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Timo Hakulinen

Publications and source records attributed to Timo Hakulinen.

At least 19 recordsLinked to original sources

Predicting the lung cancer burden: Accounting for selection of the patients with respect to general population mortality.

Incidence, survival, prevalence and mortality are the elements of the cancer burden. The cancer burden is thus contributed by the same individuals from the diagnosis of cancer (incidence) until possible death from cancer (mortality). It would therefore be natural that predictions of future cancer burden, those needed by health administration, for example, could be based on individual data. This paper presents a new model for estimating future cancer burden, a model where individuals are followed from birth to death with or without a diagnosis of cancer. The model can formally be expressed as a summation of log-likelihoods of getting cancer and of surviving the cancer and other causes of death until death or censoring. The new model is illustrated with data of Finnish males with or without a diagnosis of lung cancer in calendar period 1987-1997. Incidence is modelled with a general age-cohort model with a drift and survival from cancer with a parametric mixture model. In a model for survival from other causes of death, selection of patients with respect to general population mortality is accounted for. Future cancer burden is illustrated with short-term predictions of prevalence and mortality.

Adult↗

Effects of different phases of an invitational screening program on breast cancer incidence.

The aim of this study was to quantify the effects of separate phases of an invitational screening program on breast cancer incidence at different ages. Our database included detailed municipality-specific information about invitations for mass-screening for breast cancer in 267 Finnish municipalities from time period 1987-2001. The age range was 50-74. For this study, the program was divided into 7 separate phases, and those that had not been invited served as a baseline. The incidence rate was modeled using Poisson regression. To study the differences between age groups within each program phase, an interaction term between age group and phase of screening was included in the model. The modeling was done separately for localized breast cancers, nonlocalized breast cancers and all stages combined. For localized cancers, the risk compared to the noninvited increased during the first years of the 2-year screening rounds in all age groups, and declined below the baseline during the second years. This effect was larger during the first round compared to the subsequent ones. In nonlocalized cancers, a clear incidence peak was detected only during the first year of the first round. A decreasing post screening effect was detected in nonlocalized cancers in women aged 60-69, but not in localized cancers. Cumulating over ages 50-74, extra incidence caused by regular screening in localized cancers was 5.2% if the program was continued up to age 59, and 28.0% if it continued up to age 69. Corresponding figures for nonlocalized cancers were decreases of 19.8% and 20.9%, respectively.

Age Distribution↗

Time trend analysis of the skin melanoma incidence of Finland from 1953 through 2003 including 16,414 cases.

Site-specific analyses of the skin melanoma incidence show marked differences between men and women by site and over time. The aim of our study was to analyze long-term population-based incidence time trends of skin melanoma in Finland over a period of more than 50 years, with special emphasis on sex- and subsite-specific changes over time. We analyzed incidence data of the Finnish Cancer Registry from 1953 through 2003 including overall 16,414 cases. We calculated age-standardized incidence rates per 100,000 person years using the European Standard Population. From 1953 through 2003, the incidence of skin melanoma increased from 1.5 to 12.8 per 100,000 among men and from 1.8 to 10.4 per 100,000 among women. Incidence rates showed a constant increase from 1953 through the mid of the 1980s. Thereafter, the rate of increase leveled off. The highest relative incidence increases occurred on the trunk among men and on the legs and hips among women. Within the skin area of the head, melanoma of the ear showed the highest relative increase among both men and women. Subsite-specific sex differences in the early registration period tended to become more pronounced in the most recent period. The highest body surface adjusted incidence rates occurred on the head. Only skin melanoma of the head showed an exponential age-specific incidence pattern and the aetiology of these skin melanomas may differ from skin melanoma on other subsites.

Adult↗

Up-to-date and precise estimates of cancer patient survival: model-based period analysis.

Monitoring of progress in cancer patient survival by cancer registries should be as up-to-date as possible. Period analysis has been shown to provide more up-to-date survival estimates than do traditional methods of survival analysis. However, there is a trade-off between up-to-dateness and the precision of period estimates, in that increasing the up-to-dateness of survival estimates by restricting the analysis to a relatively short, recent time period, such as the most recent calendar year for which cancer registry data are available, goes along with a loss of precision. The authors propose a model-based approach to maximize the up-to-dateness of period estimates at minimal loss of precision. The approach is illustrated for monitoring of 5-year relative survival of patients diagnosed with one of 20 common forms of cancer in Finland between 1953 and 2002 by use of data from the nationwide Finnish Cancer Registry. It is shown that the model-based approach provides survival estimates that are as up-to-date as the most up-to-date conventional period estimates and at the same time much more precise than the latter. The modeling approach may further enhance the use of period analysis for deriving up-to-date cancer survival rates.

