Cervical Cancer, Genital Warts
Conditions
Brief summary
The primary purpose of the study is to determine if GARDASIL™ (V501) is able to prevent cervical cancer.
Detailed description
In the 4-year Base Study (V501-015) (NCT00092534), participants were randomized in a 1:1 order to receive 3 doses of GARDASIL™ or matching placebo at Day 1, Month 2, and Month 6 and were assessed for efficacy, immunogenicity, and safety. In the Base Study Extension (EXT) \[V501-015-10\], participants who received placebo or only 1 dose of GARDASIL™ in the Base Study, were given 3 doses of open-label GARDASIL™ at EXT Day 1, EXT Month 2, and EXT Month 6, and were followed to EXT Month 7. Participants who who received 2 doses of GARDASIL™ in the Base Study were given 1 dose of GARDASIL™ at EXT Day 1 and were followed for 15 days (day of vaccination plus 14 days). In the 10-year Base Study Long-Term Follow-Up (LTFU) \[V501-015-21\] the effectiveness, immunogenicity and safety of GARDASIL™ was assessed during a period of 10 years following completion of the Base Study (V501-015) \[14 years after the first dose of GARDASIL™\] and, for some measures, the Base Study EXT (V501-015-10) \[10 years after the first dose of GARDASIL™\]. Participants from Denmark, Iceland, Norway and Sweden who participated in the Base Study were eligible to enroll in the LTFU. Effectiveness and safety was assessed by registry-based follow-up, and immunogenicity was assessed by serological testing at approximately Year 5 and Year 10 of the V501-015-21 LTFU. An 8-year extension was added to the LTFU (V501-015-22\] to continue the evaluation of the long-term effectiveness and immunogenicity of GARDASIL™. Effectiveness and safety will be assessed by registry-based follow-up, and immunogenicity will be assessed by serological testing at approximately Year 4 and Year 8 of the extension of the LTFU.
Interventions
BIOLOGICALGardasil, human papillomavirus (type 6, 11, 16, 18) recombinant vaccine
A 0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6 in the Base Study.
BIOLOGICALMatching Placebo
A placebo 0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6 in the Base Study.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 23 Years
Healthy volunteers
Yes
Inclusion criteria
for the Base Study: * Healthy women with an intact uterus with lifetime history of 0-4 sexual partners --For Extension Phase: * Participant received placebo or an incomplete vaccination series in the original study --For LTFU: * Participant was randomized into the Base Study from Denmark, Iceland, Norway, or Sweden. * Agreed to allow passive follow-up (retrospective review of registry data), analysis of biopsy specimens, future contact from National Registry Study Center and serum collection
Exclusion criteria
for the Base Study: * Prior Human Papilloma Virus (HPV) vaccination * Prior abnormal Paps * Prior history of genital warts --For Extension Phase: * Prior complete HPV vaccination series * Subject lives in a country in which Gardasil is approved and is within the age range of the local labeling for Gardasil --For LTFU Study: * There were no
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Base Study | Up to 4 years | This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine consensus diagnosis of CIN 2 or worse up to 4 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, adenocarcinoma in situ (AIS) or cervical cancer related to HPV 16 or 18. |
| Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Long-term Follow-up (LTFU) Study | Up to 14 years since Vaccine Dose 1 | This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine Nordic pathology panel (NPP) consensus diagnosis of CIN 2 or worse up to 14 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to HPV 16 or 18. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis. |
| Incidence of the Composite Endpoint of HPV16/18-related CIN 2 or Worse in the Long-term Follow-up (LTFU) Study | up to 22 years post Vaccination Dose 1 | This measure is defined to have occurred when, on a single cervical biopsy, ECC, LEEP, or conization specimen, there was HPV Vaccine NPP consensus diagnosis of CIN 2 or worse up to 22 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to HPV 16 or 18. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU will be included. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Anti-Human Papillomavirus (HPV) 18 Titer ≥24 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | Week 4 Postdose 3 | Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 18 pseudovirions in vitro; thus, the number of participants with anti-HPV 18 ≥24 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined. |
| Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 31/33/35/39/45/51/52/56/58/59-related Cervical Intraepithelial Neoplasia (CIN) Grade 2 or Worse in the Long-term Follow-up (LTFU) Study | Up to 14 years since Vaccination Dose 1 | This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine Nordic pathology panel (NPP) consensus diagnosis of CIN 2 or worse related to nonvaccine HPV types up to 14 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to nonvaccine HPV types 31, 33, 35, 39, 45, 51, 52, 56, 58, or 59. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis. |
