Optimizing cervical cancer prevention through screening and HPV vaccination
Author: Elfström, Klara Miriam
Date: 2015-06-15
Location: Lecture hall Petrén, Nobels väg 12B, Karolinska Institutet, Solna
Time: 09.00
Department: Inst för medicinsk epidemiologi och biostatistik / Dept of Medical Epidemiology and Biostatistics
Abstract
Effective primary and secondary prevention tools exist for cervical cancer in the form
of human papillomavirus (HPV) vaccines and cervical screening. In order to maximize the
impact of prevention strategies in Sweden and European countries, this thesis sought to
investigate the long-term effectiveness of different screening strategies and the long-term
risk associated with HPV infections, the organization and quality of existing screening
programs, and the effectiveness of alternative vaccination strategies.
HPV-based screening has been evaluated using intermediate outcomes while its effectiveness against cancer had not been fully examined. In Study I, the European randomized controlled trials (RCT) of screening methods were pooled to investigate the relative efficacy of HPV-based versus cytology-based screening for the prevention of invasive cervical cancer. We found that HPV-based screening provides 60-70% greater protection against invasive cervical cancer compared to cytology-based screening.
To address the issue of determining intervals for HPV-based screening and to investigate concerns regarding overdiagnosis with HPV-based screening, a long-term follow-up of the Swedescreen RCT was completed in Study II. The longitudinal performance of cytology- and HPV-based screening was explored and the sensitivity for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of HPV testing at 5 years of follow-up was similar to that of cytology testing at 3 years. Over 13 years of follow-up, we found that the increased sensitivity of HPV screening for CIN2+ reflects earlier diagnosis rather than overdiagnosis and low long-term risks among HPV negative women suggest that extending screening intervals with HPV-based screening would be possible.
The incidence of low-grade cervical lesions is increasing in Sweden. Low-grade lesions require follow-up, creating a burden to the woman and the healthcare system. Examining the long-term HPV-type-specific risk for atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesions (LSIL) and cervical intraepithelial neoplasia grade 1 (CIN1) is of interest to inform screening and vaccination programs. In Study III, we investigated the long-term type-specific absolute risk, population attributable proportion, and incidence rate ratios for ASCUS/LSIL by HPV type. The type-specific IRRs for ASCUS/LSIL were high in the first screening round but decreased over subsequent screening rounds. Type 16 contributed to the greatest proportion of low-grade lesions in the population followed by type 31. Most lesions were caused by new infections and found in the first screening round.
Organized, population-based screening with quality assurance (QA) at all levels is recommended by the European Commission to ensure equity and cost-effectiveness of programs. Significant differences in cervical cancer incidence and mortality exist between European countries. In Study IV, a comprehensive questionnaire was developed and circulated among EU/EFTA countries to map current organization of programs and quality assurance efforts to understand prevention activities and inform future guidelines. The findings show that organized efforts for QA, monitoring and evaluation differed between and within countries, making it difficult to compare program effectiveness.
HPV vaccination is underway in most European countries but efforts to organize and standardize vaccination program monitoring and evaluation are limited. Using the same questionnaire as in Study IV, we collected detailed information on HPV vaccination programs in EU/EFTA countries for Study V. Our findings suggest that the monitoring being performed varies across programs with regard to level of detail and the organization and quality of programs differ. There was a strong interest in the survey which affirms the significance of the issues addressed and the importance of continuing to evaluate program development and strengthen surveillance of vaccination program efforts.
Since the introduction of HPV vaccination, vaccine prices have decreased significantly making upscaling of vaccination efforts more attractive. Specifically, questions have arisen regarding vaccination of older girls and extending the vaccination program to boys. Using a dynamic transmission model, in Study VI we compared different vaccination strategies and assessed the resilience of the vaccination program to a reduction in coverage. We found that vaccination strategies including an extended catch-up of women and introducing male vaccination may accelerate the prevalence reduction of vaccine HPV types among women. Further, including males in routine vaccination improved the resilience of vaccination programs.
