Alternative technologies in cervical cancer screening: a randomised evaluation trial

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Incidence-based evaluations of cervical cancer screening programs have suggested age-specific impacts and there is uncertainty regarding the effectiveness of screening outside the ages of 30-60 years. We audited the screening histories of cervical cancer deaths and conducted a case-control evaluation of the effectiveness of organized screening in different ages with mortality as outcome. We included all 506 cervical cancer deaths in Finland in 2000-2009 due to cancers diagnosed in 1990 or later, and 3,036 controls matched by age at diagnosis to the cases. Squamous cell carcinoma constituted 59% of the cases, adenocarcinomas 29%, and the remaining 12% were other specified and unspecified cervical malignancies. Most deaths (54%) were due to cancers diagnosed more than 5 years after last screening invitation, 24% were diagnosed among nonattenders and only 14% of deaths occurred among women who had attended invitational screening. The risk reduction associated with attending a single program screen at an age below 40 was nonsignificant (OR 0.70; 95% CI 0.33-1.48), while clear risk reductions were observed after screening at the age of 40-54 (OR 0.33; CI 0.20-0.56) and 55-69 (OR 0.29; CI 0.16-0.54). This study also provides some indication of a long-lasting additional effect of screening at the age of 65. Possible avenues for improving the effectiveness of the Finnish screening program include efforts to increase attendance and an extension of the target ages to include 65-to 69-year-old women. The potential benefit of increasing the sensitivity of the screening test or shortening the screening interval is smaller.The effectiveness of cervical cancer screening by cytology has never been established in a randomized controlled trial, but numerous observational studies have confirmed the considerable potential for prevention of cancer incidence and mortality. 1 However, recent research suggests that screening may not be equally effective in all age-groups currently targeted by screening programmes. 2,3 In a case-control evaluation of the Finnish program, no effect on the risk of cancer in the following 5-year interval was found after participation at the age of 25-29. 2 Risk reductions increased with increasing age up to 40, and remained fairly constant thereafter. Similarly, a case-control study from the UK found screening to be less effective in women aged 20-34 and that the efficacy decreases with decreasing age even within this age range. 3 By contrast, a Swedish audit found screening to be equally effective in preventing cancer diagnosed in the ages 21-29 and 30-65. 4 To our knowledge no mortality based effectiveness studies have yet addressed this issue.The purpose of this study was to audit the screening histories of women who died of cervical cancer and evaluate the impact of participation in organized screening on the mortality from cervical cancer by morphology in different ages. We especially wanted to explore how screening at the age of 65 affects the mortality at advanced ages. Material and MethodsThe cerv...

Section: Methodsmentioning

confidence: 99%

Mortality audit of the Finnish cervical cancer screening program

Lönnberg

Nieminen

Luostarinen

et al. 2012

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“…The randomization methods, as well as further details on the invitation, attendance and findings have been previously published up to first 5 years of the trial. [9][10][11][12] The national screening program in Finland invited women aged 30-60 years of age with a personal letter to screening every 5 years. In some municipalities, women as young as 25 and/or old as 65 years were also invited.…”

Section: Methodsmentioning

confidence: 99%

“…The study used a randomized prospective design run within a nationwide population-based screening program in Finland. [9][10][11][12] In this study, the results on automationassisted screening are for the first time presented up to cancer incidence and mortality. Data were analyzed by detailed screening findings and particular emphasis was put on analyzing longitudinal cervical cancer patterns among women who had a negative screening test (test negative) to study sensitivity in terms of negative predictive value and effectiveness.…”

mentioning

confidence: 99%

Cervical cancer patterns with automation‐assisted and conventional cytological screening: A randomized study

