Skip to main content
Top
Published in: BMC Medicine 1/2019

Open Access 01-12-2019 | Colposcopy | Research article

Introduction of primary screening using high-risk HPV DNA detection in the Dutch cervical cancer screening programme: a population-based cohort study

Authors: Clare A. Aitken, Heleen M. E. van Agt, Albert G. Siebers, Folkert J. van Kemenade, Hubert G. M. Niesters, Willem J. G. Melchers, Judith E. M. Vedder, Rob Schuurman, Adriaan J. C. van den Brule, Hans C. van der Linden, John W. J. Hinrichs, Anco Molijn, Klaas J. Hoogduin, Bettien M. van Hemel, Inge M. C. M. de Kok

Published in: BMC Medicine | Issue 1/2019

Login to get access

Abstract

Background

In January 2017, the Dutch cervical cancer screening programme transitioned from cytomorphological to primary high-risk HPV (hrHPV) DNA screening, including the introduction of self-sampling, for women aged between 30 and 60 years. The Netherlands was the first country to switch to hrHPV screening at the national level. We investigated the health impact of this transition by comparing performance indicators from the new hrHPV-based programme with the previous cytology-based programme.

Methods

We obtained data from the Dutch nationwide network and registry of histo- and cytopathology (PALGA) for 454,573 women eligible for screening in 2017 who participated in the hrHPV-based programme between 1 January 2017 and 30 June 2018 (maximum follow-up of almost 21 months) and for 483,146 women eligible for screening in 2015 who participated in the cytology-based programme between 1 January 2015 and 31 March 2016 (maximum follow-up of 40 months). We compared indicators of participation (participation rate), referral (screen positivity; referral rate) and detection (cervical intraepithelial neoplasia (CIN) detection; number of referrals per detected CIN lesion).

Results

Participation in the hrHPV-based programme was significantly lower than that in the cytology-based programme (61% vs 64%). Screen positivity and direct referral rates were significantly higher in the hrHPV-based programme (positivity rate: 5% vs 9%; referral rate: 1% vs 3%). CIN2+ detection increased from 11 to 14 per 1000 women screened. Overall, approximately 2.2 times more clinical irrelevant findings (i.e. ≤CIN1) were found in the hrHPV-based programme, compared with approximately 1·3 times more clinically relevant findings (i.e. CIN2+); this difference was mostly due to a national policy change recommending colposcopy, rather than observation, of hrHPV-positive, ASC-US/LSIL results in the hrHPV-based programme.

