Cervical Intraepithelial Neoplasm (CIN) in Women (Gardasil) (V501-015) (FUTURE II)

• ClinicalTrials.gov Identifier: NCT00092534
• Recruitment Status: Active, not recruiting
• First Posted: September 28, 2004
• Results First Posted: November 26, 2009
• Last Update Posted: August 23, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Conditions: Cervical Cancer; Genital Warts
• Interventions: Biological: Gardasil, human papillomavirus (type 6, 11, 16, 18) recombinant vaccine; Biological: Matching Placebo
• Enrollment: 12167

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.

Arm/Group Title	Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo	Base Study EXT	LTFU: Cohort 1	LTFU: Cohort 2
Arm/Group Description	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.	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.	Participants who received placebo (N=581) or an incomplete qHPV vaccine regimen (N=13) were enrolled to receive qHPV vaccine during the base study extension; participants designated as "Not Completed" are those who did not complete all three vaccinations and/or all required follow-up visits.	Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.	Participants who received placebo in the Base Study and qHPV vaccine after completion of the Base Study and prior to entry into the LTFU. Cohort 2 provided a total of approximately 10 years of follow-up post-vaccination.
Period Title: Base Study Vaccination Period
Started	6087	6080	0	0	0
Completed	5916	5954	0	0	0
Not Completed	171	126	0	0	0
Reason Not Completed
Randomized not Vaccinated	5	5	0	0	0
Adverse Event	3	1	0	0	0
Death	5	4	0	0	0
Lost to Follow-up	41	37	0	0	0
Physician Decision	1	0	0	0	0
Pregnancy	9	7	0	0	0
Protocol Violation	2	1	0	0	0
Withdrawal by Subject	85	58	0	0	0
Moved	14	12	0	0	0
New Medical History (Not AEs)	5	0	0	0	0
Travel	1	0	0	0	0
Site Closed	0	1	0	0	0
Period Title: Base Study Follow-Up Period
Started	5942 [1]	5971 [1]	0	0	0
Completed	5626	5277	0	0	0
Not Completed	316	694	0	0	0
Reason Not Completed
Adverse Event	2	4	0	0	0
Death	2	1	0	0	0
Lost to Follow-up	120	146	0	0	0
Pregnancy	6	10	0	0	0
Protocol Violation	1	2	0	0	0
Withdrawal by Subject	71	62	0	0	0
Moved	62	58	0	0	0
Travel	10	7	0	0	0
Site Closed	0	2	0	0	0
Subjects continuing	27	31	0	0	0
Subjects in extension	15	371	0	0	0
[1] Includes subjects who did not receive 3 doses of vaccine/placebo but continued into the follow-up.
Period Title: Base Study EXT
Started	0	0	594	0	0
Completed	0	0	449	0	0
Not Completed	0	0	145	0	0
Reason Not Completed
Lost to Follow-up	0	0	41	0	0
Physician Decision	0	0	1	0	0
Pregnancy	0	0	12	0	0
Withdrawal by Subject	0	0	18	0	0
Participant moved	0	0	6	0	0
Travel	0	0	2	0	0
Site closed	0	0	21	0	0
Study ended	0	0	29	0	0
Protocol Violation	0	0	15	0	0
Period Title: Long-Term Follow-Up (LTFU) Study
Started [1]	0	0	0	2750 [2]	2097 [2]
Started: Registry-based Effectiveness [3]	0	0	0	2650	2050
Started: Immunogenicity Analysis [4]	0	0	0	2385	1849
Started: Registry-based Safety [5]	0	0	0	2448	1888
Completed	0	0	0	2749	2097
Not Completed	0	0	0	1	0
Reason Not Completed
Withdrawal by Subject	0	0	0	1	0
[1] Eligible for inclusion in the LTFU study; [2] Some Base Study participants did not consent for inclusion in the LTFU.; [3] Eligible and consented to inclusion in registry-based searches for effectiveness information; [4] Eligible and consented to provide blood samples for immunogenicity anaysis; [5] Eligible and consented to inclusion in registry-based searches for safety information

