Clinical trial NCT01077856: GARDASIL™ Vaccine Impact in Population Study (V501-033)
Official title: GARDASIL™ Vaccine Impact in Population Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Human Papillomavirus Infections
Keywords: congenital anomaly
pregnancy
GARDASIL®
Nordic
population-based
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Danish Cancer Society
name: Union for International Cancer Control
name: Norwegian Institute of Public Health
name: Karolinska Institutet
First posted: 2010-03-01
Enrollment: 54516
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: ECOLOGIC_OR_COMMUNITY
Time perspective: OTHER
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

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.

Detailed description: Time perspective: The study will be conducted using data collected both retrospectively/concurrently from registries and prospectively by questionnaire survey.

Baseline survey data were collected during a prior study from 2004-2005.

Safety Monitoring: An expert panel on teratology consisting of one teratologist from each of the participating countries will review all available medical records related to any congenital anomalies to search for any emerging patterns that may be indicative of an association between GARDASIL™ exposure in the mother and the subsequent congenital anomalies in the babies.

Eligibility criteria: Inclusion Criteria: - Registry Data: \* Female residents of participating Nordic countries who were alive on January 1st in the year the data will be used for analysis - Survey Data: --Female residents alive in the participating countries on July 1, 2011 --Women must provide consent to use questionnaire data and to link data to other registry databases - Cervical Sample Collection: --For HPV data in the general population: cervical samples from residents of the participating countries who are 45 years and under collected between 2006 and 2007, or in 2011-2012 --For HPV data in lesional samples: cervical samples from women with a diagnosis of CIN or cervical cancer between 2004-2006 and 2011-2012 Exclusion Criteria: - Registry Data: \* Women who participated in Protocol V501-015 (NCT00092534) and are included in the Long-Term Follow-Up study - Survey Data: --Women under 18 or above age 45 on July 1, 2011 --Women who participated in Protocol V501-015 and are included in the Long-Term Follow-Up study - Cervical Sample Collection: --Samples from women who participated in Protocol V501-015 and are included in the Long-Term Follow-Up study --Samples with inadequate integrity for HPV testing

Primary outcomes:
measure: Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia (CIN) for Participants of All Ages in Denmark
timeFrame: Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)
measure: Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants <=26 Years of Age in Denmark
timeFrame: Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)
measure: Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants >26 Years of Age in Denmark
timeFrame: Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)
measure: Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants of All Ages in Norway
timeFrame: Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)
measure: Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants <=26 Years of Age in Norway
timeFrame: Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)
measure: Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants >26 Years of Age in Norway
timeFrame: Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)
measure: Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants of All Ages in Sweden
timeFrame: Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)
measure: Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants <=26 Years of Age in Sweden
timeFrame: Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)
measure: Incidence of Histologically-confirmed Cervical Intraepithelial Neoplasia for Participants >26 Years of Age in Sweden
timeFrame: Three years before Gardasil licensure (2004 to 2006 combined) and annually after Gardasil licensure (2007, 2008, 2009, 2010, and 2011)
measure: Incidence of Human Papillomavirus (HPV) 6/11/16/18-related Cervical Intraepithelial Neoplasia for Participants of All Ages
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia for Participants <=26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia for Participants >26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Incidence of Cervical Intraepithelial Neoplasia Associated With High-risk HPV Types Other Than 16/18 in Participants <=26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Incidence of Cervical Intraepithelial Neoplasia Associated With High-risk HPV Types Other Than 16/18 in Participants >26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Incidence of HPV 6/11/16/18-related Cervical Cancer in Participants of All Ages
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Incidence of HPV 6/11/16/18-related Cervical Cancer in Participants <=26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Incidence of HPV 6/11/16/18-related Cervical Cancer in Participants >26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Incidence of Cervical Cancer Associated With High-risk HPV Types Other Than 16/18 in Participants <=26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Incidence of Cervical Cancer Associated With High-risk HPV Types Other Than 16/18 in Participants >26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Incidence of HPV-related Histologically Confirmed Female Genital Diseases, Including Vulvar and Vaginal Cancer and Their High-grade Precursors
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Prevalence of HPV 6/11/16/18 Infection in Participants <=26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Prevalence of HPV 6/11/16/18 Infection in Participants >26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Prevalence of HPV Infection for High-risk Types Other Than 16/18 for Participants <=26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Prevalence of HPV Infection for High-risk Types Other Than 16/18 for Participants >26 Years of Age
timeFrame: Three years before Gardasil licensure (2004 to 2006) and two years after Gardasil licensure (2011 to 2012)
measure: Percentage of Live Born Babies With a Major Congenital Anomaly
timeFrame: Up to 5 years after Gardasil licensure (2007 to 2011)
Secondary outcomes:
measure: Incidence of Cervical Intraepithelial Neoplasia by Gardasil Vaccination Status
timeFrame: Four years to 5 years after Gardasil licensure (2011 to 2012)
measure: Incidence of Cervical Cancer by Gardasil Vaccination Status
timeFrame: Four years to 5 years after Gardasil licensure (2011 to 2012)
measure: Incidence of Other HPV-related Genital Diseases by Gardasil Vaccination Status
timeFrame: Four years to 5 years after Gardasil licensure (2011 to 2012)
measure: Prevalence of HPV 6, 11, 16, and 18 Infection by Gardasil Vaccination Status
timeFrame: Four years to 5 years after Gardasil licensure (2011 to 2012)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.