Conclusions

This is the first time that comprehensive results of nationwide implementation of hrHPV-based screening have been reported using high-quality data with a long follow-up. We have shown that both benefits and potential harms are higher in one screening round of a well-implemented hrHPV-based screening programme than in an established cytology-based programme. Lower participation in the new hrHPV programme may be due to factors such as invitation policy changes and the phased roll-out of the new programme. Our findings add further to evidence from trials and modelling studies on the effectiveness of hrHPV-based screening.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJF, Arbyn M, Kitchener H, Segnan N, Gilham C, Giorgi-Rossi P, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916):524–32.CrossRef Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJF, Arbyn M, Kitchener H, Segnan N, Gilham C, Giorgi-Rossi P, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916):524–32.CrossRef
2.
go back to reference van Rosmalen J, de Kok IM, van Ballegooijen M. Cost-effectiveness of cervical cancer screening: cytology versus human papillomavirus DNA testing. BJOG. 2012;119(6):699–709.CrossRef van Rosmalen J, de Kok IM, van Ballegooijen M. Cost-effectiveness of cervical cancer screening: cytology versus human papillomavirus DNA testing. BJOG. 2012;119(6):699–709.CrossRef
3.
go back to reference Dutch Health Council: Population screening for cervical cancer [in Dutch]. The Hague: Health Council of the Netherlands; 2011. Dutch Health Council: Population screening for cervical cancer [in Dutch]. The Hague: Health Council of the Netherlands; 2011.
4.
go back to reference van der Veen N, Carpay M, van Delden J, Grievink L, B. H, Lock A, Salverda J: Feasibility study for improvements to the population screening for cervical cancer [in Dutch]. Bilthoven: Rijksinstituut voor Volksgezondheid en Milieu (RIVM); 2013. van der Veen N, Carpay M, van Delden J, Grievink L, B. H, Lock A, Salverda J: Feasibility study for improvements to the population screening for cervical cancer [in Dutch]. Bilthoven: Rijksinstituut voor Volksgezondheid en Milieu (RIVM); 2013.
5.
go back to reference van der Veen N: Framework for the execution of cervical cancer population screening [in Dutch]. Bilthoven: Rijksinstituut voor Volksgezondheid en Milieu (RIVM); 2017. van der Veen N: Framework for the execution of cervical cancer population screening [in Dutch]. Bilthoven: Rijksinstituut voor Volksgezondheid en Milieu (RIVM); 2017.
6.
go back to reference Naber SK, Matthijsse SM, Jansen EEL, De Kok IM, de Koning HJ, van Ballegooijen M. Effecten en kosten van het vernieuwde bevolkingsonderzoek naar baarmoederhalskanker in Nederland naar aanleiding van recente ontwikkelingen. In. Rotterdam: Department of Public Health, Erasmus MC University Medical Center; 2016. Naber SK, Matthijsse SM, Jansen EEL, De Kok IM, de Koning HJ, van Ballegooijen M. Effecten en kosten van het vernieuwde bevolkingsonderzoek naar baarmoederhalskanker in Nederland naar aanleiding van recente ontwikkelingen. In. Rotterdam: Department of Public Health, Erasmus MC University Medical Center; 2016.
7.
go back to reference Rebolj M, van Ballegooijen M, Berkers LM, Habbema D. Monitoring a national cancer prevention program: successful changes in cervical cancer screening in the Netherlands. Int J Cancer. 2007;120(4):806–12.CrossRef Rebolj M, van Ballegooijen M, Berkers LM, Habbema D. Monitoring a national cancer prevention program: successful changes in cervical cancer screening in the Netherlands. Int J Cancer. 2007;120(4):806–12.CrossRef
8.
go back to reference Arbyn M, Anttila A, Jordan J, Ronco G, Schenck U, Segnan N, Wiener HG, Herbert A, Daniel J, von Karsa L. European guidelines for quality assurance in cervical cancer screening: second edition. Belgium: International Agency for Research on Cancer; 2008. Arbyn M, Anttila A, Jordan J, Ronco G, Schenck U, Segnan N, Wiener HG, Herbert A, Daniel J, von Karsa L. European guidelines for quality assurance in cervical cancer screening: second edition. Belgium: International Agency for Research on Cancer; 2008.