Adolescent↗

Cancer risk among Chernobyl cleanup workers in Estonia and Latvia, 1986-1998.

Two cohorts of Chernobyl cleanup workers from Estonia (4,786 men) and Latvia (5,546 men) were followed from 1986 to 1998 to investigate cancer incidence among persons exposed to ionizing radiation from the Chernobyl accident. Each cohort was identified from various independent sources and followed using nationwide population and mortality registries. Cancers were ascertained by linkage with nationwide cancer registries. Overall, 75 incident cancers were identified in the Estonian cohort and 80 in the Latvian cohort. The combined-cohort standardized incidence ratio (SIR) for all cancers was 1.15 (95% confidence interval (CI) = 0.98-1.34) and for leukemia, 1.53 (95% CI = 0.62-3.17; n = 7). Statistically significant excess cases of thyroid (SIR = 7.06, 95% CI = 2.84-14.55; n = 7) and brain cancer (SIR = 2.14, 95% CI = 1.07-3.83; n = 11) were found, mainly based on Latvian data. However, there was no evidence of a dose response for any of these sites, and the relationship to radiation exposure remains to be established. Excess of thyroid cancer cases observed may have been due to screening, the leukemia cases included 2 unconfirmed diagnoses, and the excess cases of brain tumors may have been a chance finding. There was an indication of increased risk associated with early entry to the Chernobyl area and late follow-up, though not statistically significant. Further follow-up of Chernobyl cleanup workers is warranted to clarify the possible health effects of radiation exposure.

Adolescent↗

Period estimates of cancer patient survival are more up-to-date than complete estimates even at comparable levels of precision.

BACKGROUND AND OBJECTIVE: Period analysis provides more up-to-date estimates of cancer patient survival than traditional methods, but there is a trade-off between up-to-dateness and precision. Our objective was to compare the performance of period and complete analysis in terms of up-to-dateness and precision of survival estimates. STUDY DESIGN AND SETTING: Five-year relative survival data actually observed for patients diagnosed with 1 of 20 common forms of cancer in Finland in 36 overlapping 5-year periods between 1958-1962 and 1993-1997 were compared with period estimates and various variants of complete estimates of 5-year relative survival potentially available during these periods. RESULTS: At comparable levels of up-to-dateness, survival estimates from period analysis were more precise than survival estimates from complete analysis. At comparable levels of precision, period analysis provided more up-to-date survival estimates than did complete analysis. CONCLUSION: These results further encourage more widespread use of period analysis as a standard tool for up-to-date monitoring of cancer patient survival by population-based cancer registries.

Finland↗

Episode sensitivity in association with process indicators in the Finnish breast cancer screening program.

We assessed the episode sensitivity of the Finnish mammography program for women aged 50-59 (partly 60-64) years and explored associations between the episode sensitivity and the screening process indicators from 1991 to 1999. For the study period, data were available from 10 screening centers. Records of 721,000 screening visits were linked to the files of the nationwide Finnish Cancer Registry from 1991 to 2001 at an individual level. The rates of screen-detected and interval breast cancers were calculated at the first and at the subsequent screens. The episode sensitivity was determined by contrasting the incidence of interval cancers with the expected population incidence rate without screening (incidence method) and as a proportion of interval cancers out of all cancers detected (detection method). At the subsequent screens, the episode sensitivity determined by the incidence method was 54% and by the detection method 65%. The sensitivity 0-11 and 12-23 months after the screening was 70% and 38%, respectively. The episode sensitivity decreased toward the end of the study period and increased with age. The center-specific sensitivity increased 13% per 1% absolute increase in the recall rate. In general, our study provides further information on the effectiveness of screening programs. The sensitivity estimates were comparable with those from other European service screening programs. The variability in the episode sensitivity suggests potential for variations in the future screening outcome.

Breast Neoplasms↗

Influence of alternative mammographic screening scenarios on breast cancer incidence predictions (Finland).