Baseline Characteristics

Arm/Group Title		Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo	Total
Arm/Group Description		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.	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.	Total of all reporting groups
Overall Number of Baseline Participants		6087	6080	12167
Baseline Analysis Population Description		The Baseline Analysis population is from the V501-015 Base Study.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	6087 participants	6080 participants	12167 participants
		20.0 (2.2)	19.9 (2.1)	19.9 (2.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6087 participants	6080 participants	12167 participants
	Female	6087 100.0%	6080 100.0%	12167 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6087 participants	6080 participants	12167 participants
	Asian	151 2.5%	135 2.2%	286 2.4%
	Black	171 2.8%	227 3.7%	398 3.3%
	Hispanic American	555 9.1%	557 9.2%	1112 9.1%
	Native American	1 0.0%	1 0.0%	2 0.0%
	White	4584 75.3%	4550 74.8%	9134 75.1%
	Other-Unspecified	625 10.3%	610 10.0%	1235 10.2%

Outcome Measures

1. Primary Outcome

Title	Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Base Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	5306	5262
Measure Type: Number; Unit of Measure: Incidence per 100 person-years
	0.0	0.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Base Study Group 1: qHPV Vaccine, Base Study Group 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percent relative risk reduction
	Estimated Value	96.6
	Confidence Interval	95%; 88.2 to 99.6
	Estimation Comments	Confidence Interval (CI) based on binomial tail probabilities and not from a dispersion parameter

2. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	LTFU: Cohort 1
Arm/Group Description:	Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed	2121
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Incidence per 100 person-years
	0.0; (0.0 to 0.1)

3. Primary Outcome

Title	Incidence of the Composite Endpoint of HPV16/18-related CIN 2 or Worse in the Long-term Follow-up (LTFU) Study
Description	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

Outcome Measure Data Not Reported

4. Secondary Outcome

Title	Number of Participants With Anti-Human Papillomavirus (HPV) 6 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	1056	1057
Measure Type: Number; Unit of Measure: Number of Participants
	1054	13

5. Secondary Outcome

Title	Number of Participants With Anti-Human Papillomavirus (HPV) 11 Titer ≥16 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	1057	1057
Measure Type: Number; Unit of Measure: Number of Participants
	1054	5

6. Secondary Outcome

Title	Number of Participants With Anti-Human Papillomavirus (HPV) 16 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	1017	994
Measure Type: Number; Unit of Measure: Number of Participants
	1014	15

7. Secondary Outcome

Title	Number of Participants With Anti-Human Papillomavirus (HPV) 18 Titer ≥24 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	1140	1119
Measure Type: Number; Unit of Measure: Number of Participants
	1133	12

8. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	LTFU: Cohort 1
Arm/Group Description:	Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed	2355
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Incidence per 100 person-years
	0.2; (0.1 to 0.2)

9. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	LTFU: Cohort 1
Arm/Group Description:	Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed	2312
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Incidence per 100 person-years
	0.1; (0.1 to 0.1)

10. Secondary Outcome

Title	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
Description	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

Outcome Measure Data Not Reported

11. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		LTFU: Cohort 1
Arm/Group Description:		Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed		2750
Geometric Mean (95% Confidence Interval); Unit of Measure: mMU/mL
Anti-HPV 6	Number Analyzed	1234 participants
		89.2; (84.7 to 94.0)
Anti-HPV 11	Number Analyzed	1234 participants
		85.2; (80.7 to 90.0)
Anti-HPV 16	Number Analyzed	1179 participants
		348.6; (328.3 to 370.2)
Anti-HPV 18	Number Analyzed	1332 participants
		32.5; (30.2 to 34.9)

12. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		LTFU: Cohort 1
Arm/Group Description:		Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed		2750
Geometric Mean (95% Confidence Interval); Unit of Measure: mMU/mL
Anti-HPV 6	Number Analyzed	1058 participants
		78.4; (73.8 to 83.2)
Anti-HPV 11	Number Analyzed	1058 participants
		66.8; (62.6 to 71.3)
Anti-HPV 16	Number Analyzed	1005 participants
		291.2; (272.1 to 311.5)
Anti-HPV 18	Number Analyzed	1131 participants
		26.1; (24.1 to 28.2)

13. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		LTFU: Cohort 1
Arm/Group Description:		Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed		2750
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Anti-HPV 6	Number Analyzed	1234 participants
		94.4; (93.0 to 95.6)
Anti-HPV 11	Number Analyzed	1234 participants
		95.5; (94.1 to 96.6)
Anti-HPV 16	Number Analyzed	1179 participants
		99.1; (98.3 to 99.5)
Anti-HPV 18	Number Analyzed	1332 participants
		59.9; (57.2 to 62.6)

14. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		LTFU: Cohort 1
Arm/Group Description:		Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed		2750
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Anti-HPV 6	Number Analyzed	1058 participants
		90.6; (88.7 to 92.3)
Anti-HPV 11	Number Analyzed	1058 participants
		91.1; (89.2 to 92.8)
Anti-HPV 16	Number Analyzed	1005 participants
		98.3; (97.3 to 99.0)
Anti-HPV 18	Number Analyzed	1131 participants
		52.4; (49.5 to 55.4)

15. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		LTFU: Cohort 1
Arm/Group Description:		Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed		2750
Geometric Mean (95% Confidence Interval); Unit of Measure: mMU/mL
Anti-HPV 6	Number Analyzed	1235 participants
		95.2; (90.5 to 100.1)
Anti-HPV 11	Number Analyzed	1235 participants
		67.4; (64.3 to 70.8)
Anti-HPV 16	Number Analyzed	1181 participants
		346.1; (327.3 to 365.9)
Anti-HPV 18	Number Analyzed	1333 participants
		46.1; (43.3 to 49.2)

16. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		LTFU: Cohort 1
Arm/Group Description:		Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed		2750
Geometric Mean (95% Confidence Interval); Unit of Measure: mMU/mL
Anti-HPV 6	Number Analyzed	1054 participants
		81.2; (76.1 to 86.5)
Anti-HPV 11	Number Analyzed	1055 participants
		53.5; (50.2 to 57.0)
Anti-HPV 16	Number Analyzed	1000 participants
		290.2; (271.0 to 310.8)
Anti-HPV 18310.8	Number Analyzed	1036 participants
		36.5; (33.7 to 39.5)

17. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		LTFU: Cohort 1
Arm/Group Description:		Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed		2750
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Anti-HPV 6	Number Analyzed	1235 participants
		97.6; (96.6 to 98.4)
Anti-HPV 11	Number Analyzed	1235 participants
		96.3; (95.1 to 97.3)
Anti-HPV 16	Number Analyzed	1181 participants
		100.0; (99.7 to 100.0)
Anti-HPV 18	Number Analyzed	1333 participants
		91.4; (89.7 to 92.8)

18. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		LTFU: Cohort 1
Arm/Group Description:		Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed		2750
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Anti-HPV 6	Number Analyzed	1054 participants
		98.1; (97.1 to 98.8)
Anti-HPV 11	Number Analyzed	1055 participants
		98.0; (97.0 to 98.8)
Anti-HPV 16	Number Analyzed	1000 participants
		100.0; (99.6 to 100.0)
Anti-HPV 18	Number Analyzed	1036 participants
		93.8; (92.2 to 95.2)

19. Secondary Outcome

Title	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
Description	Antibodies to human papillomavirus (HPV) types will be measured using IgG LIA..
Time Frame	At 216 months since Vaccination Dose 1

Outcome Measure Data Not Reported

20. Secondary Outcome

Title	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
Description	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

Outcome Measure Data Not Reported

21. Secondary Outcome

Title	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
Description	Antibodies to human papillomavirus (HPV) types will be measured using IgG LIA..
Time Frame	At 264 months since Vaccination Dose 1

Outcome Measure Data Not Reported

22. Secondary Outcome

Title	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
Description	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

