PROSPECTIVE AND RANDOMISED PUBLIC-HEALTH TRIAL ON NEURAL NETWORK-ASSISTED SCREENING FOR CERVICAL CANCER IN FINLAND: RESULTS OF THE FIRST YEAR Pekka NIEMINEN 1 * , Matti HAKAMA 2,3 , Merja VIIKKI 3 , Jussi TARKKANEN 4 and Ahti ANTTILA 3 1 Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland 2 Tampere University School of Public Health, Tampere, Finland 3 Finnish Cancer Registry, Helsinki, Finland 4 Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland Our objective was to evaluate the feasibility and relative validity of interactive neural network assisted screening (Papnet) in primary mass screening for cervical cancer as a public health policy (routine screening). A randomized, on- going trial involved 152,969 invitees and 108,686 attendees in the organized mass screening in Finland in 1999. Drawing invitations from the population registry, women were ran- domized 2:1 at an individual level to have their smear ana- lyzed either conventionally or with Papnet. The distribution of smears to different cytological categories, detection rates of dysplasias, in situ carcinomas and cancers were estimated with smears analyzed either conventionally (72,461) or by Papnet (36,225). A total of 108,686 smears were screened and 449 were histologically confirmed as dysplasias and car- cinomas. The detection rates for histologically verified carci- noma in situ/severe dysplasia, moderate and mild dysplasias were 0.14%, 0.14% and 0.13% with conventional and 0.14%, 0.14% and 0.11% with Papnet, respectively. The detection rate of invasive cancer was 0.06‰ (n  4) with conventional method and 0.08‰ (n  3) with Papnet. None of the differ- ences were statistically significant (p > 0.05). Papnet was able to identify 92.5% of healthy women (normal cytology), and the specificity of conventional smear was 92.9%. The positive predictive value (Pap Classes III–V) of Papnet was slightly but not significantly better (55% vs. 51%). Papnet screening was feasible as a part of routine screening and performed equally well compared to conventional one methods used in Finland. Organized mass screening was practiced very successfully in the last 38 years. We are going to continue the trial to study the potential trends in cervical cancer incidence in both study arms. © 2002 Wiley-Liss, Inc. Key words: cervical cancer; primary screening; automation-assisted; public health trial; Papnet The role of cytology-based screening in the prevention of cer- vical cancer is established. Organized mass screening has been especially effective in Finland compared to other organized screening programs 1,2 or to spontaneous screening practiced in the same population. 3 The program was introduced in 1963 and since then the age-standardized mortality from and the incidence of invasive disease has decreased by 80%. 4,5 Years before the screen- ing started the age-standardized incidence was about 15/100,000 women and was at its lowest during early 90s (3.5/100,000 women-years). Thereafter the trends have not been as favorable as in the past and in 1998 the rate was 4.5/100,000 women-years. An interactive computer-assisted screening system that uses neural networks (Papnet) can potentially improve the effectiveness and ef- ficacy of the cervical cancer screening program and decrease screener errors. 6 –9 There are studies indicating that it is especially suitable for quality control re-screening. 10 –12 No prospective, randomized trials to assess the effectiveness of the computer-assisted system in primary screening, however, are available. The usefulness of Papnet in pri- mary screening seems promising. Doornewaard et al. 9 and Duggan 13 have concluded that in primary screening the Papnet yields in equal sensitivity and specificity as conventional screening on basis of non- randomized studies. These studies, however, have well-known limi- tations as to bias. Finland is particularly suitable country for evaluating the per- formance of neural network-assisted screening in primary screen- ing because of the highly developed health care infrastructure and a well-functioning and continuously evaluated mass screening program. The objective of our study is to analyze whether the organized screening program for cervical cancer can even be improved by means of this new technology. We are carrying out a large pro- spective randomized trial that remains ongoing. The results of the first year, based on a large study population, illustrate the results in terms of process. The ultimate purpose is to assess whether Papnet- assisted screening can reduce the incidence of invasive cervical cancer. This, however, requires a longer follow-up time. We report the detection rates of cervical dysplasias, in situ carcinomas and cervical cancers using conventional and Papnet-assisted screening MATERIAL AND METHODS Mass screening in finland An organized mass screening program for cervical cancer was introduced in Finland in 1963. The target population of screening is the entire Finnish female population aged 30 – 60 (1.2 million women). There is some variation in the age groups because the cohorts to be screened are decided by municipal authorities. Every woman is identified from the National Population Registry and invited every 5th year by a personal letter with place and individ- ual time specified to attend the screening program. The results of the cervical smear are sent to the women and to the nationwide Mass Screening Registry. Every year about 250,000 women are invited personally and about 180,000 smears are taken within the mass screening pro- gram. The attendance rate is 72% and the coverage of the program depends on age. This varies from 70%, in the 30-years age group, to 100% (between ages 40 –55). 3 In addition, plenty of spontane- ous smears are taken by municipal health centres, occupational health services or by private gynecologist. These smears are not registered but number about 300,000 annually. Grant sponsor: Finnish Academy; Grant sponsor: Finnish Cancer Or- ganisation; Grant sponsor: European Community. *Correspondence: Dept. Obst. and Gyn., Helsinki University Central Hospital, Box 140, 00029 HUS Helsinki, Finland. Fax: +358-9-47174805. E-mail: pekka.nieminen@hus.fi Received 7 June 2002; Revised 20 August 2002; Accepted 26 September 2002 DOI 10.1002/ijc.10839 Int. J. Cancer: 103, 422– 426 (2003) © 2002 Wiley-Liss, Inc. Publication of the International Union Against Cancer