BACKGROUND: A population-based early detection programme for breast cancer has been in progress in Finland since 1987. Recently, detailed information about actual screening invitation schemes in 1987-2001 has become available in electronic form, which enables more specific modeling of breast cancer incidence. OBJECTIVES: To present a methodology for taking into account historical municipality-specific schemes of mass screening when constructing predictions for breast cancer incidence. To provide predictions for numbers of new cancer cases and incidence rates according to alternative future screening policies. METHODS: Observed municipality-specific screening invitation schemes in Finland during 1987-2001 were linked together with breast cancer data. The incidence rate during the observation period was analyzed using Poisson regression, and this was done separately for localized and non-localized cancers. For modeling, the screening programme was divided into seven different components. Alternative screening scenarios for future mass-screening practices in Finland were created and an appropriate model for incidence prediction was defined. RESULTS AND CONCLUSION: Expanding the screening programme would increase the incidence of localized breast cancers; the biggest increase would be obtained by expanding from women aged 50-59 to 50-69. The impacts of changes in the screening practices on predictions for non-localized cancers would be minor.

Adult↗

Up-to-date estimates of cancer patient survival even with common latency in cancer registration.

In an era of ongoing improvement in cancer patient survival, available long-term survival figures from cancer registries are often outdated and too pessimistic for two reasons: first, delay in availability of cancer registry data, typically in the order of a few years, and, second, application of cohort-based methods of survival analysis, which provide survival estimates for patients diagnosed many years ago. We developed a model-based period analysis approach aimed to overcome both problems. We provide extensive empirical evaluation of our approach by comparing its performance with that of previously available methods for monitoring of 5- and 10-year relative survival, with the use of data from the nationwide Finnish Cancer Registry of 490,279 patients ages >/=15 years and diagnosed with one of 20 common forms of cancer between 1953 and 1997. We show that, in most cases, the model-based approach predicts 5- and 10-year relative survival expectations of newly diagnosed patients quite closely and much better than any of the previously available methods, including standard period analysis. We conclude that the model-based approach may enable deriving up-to-date cancer survival rates even with the common latency in availability of cancer registry data.

Female↗

Associations between three types of maternal bacterial infection and risk of leukemia in the offspring.

A case-control study was nested within two maternity cohorts with a total of 7 million years of follow-up for assessment of the role of bacterial infections in childhood leukemia. Offspring of 550,000 mothers in Finland and Iceland were combined to form a joint cohort that was followed for cancer up to age 15 years during 1975-1997 through national cancer registries. For each index mother-case pair, three or four matched control mother-control pairs were identified from population registers. First-trimester serum samples were retrieved from mothers of 341 acute lymphoblastic leukemia cases and 61 other leukemia cases and from 1,212 control mothers. Sera were tested for antibodies to the genus Chlamydia, Helicobacter pylori, and Mycoplasma pneumoniae. Odds ratios and 95% confidence intervals, adjusted for sibship size, were calculated as estimates of relative risk. M. pneumoniae immunoglobulin M appeared to be associated with increased risk (odds ratio (OR) = 1.6), but the association lost statistical significance when the specificity of the immunoglobulin M was considered (OR = 1.5, 95% confidence interval: 0.9, 2.4). In Iceland, H. pylori immunoglobulin G was associated with increased risk of childhood leukemia in offspring (OR = 2.8, 95% confidence interval: 1.1, 6.9). Since H. pylori immunoglobulin G indicates chronic carriage of the microorganism, early colonization of the offspring probably differs between Iceland and Finland, two affluent countries.

Adolescent↗

Substantial overestimation of standard errors of relative survival rates of cancer patients.

Relative survival rates are among the most commonly reported outcome measures of cancer patients. They are calculated as ratios of observed survival rates and the expected survival rates in the absence of cancer. Standard errors of relative survival rates are commonly calculated by dividing the standard error for absolute survival rates by the expected survival, without taking possible random variation of the latter into account. The aim of this study was to empirically assess the validity of these commonly reported standard errors. Using data from the nationwide Finnish Cancer Registry, the authors calculated 5- and 10-year absolute, expected, and relative survival rates for patients with 25 common forms of cancer in Finland in 1989. The authors used bootstrap analysis to empirically assess the random error of absolute and relative survival rates and then compared the results with conventionally derived estimates of standard errors. The conventional and bootstrap standard errors were closely similar for all estimates of absolute survival. By contrast, the conventional estimates of standard errors of 5- and 10-year relative survival exceeded the bootstrap estimates by up to 17% and 32%, respectively. The authors conclude that conventional derivation may substantially overestimate standard errors for relative survival.

