Vaccine 32 (2014) 33–38
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Human papillomavirus vaccination and Pap testing profile in Manitoba, Canada Erich V. Kliewer a,b,c,∗ , Salaheddin M. Mahmud a,b , Alain A. Demers a,b , Pascal Lambert a a b c
Epidemiology and Cancer Registry, CancerCare Manitoba, Winnipeg, Manitoba, Canada Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC, Canada
a r t i c l e
i n f o
Article history: Received 26 June 2013 Received in revised form 22 October 2013 Accepted 24 October 2013 Available online 6 November 2013 Keywords: Human papillomavirus (HPV) Vaccination Screening Pap test Cervical cancer
a b s t r a c t Background: Females who receive the human papillomavirus (HPV) vaccine may believe they are protected from developing cervical cancer and no longer require screening. Concern has also been expressed that vaccinated females are those that would be screened regularly. This study assesses the Pap testing behavior of vaccinated and non-vaccinated females. Methods: For this population-based retrospective cohort study, vaccination and screening registries were linked for 3540 vaccinated females aged 15 years and over and 9592 matched non-vaccinated females. Conditional logistic regression, the Kaplan–Meier method and Cox regression were used to examine the association between vaccination and Pap testing. Results: Vaccinated females were more likely to have had a Pap test within the year prior to the index date than non-vaccinated females (15–19 years old: OR = 1.38, 95% CI 1.20–1.59; 20+ years old: OR = 2.34, 95% CI 1.98–2.76). In the three-year period after the index date, vaccinated females had a significantly higher cumulative probability of having a Pap test (83.3%) than non-vaccinated females (66.1%). Females who had a Pap test within three years prior to the index date were more likely to have a Pap test after the index date (vaccinated: HR = 5.03, 95% CI 4.65–5.45; non-vaccinated HR = 3.97, 95% CI 3.70–4.24). Being vaccinated had a significant effect on Pap testing (15–19 years old: HR = 1.54, 95% CI 1.39–1.69; 20+ years old: HR = 1.87, 95% CI 1.52–2.31). 80.1% of vaccinated females who had a Pap test prior to the index date also had one subsequent to it, compared to 70.1% for non-vaccinated females. 41.1% of females had not been vaccinated nor had a Pap test. Conclusion: The majority of vaccinated females continue to participate in screening, and do so at a higher rate than non-vaccinated females. Renewed efforts need to be made to include the large proportion of non–vaccinated, non–screened females in vaccination and/or screening. © 2013 Elsevier Ltd. All rights reserved.
1. Introduction There are currently two human papillomavirus (HPV) vaccines approved for use in Canada; Gardasil, which is manufactured by Merck Frosst Canada, and Cervarix, which is manufactured by GlaxoSmithKline. Gardasil is a quadrivalent vaccine that provides protection against the effects of HPV types 6, 11, 16 and 18. It was approved for sale in Canada in July 2006 for females aged 9–26 years. Recently, the approval was expanded to include women up to the age of 45 years and males 9–26 years of age. Cervarix is a bivalent HPV vaccine that provides protection against the effects of HPV types 16 and 18. It was approved for use in Canada in February
∗ Corresponding author. Tel.: +1 604 675 8000x7076; fax: +1 604 675 8233. E-mail addresses: [email protected] (E.V. Kliewer), [email protected] (S.M. Mahmud), [email protected] (A.A. Demers), [email protected] (P. Lambert). 0264-410X/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.vaccine.2013.10.082
2010 for females aged 10–25 years, but was not available during the time period this study was conducted. HPV types 16 and 18 are responsible for approximately 70% of all cervical cancers. Given that the two HPV vaccines currently available do not provide protection against all cervical cancer causing HPV types, it is essential that vaccinated females continue to participate in cervical cancer screening. There have been suggestions that females who receive the vaccine may mistakenly believe they are protected from developing cervical cancer, and therefore no longer require screening [1–6]. If such beliefs exist, one would expect to see lower cervical cancer screening rates in vaccinated females than non–vaccinated females. Alternatively, screening rates may be higher in vaccinated females. Sociodemographic characteristics may influence vaccine uptake and screening participation in a similar way [7–9]. Concern has been expressed that females receiving the vaccine are those that would have been screened regularly, and as such, the vaccine will have less of an impact on reducing rates of cervical cancer [10].
