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

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.

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

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

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.

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

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

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.

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

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

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.

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

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

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.

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

Population: 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.

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.

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

Population: 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.

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.

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

Population: 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.

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.

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

Population: 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.

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.

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

Population: 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.

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.

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

Population: 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.

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.

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

Population: 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.

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.

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

Population: 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.

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.

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

Population: 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.

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.

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

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

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.

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

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

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.

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

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

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.

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

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

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.

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

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

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

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

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

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.

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

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

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.

Time frame: Up to 5 years after Gardasil licensure (2007 to 2011)

Population: 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)

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.

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

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

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.

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

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

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.

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

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

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.

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

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

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

Time frame: Four years to 5 years after Gardasil licensure (2011 to 2012)

Population: 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.

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

Time frame: Four years to 5 years after Gardasil licensure (2011 to 2012)

Population: 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.

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

Time frame: Four years to 5 years after Gardasil licensure (2011 to 2012)

Population: 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.

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.

Time frame: Four years to 5 years after Gardasil licensure (2011 to 2012)

Population: 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.