Detection rates of precancerous and cancerous cervical lesions within one screening round of primary human papillomavirus DNA testing: prospective randomised trial in Finland2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7789 (Published 29 November 2012) Cite this as: 2012;345:e7789
- Maarit K Leinonen, scientist1,
- Pekka Nieminen, chief physician2,
- Stefan Lönnberg, scientist1,
- Nea Malila, director13,
- Matti Hakama, research professor13,
- Arun Pokhrel, scientist4,
- Pekka Laurila, chief physician5,
- Jussi Tarkkanen, physician5,
- Ahti Anttila, research director1
- 1Mass Screening Registry, Finnish Cancer Registry, FI-00130 Helsinki, Finland
- 2Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Espoo, Finland
- 3Tampere School of Health Sciences, University of Tampere, Tampere, Finland
- 4Finnish Cancer Registry
- 5Department of Pathology, HUSLAB, Helsinki University Central Hospital, Helsinki
- Correspondence to: M K Leinonen
- Accepted 8 November 2012
Objective To compare the detection rates of precancerous and cancerous cervical lesions by human papillomavirus (HPV) DNA testing and by conventional cytology screening.
Design Prospective randomised trial. Two cohorts were followed over one screening round of five years, screened initially by primary HPV DNA testing or by primary Pap test.
Setting Population based programme for cervical cancer screening in Finland.
Participants Women aged 25-65 years invited for screening in 2003-07 (101 678 in HPV arm; 101 747 in conventional cytology arm).
Intervention Women were randomly allocated (1:1) to primary HPV DNA screening followed by cytology triage if they had positive results, or to primary cytology screening. Screening method was disclosed at the screening visit. Trial personnel involved were aware of all test results.
Main outcome measures Cumulative detection rates of cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), and invasive cervical cancer before the second screening (after five years) or before 31 December 2008. Lesions detected at screening and during the five year interval were included.
Results 1010 and 701 precancerous or cancerous lesions were detected during an average follow-up of 3.6 years in the HPV and cytology arms, respectively. Among invited women, the hazard ratio was 1.53 (95% confidence interval l.28 to 1.84) for CIN grade 1, 1.54 (1.33 to 1.78) for CIN 2, 1.32 (1.09 to 1.59) for CIN 3 or AIS, and 0.81 (0.48 to 1.37) for cervical cancer. In 25-34 year old participants, the cumulative hazard (or cumulative detection rate) was 0.0057 (0.0045 to 0.0072) for HPV screening versus 0.0046 (0.0035 to 0.0059) for conventional screening; corresponding data for women aged 35 years and older were 0.0022 (0.0019 to 0.0026) and 0.0017 (0.0014 to 0.0021), respectively.
Conclusions Primary HPV DNA screening detects more cervical lesions than primary cytology within one screening round of five years. Even if the detection rate of CIN 3 or AIS increased in the HPV arm in both age groups, the absolute difference in cumulative rates in women aged 35 years or older was small. By carefully selecting age groups and screening intervals, HPV screening could increase the overall detection rate of cervical precancerous lesions only slightly. However, these findings should be interpreted in the context of the high level of opportunistic screening that occurs in Finland.
Trial registration International Standard Randomised Controlled Trial ISRCTN23885553.
We thank Timo Hakulinen and Tapio Luostarinen from the Finnish Cancer Registry for checking randomisation procedures in relation to the attendance status of the current study; Timo Hakulinen for his help with the statistical analysis; and Qiagen for providing the Hybrid Capture 2 tests at a long term developmental price, and checking the technical details of their product for this manuscript.
Contributors: MKL planned the design and method, monitored data collection and management, analysed the data, and drafted and revised the paper. PN planned the design and method, monitored laboratory analyses, and drafted and revised the paper. SL monitored data management and revised the paper. NM and MH monitored data validity and revised the paper. AP wrote the statistical analysis plan, analysed the data, and revised the paper. PL monitored laboratory analyses and revised the paper. JT monitored laboratory analyses and revised the paper. AA planned the design and method, monitored data collection and management, analysed the data, and drafted and revised the paper. MKL and AA are guarantors. MKL had full access to all the data in the study and decided to submit the manuscript for publication.
Funding: This study was supported by research grants from the Academy of Finland, the European Union through the action programme Europe Against Cancer, the Finnish Cancer Organisations, and the Finnish Medical Society Duodecim. The funders had no role in study design, data collection, data analysis, data interpretation, writing of the report or the decision to submit it for publication.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support from the Academy of Finland, the European Union through the action programme Europe Against Cancer, and the Finnish Cancer Organisations, and the Finnish Medical Society Duodecim for the submitted work; PN has done consultancy work for GlaxoSmithKline and Merck; and no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This study was approved by principal authorities in medical and ethical issues in Finland (for example, the National Authority for Medicolegal Affairs (Dnro 3950/32/300/02; Dnro THL/1223/6.02.00/2010), the ethical committee of the local hospital district (Dnro 221/E8/02; 384/13/03/032010), and health boards of the committed municipalities.
Data sharing: No additional data available.
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