Age Distribution↗

Reduction in selective under-ascertainment bias in population-based estimates of cancer patient survival by age adjustment.

Selective under-ascertainment of cancer patients by cancer registries may bias population-based estimates of cancer patient survival. As prognosis is strongly age related for many forms of cancer, age adjustment of cancer survival rates, which is primarily used to enhance the validity of comparative analyses between cancer populations, might also effectively reduce this type of bias. We empirically assessed this potential "side-effect" of age adjustment using data from the Finnish Cancer Registry. Analyses of five-year absolute and relative survival for patients diagnosed in 1990-1994, and age adjustment to the age structure of patients diagnosed in 1985-1989, were used as examples. Various patterns of selective under-ascertainment were simulated, and the bias in crude and age adjusted five-year survival rates was compared. Age adjusted estimates were less biased in most scenarios, which may be an additional argument for application of age adjustment in the analysis and reporting of population-based cancer survival rates.

Adolescent↗

Chlamydial antibodies and risk of prostate cancer.

OBJECTIVE: We assessed the risk of prostate cancer by exposure to Chlamydia trachomatis. METHOD: Seven hundred thirty eight cases of prostate cancer and 2,271 matched controls were identified from three serum sample banks in Finland, Norway, and Sweden by linkage to the population based cancer registries. RESULTS: A statistically significant inverse association (odds ratio, 0.69; 95% confidence interval, 0.51-0.94) was found. It was consistent by different serotypes and there was a consistent dose-response relationship. CONCLUSION: C. trachomatis infection is not likely to increase the risk of prostate cancer. Whether the inverse relationship is true or due to difficulties in measuring the true exposure in prostatic tissue by serology, confounders or other sources of error remain open.

Adult↗

Human papillomavirus 16, 18, and 33 infections and risk of prostate cancer: a Nordic nested case-control study.

Epidemiologic evidence of sexual history has emerged as a consistently found risk factor for prostate cancer. Some studies have reported an association between human papillomavirus (HPV) infections and prostate cancer. We did a nested case-control study within cohorts of more than 200,000 men enrolled in three Nordic biobanking projects. Follow-up using cancer registry linkages identified 804 prospectively occurring prostate cancer cases. Four control subjects per case were randomly selected from eligible sets of matched subjects that were alive and free of cancer at the time of diagnosis of the corresponding case and were matched to cases on biobank cohort, age (+/-2 years), county of residence, and date of blood sampling (+/-2 months in the Finnish and Swedish cohorts, +/-6 months in the Norwegian cohort). The serum samples were analyzed by standard ELISAs for the presence of immunoglobulin G antibodies against HPV types 16, 18, and 33. The joint HPV-16/HPV-18/HPV-33 seroprevalence in the joint cohort was 13.4% (107 of 799) among cases and 14.0% (363 of 2,596) among controls (odds ratio, 0.94; 95% confidence interval, 0.74-1.19). There were no noteworthy differences when the data were analyzed by different HPV type, country, or antibody levels. Our data do not support an association between serologic markers of HPV-16, HPV-18, and HPV-33 infections and risk of prostate cancer.

Adult↗

Survival of in situ carcinoma of cervix uteri: a 50-year follow-up in Finland.

Preinvasive lesions of cervix uteri are regarded a curable disease despite some progression to invasive cancer. The ultimate outcome is not known. We estimated the 45-year survival of 12,655 patients with carcinoma in situ lesions diagnosed in 1953-2000 and reported to the Finnish Cancer Registry. Up to 30 years of follow-up there was about 1% decrease in cumulative relative survival per 5 years of follow-up. After that the excess mortality increased and the survival at 45 years was 84%. The 15-year survival was 100% in the patients under 30 at diagnosis and became the poorer the older the patient. Survival was 89% in the patients 60-74 at diagnosis. Women with carcinoma in situ are at substantial increased risk of death (>10%) only at high ages and independent of age at diagnosis.

Adult↗