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Multicenter Study
. 2008 Oct 13:337:a1754.
doi: 10.1136/bmj.a1754.

Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study

Joakim Dillner  1 , Matejka Rebolj, Philippe Birembaut, Karl-Ulrich Petry, Anne Szarewski, Christian Munk, Silvia de Sanjose, Pontus Naucler, Belen Lloveras, Susanne Kjaer, Jack Cuzick, Marjolein van Ballegooijen, Christine Clavel, Thomas Iftner; Joint European Cohort Study
Collaborators, Affiliations
Free PMC article
Multicenter Study

Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study

Joakim Dillner et al. BMJ. .
Free PMC article

Abstract

Objective: To obtain large scale and generalisable data on the long term predictive value of cytology and human papillomavirus (HPV) testing for development of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+).

Design: Multinational cohort study with joint database analysis.

Setting: Seven primary HPV screening studies in six European countries.

Participants: 24,295 women attending cervical screening enrolled into HPV screening trials who had at least one cervical cytology or histopathology examination during follow-up.

Main outcome measure: Long term cumulative incidence of CIN3+.

Results: The cumulative incidence rate of CIN3+ after six years was considerably lower among women negative for HPV at baseline (0.27%, 95% confidence interval 0.12% to 0.45%) than among women with negative results on cytology (0.97%, 0.53% to 1.34%)). By comparison, the cumulative incidence rate for women with negative cytology results at the most commonly recommended screening interval in Europe (three years) was 0.51% (0.23% to 0.77%). The cumulative incidence rate among women with negative cytology results who were positive for HPV increased continuously over time, reaching 10% at six years, whereas the rate among women with positive cytology results who were negative for HPV remained below 3%.

Conclusions: A consistently low six year cumulative incidence rate of CIN3+ among women negative for HPV suggests that cervical screening strategies in which women are screened for HPV every six years are safe and effective.

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Conflict of interest statement

Competing interests: K-UP has received speaker’s honorarium from Digene and Roche and research grants from Digene; TI has received speaker’s honorarium from Digene; JC is on the speaker’s bureau of Digene and the advisory board for Roche and has received research grants from Roche; SK is on an advisory board for Merck and has received research grants from Merck and SPMSD; CM has received travel grants from Merck; SdeS has received travel grants from Digene and GSK and research grants from GSK and Merck/Sanofi Pasteur. The Department of Public Health of the Erasmus MC in Rotterdam, Netherlands, has received a research grant from GSK.

Ethical approval: All studies were approved by the ethical review boards in their respective countries.

Figures

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Fig 1 Kaplan-Meier plots of cumulative incidence rate for CIN3+ for women according to baseline test results in the first 72 months of follow-up in all seven countries
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Fig 2 Kaplan-Meier plots of cumulative incidence rate for CIN3+ for women according to baseline test results in first 72 months of follow-up, excluding Denmark and Tübingen
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Fig 3 Kaplan-Meier plots of cumulative incidence rate for CIN3+ for women according to baseline test reults in first 72 months of follow-up, excluding Denmark and Tübingen
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Fig 4 Comparison of cumulative incidence rate (95% confidence interval) of CIN3+ at 60 months by country and by baseline test results
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