Outcome Measure Data Not Reported

Adverse Events

Time Frame	From randomization in the Base Study to up to 10 years after completion of the Base Study (up to 14 years)
Adverse Event Reporting Description	The number of participants at risk includes randomized participants who had follow-up data available. Both serious adverse events (SAEs) and nonserious AEs were collected in the Base Study. Safety data for the LTFU were evaluated based on health outcomes data available from the national registries; in addition, AEs and SAEs associated with blood draws at LTFU Year 5 and Year 10 were also collected.
Arm/Group Title	Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo	Base Study EXT	LTFU: Cohort 1	LTFU: Cohort 2
Arm/Group Description	During the Base Study, participants received 3 qHPV vaccinations (at Day 1, Month 2 and Month 6) during the Vaccination Period and were followed for up to 4 years during the Base Study Follow-Up.	Participants received 3 placebo vaccinations (at Day 1, Month 2 and Month 6) during the Base Study Vaccination Period, and then received 3 qHPV vaccinations during the 4-year Base Study EXT.	Participants who received placebo (N=581) or an incomplete qHPV vaccine regimen (N=13) were enrolled to receive qHPV vaccine during the base study extension; participants designated as "Not Completed" are those who did not complete all three vaccinations and/or all required follow-up visits.	Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.	Participants who received placebo in the Base Study and qHPV vaccine after completion of the Base Study and prior to entry into the LTFU. Cohort 2 provided a total of approximately 10 years of follow-up post-vaccination in the LTFU.
All-Cause Mortality
	Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo	Base Study EXT	LTFU: Cohort 1	LTFU: Cohort 2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	7/6082 (0.12%)	5/6075 (0.08%)	0/594 (0.00%)	2/2448 (0.08%)	1/1888 (0.05%)
Serious Adverse Events
	Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo	Base Study EXT	LTFU: Cohort 1	LTFU: Cohort 2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	46/6082 (0.76%)	56/6075 (0.92%)	1/594 (0.17%)	0/2448 (0.00%)	0/1888 (0.00%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Cardiac disorders
Aortic valve disease * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Cardiac arrest * 1	1/6021 (0.02%)	0/6033 (0.00%)	0/594 (0.00%)	0/594 (0.00%)	0/1888 (0.00%)
Myocarditis * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Pericarditis * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Gastrointestinal disorders
Abdominal pain * 1	1/6082 (0.02%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Gastritis * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Reflux oesophagitis * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
General disorders
Chills * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Face oedema * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Pyrexia * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Injection site joint movement impairment * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Injection site pain * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Hepatobiliary disorders
Cholelithiasis * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Immune system disorders
Anaphylactic reaction * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Hypersensitivty * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Infections and infestations
Appendicitis * 1	2/6082 (0.03%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Cervicitis * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Endometritis * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Gastroenteritis * 1	2/6082 (0.03%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Gastrointestinal infection * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Infective thrombosis * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Pelvic Inflammatory disease * 1	0/6082 (0.00%)	2/6075 (0.03%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Pneumonia * 1	2/6082 (0.03%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Pyelonephritis * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Sepsis * 1	2/6082 (0.03%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Septic Shock * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Typhoid fever * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Urinary tract infection * 1	0/6082 (0.00%)	2/6075 (0.03%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Uterine infection * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Injury, poisoning and procedural complications
Chemical poisoning * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Failed forceps delivery * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Intentional overdose * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Multiple injuries * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Overdose * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Post procedural haemorrhage * 1	1/6082 (0.02%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Road traffic accident * 1	3/6082 (0.05%)	2/6075 (0.03%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Thermal burn * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Musculoskeletal and connective tissue disorders
