Infections

All Conditions

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Diseases and Abnormalities at or Before Birth

Communicable Diseases

Papillomavirus Infections

Congenital Abnormalities

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Sexually Transmitted Diseases, Viral

Virus Diseases

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Genital Diseases

Urogenital Diseases

Disease Attributes

All Drugs and Chemicals

Vaccines

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

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

Medical Director

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.

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.

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

GARDASIL™ Vaccine Impact in Population Study

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

The incidence of CIN by Gardasil vaccination status was to be assessed.

The incidence of other cervical cancers by Gardasil vaccination status was to be assessed.

The incidence of other HPV-related genital diseases, including vulvar and vaginal cancers, by Gardasil vaccination status was to be assessed.

The percentage of participants with liquid-based cervical cytology samples positive for HPV 6, 11, 16, and 18 was to be analyzed by Gardasil vaccination status.

Danish Cancer Society

Union for International Cancer Control

Cancer Registry of Norway

Karolinska Institutet

Merck Sharp & Dohme LLC

Per protocol, adverse events were not collected as part of the study database; therefore, none were collected and the number at risk is zero

Denmark Participants

Norway Participants

Sweden Participants

Participants in Denmark who completed the first survey (before licensure of GARDASIL)

Participants in Norway who completed the first survey (before licensure of GARDASIL)

Participants in Sweden who completed the first survey (before licensure of GARDASIL)

Total

Age, Continuous

Sex: Female, Male

Participants who took the first survey given before Gardasil licensure

Senior Vice President, Global Clinical Development

Denmark Participants 2004 to 2006 Before Gardasil Licensure

Denmark Participants 2007, After Gardasil Licensure

Denmark Participants 2008 After Gardasil Licensure

Denmark Participants 2009 After Gardasil Licensure

Denmark Participants 2010 After Gardasil Licensure

Denmark Participants 2011 After Gardasil Licensure

The analysis population was the entire population of qualifying women in Denmark and thus changed throughout the analysis. The number of participants analyzed given below is an estimate calculated from the number of reported cases and the incidence data.

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

The analysis population was the entire population of qualifying women \<=26 years of age in Denmark and thus changed throughout the analysis. The number of participants analyzed given below is an estimate calculated from the number of reported cases and the incidence data.

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

The analysis population was the entire population of qualifying women \>26 years of age in Denmark and thus changed throughout the analysis. The number of participants analyzed given below is an estimate calculated from the number of reported cases and the incidence data.

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

Norway Participants 2004 to 2006 Before Gardasil Licensure

Norway Participants 2007, After Gardasil Licensure

Norway Participants 2008 After Gardasil Licensure

Norway Participants 2009 After Gardasil Licensure

Norway Participants 2010 After Gardasil Licensure

Norway Participants 2011 After Gardasil Licensure

The analysis population was the entire population of qualifying women in Norway and thus changed throughout the analysis. The number of participants analyzed given below is an estimate calculated from the number of reported cases and the incidence data.

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

The analysis population was the entire population of qualifying women \<=26 years of age in Norway and thus changed throughout the analysis. The number of participants analyzed given below is an estimate calculated from the number of reported cases and the incidence data.

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

The analysis population was the entire population of women \>26 years of age in Norway and thus changed throughout the analysis. The number of participants analyzed given below is an estimate calculated from the number of reported cases and the incidence data.

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

Sweden Participants 2004 to 2006 Before Gardasil Licensure

Sweden Participants 2007, After Gardasil Licensure

Sweden Participants 2008 After Gardasil Licensure

Sweden Participants 2009 After Gardasil Licensure

Sweden Participants 2010 After Gardasil Licensure

Sweden Participants 2011 After Gardasil Licensure

The analysis population was the entire population of qualifying women in Sweden and thus changed throughout the analysis. The number of participants analyzed given below is an estimate calculated from the number of reported cases and the incidence data.

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

The analysis population was the entire population of qualifying women \<=26 years of age in Sweden and thus changed throughout the analysis. The number of participants analyzed given below is an estimate calculated from the number of reported cases and the incidence data.

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

The analysis population was the entire population of qualifying women \>26 years of age in Sweden and thus changed throughout the analysis. The number of participants analyzed given below is an estimate calculated from the number of reported cases and the incidence data.

