Acceptability of Human Papillomavirus (HPV) Vaccine in Female Sex Workers	NCT00925288	Human Papilloma...	Gardasil	18 Years - 26 Years	Johns Hopkins Bloomberg School of Public Health

Spots Global Cancer Trial Database for cervical infection