Taken together, the results of these studies seek to add evidence for the incremental optimization of prevention programs. The challenge will be translating research findings into practice and ensuring that programs have the tools they need to effectively monitor and evaluate changes.
HPV-based screening has been evaluated using intermediate outcomes while its effectiveness against cancer had not been fully examined. In Study I, the European randomized controlled trials (RCT) of screening methods were pooled to investigate the relative efficacy of HPV-based versus cytology-based screening for the prevention of invasive cervical cancer. We found that HPV-based screening provides 60-70% greater protection against invasive cervical cancer compared to cytology-based screening.
To address the issue of determining intervals for HPV-based screening and to investigate concerns regarding overdiagnosis with HPV-based screening, a long-term follow-up of the Swedescreen RCT was completed in Study II. The longitudinal performance of cytology- and HPV-based screening was explored and the sensitivity for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of HPV testing at 5 years of follow-up was similar to that of cytology testing at 3 years. Over 13 years of follow-up, we found that the increased sensitivity of HPV screening for CIN2+ reflects earlier diagnosis rather than overdiagnosis and low long-term risks among HPV negative women suggest that extending screening intervals with HPV-based screening would be possible.
The incidence of low-grade cervical lesions is increasing in Sweden. Low-grade lesions require follow-up, creating a burden to the woman and the healthcare system. Examining the long-term HPV-type-specific risk for atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesions (LSIL) and cervical intraepithelial neoplasia grade 1 (CIN1) is of interest to inform screening and vaccination programs. In Study III, we investigated the long-term type-specific absolute risk, population attributable proportion, and incidence rate ratios for ASCUS/LSIL by HPV type. The type-specific IRRs for ASCUS/LSIL were high in the first screening round but decreased over subsequent screening rounds. Type 16 contributed to the greatest proportion of low-grade lesions in the population followed by type 31. Most lesions were caused by new infections and found in the first screening round.
Organized, population-based screening with quality assurance (QA) at all levels is recommended by the European Commission to ensure equity and cost-effectiveness of programs. Significant differences in cervical cancer incidence and mortality exist between European countries. In Study IV, a comprehensive questionnaire was developed and circulated among EU/EFTA countries to map current organization of programs and quality assurance efforts to understand prevention activities and inform future guidelines. The findings show that organized efforts for QA, monitoring and evaluation differed between and within countries, making it difficult to compare program effectiveness.
HPV vaccination is underway in most European countries but efforts to organize and standardize vaccination program monitoring and evaluation are limited. Using the same questionnaire as in Study IV, we collected detailed information on HPV vaccination programs in EU/EFTA countries for Study V. Our findings suggest that the monitoring being performed varies across programs with regard to level of detail and the organization and quality of programs differ. There was a strong interest in the survey which affirms the significance of the issues addressed and the importance of continuing to evaluate program development and strengthen surveillance of vaccination program efforts.
Since the introduction of HPV vaccination, vaccine prices have decreased significantly making upscaling of vaccination efforts more attractive. Specifically, questions have arisen regarding vaccination of older girls and extending the vaccination program to boys. Using a dynamic transmission model, in Study VI we compared different vaccination strategies and assessed the resilience of the vaccination program to a reduction in coverage. We found that vaccination strategies including an extended catch-up of women and introducing male vaccination may accelerate the prevalence reduction of vaccine HPV types among women. Further, including males in routine vaccination improved the resilience of vaccination programs.
Taken together, the results of these studies seek to add evidence for the incremental optimization of prevention programs. The challenge will be translating research findings into practice and ensuring that programs have the tools they need to effectively monitor and evaluate changes.