34
E.V. Kliewer et al. / Vaccine 32 (2014) 33–38
A Medline review of the published literature found studies that hypothesized about the relationship between HPV vaccination and cervical cancer screening or examined screening awareness or intentions, but there is very limited information on the actual screening behavior of vaccinated females. The availability of linkable population–based vaccination and cervical screening registries in Manitoba provided an opportunity to examine the association between HPV vaccination and Papanicolaou (Pap) testing before and after the index date, in order to assess if vaccinated females are continuing to participate in cervical cancer screening and if the vaccine is going to both screeners and non–screeners. 2. Material and methods 2.1. Design The study used a population-based matched retrospective cohort design to examine the association between HPV vaccination and Pap testing. 2.2. Data sources 2.2.1. Manitoba HPV vaccination registry As previously described, the registry was developed from various Manitoba Health databases [11]. It is population-based and includes all females who received at least one dose of the vaccine privately, i.e. they paid for it, or through the publicly-funded school-based program, between August, 2006 and March 31, 2010. In addition, females receiving the vaccine privately in April 2010 were also included. 2.2.2. Manitoba population registry (MPR) The MPR, which is maintained by Manitoba Health (MH), includes all Manitobans who are eligible for provincial health insurance benefits. Since enrolment is free, virtually the entire Manitoba population (>99%) is included. The information available includes, among other things, coverage start and end dates. 2.2.3. Cervical cancer screening registry CervixCheck, CancerCare Manitoba’s cervical cancer screening program, maintains the cervical cancer screening registry which was established in 2001. In 2006, the Manitoba guidelines recommended screening be initiated two years after first sexual activity and that after three negative results, one year apart, screening then be done every two years [12]. The guidelines were revised in 2010 to recommend that screening be initiated three years after first sexual activity and then undertaken every two years [13]. While the program’s target audience is all sexually active women aged 20–69 years, the registry, includes the results of all Pap tests, including those done for diagnostic purposes, and follow-up tests performed, regardless of age. 2.3. Participants Females 15 years of age and over who received the HPV vaccine privately in Manitoba between September 2006 and April 2010 were identified using the Manitoba HPV vaccination registry. By linking the vaccinated cohort to the MPR, it was possible to identify females who did not receive the vaccine. Each vaccinated female was matched on birth date (±30 days) to three non-vaccinated females. In order to determine the Pap testing profile of the vaccinated and non–vaccinated females, the two cohorts were linked to the cervical cancer screening registry. Pap tests occurring between May, 2001 and August, 2010 were included in the analyses.
The data extracted for this study contained no personal identifiers. To protect confidentiality, the linkage between the three anonymous databases was performed using scrambled unique personal health identification numbers. 2.4. Statistical analysis The date of first vaccination was taken as the index date for each matched set. Participants were followed until whichever of the following came first: the date of first Pap test, date of out migration from Manitoba, date of death or August, 2010. The chi-square test was used to test the statistical significance of the differences between the characteristics of the vaccinated and non-vaccinated. Age–stratified (15–19, 20 + ) conditional logistic regression was performed to examine the relationship between Pap testing history on or prior to the index date (
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Human papillomavirus vaccination and Pap testing profile in Manitoba, Canada Erich V. Kliewer a,b,c,∗ , Salaheddin M. Mahmud a,b , Alain A. Demers a,b , Pascal Lambert a a b c
Epidemiology and Cancer Registry, CancerCare Manitoba, Winnipeg, Manitoba, Canada Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC, Canada
a r t i c l e
i n f o
Article history: Received 26 June 2013 Received in revised form 22 October 2013 Accepted 24 October 2013 Available online 6 November 2013 Keywords: Human papillomavirus (HPV) Vaccination Screening Pap test Cervical cancer
a b s t r a c t Background: Females who receive the human papillomavirus (HPV) vaccine may believe they are protected from developing cervical cancer and no longer require screening. Concern has also been expressed that vaccinated females are those that would be screened regularly. This study assesses the Pap testing behavior of vaccinated and non-vaccinated females. Methods: For this population-based retrospective cohort study, vaccination and screening registries were linked for 3540 vaccinated females aged 15 years and over and 9592 matched non-vaccinated females. Conditional logistic regression, the Kaplan–Meier method and Cox regression were used to examine the association between vaccination and Pap testing. Results: Vaccinated females were more likely to have had a Pap test within the year prior to the index date than non-vaccinated females (15–19 years old: OR = 1.38, 95% CI 1.20–1.59; 20+ years old: OR = 2.34, 95% CI 1.98–2.76). In the three-year period after the index date, vaccinated females had a significantly higher cumulative probability of having a Pap test (83.3%) than non-vaccinated females (66.1%). Females who had a Pap test within three years prior to the index date were more likely to have a Pap test after the index date (vaccinated: HR = 5.03, 95% CI 4.65–5.45; non-vaccinated HR = 3.97, 95% CI 3.70–4.24). Being vaccinated had a significant effect on Pap testing (15–19 years old: HR = 1.54, 95% CI 1.39–1.69; 20+ years old: HR = 1.87, 95% CI 1.52–2.31). 80.1% of vaccinated females who had a Pap test prior to the index date also had one subsequent to it, compared to 70.1% for non-vaccinated females. 41.1% of females had not been vaccinated nor had a Pap test. Conclusion: The majority of vaccinated females continue to participate in screening, and do so at a higher rate than non-vaccinated females. Renewed efforts need to be made to include the large proportion of non–vaccinated, non–screened females in vaccination and/or screening. © 2013 Elsevier Ltd. All rights reserved.