| Incidence of the Composite Endpoint of HPV 6/11/16/18-related CIN (Any Grade), AIS, Cervical Cancer, Vulvar Cancer or Vaginal Cancer the Long-term Follow-up (LTFU) Study | Up to 14 years since Vaccination Dose 1 | This measure was defined to have occurred if on a single biopsy or excised tissue, there was the NPP consensus diagnosis of CIN 1, CIN 2, CIN 3, AIS, cervical cancer, vulvar cancer or vaginal cancer AND at least 1 of HPV types 6, 11, 16 or 18 was detected by Thin-section PCR in an adjacent section from the same tissue block. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis. |
| Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | At 108 months since Vaccination Dose 1 | Antibodies to human papillomavirus (HPV) types were measured using cLIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis. |
| Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | At 168 months since Vaccination Dose 1 | Antibodies to human papillomavirus (HPV) types were measured using cLIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis. |
| Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | At 108 months since Vaccination Dose 1 | Antibodies to human papillomavirus (HPV) types were measured using cLIA. Seropositivity was assessed by competitive Luminex Immunoassay (cLIA); the serostatus cut-offs for anti-HPV 6, 11, 16 and 18 serum cLIA were 20, 16, 20 and 24 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis. |
| Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | At 168 months since Vaccination Dose 1 | Antibodies to human papillomavirus (HPV) types were measured using cLIA. Seropositivity was assessed by cLIA; the serostatus cut-offs for anti-HPV 6, 11, 16 and 18 serum cLIA were 20, 16, 20 and 24 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis. |
| Number of Participants With Anti-Human Papillomavirus (HPV) 6 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | Month 7 (4 weeks after Vaccination 3) | Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 6 pseudovirions in vitro; thus, the number of participants with anti-HPV 6 ≥20 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined. |
| Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | At 168 months since Vaccination Dose 1 | Antibodies to human papillomavirus (HPV) types were measured using IgG LIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis. |
| Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | At 108 months since Vaccination Dose 1 | Antibodies to HPV types were measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 at Month 108 were 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis. |
| Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | At 168 months since Vaccination Dose 1 | Antibodies to HPV types were measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 at Month 168 were 9, 6, 5, and 5 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis. |
| Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 216 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | At 216 months since Vaccination Dose 1 | Antibodies to human papillomavirus (HPV) types will be measured using IgG LIA.. |
| Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 216 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) ) in the Long-Term Follow-Up (LTFU) Study | At 216 months since Vaccination Dose 1 | Antibodies to HPV types will be measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 are 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. The percentage of participants that are seropositive for each type will be summarized. |
| Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 264 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | At 264 months since Vaccination Dose 1 | Antibodies to human papillomavirus (HPV) types will be measured using IgG LIA.. |
| Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 264 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | At 264 months since Vaccination Dose 1 | Antibodies to HPV types will be measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 are 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. The percentage of participants that are seropositive for each type will be summarized. |
| Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | At 108 months since Vaccination Dose 1 | Antibodies to human papillomavirus (HPV) types were measured using IgG LIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis. |
| Number of Participants With Anti-Human Papillomavirus (HPV) 11 Titer ≥16 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | Week 4 Postdose 3 | Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 11 virions in vitro; thus, the number of participants with anti-HPV 11 ≥16 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined. |
| Number of Participants With Anti-Human Papillomavirus (HPV) 16 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | Week 4 Postdose 3 | Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 16 pseudovirions in vitro; thus, the number of participants with anti-HPV 16 ≥20 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined. |
Participant flow
Recruitment details
Female participants were randomized to receive quadrivalent human papillomavirus (qHPV) vaccine (GARDASIL™) or placebo in the Base Study (V501-015, NCT00092534), and were followed for 4 years. Participants who received placebo in the Base Study were eligible to receive the 3-dose qHPV vaccine series during the Base Study Extension (EXT).