9.
go back to reference Gultekin M, Zayifoglu Karaca M, Kucukyildiz I, Dundar S, Boztas G, Semra Turan H, Hacikamiloglu E, Murtuza K, Keskinkilic B, Sencan I. Initial results of population based cervical cancer screening program using HPV testing in one million Turkish women. Int J Cancer. 2018;142(9):1952–8.CrossRef Gultekin M, Zayifoglu Karaca M, Kucukyildiz I, Dundar S, Boztas G, Semra Turan H, Hacikamiloglu E, Murtuza K, Keskinkilic B, Sencan I. Initial results of population based cervical cancer screening program using HPV testing in one million Turkish women. Int J Cancer. 2018;142(9):1952–8.CrossRef
10.
go back to reference Ronco G, Giorgi Rossi P, Giubilato P, Del Mistro A, Zappa M, Carozzi F, group HPVss. A first survey of HPV-based screening in routine cervical cancer screening in Italy. Epidemiol Prev. 2015;39(3 Suppl 1):77–83.PubMed Ronco G, Giorgi Rossi P, Giubilato P, Del Mistro A, Zappa M, Carozzi F, group HPVss. A first survey of HPV-based screening in routine cervical cancer screening in Italy. Epidemiol Prev. 2015;39(3 Suppl 1):77–83.PubMed
11.
go back to reference Casparie M, Tiebosch AT, Burger G, Blauwgeers H, van de Pol A, van Krieken JH, Meijer GA. Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive. Cell Oncol. 2007;29(1):19–24.PubMedPubMedCentral Casparie M, Tiebosch AT, Burger G, Blauwgeers H, van de Pol A, van Krieken JH, Meijer GA. Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive. Cell Oncol. 2007;29(1):19–24.PubMedPubMedCentral
12.
go back to reference Ketelaars PJW, Bosgraaf RP, Siebers AG, Massuger L, van der Linden JC, Wauters CAP, Rahamat-Langendoen JC, van den Brule AJC, IntHout J, Melchers WJG, et al. High-risk human papillomavirus detection in self-sampling compared to physician-taken smear in a responder population of the Dutch cervical screening: results of the VERA study. Prev Med. 2017;101:96–101.CrossRef Ketelaars PJW, Bosgraaf RP, Siebers AG, Massuger L, van der Linden JC, Wauters CAP, Rahamat-Langendoen JC, van den Brule AJC, IntHout J, Melchers WJG, et al. High-risk human papillomavirus detection in self-sampling compared to physician-taken smear in a responder population of the Dutch cervical screening: results of the VERA study. Prev Med. 2017;101:96–101.CrossRef
13.
go back to reference Arbyn M, Ronco G, Anttila A, Meijer CJ, Poljak M, Ogilvie G, Koliopoulos G, Naucler P, Sankaranarayanan R, Peto J. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012;30(Suppl 5):F88–99.CrossRef Arbyn M, Ronco G, Anttila A, Meijer CJ, Poljak M, Ogilvie G, Koliopoulos G, Naucler P, Sankaranarayanan R, Peto J. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012;30(Suppl 5):F88–99.CrossRef
14.
go back to reference Heideman DAM, Hesselink AT, Berkhof J, van Kemenade F, Melchers WJG, Daalmeijer NF, Verkuijten M, Meijer CJLM, Snijders PJF. Clinical validation of the cobas 4800 HPV test for cervical screening purposes. J Clin Microbiol. 2011;49(11):3983–5.CrossRef Heideman DAM, Hesselink AT, Berkhof J, van Kemenade F, Melchers WJG, Daalmeijer NF, Verkuijten M, Meijer CJLM, Snijders PJF. Clinical validation of the cobas 4800 HPV test for cervical screening purposes. J Clin Microbiol. 2011;49(11):3983–5.CrossRef
15.
go back to reference Bosgraaf RP, Verhoef VM, Massuger LF, Siebers AG, Bulten J, de Kuyper-de Ridder GM, Meijer CJ, Snijders PJ, Heideman DA, IntHout J, et al. Comparative performance of novel self-sampling methods in detecting high-risk human papillomavirus in 30,130 women not attending cervical screening. Int J Cancer. 2015;136(3):646–55.PubMed Bosgraaf RP, Verhoef VM, Massuger LF, Siebers AG, Bulten J, de Kuyper-de Ridder GM, Meijer CJ, Snijders PJ, Heideman DA, IntHout J, et al. Comparative performance of novel self-sampling methods in detecting high-risk human papillomavirus in 30,130 women not attending cervical screening. Int J Cancer. 2015;136(3):646–55.PubMed
17.
go back to reference Dutch Hospital Data: Landelijke Medische Registratie. In. Utrecht, the Netherlands; 2010. Dutch Hospital Data: Landelijke Medische Registratie. In. Utrecht, the Netherlands; 2010.
18.