1. Introduction There are currently two human papillomavirus (HPV) vaccines approved for use in Canada; Gardasil, which is manufactured by Merck Frosst Canada, and Cervarix, which is manufactured by GlaxoSmithKline. Gardasil is a quadrivalent vaccine that provides protection against the effects of HPV types 6, 11, 16 and 18. It was approved for sale in Canada in July 2006 for females aged 9–26 years. Recently, the approval was expanded to include women up to the age of 45 years and males 9–26 years of age. Cervarix is a bivalent HPV vaccine that provides protection against the effects of HPV types 16 and 18. It was approved for use in Canada in February
∗ Corresponding author. Tel.: +1 604 675 8000x7076; fax: +1 604 675 8233. E-mail addresses: [email protected] (E.V. Kliewer), [email protected] (S.M. Mahmud), [email protected] (A.A. Demers), [email protected] (P. Lambert). 0264-410X/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.vaccine.2013.10.082
2010 for females aged 10–25 years, but was not available during the time period this study was conducted. HPV types 16 and 18 are responsible for approximately 70% of all cervical cancers. Given that the two HPV vaccines currently available do not provide protection against all cervical cancer causing HPV types, it is essential that vaccinated females continue to participate in cervical cancer screening. There have been suggestions that females who receive the vaccine may mistakenly believe they are protected from developing cervical cancer, and therefore no longer require screening [1–6]. If such beliefs exist, one would expect to see lower cervical cancer screening rates in vaccinated females than non–vaccinated females. Alternatively, screening rates may be higher in vaccinated females. Sociodemographic characteristics may influence vaccine uptake and screening participation in a similar way [7–9]. Concern has been expressed that females receiving the vaccine are those that would have been screened regularly, and as such, the vaccine will have less of an impact on reducing rates of cervical cancer [10].
34
E.V. Kliewer et al. / Vaccine 32 (2014) 33–38
A Medline review of the published literature found studies that hypothesized about the relationship between HPV vaccination and cervical cancer screening or examined screening awareness or intentions, but there is very limited information on the actual screening behavior of vaccinated females. The availability of linkable population–based vaccination and cervical screening registries in Manitoba provided an opportunity to examine the association between HPV vaccination and Papanicolaou (Pap) testing before and after the index date, in order to assess if vaccinated females are continuing to participate in cervical cancer screening and if the vaccine is going to both screeners and non–screeners. 2. Material and methods 2.1. Design The study used a population-based matched retrospective cohort design to examine the association between HPV vaccination and Pap testing. 2.2. Data sources 2.2.1. Manitoba HPV vaccination registry As previously described, the registry was developed from various Manitoba Health databases [11]. It is population-based and includes all females who received at least one dose of the vaccine privately, i.e. they paid for it, or through the publicly-funded school-based program, between August, 2006 and March 31, 2010. In addition, females receiving the vaccine privately in April 2010 were also included. 2.2.2. Manitoba population registry (MPR) The MPR, which is maintained by Manitoba Health (MH), includes all Manitobans who are eligible for provincial health insurance benefits. Since enrolment is free, virtually the entire Manitoba population (>99%) is included. The information available includes, among other things, coverage start and end dates. 2.2.3. Cervical cancer screening registry CervixCheck, CancerCare Manitoba’s cervical cancer screening program, maintains the cervical cancer screening registry which was established in 2001. In 2006, the Manitoba guidelines recommended screening be initiated two years after first sexual activity and that after three negative results, one year apart, screening then be done every two years [12]. The guidelines were revised in 2010 to recommend that screening be initiated three years after first sexual activity and then undertaken every two years [13]. While the program’s target audience is all sexually active women aged 20–69 years, the registry, includes the results of all Pap tests, including those done for diagnostic purposes, and follow-up tests performed, regardless of age. 2.3. Participants Females 15 years of age and over who received the HPV vaccine privately in Manitoba between September 2006 and April 2010 were identified using the Manitoba HPV vaccination registry. By linking the vaccinated cohort to the MPR, it was possible to identify females who did not receive the vaccine. Each vaccinated female was matched on birth date (±30 days) to three non-vaccinated females. In order to determine the Pap testing profile of the vaccinated and non–vaccinated females, the two cohorts were linked to the cervical cancer screening registry. Pap tests occurring between May, 2001 and August, 2010 were included in the analyses.
The data extracted for this study contained no personal identifiers. To protect confidentiality, the linkage between the three anonymous databases was performed using scrambled unique personal health identification numbers. 2.4. Statistical analysis The date of first vaccination was taken as the index date for each matched set. Participants were followed until whichever of the following came first: the date of first Pap test, date of out migration from Manitoba, date of death or August, 2010. The chi-square test was used to test the statistical significance of the differences between the characteristics of the vaccinated and non-vaccinated. Age–stratified (15–19, 20 + ) conditional logistic regression was performed to examine the relationship between Pap testing history on or prior to the index date (