Pre-assignment details
Participants who received 3 doses of qHPV vaccine either during the Base Study or Base Study EXT were eligible for enrollment in the Long-Term Follow-Up (LTFU) Study (V501-015-21). The 10-year-long registry-based LTFU was conducted at 4 National Registry Study Centers (NRSC) in Denmark, Iceland, Norway, and Sweden.
Participants by arm
| Arm | Count |
|---|---|
| Base Study Group 1: qHPV Vaccine During the Base Study, participants received 3 qHPV vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years. | 6,087 |
| Base Study Group 2: Placebo During the Base Study, participants received 3 placebo vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years. | 6,080 |
| Total | 12,167 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Base Study EXT | Lost to Follow-up | 0 | 0 | 41 | 0 | 0 |
| Base Study EXT | Participant moved | 0 | 0 | 6 | 0 | 0 |
| Base Study EXT | Physician Decision | 0 | 0 | 1 | 0 | 0 |
| Base Study EXT | Pregnancy | 0 | 0 | 12 | 0 | 0 |
| Base Study EXT | Protocol Violation | 0 | 0 | 15 | 0 | 0 |
| Base Study EXT | Site closed | 0 | 0 | 21 | 0 | 0 |
| Base Study EXT | Study ended | 0 | 0 | 29 | 0 | 0 |
| Base Study EXT | Travel | 0 | 0 | 2 | 0 | 0 |
| Base Study EXT | Withdrawal by Subject | 0 | 0 | 18 | 0 | 0 |
| Base Study Follow-Up Period | Adverse Event | 2 | 4 | 0 | 0 | 0 |
| Base Study Follow-Up Period | Death | 2 | 1 | 0 | 0 | 0 |
| Base Study Follow-Up Period | Lost to Follow-up | 120 | 146 | 0 | 0 | 0 |
| Base Study Follow-Up Period | Moved | 62 | 58 | 0 | 0 | 0 |
| Base Study Follow-Up Period | Pregnancy | 6 | 10 | 0 | 0 | 0 |
| Base Study Follow-Up Period | Protocol Violation | 1 | 2 | 0 | 0 | 0 |
| Base Study Follow-Up Period | Site Closed | 0 | 2 | 0 | 0 | 0 |
| Base Study Follow-Up Period | Subjects continuing | 27 | 31 | 0 | 0 | 0 |
| Base Study Follow-Up Period | Subjects in extension | 15 | 371 | 0 | 0 | 0 |
| Base Study Follow-Up Period | Travel | 10 | 7 | 0 | 0 | 0 |
| Base Study Follow-Up Period | Withdrawal by Subject | 71 | 62 | 0 | 0 | 0 |
| Base Study Vaccination Period | Adverse Event | 3 | 1 | 0 | 0 | 0 |
| Base Study Vaccination Period | Death | 5 | 4 | 0 | 0 | 0 |
| Base Study Vaccination Period | Lost to Follow-up | 41 | 37 | 0 | 0 | 0 |
| Base Study Vaccination Period | Moved | 14 | 12 | 0 | 0 | 0 |
| Base Study Vaccination Period | New Medical History (Not AEs) | 5 | 0 | 0 | 0 | 0 |
| Base Study Vaccination Period | Physician Decision | 1 | 0 | 0 | 0 | 0 |
| Base Study Vaccination Period | Pregnancy | 9 | 7 | 0 | 0 | 0 |
| Base Study Vaccination Period | Protocol Violation | 2 | 1 | 0 | 0 | 0 |
| Base Study Vaccination Period | Randomized not Vaccinated | 5 | 5 | 0 | 0 | 0 |
| Base Study Vaccination Period | Site Closed | 0 | 1 | 0 | 0 | 0 |
| Base Study Vaccination Period | Travel | 1 | 0 | 0 | 0 | 0 |
| Base Study Vaccination Period | Withdrawal by Subject | 85 | 58 | 0 | 0 | 0 |
| Long-Term Follow-Up (LTFU) Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Base Study Group 2: Placebo | Total | Base Study Group 1: qHPV Vaccine |
|---|---|---|---|
| Age, Continuous | 19.9 years STANDARD_DEVIATION 2.1 | 19.9 years STANDARD_DEVIATION 2.1 | 20.0 years STANDARD_DEVIATION 2.2 |
| Race/Ethnicity, Customized Asian | 135 Participants | 286 Participants | 151 Participants |
| Race/Ethnicity, Customized Black | 227 Participants | 398 Participants | 171 Participants |
| Race/Ethnicity, Customized Hispanic American | 557 Participants | 1112 Participants | 555 Participants |
| Race/Ethnicity, Customized Native American | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Other-Unspecified | 610 Participants | 1235 Participants | 625 Participants |
| Race/Ethnicity, Customized White | 4550 Participants | 9134 Participants | 4584 Participants |
| Sex: Female, Male Female | 6080 Participants | 12167 Participants | 6087 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 6,082 | 5 / 6,075 | 0 / 594 | 2 / 2,448 | 1 / 1,888 |
| other Total, other adverse events | 551 / 6,082 | 499 / 6,075 | 0 / 594 | 0 / 2,448 | 0 / 1,888 |
| serious Total, serious adverse events | 46 / 6,082 | 56 / 6,075 | 1 / 594 | 0 / 2,448 | 0 / 1,888 |
Outcome results
Primary
Incidence of the Composite Endpoint of HPV16/18-related CIN 2 or Worse in the Long-term Follow-up (LTFU) Study
This measure is defined to have occurred when, on a single cervical biopsy, ECC, LEEP, or conization specimen, there was HPV Vaccine NPP consensus diagnosis of CIN 2 or worse up to 22 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to HPV 16 or 18. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU will be included.