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

Overall CIN

HPV 6/11/16/18-related CIN

Denmark Participants 2011 to 2012 After Gardasil Licensure

Norway Participants 2011 to 2012 After Gardasil Licensure

Sweden Participants 2011 to 2012 After Gardasil Licensure

The analysis population was participants of all ages with newly-diagnosed high-grade CIN and lesional tissue samples analyzed for HPV types

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

The analysis population was participants \<=26 years of age with newly-diagnosed high-grade CIN and lesional tissue samples analyzed for HPV types

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

The analysis population was participants \>26 years of age with newly-diagnosed high-grade CIN and lesional tissue samples analyzed for HPV types

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

CIN not related to HPV 16/18

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

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

Overall cervical cancer

HPV 6/11/16/18-related cervical cancer

The analysis population was participants with newly-diagnosed cervical cancer and lesional tissue samples analyzed for HPV types

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

The analysis population was participants \<=26 years of age with newly-diagnosed cervical cancer and lesional tissue samples analyzed for HPV types

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

The analysis population was participants \>26 years of age with newly-diagnosed cervical cancer and lesional tissue samples analyzed for HPV types

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

Cervical cancer not related to HPV 16/18

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

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

Analysis of this endpoint was not planned nor were the data collected. Thus, the number of participants analyzed is zero.

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

The analysis population was participants \<=26 years of age with liquid-based cytology samples analyzed for HPV types

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

The analysis population was participants \>26 years of age with liquid-based cytology samples analyzed for HPV types

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

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

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

Live babies born between 2007 and 2011 to Denmark participants who received Gardasil during pregnancy

Babies Born to Denmark Participants Who Received Gardasil

Live babies born between 2007 and 2011 to Denmark participants in the general population, including participants who did and did not receive Gardasil

Babies Born to Denmark Participants

Live babies born between 2007 and 2011 to Norway participants who received Gardasil during pregnancy

Babies Born to Norway Participants Who Received Gardasil

Live babies born between 2007 and 2011 to Norway participants in the general population, including participants who did and did not receive Gardasil

Babies Born to Norway Participants

Live babies born between 2007 and 2011 to Sweden participants who received Gardasil during pregnancy

Babies Born to Sweden Participants Who Received Gardasil

Live babies born between 2007 and 2011 to Sweden participants in the general population, including participants who did and did not received Gardasil

Babies Born to Sweden Participants

The analysis population represents the babies born to participating mothers, instead of female participants, because the number of babies represents the denominator for the percentage calculation, not female participants (i.e., mothers)

Percentage of Live Born Babies With a Major Congenital Anomaly

Denmark participants who received Gardasil on or before March 2012

Denmark Participants Who Received Gardasil

Denmark Participants Who Did Not Receive Gardasil

Norway participants who received Gardasil on or before March 2012

Norway Participants Who Received Gardasil

Norway Participants Who Did Not Receive Gardasil

Sweden participants who received Gardasil on or before March 2012

Sweden Participants Who Received Gardasil

Sweden Participants Who Did Not Receive Gardasil

The analysis population was to be women who underwent cervical screening. A joint decision was made by the study team to forgo the stratified analysis by vaccination status because there were few women who had both been vaccinated with Gardasil and undergone cervical cancer screening. Thus, the number of participants analyzed is zero.

Incidence of Cervical Intraepithelial Neoplasia by Gardasil Vaccination Status

Incidence of Cervical Cancer by Gardasil Vaccination Status

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

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

Overall Study

The patient must have been diagnosed with cancer at ≤25 years of age and have been diagnosed with one or more congenital anomalies reported through the APEC14B1 registry intake data. For all patients in APEC14B1 with self-reported congenital anomalies the investigators will: 1) recruit cases; 2) administer the GOBACK Study questionnaire; 3) collect biological samples for sequencing; and 4) obtain medical records to verify anomalies. Medical records will be used to validate self-reported congenital anomalies and is a crucial step prior to sequencing. Additionally, the investigators will be able to identify those with well-established cancer predisposition syndromes that involve congenital anomalies, such as WAGR syndrome.

Saliva collection and request for banked blood and tumor samples for sequencing

Whole Genome Sequencing

Study questionnaire will include modules that collect information on maternal reproductive history, exposure to known teratogens, medical history, and previous genetic testing.

