Efficacy of HPV-based screening for prevention of invasive cervical cancer: Follow-up of four European randomised controlled trials

Guglielmo Ronco, Joakim Dillner, K. Miriam Elfström, Sara Tunesi, Peter J F Snijders, Marc Arbyn, Henry Kitchener, Nereo Segnan, Clare Gilham, Paolo Giorgi-Rossi, Johannes Berkhof, Julian Peto, Chris J L M Meijer, Jack Cuzick, Marco Zappa, Francesca Carozzi, Massimo Confortini, Paolo Dalla Palma, Manuel Zorzi, Annarosa Del MistroAnna Gillio-Tos, Carlo Naldoni, Dorien Rijkaart, Folkert Van Kemenade, Nicole Bulkmans, Danielle Heideman, Rence Rozendaal, Gemma Kenter, Maribel Almonte, Christopher Roberts, Mina Desai, Alexandra Sargent, Walter Ryd, Pontus Naucler

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Abstract

Background: In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes. Methods: 176 464 women aged 20-64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1 214 415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma. Findings: The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95% CI 0·40-0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46-1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25-0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15-0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 105 (1·1-12·1) and 8·7 per 105 (3·3- 18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 105 (7·9-27·0) and 36·0 per 105 (23·2-53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14-0·69) than for squamous-cell carcinoma (0·78, 0·49-1·25). The rate ratio was lowest in women aged 30-34 years (0·36, 0·14-0·94). Interpretation: HPV-based screening provides 60-70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years. Funding: European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.

Original languageEnglish
Pages (from-to)524-532
Number of pages9
JournalLancet
Volume383
Issue number9916
DOIs
Publication statusPublished - 2014

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Uterine Cervical Neoplasms
Randomized Controlled Trials
Carcinoma
Cell Biology
Early Detection of Cancer
Netherlands
Neoplasms
Incidence
Health
European Union
England
Italy
Registries
Squamous Cell Carcinoma
Adenocarcinoma
Organizations
Pathology
Research

ASJC Scopus subject areas

  • Medicine(all)

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Ronco, G., Dillner, J., Elfström, K. M., Tunesi, S., Snijders, P. J. F., Arbyn, M., ... Naucler, P. (2014). Efficacy of HPV-based screening for prevention of invasive cervical cancer: Follow-up of four European randomised controlled trials. Lancet, 383(9916), 524-532. https://doi.org/10.1016/S0140-6736(13)62218-7

Efficacy of HPV-based screening for prevention of invasive cervical cancer : Follow-up of four European randomised controlled trials. / Ronco, Guglielmo; Dillner, Joakim; Elfström, K. Miriam; Tunesi, Sara; Snijders, Peter J F; Arbyn, Marc; Kitchener, Henry; Segnan, Nereo; Gilham, Clare; Giorgi-Rossi, Paolo; Berkhof, Johannes; Peto, Julian; Meijer, Chris J L M; Cuzick, Jack; Zappa, Marco; Carozzi, Francesca; Confortini, Massimo; Dalla Palma, Paolo; Zorzi, Manuel; Del Mistro, Annarosa; Gillio-Tos, Anna; Naldoni, Carlo; Rijkaart, Dorien; Van Kemenade, Folkert; Bulkmans, Nicole; Heideman, Danielle; Rozendaal, Rence; Kenter, Gemma; Almonte, Maribel; Roberts, Christopher; Desai, Mina; Sargent, Alexandra; Ryd, Walter; Naucler, Pontus.

In: Lancet, Vol. 383, No. 9916, 2014, p. 524-532.