Time frame: up to 22 years post Vaccination Dose 1
Primary
Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Base Study
This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine consensus diagnosis of CIN 2 or worse up to 4 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, adenocarcinoma in situ (AIS) or cervical cancer related to HPV 16 or 18.
Time frame: Up to 4 years
Population: Participants who received 3 qHPV doses in 1 year, had no protocol violations that could affect evaluation of vaccine efficacy, were polymerase chain reaction (PCR)-negative and seronegative based on competitive Luminex immunoassay (cLIA) to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7, and had data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Base Study Group 1: qHPV Vaccine | Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Base Study | 0.0 Incidence per 100 person-years |
| Base Study Group 2: Placebo | Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Base Study | 0.4 Incidence per 100 person-years |
95% CI: [88.2, 99.6]
Primary
Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Long-term Follow-up (LTFU) Study
This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine Nordic pathology panel (NPP) consensus diagnosis of CIN 2 or worse up to 14 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to HPV 16 or 18. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis.
Time frame: Up to 14 years since Vaccine Dose 1
Population: Participants in Cohort 1 who received 3 qHPV vaccine doses in 1 year, had no protocol violations that could affect evaluation of efficacy, had been PCR-negative and seronegative based on cLIA at Day 1 and PCR-negative through Month 7 of the Base Study to the relevant HPV type(s), and had LTFU data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Base Study Group 1: qHPV Vaccine | Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Long-term Follow-up (LTFU) Study | 0.0 Incidence per 100 person-years |
Secondary
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to human papillomavirus (HPV) types were measured using cLIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time frame: At 108 months since Vaccination Dose 1
Population: Participants in Cohort 1 who received 3 qHPV vaccine doses in 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were PCR-negative and seronegative based on cLIA to relevant type at Day 1 and PCR-negative to the relevant type through Month 7. No data were collected for Cohort 2.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 6 | 89.2 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 11 | 85.2 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 16 | 348.6 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 18 | 32.5 mMU/mL |
Secondary
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to human papillomavirus (HPV) types were measured using IgG LIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time frame: At 108 months since Vaccination Dose 1
Population: Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7. No data were collected for Cohort 2.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 6 | 95.2 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 11 | 67.4 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 16 | 346.1 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 18 | 46.1 mMU/mL |
Secondary
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to human papillomavirus (HPV) types were measured using cLIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time frame: At 168 months since Vaccination Dose 1
Population: Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 11 | 66.8 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 16 | 291.2 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 18 | 26.1 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 6 | 78.4 mMU/mL |
Secondary
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to human papillomavirus (HPV) types were measured using IgG LIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time frame: At 168 months since Vaccination Dose 1
Population: Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 6 | 81.2 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 11 | 53.5 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 16 | 290.2 mMU/mL |
| Base Study Group 1: qHPV Vaccine | Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 18310.8 | 36.5 mMU/mL |
Secondary
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 216 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to human papillomavirus (HPV) types will be measured using IgG LIA..
