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 language | English |
|---|---|
| Pages (from-to) | 524-532 |
| Number of pages | 9 |
| Journal | Lancet |
| Volume | 383 |
| Issue number | 9916 |
| DOIs | |
| Publication status | Published - 2014 |
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ASJC Scopus subject areas
- Medicine(all)
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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 journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=84895909567&partnerID=8YFLogxK
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U2 - 10.1016/S0140-6736(13)62218-7
DO - 10.1016/S0140-6736(13)62218-7
M3 - Article
AN - SCOPUS:84895909567
VL - 383
SP - 524
EP - 532
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 9916
ER -