go back to reference Siljander I, Lehtinen M, Makkonen P, Pankakoski M, Helander S, Sarkeala T, Heinavaara S, Anttila A: EU-TOPIA Deliverable 2.1: definition of benefits and harms of cancer screening. In. Edited by EU-TOPIA. Finland: Finnish Cancer Registry, Helsinki; 2016. Siljander I, Lehtinen M, Makkonen P, Pankakoski M, Helander S, Sarkeala T, Heinavaara S, Anttila A: EU-TOPIA Deliverable 2.1: definition of benefits and harms of cancer screening. In. Edited by EU-TOPIA. Finland: Finnish Cancer Registry, Helsinki; 2016.
19.
go back to reference Korfage IJ, Essink-Bot ML, Westenberg SM, Helmerhorst T, Habbema JD, van Ballegooijen M. How distressing is referral to colposcopy in cervical cancer screening?: a prospective quality of life study. Gynecol Oncol. 2014;132(1):142–8.CrossRef Korfage IJ, Essink-Bot ML, Westenberg SM, Helmerhorst T, Habbema JD, van Ballegooijen M. How distressing is referral to colposcopy in cervical cancer screening?: a prospective quality of life study. Gynecol Oncol. 2014;132(1):142–8.CrossRef
20.
go back to reference Drolet M, Brisson M, Maunsell E, Franco EL, Coutlée F, Ferenczy A, Fisher W, Mansi JA. The psychosocial impact of an abnormal cervical smear result. Psycho-Oncology. 2012;21(10):1071–81.CrossRef Drolet M, Brisson M, Maunsell E, Franco EL, Coutlée F, Ferenczy A, Fisher W, Mansi JA. The psychosocial impact of an abnormal cervical smear result. Psycho-Oncology. 2012;21(10):1071–81.CrossRef
21.
go back to reference The Tombola Group. After-effects reported by women following colposcopy, cervical biopsies and LLETZ: results from the TOMBOLA trial. BJOG. 2009;116(11):1506–14.CrossRef The Tombola Group. After-effects reported by women following colposcopy, cervical biopsies and LLETZ: results from the TOMBOLA trial. BJOG. 2009;116(11):1506–14.CrossRef
22.
go back to reference Gok M, Heideman DA, van Kemenade FJ, Berkhof J, Rozendaal L, Spruyt JW, Voorhorst F, Belien JA, Babovic M, Snijders PJ, et al. HPV testing on self collected cervicovaginal lavage specimens as screening method for women who do not attend cervical screening: cohort study. BMJ. 2010;340:c1040.CrossRef Gok M, Heideman DA, van Kemenade FJ, Berkhof J, Rozendaal L, Spruyt JW, Voorhorst F, Belien JA, Babovic M, Snijders PJ, et al. HPV testing on self collected cervicovaginal lavage specimens as screening method for women who do not attend cervical screening: cohort study. BMJ. 2010;340:c1040.CrossRef
24.
go back to reference Bosgraaf RP, Ketelaars PJ, Verhoef VM, Massuger LF, Meijer CJ, Melchers WJ, Bekkers RL. Reasons for non-attendance to cervical screening and preferences for HPV self-sampling in Dutch women. Prev Med. 2014;64:108–13.CrossRef Bosgraaf RP, Ketelaars PJ, Verhoef VM, Massuger LF, Meijer CJ, Melchers WJ, Bekkers RL. Reasons for non-attendance to cervical screening and preferences for HPV self-sampling in Dutch women. Prev Med. 2014;64:108–13.CrossRef
25.
go back to reference Tacken MA, Braspenning JC, Hermens RP, Spreeuwenberg PM, van den Hoogen HJ, de Bakker DH, Groenewegen PP, Grol RP. Uptake of cervical cancer screening in The Netherlands is mainly influenced by women’s beliefs about the screening and by the inviting organization. Eur J Pub Health. 2007;17(2):178–85.CrossRef Tacken MA, Braspenning JC, Hermens RP, Spreeuwenberg PM, van den Hoogen HJ, de Bakker DH, Groenewegen PP, Grol RP. Uptake of cervical cancer screening in The Netherlands is mainly influenced by women’s beliefs about the screening and by the inviting organization. Eur J Pub Health. 2007;17(2):178–85.CrossRef
26.
go back to reference Huijsmans CJ, Geurts-Giele WR, Leeijen C, Hazenberg HL, van Beek J, de Wild C, van der Linden JC, van den Brule AJ. HPV prevalence in the Dutch cervical cancer screening population (DuSC study): HPV testing using automated HC2, cobas and Aptima workflows. BMC Cancer. 2016;16(1):922.CrossRef Huijsmans CJ, Geurts-Giele WR, Leeijen C, Hazenberg HL, van Beek J, de Wild C, van der Linden JC, van den Brule AJ. HPV prevalence in the Dutch cervical cancer screening population (DuSC study): HPV testing using automated HC2, cobas and Aptima workflows. BMC Cancer. 2016;16(1):922.CrossRef