Pain in extremity * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Nervous system disorders
Convulsion * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Dizziness * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Headache * 1	2/6082 (0.03%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Pregnancy, puerperium and perinatal conditions
Abortion threatened * 1	3/6082 (0.05%)	4/6075 (0.07%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Breech presentation * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Brow presentation * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Cephalo-pelvic disproportion * 1	0/6082 (0.00%)	5/6075 (0.08%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Cervix dystocia * 1	1/6082 (0.02%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Ectopic pregnancy † 1	1/6082 (0.02%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Failed trial of labour * 1	3/6082 (0.05%)	3/6075 (0.05%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Foetal distress syndrome * 1	3/6082 (0.05%)	2/6075 (0.03%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Foetal malpresentation * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Hyperemesis gravidarum * 1	2/6082 (0.03%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Imminent abortion * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Oligohydramnios * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Postpartum haemorrhage * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Pre-eclampsia * 1	1/6082 (0.02%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Pregnancy induced hypertension * 1	2/6082 (0.03%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Premature labour * 1	3/6082 (0.05%)	5/6075 (0.08%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Premature rupture of membranes * 1	1/6082 (0.02%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Prolonged pregnancy * 1	0/6082 (0.00%)	2/6075 (0.03%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Uterine contractions during pregnancy * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Cervical incompetence * 1	0/6082 (0.00%)	2/6075 (0.03%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Psychiatric disorders
Bipolar disorder * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Completed suicide * 1	0/6082 (0.00%)	2/6075 (0.03%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Panic attack * 1	0/6082 (0.00%)	0/6075 (0.00%)	1/594 (0.17%)	0/2448 (0.00%)	0/1888 (0.00%)
Renal and urinary disorders
Urinary retention * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Reproductive system and breast disorders
Cervix haemorrhage uterine * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Ovarian cyst * 1	2/6082 (0.03%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Vaginal laceration * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Vulvovaginal discomfort * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Respiratory, thoracic and mediastinal disorders
Asphyxia * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Asthma * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Neonatal asphyxia * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Pneumomediastinum * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Pulmonary embolism * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Skin and subcutaneous tissue disorders
Cutaneous vasculitis * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Dermatitis contact * 1	0/6082 (0.00%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Vascular disorders
Deep vein thrombosis * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Hypertension * 1	1/6082 (0.02%)	1/6075 (0.02%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Thrombophlebitis * 1	1/6082 (0.02%)	0/6075 (0.00%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
1 Term from vocabulary, MedDRA 11.0; * Indicates events were collected by non-systematic assessment; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Base Study Group 1: qHPV Vaccine	Base Study Group 2: Placebo	Base Study EXT	LTFU: Cohort 1	LTFU: Cohort 2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	551/6082 (9.06%)	499/6075 (8.21%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
General disorders
Injection site erythema * 1	142/6082 (2.33%)	120/6075 (1.98%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Injection site pain * 1	503/6082 (8.27%)	433/6075 (7.13%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Injection site swelling * 1	97/6082 (1.59%)	76/6075 (1.25%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
Nervous system disorders
Headache * 1	162/6082 (2.66%)	167/6075 (2.75%)	0/594 (0.00%)	0/2448 (0.00%)	0/1888 (0.00%)
1 Term from vocabulary, MedDRA 11.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.