List of papers:
I. Ronco G, Dillner J, Elfstrom KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014 Feb 8;383(9916):524-32
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Elfstrom KM, Smelov V, Johansson AL, Eklund C, Naucler P, ArnheimDahlstrom L, et al. Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial. BMJ. 2014;348:g130.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Elfstrom KM, Smelov V, Johansson AL, Eklund C, Naucler P, ArnheimDahlstrom L, et al. Long-term HPV type-specific risks for ASCUS and LSIL: A 14-year follow-up of a randomized primary HPV screening trial. Int J Cancer. 2015 Jan 15;136(2):350-9.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Elfstrom KM, Arnheim-Dahlstrom L, von Karsa L, Dillner J. Cervical cancer screening in Europe: Quality assurance and organization of programs. Eur J Cancer. 2015. 2015 May;51(8):950-68
Fulltext (DOI)
Pubmed
V. Elfstrom KM, Dillner J, Arnheim-Dahlstrom L. Organization and quality of HPV vaccination programs in Europe. Vaccine. 2015 Mar 30;33(14):1673-81
Fulltext (DOI)
Pubmed
View record in Web of Science®
VI. Elfstrom KM, Lazzarato L, Franceschi S, Dillner J, Baussano I. Human papillomavirus vaccination of boys and extended catch-up vaccination: Effects on the resilience of Programs. [Submitted]
I. Ronco G, Dillner J, Elfstrom KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014 Feb 8;383(9916):524-32
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Elfstrom KM, Smelov V, Johansson AL, Eklund C, Naucler P, ArnheimDahlstrom L, et al. Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial. BMJ. 2014;348:g130.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Elfstrom KM, Smelov V, Johansson AL, Eklund C, Naucler P, ArnheimDahlstrom L, et al. Long-term HPV type-specific risks for ASCUS and LSIL: A 14-year follow-up of a randomized primary HPV screening trial. Int J Cancer. 2015 Jan 15;136(2):350-9.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Elfstrom KM, Arnheim-Dahlstrom L, von Karsa L, Dillner J. Cervical cancer screening in Europe: Quality assurance and organization of programs. Eur J Cancer. 2015. 2015 May;51(8):950-68
Fulltext (DOI)
Pubmed
V. Elfstrom KM, Dillner J, Arnheim-Dahlstrom L. Organization and quality of HPV vaccination programs in Europe. Vaccine. 2015 Mar 30;33(14):1673-81
Fulltext (DOI)
Pubmed
View record in Web of Science®
VI. Elfstrom KM, Lazzarato L, Franceschi S, Dillner J, Baussano I. Human papillomavirus vaccination of boys and extended catch-up vaccination: Effects on the resilience of Programs. [Submitted]
Institution: Karolinska Institutet
Supervisor: Arnheim Dahlström, Lisen
Issue date: 2015-05-21
Rights:
Publication year: 2015
ISBN: 978-91-7549-974-1
Statistics
Total Visits
Views | |
---|---|
Optimizing ...(legacy) | 1204 |
Optimizing ... | 881 |
Total Visits Per Month
September 2023 | October 2023 | November 2023 | December 2023 | January 2024 | February 2024 | March 2024 | |
---|---|---|---|---|---|---|---|
Optimizing ... | 13 | 40 | 18 | 21 | 18 | 16 | 17 |
File Visits
Views | |
---|---|
Thesis_Klara_Miriam_Elfström.pdf(legacy) | 1259 |
Thesis_Klara_Miriam_Elfström.pdf | 731 |
Appendix_Klara_Miriam_Elfström.pdf(legacy) | 132 |
Appendix_Klara_Miriam_Elfström.pdf | 71 |
Top country views
Views | |
---|---|
United States | 400 |
Sweden | 390 |
Denmark | 283 |
Germany | 106 |
United Kingdom | 103 |
Australia | 82 |
Ireland | 62 |
China | 44 |
Canada | 38 |
South Korea | 36 |
Top cities views
Views | |
---|---|
Ashburn | 134 |
Copenhagen | 96 |
Sydney | 73 |
Stockholm | 64 |
Dublin | 61 |
Ballerup | 39 |
Seoul | 32 |
Karlstad | 29 |
Menlo Park | 26 |
Beijing | 22 |