Research output: Contribution to journalArticle

Ronco, G, Dillner, J, Elfström, KM, Tunesi, S, Snijders, PJF, Arbyn, M, Kitchener, H, Segnan, N, Gilham, C, Giorgi-Rossi, P, Berkhof, J, Peto, J, Meijer, CJLM, Cuzick, J, Zappa, M, Carozzi, F, Confortini, M, Dalla Palma, P, Zorzi, M, Del Mistro, A, Gillio-Tos, A, Naldoni, C, Rijkaart, D, Van Kemenade, F, Bulkmans, N, Heideman, D, Rozendaal, R, Kenter, G, Almonte, M, Roberts, C, Desai, M, Sargent, A, Ryd, W & Naucler, P 2014, 'Efficacy of HPV-based screening for prevention of invasive cervical cancer: Follow-up of four European randomised controlled trials', Lancet, vol. 383, no. 9916, pp. 524-532. https://doi.org/10.1016/S0140-6736(13)62218-7
Ronco, Guglielmo ; Dillner, Joakim ; Elfström, K. Miriam ; Tunesi, Sara ; Snijders, Peter J F ; Arbyn, Marc ; Kitchener, Henry ; Segnan, Nereo ; Gilham, Clare ; Giorgi-Rossi, Paolo ; Berkhof, Johannes ; Peto, Julian ; Meijer, Chris J L M ; Cuzick, Jack ; Zappa, Marco ; Carozzi, Francesca ; Confortini, Massimo ; Dalla Palma, Paolo ; Zorzi, Manuel ; Del Mistro, Annarosa ; Gillio-Tos, Anna ; Naldoni, Carlo ; Rijkaart, Dorien ; Van Kemenade, Folkert ; Bulkmans, Nicole ; Heideman, Danielle ; Rozendaal, Rence ; Kenter, Gemma ; Almonte, Maribel ; Roberts, Christopher ; Desai, Mina ; Sargent, Alexandra ; Ryd, Walter ; Naucler, Pontus. / Efficacy of HPV-based screening for prevention of invasive cervical cancer : Follow-up of four European randomised controlled trials. In: Lancet. 2014 ; Vol. 383, No. 9916. pp. 524-532.
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abstract = "Background: In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes. Methods: 176 464 women aged 20-64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1 214 415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma. Findings: The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95{\%} CI 0·40-0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46-1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25-0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15-0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 105 (1·1-12·1) and 8·7 per 105 (3·3- 18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 105 (7·9-27·0) and 36·0 per 105 (23·2-53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14-0·69) than for squamous-cell carcinoma (0·78, 0·49-1·25). The rate ratio was lowest in women aged 30-34 years (0·36, 0·14-0·94). Interpretation: HPV-based screening provides 60-70{\%} greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years. Funding: European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.",
author = "Guglielmo Ronco and Joakim Dillner and Elfstr{\"o}m, {K. Miriam} and Sara Tunesi and Snijders, {Peter J F} and Marc Arbyn and Henry Kitchener and Nereo Segnan and Clare Gilham and Paolo Giorgi-Rossi and Johannes Berkhof and Julian Peto and Meijer, {Chris J L M} and Jack Cuzick and Marco Zappa and Francesca Carozzi and Massimo Confortini and {Dalla Palma}, Paolo and Manuel Zorzi and {Del Mistro}, Annarosa and Anna Gillio-Tos and Carlo Naldoni and Dorien Rijkaart and {Van Kemenade}, Folkert and Nicole Bulkmans and Danielle Heideman and Rence Rozendaal and Gemma Kenter and Maribel Almonte and Christopher Roberts and Mina Desai and Alexandra Sargent and Walter Ryd and Pontus Naucler",
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doi = "10.1016/S0140-6736(13)62218-7",
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volume = "383",
pages = "524--532",
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issn = "0140-6736",
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TY - JOUR

T1 - Efficacy of HPV-based screening for prevention of invasive cervical cancer

T2 - Follow-up of four European randomised controlled trials

AU - Ronco, Guglielmo

AU - Dillner, Joakim

AU - Elfström, K. Miriam

AU - Tunesi, Sara

AU - Snijders, Peter J F

AU - Arbyn, Marc

AU - Kitchener, Henry

AU - Segnan, Nereo

AU - Gilham, Clare

AU - Giorgi-Rossi, Paolo

AU - Berkhof, Johannes

AU - Peto, Julian

AU - Meijer, Chris J L M

AU - Cuzick, Jack

AU - Zappa, Marco

AU - Carozzi, Francesca

AU - Confortini, Massimo

AU - Dalla Palma, Paolo

AU - Zorzi, Manuel

AU - Del Mistro, Annarosa

AU - Gillio-Tos, Anna

AU - Naldoni, Carlo

AU - Rijkaart, Dorien

AU - Van Kemenade, Folkert

AU - Bulkmans, Nicole

AU - Heideman, Danielle

AU - Rozendaal, Rence

AU - Kenter, Gemma

AU - Almonte, Maribel

AU - Roberts, Christopher

AU - Desai, Mina

AU - Sargent, Alexandra

AU - Ryd, Walter

AU - Naucler, Pontus

PY - 2014

Y1 - 2014

N2 - Background: In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes. Methods: 176 464 women aged 20-64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1 214 415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma. Findings: The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95% CI 0·40-0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46-1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25-0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15-0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 105 (1·1-12·1) and 8·7 per 105 (3·3- 18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 105 (7·9-27·0) and 36·0 per 105 (23·2-53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14-0·69) than for squamous-cell carcinoma (0·78, 0·49-1·25). The rate ratio was lowest in women aged 30-34 years (0·36, 0·14-0·94). Interpretation: HPV-based screening provides 60-70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years. Funding: European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.

AB - Background: In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes. Methods: 176 464 women aged 20-64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1 214 415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma. Findings: The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95% CI 0·40-0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46-1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25-0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15-0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 105 (1·1-12·1) and 8·7 per 105 (3·3- 18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 105 (7·9-27·0) and 36·0 per 105 (23·2-53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14-0·69) than for squamous-cell carcinoma (0·78, 0·49-1·25). The rate ratio was lowest in women aged 30-34 years (0·36, 0·14-0·94). Interpretation: HPV-based screening provides 60-70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years. Funding: European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.

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