Results Point of Contact

• Name/Title: Executive Vice President, Clinical and Quantitative Sciences
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Kjaer SK, Nygard M, Dillner J, Brooke Marshall J, Radley D, Li M, Munk C, Hansen BT, Sigurdardottir LG, Hortlund M, Tryggvadottir L, Joshi A, Das R, Saah AJ. A 12-Year Follow-up on the Long-Term Effectiveness of the Quadrivalent Human Papillomavirus Vaccine in 4 Nordic Countries. Clin Infect Dis. 2018 Jan 18;66(3):339-345. doi: 10.1093/cid/cix797.

Other Publications:

FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27. doi: 10.1056/NEJMoa061741.

Garland SM, Steben M, Sings HL, James M, Lu S, Railkar R, Barr E, Haupt RM, Joura EA. Natural history of genital warts: analysis of the placebo arm of 2 randomized phase III trials of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine. J Infect Dis. 2009 Mar 15;199(6):805-14. doi: 10.1086/597071.

Barr E, Gause CK, Bautista OM, Railkar RA, Lupinacci LC, Insinga RP, Sings HL, Haupt RM. Impact of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine in a sexually active population of North American women. Am J Obstet Gynecol. 2008 Mar;198(3):261.e1-11. doi: 10.1016/j.ajog.2007.09.001.

Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Garland SM, Harper DM, Tang GW, Ferris DG, Steben M, Jones RW, Bryan J, Taddeo FJ, Bautista OM, Esser MT, Sings HL, Nelson M, Boslego JW, Sattler C, Barr E, Paavonen J. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet. 2007 May 19;369(9574):1693-702. doi: 10.1016/S0140-6736(07)60777-6.

Perez G, Lazcano-Ponce E, Hernandez-Avila M, Garcia PJ, Munoz N, Villa LL, Bryan J, Taddeo FJ, Lu S, Esser MT, Vuocolo S, Sattler C, Barr E. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like-particle vaccine in Latin American women. Int J Cancer. 2008 Mar 15;122(6):1311-8. doi: 10.1002/ijc.23260.

FUTURE II Study Group. Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection. J Infect Dis. 2007 Nov 15;196(10):1438-46. doi: 10.1086/522864. Epub 2007 Oct 31.

Ault KA; Future II Study Group. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet. 2007 Jun 2;369(9576):1861-1868. doi: 10.1016/S0140-6736(07)60852-6.

Giuliano AR, Lazcano-Ponce E, Villa L, Nolan T, Marchant C, Radley D, Golm G, McCarroll K, Yu J, Esser MT, Vuocolo SC, Barr E. Impact of baseline covariates on the immunogenicity of a quadrivalent (types 6, 11, 16, and 18) human papillomavirus virus-like-particle vaccine. J Infect Dis. 2007 Oct 15;196(8):1153-62. doi: 10.1086/521679. Epub 2007 Sep 17.

Garland SM, Insinga RP, Sings HL, Haupt RM, Joura EA. Human papillomavirus infections and vulvar disease development. Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1777-84. doi: 10.1158/1055-9965.EPI-09-0067.

Skjeldestad FE, Mehta V, Sings HL, Ovreness T, Turpin J, Su L, Boerckel P, Roberts C, Bryan J, Jansen KU, Esser MT, Liaw KL. Seroprevalence and genital DNA prevalence of HPV types 6, 11, 16 and 18 in a cohort of young Norwegian women: study design and cohort characteristics. Acta Obstet Gynecol Scand. 2008;87(1):81-8. doi: 10.1080/00016340701714703.

Nygard M, Saah A, Munk C, Tryggvadottir L, Enerly E, Hortlund M, Sigurdardottir LG, Vuocolo S, Kjaer SK, Dillner J. Evaluation of the Long-Term Anti-Human Papillomavirus 6 (HPV6), 11, 16, and 18 Immune Responses Generated by the Quadrivalent HPV Vaccine. Clin Vaccine Immunol. 2015 Aug;22(8):943-8. doi: 10.1128/CVI.00133-15. Epub 2015 Jun 17.

Tay EH, Garland S, Tang G, Nolan T, Huang LM, Orloski L, Lu S, Barr E. Clinical trial experience with prophylactic HPV 6/11/16/18 VLP vaccine in young women from the Asia-Pacific region. Int J Gynaecol Obstet. 2008 Sep;102(3):275-83. doi: 10.1016/j.ijgo.2008.03.021. Epub 2008 Jun 16.

Majewski S, Bosch FX, Dillner J, Iversen OE, Kjaer SK, Munoz N, Olsson SE, Paavonen J, Sigurdsson K, Bryan J, Esser MT, Giacoletti K, James M, Taddeo F, Vuocolo S, Barr E. The impact of a quadrivalent human papillomavirus (types 6, 11, 16, 18) virus-like particle vaccine in European women aged 16 to 24. J Eur Acad Dermatol Venereol. 2009 Oct;23(10):1147-55. doi: 10.1111/j.1468-3083.2009.03266.x. Epub 2009 Apr 23.

Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Brown DR, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch FX, Dillner J, Joura EA, Majewski S, Munoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Maansson R, Lu S, Vuocolo S, Hesley TM, Saah A, Barr E, Haupt RM. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against high-grade cervical and external genital lesions. Cancer Prev Res (Phila). 2009 Oct;2(10):868-78. doi: 10.1158/1940-6207.CAPR-09-0031. Epub 2009 Sep 29.

FUTURE I/II Study Group; Dillner J, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch FX, Joura EA, Majewski S, Munoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan JT, Maansson R, Lu S, Vuocolo S, Hesley TM, Barr E, Haupt R. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial. BMJ. 2010 Jul 20;341:c3493. doi: 10.1136/bmj.c3493.

Olsson SE, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Brown DR, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch FX, Dillner J, Joura EA, Majewski S, Munoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Maansson R, Vuocolo S, Hesley TM, Saah A, Barr E, Haupt RM. Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection. Hum Vaccin. 2009 Oct;5(10):696-704. doi: 10.4161/hv.5.10.9515. Epub 2009 Oct 1.

Haupt RM, Wheeler CM, Brown DR, Garland SM, Ferris DG, Paavonen JA, Lehtinen MO, Steben M, Joura EA, Giacoletti KE, Radley DR, James MK, Saah AJ, Sings HL; FUTURE I and II Investigators. Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection. Int J Cancer. 2011 Dec 1;129(11):2632-42. doi: 10.1002/ijc.25940. Epub 2011 Apr 13.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lehtinen M, Lagheden C, Luostarinen T, Eriksson T, Apter D, Bly A, Gray P, Harjula K, Heikkila K, Hokkanen M, Karttunen H, Kuortti M, Nieminen P, Nummela M, Paavonen J, Palmroth J, Petaja T, Pukkala E, Soderlund-Strand A, Veivo U, Dillner J. Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial. BMJ Open. 2021 Dec 30;11(12):e050669. doi: 10.1136/bmjopen-2021-050669.

Enerly E, Berger S, Kjaer SK, Sundstrom K, Campbell S, Tryggvadottir L, Munk C, Hortlund M; Thomas Group. Electronic address: thomas_group@merck.com; Joshi A, Saah AJ, Nygard M. Use of real-world data for HPV vaccine trial follow-up in the Nordic region. Contemp Clin Trials. 2020 May;92:105996. doi: 10.1016/j.cct.2020.105996. Epub 2020 Apr 1.

Doshi P, Bourgeois F, Hong K, Jones M, Lee H, Shamseer L, Spence O, Jefferson T. Adjuvant-containing control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology. BMJ Evid Based Med. 2020 Dec;25(6):213-219. doi: 10.1136/bmjebm-2019-111331. Epub 2020 Mar 17.

Giuliano AR, Joura EA, Garland SM, Huh WK, Iversen OE, Kjaer SK, Ferenczy A, Kurman RJ, Ronnett BM, Stoler MH, Bautista OM, Moeller E, Ritter M, Shields C, Luxembourg A. Nine-valent HPV vaccine efficacy against related diseases and definitive therapy: comparison with historic placebo population. Gynecol Oncol. 2019 Jul;154(1):110-117. doi: 10.1016/j.ygyno.2019.03.253. Epub 2019 Apr 11.

Garland SM, Joura EA, Ault KA, Bosch FX, Brown DR, Castellsague X, Ferenczy A, Ferris DG, Giuliano AR, Hernandez-Avila M, Huh WK, Iversen OE, Kjaer SK, Kurman RJ, Luna J, Monsonego J, Munoz N, Paavonen J, Pitisuttihum P, Ronnett BM, Steben M, Stoler MH, Wheeler CM, Wiley DJ, Perez G, Saah AJ, Luxembourg A, Li S, DiNubile MJ, Wagner M, Velicer C. Human Papillomavirus Genotypes From Vaginal and Vulvar Intraepithelial Neoplasia in Females 15-26 Years of Age. Obstet Gynecol. 2018 Aug;132(2):261-270. doi: 10.1097/AOG.0000000000002736.