Time frame: At 216 months since Vaccination Dose 1
Secondary
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 264 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to human papillomavirus (HPV) types will be measured using IgG LIA..
Time frame: At 264 months since Vaccination Dose 1
Secondary
Incidence of the Composite Endpoint of HPV 6/11/16/18-related CIN (Any Grade), AIS, Cervical Cancer, Vulvar Cancer or Vaginal Cancer the Long-term Follow-up (LTFU) Study
This measure is defined to have occurred if on a single biopsy or excised tissue, there is the NPP consensus diagnosis of CIN 1, CIN 2, CIN 3, AIS, cervical cancer, vulvar cancer or vaginal cancer AND at least 1 of HPV types 6, 11, 16 or 18 is detected by Thin-section PCR in an adjacent section from the same tissue block.
Time frame: up to 22 years since Vaccination Dose 1
Secondary
Incidence of the Composite Endpoint of HPV 6/11/16/18-related CIN (Any Grade), AIS, Cervical Cancer, Vulvar Cancer or Vaginal Cancer the Long-term Follow-up (LTFU) Study
This measure was defined to have occurred if on a single biopsy or excised tissue, there was the NPP consensus diagnosis of CIN 1, CIN 2, CIN 3, AIS, cervical cancer, vulvar cancer or vaginal cancer AND at least 1 of HPV types 6, 11, 16 or 18 was detected by Thin-section PCR in an adjacent section from the same tissue block. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis.
Time frame: Up to 14 years since Vaccination Dose 1
Population: Participants in Cohort 1 who received 3 qHPV vaccine doses in 1 year, had no protocol violations that could affect efficacy, had been PCR-negative and seronegative based on cLIA at Day 1 and PCR-negative through Month 7 of the Base Study to relevant HPV type(s), and had LTFU data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Base Study Group 1: qHPV Vaccine | Incidence of the Composite Endpoint of HPV 6/11/16/18-related CIN (Any Grade), AIS, Cervical Cancer, Vulvar Cancer or Vaginal Cancer the Long-term Follow-up (LTFU) Study | 0.1 Incidence per 100 person-years |
Secondary
Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 31/33/35/39/45/51/52/56/58/59-related Cervical Intraepithelial Neoplasia (CIN) Grade 2 or Worse in the Long-term Follow-up (LTFU) Study
This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine Nordic pathology panel (NPP) consensus diagnosis of CIN 2 or worse related to nonvaccine HPV types up to 14 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to nonvaccine HPV types 31, 33, 35, 39, 45, 51, 52, 56, 58, or 59. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis.
