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De Fine Licht S.,Danish Cancer Society | Winther J.F.,Danish Cancer Society | Gudmundsdottir T.,Danish Cancer Society | Holmqvist A.S.,Skåne University Hospital | And 11 more authors.
The Lancet | Year: 2014

Background The pattern of endocrine disorders in long-term survivors of childhood cancer has not been investigated comprehensively. Here, we aimed to assess the lifetime risk of these disorders in Nordic survivors of childhood cancer. Methods From the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden, we identified 31 723 1-year survivors of childhood cancer, notified since the start of registration in the 1940s and 1950s. From the national population registries, we randomly selected a comparison cohort of people matched by age, sex, and country. Study participants were linked to the national hospital registries, and observed numbers of first-time hospital contacts for endocrine disorders in survivors of childhood cancer were compared with the expected numbers derived from the population comparison cohort. We calculated the absolute excess risks attributable to status as a childhood cancer survivor and standardised hospitalisation rate ratios (SHRRs). Findings Of the childhood cancer survivors, 3292 had contact with a hospital for an endocrine disorder, yielding a SHRR of 4·8 (95% CI 4·6-5·0) ; the highest risks were in survivors of leukaemia (SHRR 7·3 [95% CI 6·7-7·9]), CNS tumours (6·6 [6·2-7·0]), and Hodgkin's lymphoma (6·2 [5·6-7·0]). The absolute excess risk for endocrine disorders was roughly 1000 per 100 000 person-years before 20 years of age, and 400 per 100 000 person-years during the remaining lifetime. For children with cancer diagnosed at 5-9 years of age, the cumulative risk for endocrine disorders was highest, and reached 43% at the age of 60 years. Diagnoses of pituitary hypofunction (SHRR 88·0), hypothyroidism (9·9), and testicular and ovarian dysfunction (42·5 and 4·7, respectively) together constituted 61% (655 of 1078) of all excess disease-induced and treatment-induced endocrine disorders in survivors of childhood cancer. Interpretation A cumulative risk for endocrine disorders at 60 years of age of above 40% in survivors of childhood cancer emphasises the importance of minimisation of damaging treatment, intensification of secondary prevention, and targeting of survivor follow-up throughout life. Since most long-term childhood cancer survivors are not followed in a specialised late-effect clinic, they are a growing challenge for the primary care physician and medical specialists working outside the late-effect area.

Schroder F.H.,Erasmus University Rotterdam | Hugosson J.,Sahlgrenska University Hospital | Carlsson S.,Sahlgrenska University Hospital | Tammela T.,University of Tampere | And 5 more authors.
European Urology | Year: 2012

Background: Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal. Objective: To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial. Design, setting, and participants: Data were available for 76 813 men aged 55-69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up. Intervention: Regular screening based on serum PSA measurements was offered to 36 270 men randomized to the screening arm, while no screening was provided to the 40 543 men in the control arm. Outcome measurements and statistical analysis: The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease. Results and limitations: After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively (p < 0.001). This finding translated into a relative reduction of 30% (hazard ratio [HR]: 0.70; 95% confidence interval [CI], 0.60-0.82; p = 0.001) in the intention-to-screen analysis and a 42% (p = 0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41-0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up. Conclusions: PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases. The ERSPC trial is registered under number ISRCTN49127736. © 2012 European Association of Urology.

Malila N.,Finnish Cancer Registry | Senore C.,University of Turin | Armaroli P.,University of Turin
Endoscopy | Year: 2012

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on organisation includes 29 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of the screening process, including multi-disciplinary diagnosis and management of the disease. © Georg Thieme Verlag KG Stuttgart, New York.

Arbyn M.,Scientific Institute of Public Health | Verdoodt F.,Scientific Institute of Public Health | Snijders P.J.F.,VU University Amsterdam | Verhoef V.M.J.,VU University Amsterdam | And 8 more authors.
The Lancet Oncology | Year: 2014

