GARDASIL™ Vaccine Impact in Population Study (V501-033)

NCT01077856 | Completed Results DMC

• 3 other identifiers: V501-0332010_018EP08014.033
• Study Type: observational
• Target: 54,516
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will assess the impact of GARDASIL™ human papillomavirus (HPV) vaccine in the general female population by utilizing nationwide registry databases in the participating Nordic countries.

Conditions

Human Papillomavirus Infections

Keywords

congenital anomaly; pregnancy; GARDASIL®; Nordic; population-based

Outcome Measures

Primary Outcomes (25)

• Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia (CIN) for Participants of All Ages in Denmark

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. The collection of such data in these registries is mandated by law and compliance is generally very high. The number of new cases of high-grade (2/3) CIN registered during the assessment periods in Denmark was recorded. Incidence rates are for all age groups and were age-adjusted using the European Standard Population. The incidence before Gardasil licensure is an average over the 3-year period.

  Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)

• Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants <=26 Years of Age in Denmark

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. The collection of such data in these registries is mandated by law and compliance is generally very high. The number of new cases of high-grade (2/3) CIN registered during the assessment periods in Denmark was recorded. Incidence rates are for women \<=26 years of age and were age-adjusted using the European Standard Population. The incidence before Gardasil licensure is an average over the 3-year period.

  Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)

• Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants >26 Years of Age in Denmark

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. The collection of such data in these registries is mandated by law and compliance is generally very high. The number of new cases of high-grade (2/3) CIN registered during the assessment periods in Denmark was recorded. Incidence rates are for women \>26 years of age and were age-adjusted using the European Standard Population. The incidence before Gardasil licensure is an average over the 3-year period.

  Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)

• Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants of All Ages in Norway

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. The collection of such data in these registries is mandated by law and compliance is generally very high. The number of new cases of high-grade (2/3) CIN registered during the assessment periods in Norway was recorded. Incidence rates are for all age groups and were age-adjusted using the European Standard Population. The incidence before Gardasil licensure is an average over the 3-year period.

  Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)

• Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants <=26 Years of Age in Norway

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. The collection of such data in these registries is mandated by law and compliance is generally very high. The number of new cases of high-grade (2/3) CIN registered during the assessment periods in Norway was recorded. Incidence rates are for women \<=26 years of age and were age-adjusted using the European Standard Population. The incidence before Gardasil licensure is an average over the 3-year period.

  Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)

• Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants >26 Years of Age in Norway

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. The collection of such data in these registries is mandated by law and compliance is generally very high. The number of new cases of high-grade (2/3) CIN registered during the assessment periods in Norway was recorded. Incidence rates are for women \>26 years of age were age-adjusted using the European Standard Population. The incidence before Gardasil licensure is an average over the 3-year period.

  Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)

• Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants of All Ages in Sweden

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. The collection of such data in these registries is mandated by law and compliance is generally very high. The number of new cases of high-grade (2/3) CIN registered during the assessment periods in Sweden was recorded. Incidence rates are for all age groups and were age-adjusted using the European Standard Population. The incidence before Gardasil licensure is an average over the 3-year period.

  Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)

• Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants <=26 Years of Age in Sweden

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. The collection of such data in these registries is mandated by law and compliance is generally very high. The number of new cases of high-grade (2/3) CIN registered during the assessment periods in Sweden was recorded. Incidence rates are for women \<=26 years of age and were age-adjusted using the European Standard Population. The incidence before Gardasil licensure is an average over the 3-year period.

  Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)

• Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants >26 Years of Age in Sweden

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. The collection of such data in these registries is mandated by law and compliance is generally very high. The number of new cases of high-grade (2/3) CIN registered during the assessment periods in Sweden was recorded. Incidence rates are for women \>26 years of age and were age-adjusted using the European Standard Population. The incidence before Gardasil licensure is an average over the 3-year period.

  Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)

• Incidence of Human Papillomavirus (HPV) 6/11/16/18-related Cervical Intraepithelial Neoplasia for Participants of All Ages

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The number of new cases of HPV 6/11/16/18-related high-grade (2/3) CIN was estimated based on the proportion of HPV 6/11/16/18 in all CIN in a representative sample. Incidence was age-adjusted according to Nordic Standard Population.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia for Participants <=26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The number of new cases of HPV 6/11/16/18-related high-grade (2/3) CIN was estimated based on the proportion of HPV 6/11/16/18 in all CIN in a representative sample. Incidence was age-adjusted according to Nordic Standard Population.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia for Participants >26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The number of new cases of HPV 6/11/16/18-related high-grade (2/3) CIN was estimated based on the proportion of HPV 6/11/16/18 in all CIN in a representative sample. Incidence was age-adjusted according to Nordic Standard Population.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Incidence of Cervical Intraepithelial Neoplasia Associated With High-risk HPV Types Other Than 16/18 in Participants <=26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The percentage of new cases of high-grade (2/3) CIN related to high-risk HPV types other than 16 and 18 was analyzed. High-risk HPV types include 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. Incidence was age-adjusted according to Nordic Standard Population.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Incidence of Cervical Intraepithelial Neoplasia Associated With High-risk HPV Types Other Than 16/18 in Participants >26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The percentage of new cases of high-grade (2/3) CIN related to high-risk HPV types other than 16 and 18 was analyzed. High-risk HPV types include 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. Incidence was age-adjusted according to Nordic Standard Population.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Incidence of HPV 6/11/16/18-related Cervical Cancer in Participants of All Ages

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The number of new cases of HPV 6/11/16/18-related cervical cancer was estimated based on the proportion of HPV 6/11/16/18 in all cervical cancers in a representative sample. Incidence was age-adjusted according to Nordic Standard Population.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Incidence of HPV 6/11/16/18-related Cervical Cancer in Participants <=26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The number of new cases of HPV 6/11/16/18-related cervical cancer was estimated based on the proportion of HPV 6/11/16/18 in all cervical cancers in a representative sample. Incidence was age-adjusted according to Nordic Standard Population.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Incidence of HPV 6/11/16/18-related Cervical Cancer in Participants >26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The number of new cases of HPV 6/11/16/18-related cervical cancer was estimated based on the proportion of HPV 6/11/16/18 in all cervical cancers in a representative sample. Incidence was age-adjusted according to Nordic Standard Population.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Incidence of Cervical Cancer Associated With High-risk HPV Types Other Than 16/18 in Participants <=26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The percentage of new cases of cervical cancer associated with high-risk HPV types other than 16 and 18 was estimated based on the proportion of HPV 16/18 in all cervical cancer in a representative sample. Incidence was age-adjusted according to Nordic Standard Population.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Incidence of Cervical Cancer Associated With High-risk HPV Types Other Than 16/18 in Participants >26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The percentage of new cases of cervical cancer associated with high-risk HPV types other than 16 and 18 was estimated based on the proportion of HPV 16/18 in all cervical cancer in a representative sample. Incidence was age-adjusted according to Nordic Standard Population.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Incidence of HPV-related Histologically Confirmed Female Genital Diseases, Including Vulvar and Vaginal Cancer and Their High-grade Precursors

  The incidence of HPV-related histologically confirmed female genital diseases, including vulvar and vaginal cancer and their high-grade precursors was to be assessed.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Prevalence of HPV 6/11/16/18 Infection in Participants <=26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The percentage of liquid-based cervical cytology samples positive for HPV 6, 11, 16, or 18 was analyzed.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Prevalence of HPV 6/11/16/18 Infection in Participants >26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The percentage of liquid-based cervical cytology samples positive for HPV 6, 11, 16, or 18 was analyzed.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Prevalence of HPV Infection for High-risk Types Other Than 16/18 for Participants <=26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The percentage of liquid-based cervical cytology samples positive for high-risk HPV Types other than 16 or 18, and not co-infected with Types 16 or 18, was analyzed.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Prevalence of HPV Infection for High-risk Types Other Than 16/18 for Participants >26 Years of Age

  All Nordic countries participating in this study have national cervical cancer screening programs and registry systems that routinely collect information on cervical cytology, histology, and/or definitive therapy results. In addition, lesional tissue samples were routinely collected and stored; the 2004 to 2006 period was chosen because it was sufficiently recent to reflect HPV type status immediately before licensure of Gardasil. The percentage of liquid-based cervical cytology samples positive for high-risk HPV Types other than 16 or 18, and not co-infected with Types 16 or 18, was analyzed.

  Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)

• Percentage of Live Born Babies With a Major Congenital Anomaly

  The percentage of live born babies with major congenital anomalies (MCA) born to women vaccinated with Gardasil during pregnancy and to women in the general population was assessed. For Denmark and Sweden diagnoses of congenital anomaly within 1 year of birth are included; for Norway diagnoses at birth are included.

  Up to 5 years after Gardasil licensure (2007 to 2011)

Secondary Outcomes (4)

• Incidence of Cervical Intraepithelial Neoplasia by Gardasil Vaccination Status

  Four years to 5 years after Gardasil licensure (2011 to 2012)

• Incidence of Cervical Cancer by Gardasil Vaccination Status

  Four years to 5 years after Gardasil licensure (2011 to 2012)

• Incidence of Other HPV-related Genital Diseases by Gardasil Vaccination Status

  Four years to 5 years after Gardasil licensure (2011 to 2012)

• Prevalence of HPV 6, 11, 16, and 18 Infection by Gardasil Vaccination Status

  Four years to 5 years after Gardasil licensure (2011 to 2012)

Study Arms (2)

Pre-Vaccine

Registry, survey, and HPV status data from 2004-2006

Post-Vaccine

Registry, survey, and HPV status data from 2011-2012

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Registry data from the Population, Cervical Cancer Screening, Pathology, Cancer, and Death registries; Survey: Questionnaire sent to random sampling of women from the Central Population Registry Database; HPV Data: liquid-based cytology and histology samples from hospitals in participating countries

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Danish Cancer Society: collaborator
• Union for International Cancer Control: collaborator
• Norwegian Institute of Public Health: collaborator
• Karolinska Institutet: collaborator

Related Publications (3)

• Bonanni P, Cohet C, Kjaer SK, Latham NB, Lambert PH, Reisinger K, Haupt RM. A summary of the post-licensure surveillance initiatives for GARDASIL/SILGARD. Vaccine. 2010 Jul 5;28(30):4719-30. doi: 10.1016/j.vaccine.2010.04.070. Epub 2010 May 6.

  PMID: 20451636 BACKGROUND

• Baldur-Felskov B, Dehlendorff C, Munk C, Kjaer SK. Early impact of human papillomavirus vaccination on cervical neoplasia--nationwide follow-up of young Danish women. J Natl Cancer Inst. 2014 Mar;106(3):djt460. doi: 10.1093/jnci/djt460. Epub 2014 Feb 19.

  PMID: 24552678 RESULT

• Nygard M, Hansen BT, Kjaer SK, Hortlund M, Tryggvadottir L, Munk C, Lagheden C, Sigurdardottir LG, Campbell S, Liaw KL, Dillner J. Human papillomavirus genotype-specific risks for cervical intraepithelial lesions. Hum Vaccin Immunother. 2021 Apr 3;17(4):972-981. doi: 10.1080/21645515.2020.1814097. Epub 2020 Sep 29.

  PMID: 32990181 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Tissue, cervical cells

MeSH Terms

Conditions

Papillomavirus Infections; Congenital Abnormalities

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: ECOLOGIC OR COMMUNITY
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2010
• First Posted: March 1, 2010
• Study Start: May 29, 2007
• Primary Completion: December 2, 2014
• Study Completion: December 2, 2014
• Last Updated: September 13, 2022
• Results First Posted: December 10, 2015

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share