Time frame: Up to 14 years since Vaccination Dose 1
Population: Participants in Cohort 1 who had received ≥1 qHPV vaccination, had any follow up visit in the LTFU, and had been PCR-negative and seronegative based on cLIA to the appropriate HPV type(s) at Day 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Base Study Group 1: qHPV Vaccine | Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 31/33/35/39/45/51/52/56/58/59-related Cervical Intraepithelial Neoplasia (CIN) Grade 2 or Worse in the Long-term Follow-up (LTFU) Study | 0.2 Incidence per 100 person-years |
Secondary
Number of Participants With Anti-Human Papillomavirus (HPV) 11 Titer ≥16 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 11 virions in vitro; thus, the number of participants with anti-HPV 11 ≥16 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Time frame: Week 4 Postdose 3
Population: Participants who received 3 qHPV vaccine doses and had Month 7 results within acceptable ranges, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were polymerase chain reaction (PCR)-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Base Study Group 1: qHPV Vaccine | Number of Participants With Anti-Human Papillomavirus (HPV) 11 Titer ≥16 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | 1054 Number of Participants |
| Base Study Group 2: Placebo | Number of Participants With Anti-Human Papillomavirus (HPV) 11 Titer ≥16 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | 5 Number of Participants |
Secondary
Number of Participants With Anti-Human Papillomavirus (HPV) 16 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 16 pseudovirions in vitro; thus, the number of participants with anti-HPV 16 ≥20 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Time frame: Week 4 Postdose 3
Population: Participants who received 3 qHPV vaccine doses and had Month 7 results within acceptable ranges, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were polymerase chain reaction (PCR)-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Base Study Group 1: qHPV Vaccine | Number of Participants With Anti-Human Papillomavirus (HPV) 16 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | 1014 Number of Participants |
| Base Study Group 2: Placebo | Number of Participants With Anti-Human Papillomavirus (HPV) 16 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | 15 Number of Participants |
Secondary
Number of Participants With Anti-Human Papillomavirus (HPV) 18 Titer ≥24 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 18 pseudovirions in vitro; thus, the number of participants with anti-HPV 18 ≥24 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Time frame: Week 4 Postdose 3
Population: Participants who received 3 qHPV vaccine doses and had Month 7 results within acceptable ranges, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were polymerase chain reaction (PCR)-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Base Study Group 1: qHPV Vaccine | Number of Participants With Anti-Human Papillomavirus (HPV) 18 Titer ≥24 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | 1133 Number of Participants |
| Base Study Group 2: Placebo | Number of Participants With Anti-Human Papillomavirus (HPV) 18 Titer ≥24 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | 12 Number of Participants |
Secondary
Number of Participants With Anti-Human Papillomavirus (HPV) 6 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 6 pseudovirions in vitro; thus, the number of participants with anti-HPV 6 ≥20 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Time frame: Month 7 (4 weeks after Vaccination 3)
Population: Participants who received 3 qHPV vaccine doses and had Month 7 results within acceptable ranges, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were polymerase chain reaction (PCR)-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Base Study Group 1: qHPV Vaccine | Number of Participants With Anti-Human Papillomavirus (HPV) 6 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | 1054 Number of Participants |
| Base Study Group 2: Placebo | Number of Participants With Anti-Human Papillomavirus (HPV) 6 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study | 13 Number of Participants |
Secondary
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to human papillomavirus (HPV) types were measured using cLIA. Seropositivity was assessed by competitive Luminex Immunoassay (cLIA); the serostatus cut-offs for anti-HPV 6, 11, 16 and 18 serum cLIA were 20, 16, 20 and 24 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time frame: At 108 months since Vaccination Dose 1
Population: Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7. No data were collected for Cohort 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 6 | 94.4 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 11 | 95.5 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 18 | 59.9 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 16 | 99.1 Percentage of Participants |
Secondary
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to HPV types were measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 at Month 108 were 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time frame: At 108 months since Vaccination Dose 1
Population: Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7. No data were collected for Cohort 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 6 | 97.6 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 11 | 96.3 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 16 | 100.0 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 18 | 91.4 Percentage of Participants |
Secondary
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to human papillomavirus (HPV) types were measured using cLIA. Seropositivity was assessed by cLIA; the serostatus cut-offs for anti-HPV 6, 11, 16 and 18 serum cLIA were 20, 16, 20 and 24 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time frame: At 168 months since Vaccination Dose 1
Population: Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 6 | 90.6 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 11 | 91.1 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 16 | 98.3 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 18 | 52.4 Percentage of Participants |
Secondary
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to HPV types were measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 at Month 168 were 9, 6, 5, and 5 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time frame: At 168 months since Vaccination Dose 1
Population: Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 6 | 98.1 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 11 | 98.0 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 16 | 100.0 Percentage of Participants |
| Base Study Group 1: qHPV Vaccine | Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study | Anti-HPV 18 | 93.8 Percentage of Participants |
Secondary
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 216 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) ) in the Long-Term Follow-Up (LTFU) Study
Antibodies to HPV types will be measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 are 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. The percentage of participants that are seropositive for each type will be summarized.
Time frame: At 216 months since Vaccination Dose 1
Secondary
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 264 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Antibodies to HPV types will be measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 are 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. The percentage of participants that are seropositive for each type will be summarized.
Time frame: At 264 months since Vaccination Dose 1