Kari Pasanen

Seroprevalence atlas of infections with oncogenic and non‐oncogenic human papillomaviruses in Finland in the 1980s and 1990s

Vaccines against high‐risk (hr) human papillomaviruses (HPVs) causing cervical cancer may soon be licensed. Thus, nature of HPV epidemics needs to be studied now. Random sampling for studies on HPV epidemiology was done from all 230,998 women belonging to the population‐based Finnish Maternity Cohort and having a minimum of 2 pregnancies between 1983 and 1994. First pregnancy serum specimens were retrieved for 7,805 subjects, and were analyzed for antibodies to HPV6/11, 16 and 18 with standard ELISAs. HPV16 seroprevalence almost doubled from the 1980s to the 1990s, and the epidemic spread to new areas in 23–31 year olds, i.e. the bulk of pregnant female population in the southwest part of the country. The HPV16 epidemic in the 14–22 year olds in 1983–1988 (1961–1974 birth cohorts) and in the 23–31 year olds in 1989–1994 (1958–1971 birth cohorts) overlapped with strong clustering of HPV16 and HPV18 infections in the latter (odds ratio 8.0, 95% confidence interval 6.6–9.7). Similar clustering of HPV16 and HPV6/11 infections was not found. The epidemic and the clustering may be due to high transmission probability of the hrHPV types and increase in sexual activity of the index birth cohorts.

Mortality Among Population With Exposure to Industrial Air Pollution Containing Nickel and Other Toxic Metals

Objective: To assess disease mortality among people with exposure to metal-rich particulate air pollution. Methods: We conducted a cohort study on mortality from 1981 to 2005 among 33,573 people living near a nickel/copper smelter in Harjavalta, Finland. Nickel concentration in soil humus was selected as an indicator for long-term exposure. Relative risks—adjusted for age, socioeconomic status, and calendar period—were calculated for three exposure zones. Results: The relative risks for diseases of the circulatory system by increasing exposure were 0.93 (95% confidence interval = 0.79 to 1.09), 1.20 (1.04 to 1.39), and 1.18 (1.00 to 1.39) among men and 1.01 (0.88 to 1.17), 1.20 (1.04 to 1.38), and 1.14 (0.97 to 1.33) among women. Exclusion of smelter workers from the cohort did not materially change the results. Conclusions: Long-term environmental exposure to metal-rich air pollution was associated with increased mortality from circulatory diseases.

Geographic distribution of cervical cancer-associated human leucocyte antigens and cervical cancer incidence in Finland.

Cervical cancer (CxCa) is a long-term sequelae caused by persistent human papillomavirus (HPV) infection. Genetic susceptibility to the persistent infection and CxCa is associated with certain human leucocyte antigen (HLA) types. The same susceptibility genes may also determine whether a woman will be protected against the persistent infection and against CxCa by HPV vaccination or not. A systematic review of literature identified following HLAs to be associated with CxCa: A11 (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.1–2.0); B7 (1.5, 1.1–2.0); B15 (0.6, 0.4–0.8); DR2 (1.2, 1.1–1.4) and DR6 (0.6, 0.5–0.8). In the Caucasian population, HLA-B7 and DR6, and DR2 and B15 antigens showed at least borderline associations. In view of a bone marrow donor registry at the Finnish Red Cross and the Finnish Cancer Registry, we created geographic distribution maps of index HLA frequencies and CxCa incidence in the fertile-aged Finnish population. Increased incidence of CxCa was found in a region of western coastal Finland, where frequency of two CxCa susceptibility genes (HLA-DR2 and B7) was increased, and frequency of one CxCa resistance gene (HLA-B15) was decreased. Whether or not HLA type determines also regional susceptibility to persistent HPV infection, and the success of HPV vaccination in preventing both the persistent infection and CxCa warrants further investigation.

Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides-Cutaneous T-cell lymphoma: Clinical implications

Mycosis fungoides (MF) is the most common variant of primary cutaneous T‐cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia‐inducible factor 1 alpha (HIF‐1α) may regulate FoxP3 expression; however, it is unknown whether HIF‐1α is expressed in the CD4+ T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF‐1α and FoxP3 in CD4+ T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4+ T cells with an aberrant phenotype among early stage MF patients. HIF‐1α was overexpressed in these CD4+ T cells. In addition, we found a decrease in the percentage of FoxP3+ cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF‐1α and FoxP3 expression. Skin HIF‐1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF‐1α degradation increases the percentage of FoxP3+ T cells in skin lesions. Our results suggest that overexpression of HIF‐1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.

Chernobyl fallout and cancer incidence in Finland.