Questionnaire Administration

Saliva collection and request for banked blood and tumor samples for sequencing and biomarker analysis

Biospecimen collection

Saliva collection and request for banked blood and tumor samples for biomarker analysis

Laboratory Biomarker Analysis

Philip Lupo, PhD

One of the strongest risk factors for cancer in children and adolescents is being born with a congenital anomaly. In fact, data from registry linkage studies imply that 10-15% of childhood cancer risk could be attributable to having a congenital anomaly. As an estimated 10 million children worldwide are born with a congenital anomaly per year, the public health implications of identifying why some of these children develop cancer are thus substantial. While these studies have been informative, registry data alone offers no possibility of molecular or sequencing studies to identify the specific genetic basis underlying the co-occurrence of anomalies and cancer susceptibility. Therefore, the investigators developed the first phase of the Genetic Overlap Between Anomalies and Cancer in Kids (GOBACK) Study to address these limitations. Using data from birth defects and cancer registries from four states, the investigators identified numerous novel specific anomaly-cancer associations. In the GOBACK Study the investigators identified an increase in cancer risk among children with any chromosomal abnormality and any non-chromosomal birth defect. Additionally, children with congenital anomalies developed a variety of cancers, therefore the investigators propose to evaluate a range of cancers among children with congenital anomalies. By pooling registry data across four states in the GOBACK Study, the investigators found that children with non-chromosomal birth defects have a significantly elevated risk of several childhood cancers. Notably several of these congenital anomalies are not characteristic of known cancer predisposition syndromes. Therefore, our preliminary studies lay the framework for this application. The objectives of the current study are to (1) interrogate the genomes of children with co-occurring non-chromosomal congenital anomalies and cancer enrolled in Project:EveryChild to identify genetic features associated with these combined phenotypes, and (2) verify congenital anomalies and determine the phenotypic spectrum among children with cancer enrolled in Project:EveryChild with self-reported congenital anomalies ("deep phenotyping"). For this study the investigators will utilize Project:EveryChild to identify, contact, and enroll case-parent trios for children with co-occurring non-chromosomal congenital anomalies and cancers. From each enrolled family the investigators e will collect DNA from the affected case and one or both biological parents to comprise each case-parent trio. The investigators will include siblings if available. The investigators will also characterize case-parent trios based on demographic and clinical characteristics utilizing information collected via self-administered questionnaires and medical records. Ultimately the findings from this study could lead to 1) determining the potential genetic mechanisms that underlie these co-occurring conditions; 2) improving cancer risk-management strategies among children with birth defects; and 3) identifying the role congenital anomalies play in outcomes and survivorship among children diagnosed with cancer.

OBJECTIVES:

1.1 Primary Aim Interrogate the genomes of children with co-occurring non-chromosomal congenital anomalies and cancer enrolled in Project:EveryChild to identify genetic features associated with these combined phenotypes.

1.2 Secondary Aim Verify congenital anomalies and determine the phenotypic spectrum among children with cancer enrolled in Project:EveryChild with self-reported congenital anomalies ("deep phenotyping").

Genetic Overlap Between Anomalies and Cancer in Kids in the Children's Oncology Group: The COG GOBACK Study

Analyze de novo single-nucleotide variants (SNVs), copy number variants (CNVs), and insertions/deletions (INDELs) obtained through whole-genome sequencing of co-occurring non-chromosomal congenital anomalies and cancer case-parent trios, which are necessary to identify genes with de novo mutations. The investigators plan to enroll a maximum of 1,000 case-parent trios. For individuals on COG therapeutic studies, no treatment outcomes would be requested or reported as part of this study.

The primary analyses of data generated in this secondary aim will be descriptive in nature. The objective will largely be to verify congenital anomalies and determine the phenotypic spectrum of children with congenital anomalies and cancer.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
GARDASIL™ Vaccine Impact in Population Study (V501-033)	NCT01077856	Human Papilloma...		18 Years - 45 Years	Merck Sharp & Dohme LLC
Genetic Overlap Between Anomalies and Cancer in Kids in the Children's Oncology Group: The COG GOBACK Study	NCT05071859	Congenital Anom... Pediatric Cance...	Whole Genome Se... Questionnaire A... Biospecimen col... Laboratory Biom...	0 Years -	Children's Oncology Group

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