Background: Screening for human papillomavirus (HPV) infection is more effective in reducing the incidence of cervical cancer than screening using Pap smears. Moreover, HPV testing can be done on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage. However, the clinical accuracy of HPV testing on self-samples is not well-known. We assessed whether HPV testing on self-collected samples is equivalent to HPV testing on samples collected by clinicians. Methods: We identified relevant studies through a search of PubMed, Embase, and CENTRAL. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: a cervical cell sample was self-collected by a woman followed by a sample taken by a clinician; a high-risk HPV test was done on the self-sample (index test) and HPV-testing or cytological interpretation was done on the specimen collected by the clinician (comparator tests); and the presence or absence of cervical intraepithelial neoplasia grade 2 (CIN2) or worse was verified by colposcopy and biopsy in all enrolled women or in women with one or more positive tests. The absolute accuracy for finding CIN2 or worse, or CIN grade 3 (CIN3) or worse of the index and comparator tests as well as the relative accuracy of the index versus the comparator tests were pooled using bivariate normal models and random effect models. Findings: We included data from 36 studies, which altogether enrolled 154 556 women. The absolute accuracy varied by clinical setting. In the context of screening, HPV testing on self-samples detected, on average, 76% (95% CI 69-82) of CIN2 or worse and 84% (72-92) of CIN3 or worse. The pooled absolute specificity to exclude CIN2 or worse was 86% (83-89) and 87% (84-90) to exclude CIN3 or worse. The variation of the relative accuracy of HPV testing on self-samples compared with tests on clinician-taken samples was low across settings, enabling pooling of the relative accuracy over all studies. The pooled sensitivity of HPV testing on self-samples was lower than HPV testing on a clinician-taken sample (ratio 0·88 [95% CI 0·85-0·91] for CIN2 or worse and 0·89 [0·83-0·96] for CIN3 or worse). Also specificity was lower in self-samples versus clinician-taken samples (ratio 0·96 [0·95-0·97] for CIN2 or worse and 0·96 [0·93-0·99] for CIN3 or worse). HPV testing with signal-based assays on self-samples was less sensitive and specific than testing on clinician-based samples. By contrast, some PCR-based HPV tests generally showed similar sensitivity on both self-samples and clinician-based samples. Interpretation: In screening programmes using signal-based assays, sampling by a clinician should be recommended. However, HPV testing on a self-sample can be suggested as an additional strategy to reach women not participating in the regular screening programme. Some PCR-based HPV tests could be considered for routine screening after careful piloting assessing feasibility, logistics, population compliance, and costs. Funding: The 7th Framework Programme of the European Commission, the Belgian Foundation against Cancer, the International Agency for Research on Cancer, and the German Guideline Program in Oncology. © 2014 Elsevier Ltd.

Peltoniemi P.,University of Tampere | Peltola M.,Finnish National Institute for Health and Welfare | Hakulinen T.,Finnish Cancer Registry | Hakkinen U.,Finnish National Institute for Health and Welfare | And 2 more authors.
Annals of Surgical Oncology | Year: 2011

Background: This study was conducted to investigate whether annual surgical unit caseload affects extent of breast cancer surgery, breast cancer recurrence or breast cancer-specific survival. Methods: In a population-based cohort study, 12,604 women diagnosed with breast cancer in Finland during the years 1998-2001 were followed up until the end of year 2008. Surgical units were divided into subgroups: >200, 100-200, 50-99 or <50 breast cancer operations per year. Information on patients, treatment, and follow-up was obtained from two national registries. The analyses were adjusted for age and disease stage. The reliability of the registry information was validated by comparison with information from one hospital area. Cox proportional hazard and logistic regression models were employed in the analyses. Results: Validation of the registry data showed that date of diagnosis, age, stage, extent of surgery, and date and cause of death were reliably recorded in the registers. Information on radiotherapy was obtained by combining different registry data. Data on local and distant recurrences were not reliable enough to allow analyses. Patients in hospitals with smaller caseloads underwent mastectomy more often than those operated in hospitals with higher caseloads (P < 0.001). Higher caseloads were also related to improved survival (P = 0.031). Conclusions: National registries should include information on both local and distant recurrences in order to provide reliable population-based data for evaluation of treatment results. Centralization of surgery to high-volume centers is supported by a higher incidence of conservative surgery and better survival. © 2010 Society of Surgical Oncology.

Sihto H.,Laboratory of Molecular Oncology | Sihto H.,University of Helsinki | Kukko H.,University of Helsinki | Koljonen V.,University of Helsinki | And 4 more authors.
Clinical Cancer Research | Year: 2011

Purpose: Merkel cell carcinoma (MCC) is rare skin cancer that is often associated with Merkel cell polyomavirus (MCPyV) infection. Polyomaviruses repress tumor suppressor proteins, thus influencing cell-cycle progression, but the effect of MCPyV on the key cell-cycle regulating proteins is poorly understood. Experimental Design: We evaluated expression of the MCPyV large T-antigen (LTA), Ki-67, and the key putative tumor suppressor proteins, the retinoblastoma protein (RB and phospho-RB) and p53, and their regulatory proteins (cyclin D1, cyclin E, p16, p21, p27, and MDM2) by using immunohistochemistry from tumors of 91 MCC patients identified from a population-based nationwide cohort. Tumor MCPyV DNA was measured by using quantitative PCR, and TP53 mutations were identified with sequencing. Results: MCPyV LTA expression was strongly associated with presence of MCPyV DNA in tumor, and it was almost invariably associated with tumor RB expression (P < 0.0001 for both comparisons). Both MCC LTA and RB expression were strongly associated with favorable MCC-specific and overall survival in univariable analyses (P ≤ 0.01 for all four analyses). Presence of MCPyV LTA was also associated with the female gender, the intermediate type of tumor histology, location of the tumor in a limb, cell proliferation rate, and absence of p53 expression. TP53 mutations were detected only in MCPyV DNA-negative tumors. Conclusions: MCPyV DNA-positive MCC has several clinical and molecular features that differ from MCPyV DNA-negative cancers. MCPyV-associated MCCs express RB, but may not harbor TP53 mutations. These findings provide further support that MCPyV causes the majority of MCCs. ©2011 AACR.