Anttila

Pokhrel

Kotaniemi-Talonen

et al. 2010

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The purpose was to evaluate alternative cytological screening methods in population-based screening for cervical cancer up to cancer incidence and mortality outcome. Automation-assisted screening was compared to conventional cytological screening in a randomized design. The study was based on follow-up of 503,391 women invited in the Finnish cervical cancer screening program during 1999-2003. The endpoints were incident cervical cancer, severe intraepithelial neoplasia and deaths from cervical cancer. One third of the women had been randomly allocated to automation-assisted screening and two thirds to conventional cytology. Information on cervical cancer and severe neoplasia were obtained through 1999-2007 from a linkage between screening and cancer registry files. There were altogether 3.2 million woman-years at risk, and the average follow-up time was 6.3 years. There was no difference in the risk of cervical cancer between the automation-assisted and conventional screening methods; the relative risk (RR) of cervical cancer between the study and control arm was 1.00 (95% confidence interval [CI] 5 0.76-1.29) among all invited and 1.08 (95% CI 5 0.76-1.51) among women who were test negative at entry. Comparing women who were test negative with nonscreened, RR of cervical cancer incidence was 0.26, 95% CI 5 0.19-0.36 and of mortality 0.24 (0.13-0.43). Both methods were valid for screening. Because cervical cancer is rare in our country, we cannot rule out small differences between methods. Evidence on alternative methods for cervical cancer screening is increasing and it is thus feasible to evaluate new methods in large-scale population-based screening programs up to cancer outcome.Incidence and mortality of invasive cancer is the most informative outcome (gold standard) when evaluating screening programs and screening methods. 1,2 Until now cancer incidence and mortality data has been available only from some conventional Pap-smear screening programs. Alternative technologies such as automation-assisted or liquid-based cytology or human papillomavirus (HPV) testing have been proposed during the last 15-20 years to improve cervical cancer prevention. 2 Most data from these techniques are based on surrogate markers, e.g., cross-sectional cervical intraepithelial neoplasia (CIN) rates or sometimes only on cytological findings. 3 Longitudinal follow-up information on the surrogate markers or cancer is rarely available. 4-8 These indicators may not reflect the real effect.When considering large-scale use of the novel alternative methods, information on the effectiveness need to be obtained. Another drawback is that new methods might be that the overall or incremental cost-effectiveness may not be the same as for the conventional method. It has not been straightforward to decide about use of the new methods in population-based screening.The purpose of our study was to evaluate cervical cancer patterns when using alternative cytological screening methods in population-based organized screening for cervical cancer. We ...

“…Further details for the randomisation and screening protocols are published elsewhere. 6,19,20 Running of the trial within the Finnish cervical screening programme was accepted by the principal authorities in medicoethical issues in Finland, the National Authority for Medicolegal Affairs, the ethical committee of local hospital district, and health boards of the committed municipalities.…”

Section: Study Populationmentioning

confidence: 99%

Prevalence of oncogenic human papillomavirus infection in an organised screening population in Finland

Leinonen

Kotaniemi-Talonen

Anttila

et al. 2008

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A persistent high-risk human papillomavirus (hrHPV) infection is a necessary condition for developing a cervical intraepithelial neoplasia and cervical cancer. The viral aetiology in cervical carcinogenesis has stimulated attempts to use HPV DNA detection in cervical cancer screening. In Finland there is an ongoing study assessing the benefits of primary HPV DNA testing in the setting of centrally organised mass screening for cervical cancer. Here we present the age-specific prevalence of hrHPV infection and associated sociodemographic factors of 16,895 women aged 25-65 years attending the 5-yearly cervical cancer screening between years 2003 and 2004. The overall hrHPV prevalence rate was 7.5%. The peak prevalence at the age group of 25-29 was 24.1% decreasing steadily thereafter to approximately 2.9% in women aged 65 years. Young age and marital status were the main determinants for oncogenic HPV types. Our study confirms the inverse relationship between age and hrHPV prevalence reported in many developed countries. As our prevalence rates and hence background risk for cervical cancer are not lower than in other European countries, it is likely that our lowest cervical cancer burden in Europe is due to health care actions justifying the organised cervical cancer screening. ' 2008 Wiley-Liss, Inc.Key words: high-risk HPV; prevalence; age; cervical cancer; screeningIn Finland an organised nationwide screening programme has been running over 40 years, reducing the age-adjusted incidence and mortality of cervical cancer by 80%, 1 incidence rate being about 4 cases per 100,000 woman-years nowadays. Nevertheless, there are still about 160 new cancer cases every year making the cervical cancer the third most common gynaecological cancer, but 20th of all female cancers, in Finland. 2 However, during the last 10 years, the cervical cancer incidence rate has been increasing among young target ages of the screening programme which is mainly due to inadequate attendance rates to the screening programme. 1 Cohort effects related to changes in exposure to risk factors such as sexual behaviour and smoking habits may also partly explain the increase.Despite the enormous impacts of cytology based screening on cervical cancer incidence and mortality rates in Finland, the Pap test has its limitations as errors in sample taking and in interpretation. As it is known that a persistent high-risk human papillomavirus (hrHPV) infection is a necessary condition for developing a cervical intraepithelial neoplasia (CIN) and cervical cancer 3 and moreover, hrHPV DNA is found in virtually all cases of cervical cancer, 4,5 HPV DNA detection has been suggested for cervical cancer screening as the primary test.To find out whether using HPV DNA detection can bring increase into the routine population-based screening programme effectiveness in Finland, a commercial hrHPV detection test, Hybrid Capture 2 (HC 2, Digene Corporation, Gaithersburg, MD), has been implemented into cervical cancer screening programme as the primary screening test sinc...