Castellsague X, Ault KA, Bosch FX, Brown D, Cuzick J, Ferris DG, Joura EA, Garland SM, Giuliano AR, Hernandez-Avila M, Huh W, Iversen OE, Kjaer SK, Luna J, Monsonego J, Munoz N, Myers E, Paavonen J, Pitisuttihum P, Steben M, Wheeler CM, Perez G, Saah A, Luxembourg A, Sings HL, Velicer C. Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region. Papillomavirus Res. 2016 Dec;2:61-69. doi: 10.1016/j.pvr.2016.03.002. Epub 2016 Mar 14.

Clark LR, Myers ER, Huh W, Joura EA, Paavonen J, Perez G, James MK, Sings HL, Haupt RM, Saah AJ, Garner EI. Clinical trial experience with prophylactic human papillomavirus 6/11/16/18 vaccine in young black women. J Adolesc Health. 2013 Mar;52(3):322-9. doi: 10.1016/j.jadohealth.2012.07.003. Epub 2012 Aug 15.

Ruiz AM, Ruiz JE, Gavilanes AV, Eriksson T, Lehtinen M, Perez G, Sings HL, James MK, Haupt RM; FUTURE I and II Study Group. Proximity of first sexual intercourse to menarche and risk of high-grade cervical disease. J Infect Dis. 2012 Dec 15;206(12):1887-96. doi: 10.1093/infdis/jis612. Epub 2012 Oct 12.

Joura EA, Garland SM, Paavonen J, Ferris DG, Perez G, Ault KA, Huh WK, Sings HL, James MK, Haupt RM; FUTURE I and II Study Group. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data. BMJ. 2012 Mar 27;344:e1401. doi: 10.1136/bmj.e1401.

Lehtinen M, Ault KA, Lyytikainen E, Dillner J, Garland SM, Ferris DG, Koutsky LA, Sings HL, Lu S, Haupt RM, Paavonen J; FUTURE I and II Study Group. Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia. Sex Transm Infect. 2011 Aug;87(5):372-6. doi: 10.1136/sti.2010.044354. Epub 2011 Apr 6.

Ault KA, Joura EA, Kjaer SK, Iversen OE, Wheeler CM, Perez G, Brown DR, Koutsky LA, Garland SM, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Majewski S, Munoz N, Sings HL, Harkins K, Rutkowski MA, Haupt RM, Garner EI; FUTURE I and II Study Group. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine. Int J Cancer. 2011 Mar 15;128(6):1344-53. doi: 10.1002/ijc.25723. Epub 2011 Jan 12.

Garland SM, Ault KA, Gall SA, Paavonen J, Sings HL, Ciprero KL, Saah A, Marino D, Ryan D, Radley D, Zhou H, Haupt RM, Garner EIO; Quadrivalent Human Papillomavirus Vaccine Phase III Investigators. Pregnancy and infant outcomes in the clinical trials of a human papillomavirus type 6/11/16/18 vaccine: a combined analysis of five randomized controlled trials. Obstet Gynecol. 2009 Dec;114(6):1179-1188. doi: 10.1097/AOG.0b013e3181c2ca21.

Brown DR, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Dillner J, Joura EA, Kurman RJ, Majewski S, Munoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC, Giacoletti KE, Sings HL, James M, Hesley TM, Barr E. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years. J Infect Dis. 2009 Apr 1;199(7):926-35. doi: 10.1086/597307.

Wheeler CM, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Dillner J, Joura EA, Kurman RJ, Majewski S, Munoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC, Giacoletti KE, James M, Vuocolo S, Hesley TM, Barr E. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in sexually active women aged 16-26 years. J Infect Dis. 2009 Apr 1;199(7):936-44. doi: 10.1086/597309.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00092534
• Other Study ID Numbers: V501-015; 2004_082; V501-015 ( Other Identifier: Merck )
• First Submitted: September 23, 2004
• First Posted: September 28, 2004
• Results First Submitted: July 20, 2009
• Results First Posted: November 26, 2009
• Last Update Posted: August 23, 2022