27.
go back to reference Polman NJ, Ebisch RMF, Heideman DAM, Melchers WJG, Bekkers RLM, Molijn AC, Meijer CJLM, Quint WGV, Snijders PJF, Massuger LFAG, et al. Performance of human papillomavirus testing on self-collected versus clinician-collected samples for the detection of cervical intraepithelial neoplasia of grade 2 or worse: a randomised, paired screen-positive, non-inferiority trial. Lancet Oncol. 2019;20(2):229-38.CrossRef Polman NJ, Ebisch RMF, Heideman DAM, Melchers WJG, Bekkers RLM, Molijn AC, Meijer CJLM, Quint WGV, Snijders PJF, Massuger LFAG, et al. Performance of human papillomavirus testing on self-collected versus clinician-collected samples for the detection of cervical intraepithelial neoplasia of grade 2 or worse: a randomised, paired screen-positive, non-inferiority trial. Lancet Oncol. 2019;20(2):229-38.CrossRef
28.
go back to reference Wentzensen N, Schiffman M, Palmer T, Arbyn M. Triage of HPV positive women in cervical cancer screening. J Clin Virol. 2016;76(Suppl 1):S49–55.CrossRef Wentzensen N, Schiffman M, Palmer T, Arbyn M. Triage of HPV positive women in cervical cancer screening. J Clin Virol. 2016;76(Suppl 1):S49–55.CrossRef
29.
go back to reference Castle PE, Kinney WK, Xue X, Cheung LC, Gage JC, Poitras NE, Lorey TS, Katki HA, Wentzensen N, Schiffman M. Role of screening history in clinical meaning and optimal management of positive cervical screening results. J Natl Cancer Inst. 2018; Castle PE, Kinney WK, Xue X, Cheung LC, Gage JC, Poitras NE, Lorey TS, Katki HA, Wentzensen N, Schiffman M. Role of screening history in clinical meaning and optimal management of positive cervical screening results. J Natl Cancer Inst. 2018;
30.
go back to reference Ronco G, Ballegooijen MV, Becker N, Chil A, Fender M, Giubilato P, Kurtinaitis J, Lancucki L, Lynge E, Morais A, et al. Process performance of cervical screening programmes in Europe. Eur J Cancer. 2009;45(15):2659–70.CrossRef Ronco G, Ballegooijen MV, Becker N, Chil A, Fender M, Giubilato P, Kurtinaitis J, Lancucki L, Lynge E, Morais A, et al. Process performance of cervical screening programmes in Europe. Eur J Cancer. 2009;45(15):2659–70.CrossRef
31.
go back to reference Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NWJ, Heideman DAM, Kenter GG, Cuzick J, Snijders PJF, Meijer CJLM. Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol. 2012;13(1):78–88.CrossRef Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NWJ, Heideman DAM, Kenter GG, Cuzick J, Snijders PJF, Meijer CJLM. Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol. 2012;13(1):78–88.CrossRef
32.
go back to reference Naber SK, Matthijsse SM, Rozemeijer K, Penning C, de Kok IM, van Ballegooijen M. Cervical cancer screening in partly HPV vaccinated cohorts - a cost-effectiveness analysis. PLoS One. 2016;11(1):e0145548.CrossRef Naber SK, Matthijsse SM, Rozemeijer K, Penning C, de Kok IM, van Ballegooijen M. Cervical cancer screening in partly HPV vaccinated cohorts - a cost-effectiveness analysis. PLoS One. 2016;11(1):e0145548.CrossRef
33.
go back to reference van den Akker-van Marle ME, van Ballegooijen M, Habbema JD. Low risk of cervical cancer during a long period after negative screening in the Netherlands. Br J Cancer. 2003;88(7):1054–7.CrossRef van den Akker-van Marle ME, van Ballegooijen M, Habbema JD. Low risk of cervical cancer during a long period after negative screening in the Netherlands. Br J Cancer. 2003;88(7):1054–7.CrossRef
Metadata
Title
Introduction of primary screening using high-risk HPV DNA detection in the Dutch cervical cancer screening programme: a population-based cohort study
Authors
Clare A. Aitken
Heleen M. E. van Agt
Albert G. Siebers
Folkert J. van Kemenade
Hubert G. M. Niesters
Willem J. G. Melchers
Judith E. M. Vedder
Rob Schuurman
Adriaan J. C. van den Brule
Hans C. van der Linden
John W. J. Hinrichs
Anco Molijn
Klaas J. Hoogduin
Bettien M. van Hemel
Inge M. C. M. de Kok
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2019
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-019-1460-0

Other articles of this Issue 1/2019

BMC Medicine 1/2019 Go to the issue