Heinavaara S.,Finnish Cancer Registry | Sarkeala T.,Finnish Cancer Registry | Anttila A.,Finnish Cancer Registry
British journal of cancer | Year: 2014

Overdiagnosis is the most important adverse event of breast cancer screening with the estimates ranging from 0% to 40-50% depending on invitational age and methods. We updated the estimates of overdiagnosis in Helsinki service screening study in Finland by comparing the observed and expected cumulative incidence of all breast carcinomas and invasive breast carcinomas. Women aged 50-59 years have been invited to Helsinki service screening since 1986. The incidence of breast carcinoma in the first invited birth cohorts born in 1935-1939 was compared with older, non-invited cohorts. The minimum follow-up time of the invitees after the last screening round was 14 years. Expected cumulative incidence rates were estimated with two alternative approaches. For both any breast carcinoma and invasive breast carcinoma, the estimates of overdiagnosis varied from 5% (95% CI=-1, 11%) to 7% (95% CI=1, 13%) depending on the approach. Our estimates of overdiagnosis are of the same magnitude than other plausible estimates in Europe. Both alternative approaches produced similar estimates for the expected cumulative incidence, which increased the confidence in the estimates of overdiagnosis.

Kilpelainen T.P.,University of Tampere | Tammela T.L.,University of Tampere | Malila N.,Finnish Cancer Registry | Hakama M.,Finnish Cancer Registry | And 5 more authors.
Journal of the National Cancer Institute | Year: 2013

BackgroundProstate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality.MethodsA total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0ng/mL or 3.0 to 3.99ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided.ResultsPC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P <. 001). For PC mortality, no statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis). To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms.ConclusionsAt 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis. © The Author 2013. Published by Oxford University Press. All rights reserved.

Lonnberg S.,Finnish Cancer Registry | Leinonen M.,Finnish Cancer Registry | Malila N.,Finnish Cancer Registry | Anttila A.,Finnish Cancer Registry
Acta Oncologica | Year: 2012

Background. Monitoring and evaluation of cancer screening programmes require accurate data on invitations, visits, test results, diagnoses and management. The purpose of this study was to evaluate the completeness and accuracy of histological diagnoses (cervical precancerous lesions and cancer) in the Finnish cervical cancer screening register by comparing data with the cancer register and the administrative hospital discharge register. Material and methods. Screening data covering all 16 353 screening episodes that resulted in a referral for colposcopy over the period of 19982007 were individually linked with hospital discharge and cancer register data using the unique personal identifier. Agreement between registers, as well as sensitivity, coverage and positive predictive values (PPV) for the screening register and the hospital discharge register diagnosis, were estimated. Invasive cases in the cancer register and pooled cases of precancerous lesions were used as reference case populations. Results. The sensitivity of the screening register for cervical cancer was 69%, the coverage 100% and the PPV 77%. Corresponding values for the hospital discharge register were 81%, 100% and 83%, respectively. Sensitivity of the screening register for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) against the pooled case population was 89% and coverage 99%. Corresponding values for the hospital discharge register were 78% and 93%. Kappa-values for pair-wise agreement between the three registers ranged between 0.73 and 0.79, often the lesion grade was lower in the screening register than in the other two registers. Conclusions. The data in the screening register has high coverage and is thus useful for statistical and evaluation purposes. However, in order to improve the accuracy of diagnostic information, there are grounds to consider data retrieval through systematic linkage to other health care registers. © 2012 Informa Healthcare.

Virtanen A.,Mass Screening Registry | Nieminen P.,University of Helsinki | Niironen M.,Mass Screening Registry | Luostarinen T.,Finnish Cancer Registry | Anttila A.,Mass Screening Registry
Gynecologic Oncology | Year: 2014

Objective. High coverage and attendance is essential to positive cervical cancer screening results. Offering self-sampling for HPV-testing to the non-attendees of the program may improve attendance rates. Information on women's perceptions and experiences with self-sampling (acceptability) is needed to further optimize attendance by this method. Methods. A questionnaire study focusing on women's experiences on the screening method was embedded in a trial investigating the effects and feasibility of self-sampling among non-attendees of cervical screening in 31 Finnish municipalities in 2011-2012 (n = 4688). Reasons for non-attendance in routine screening were also surveyed. Results. Response rate to the questionnaire was 98.8% (909/920) among women who performed self-sampling. Self-sampling participants reported mainly good experiences. Negative experiences (difficulties in sample taking, pain, fear, anxiety, insecurity) were reported rarely, but more commonly among women with a mother tongue other than Finnish or Swedish (immigrants). Most common reason for non-attendance in routine screening was a recent Pap-smear elsewhere (opportunistic screening). Practical reasons (pregnancy, scheduling difficulties) were reported by 42%, emotional or attitudinal reasons by 17%, and 16% forgot to take part. Response yield to questionnaire was unsatisfactory among those women who declined the self-sampling option. Conclusions. Optimizing the practical aspects of screening and offering a self-sampling option to non-attendees can help to overcome a large variety of both practical and emotional barriers to traditional screening. More research is needed among the non-attendees to routine screening who decline also the self-sampling option. © 2014 Elsevier Inc. All rights reserved.

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