Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within organised screening programmeBMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1804 (Published 27 April 2010) Cite this as: BMJ 2010;340:c1804
- Ahti Anttila, research director of the mass screening registry1,
- Laura Kotaniemi-Talonen, researcher1,
- Maarit Leinonen, researcher1,
- Matti Hakama, professor1,
- Pekka Laurila, chief physician2,
- Jussi Tarkkanen, senior consultant in pathology2,
- Nea Malila, director of the mass screening registry, professor13,
- Pekka Nieminen, chief physician45
- 1Mass Screening Registry of the Finnish Cancer Registry, Pieni Roobertinkatu 9, FIN-00130 Helsinki, Finland
- 2HUSLAB Kätilöopisto Pathology Laboratory, Helsinki
- 3School of Public Health, University of Tampere, Tampere
- 4Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki
- 5Pathology Laboratory of the Finnish Cancer Society, Helsinki
- Correspondence to: A Anttila
- Accepted 11 January 2010
Objective To assess the performance and impact of primary human papillomavirus (HPV) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions.
Design Randomised trial.
Setting Population based screening programme for cervical cancer in southern Finland in 2003-5.
Participants 58 076 women, aged 30-60, invited to the routine population based screening programme for cervical cancer.
Interventions Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological screening (reference).
Main outcome measures Rate of cervical cancer, cervical intraepithelial neoplasia (CIN) grade III, and adenocarcinoma in situ (as a composite outcome referred to as CIN III+) during 2003-7 through record linkage between files from the screening registry and the national cancer registry.
Results In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+, respectively (of which six and eight were cervical cancers). The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 (95% confidence interval 1.01 to 2.05) among all women invited for screening and 1.77 (1.16 to 2.74) among those who attended. Among women with a normal or negative test result, the relative rate of subsequent CIN III+ was 0.28 (0.04 to 1.17). The rate of cervical cancer between arms was 0.75 (0.25 to 2.16) among women invited for screening and 1.98 (0.52 to 9.38) among those who attended.
Conclusions When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions. The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention.
Trial registration Current Controlled Trials ISRCTN23885553.
We thank the staff of the Mass Screening Registry and the Finnish Cancer Registry, the Pathology Laboratory of the Finnish Cancer Society in Helsinki, and the HUSLAB Kätilöopisto Pathology Laboratory, Helsinki, for their valuable contribution throughout the study.
Contributors: AA, MH, and PN were involved in the planning, design, data collection, analyses, and reporting. LK-T and ML contributed to the coordination of the trial and the data collection, analysis, and reporting. NM, JT, and PL have contributed to data collection, analysis, and reporting. PN is guarantor.
Funding: The study was partially financed by grants from the European Commission, Europe Against Cancer action programme through European Cervical Cancer Screening Network; the Academy of Finland; and the Cancer Organisation of Finland.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that all authors had: (1) No financial support for the submitted work from anyone other than their employer; (2) No financial relationships with commercial entities that might have an interest in the submitted work; (3) No spouses, partners, or children with relationships with commercial entities that might have an interest in the submitted work; (4) No Non-financial interests that may be relevant to the submitted work.
Ethical approval: The protocol for the randomised screening study was approved by the ethical committee of the National Research and Development Centre for Welfare and Health (STAKES, 4151/54/98), the ethical committee of the Obstetrics and Gynaecology in Hospital District of Helsinki and Uusimaa (221/E8/02), and the National Authority for Medicolegal Affairs (3950/32/300/02). Every woman was informed about the test and could refuse the assigned HPV test and receive the conventional test instead.
Data sharing: No additional data available.
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