Twenty‐five years have passed since the Chernobyl accident, but its health consequences remain to be well established. Finland was one of the most heavily affected countries by the radioactive fallout outside the former Soviet Union. We analyzed the relation of the estimated external radiation exposure from the fallout to cancer incidence in Finland in 1988–2007. The study cohort comprised all ∼3.8 million Finns who had lived in the same dwelling for 12 months following the accident (May 1986–April 1987). Radiation exposure was estimated using data from an extensive mobile dose rate survey. Cancer incidence data were obtained for the cohort divided into four exposure categories (the lowest with the first‐year committed dose <0.1 mSv and the highest ≥0.5 mSv) allowing for a latency of 5 years for leukemia and thyroid cancer, and 10 years for other cancers. Of the eight predefined cancer sites regarded as radiation‐related from earlier studies, only colon cancer among women showed an association with exposure from fallout [excess rate ratio per increment in exposure category 0.06, 95% confidence interval (CI) 0.02–0.11]. No such effect was observed for men, or other cancer sites. Our analysis of a large cohort over two decades did not reveal an increase in cancer incidence following the Chernobyl accident, with the possible exception of colon cancer among women. The largely null findings are consistent with extrapolation from previous studies suggesting that the effect is likely to remain too small to be empirically detectable and of little public health impact.

Incidence of Pediatric Inflammatory Bowel Disease in Finland: An Environmental Study.

Objectives: The aim of this study was to explore possible environmental factors behind the regional differences in the incidence of pediatric inflammatory bowel disease (IBD). Methods: All of the patients diagnosed with IBD who were aged 0 to 14 years in Finland between 1987 and 2003 were identified from the Social Insurance Institution database. Finland was divided into squares of 250 × 250 m, and spatial variations of incidence rates were evaluated accordingly. The role of the environmental determinants (pediatric population density, agricultural industry, chemical contaminants of tap water and proximity to the sea or paper mills) in the geographic variations of the incidence rates was evaluated. Results: During the study period, the overall incidence of pediatric IBD was 6.5 of 100,000 (95% confidence interval [CI] 6.1–6.9). The incidence in very sparsely populated areas (⩽10 person-years per 250 × 250 m2) was 9.2 of 100,000 (95% CI 6.3–13.1) and 5.6 of 100,000 (95% CI 4.8–6.4) in the districts with the highest population density (>800 person-years per 250 × 250 m2). A nonsignificant trend toward the same direction was also seen for ulcerative colitis (trend P = 0.09). Chemical contaminant concentrations of tap water, residence near the seaside, or proximity to paper mills were not associated with the incidence of pediatric IBD. Conclusions: Our findings suggest higher incidence rates of pediatric IBD in the districts with low compared with high density of child population, but the differences cannot be explained by variations in the environmental exposures evaluated here.

A GIS-based method for the selection of the location of residence

Homebuyers are usually interested in both the accessibility of services and the quality of the local environment, and real estate agents frequently offer some web-based systems for home searches. There is however hardly any information about the quality of local living environment in those web-based systems. The purpose of this study was to develop a method for homebuyers, adaptable to the environmental variables of interest to homebuyers when selecting a home location. In this paper, a multicriteria spatial analysis method is proposed and demonstrated for the homebuyers’ selection process, using data from the City of Kuopio, Finland. Several spatial variables are applied, including environmental and service factors in the home searching process. A geographical information system (GIS) is used for creating maps for decision variables and mapping suitable areas. The method for ranking alternative dwellings is based on the difference between levels of the decision variables for each dwelling and the target levels given by the user. The method presented in this paper is adaptable to other geographical and social contexts. This decision analysis tool will be useful for both customers and real estate agents, and can also be used for city planning as a participatory-GIS (P-GIS) tool. It introduces new possibilities in the home selection process. The availability of spatial data on the living environment in the web-based services for homebuyers is likely to have effects on customers’ requirements and house markets, and also promote better spatial city organization in the long run.

Chernobyl fallout and cancer incidence in Finland 1988-2007: Chernobyl and Cancer in Finland

Twenty‐five years have passed since the Chernobyl accident, but its health consequences remain to be well established. Finland was one of the most heavily affected countries by the radioactive fallout outside the former Soviet Union. We analyzed the relation of the estimated external radiation exposure from the fallout to cancer incidence in Finland in 1988–2007. The study cohort comprised all ∼3.8 million Finns who had lived in the same dwelling for 12 months following the accident (May 1986–April 1987). Radiation exposure was estimated using data from an extensive mobile dose rate survey. Cancer incidence data were obtained for the cohort divided into four exposure categories (the lowest with the first‐year committed dose <0.1 mSv and the highest ≥0.5 mSv) allowing for a latency of 5 years for leukemia and thyroid cancer, and 10 years for other cancers. Of the eight predefined cancer sites regarded as radiation‐related from earlier studies, only colon cancer among women showed an association with exposure from fallout [excess rate ratio per increment in exposure category 0.06, 95% confidence interval (CI) 0.02–0.11]. No such effect was observed for men, or other cancer sites. Our analysis of a large cohort over two decades did not reveal an increase in cancer incidence following the Chernobyl accident, with the possible exception of colon cancer among women. The largely null findings are consistent with extrapolation from previous studies suggesting that the effect is likely to remain too small to be empirically detectable and of little public health impact.