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E Pukkala

Publications and source records attributed to E Pukkala.

At least 73 records · Page 4Linked to original sources
PubMed2000

Prospects for phase III-IV HPV vaccination trials in the Nordic countries and in Estonia.

BACKGROUND: oncogenic, i.e. high risk human papillomavirus (hrHPV) types are the major cause of invasive cervical cancer (ICC). Putatively licensable vaccines against the hrHPVs have been developed and are approaching clinical phase III trials that use persistent HPV infection as end point. Direct extension of the phase III trials towards long-term end points (ICC and its immediate precursors: carcinoma in situ and severe dysplasia, i.e. cervical intraepithelial neoplasia grade III, CINIII) is important, to avoid early contamination of the target population by opportunistic use of licensed HPV vaccines. Country-wide registration on population and health events in a stable population of 25 million make Estonia and the Nordic countries a unique venue for long-term evaluation of cervical cancer control measures. Mass-screening programmes exist in all Nordic countries, but not in Estonia. AIM: design of phase III-IV trials for evaluation of protection against ICC and CINIII by preventive HPV vaccines based on cancer registry follow-up. RESULTS: in the Nordic countries, population based randomisation of all 15-year-old women to the vaccination (vaccine and placebo) and reference cohorts entering conventional Pap-smear screening after a clinical phase III trial would assure comparability of the cohorts. Enrollment of 10094 vaccinees +10094 placebo vaccinees +30282 other hrHPV negative women without vaccination at the age of 16 would give 80% power for the demonstration of 70% vaccine efficacy (VE) against ICC in 20 years by cancer registry follow-up. On the other hand, vaccination of 8303 Estonian hrHPV negative women among the entire 15-year-old female birth cohort (about 10000 women) with an already licensed HPV vaccine would enable demonstration of 70% VE against ICC by 20 years of registry follow-up of these and comparable 16606 women identified among the 16-19-year-old birth cohorts. CONCLUSIONS: evaluation of the protective effect of an HPV vaccine against ICC is possible both in countries with or without mass-screening. The effects of vaccination on spread of different HPVs in the population would need to be monitored, especially in Estonia. Ethical aspects, cost-benefit evaluation and comparisons with other new means of cervical cancer control warrant further investigation.

Adolescent↗
PubMed2000

The effect of physical activity on breast cancer risk: a cohort study of 30,548 women.

BACKGROUND: In epidemiological studies abundant physical activity has been related to decreased breast cancer risk, though the results have been inconsistent. The purpose of this paper was to study the association of physical activity at leisure and commuting to work and incidence of breast cancer. METHODS: The study cohort consisted of 30,548 female participants of the Finnish adult health behaviour survey, based on annual random samples of Finns aged 15-64, collected in 1978-1993. By the end of 1995, 332 breast cancer cases had been diagnosed in the cohort. Relative risks of breast cancer were adjusted for age at survey, body mass index (BMI), education, length of follow-up, parity and age at first birth using Poisson regression models. RESULTS: Compared to women exercising less than once a week, the adjusted relative risk of breast cancer for women exercising once a week was 0.80 (95% confidence interval (CI): 0.58-1.10), for women exercising 2-3 times per week 0.92 (95% CI: 0.78-1.22) and for women exercising daily 1.01 (95% CI: 0.72-1.42). Women who reported commuting, walking or bicycling to work 30 min or more daily had slightly lower adjusted risk of breast cancer (RR: 0.87, 95% CI: 0.62-1.24) than women working at home, being unemployed or driving a car to working place. CONCLUSION: Although a small protective effect of regular physical activity for breast cancer incidence was found in physical activity when commuting to work, the role of the physical activity in breast cancer prevention is still an open question.

Adolescent↗
PubMed2000

Increased risk of secondary cancers in patients with primary cutaneous T cell lymphoma.

As putative etiologic factors of primary cutaneous T cell lymphomas may have a general cancerogenic effect, we wanted to assess the risk of secondary malignancies in 319 patients diagnosed with histopathologically verified cutaneous T cell lymphomas and reported to the Finnish Cancer Registry during the years 1953-95. Standardized incidence ratios were defined as the ratio of observed to expected numbers of cases. To obtain the expected numbers of cancer, age-, sex-, and period-specific Finnish incidence rates were applied to the appropriate person-years under observation. Ninety-five percent confidence intervals were calculated assuming a Poisson distribution. For the whole period, we detected 36 secondary cancers whereas 26 were expected (standardized incidence ratios 1.4, 95% confidence intervals 1.0-1.9). The overall risk of lung cancer was significantly increased (standardized incidence ratio was 2.7, 95% confidence intervals were 1.4-4.8); and in particular small-cell lung cancer showed high standardized incidence ratios (standardized incidence ratio was 8.5, 95% confidence intervals were 2.8-20). Also, the risk of lymphomas was elevated (standardized incidence ratios for Hodgkin and non-Hodgkin lymphomas combined were 7.0, 95% confidence intervals were 1.9-18). The incidence of other cancers was similar to the national ratios. An increased risk of secondary cancers and in particular small-cell cancer of the lung and lymphomas among patients with primary cutaneous T cell lymphoma is demonstrated. In clinical practice, lung cancer and lymphomas must be kept in mind when following up patients with cutaneous T cell lymphomas.

Adolescent↗
PubMed2000

Psoriasis, its treatment, and cancer in a cohort of Finnish patients.

This study was designed to estimate the relative cancer risk of patients with moderate to severe psoriasis, with reference to different treatments. A cohort of 5687 hospitalized patients with psoriasis obtained from the Finnish Hospital Discharge Register in 1973-84 was linked with the records of the Finnish Cancer Registry. Standardized incidence ratios for cancer were calculated by dividing the observed number of cases by the expected cases, which were based on the national sex-specific and age-specific cancer incidence rates. By the end of 1995, 533 cancer cases were observed in the cohort. The overall cancer incidence was increased (standardized incidence ratio 1.3, 95% confidence interval 1.2-1.4). The estimated relative risks were highest for Hodgkin's disease (standardized incidence ratio 3.3, 95% confidence interval 1.4-6.4), squamous cell skin carcinoma (standardized incidence ratio 3.2, 95% confidence interval 2.3-4.4), non-Hodgkin's lymphoma (standardized incidence ratio 2.2, 95% confidence interval 1.4-3.4), and laryngeal cancer (standardized incidence ratio 2.9, 95% confidence interval 1.5-5.0). The role of prior oral antipsoriatic medications or phototherapy on the development of these cancers was assessed in a nested case-control study, for which 67 cases and 199 sex and age matched controls were selected from the psoriasis cohort. The relative risks were estimated using conditional logistic regression analysis. Oral 8-methoxy-psoralen plus ultraviolet-A radiation therapy and the use of retinoids were associated with an increased risk of squamous cell skin carcinoma (relative risk adjusted for the other treatment variables 6.5, 95% confidence interval 1.4-31, and 7.4, 95% confidence interval 1.4-40, respectively), whereas none of the treatments could be linked with the occurrence of non-Hodgkin's lymphoma.

Carcinoma, Squamous Cell↗
PubMed2000

Cancer incidence among Finnish world class male athletes.

A cohort of 2269 male world class athletes from the years 1920-65 was followed up through the Finnish Cancer Registry for cancer incidence during 1967-95. There were 331 cases of cancer while the expected number based on the national cancer incidence rates was 404; the standardized incidence ratio (SIR) was 0.82 and its 95% confidence interval (CI) 0.73-0.91. There was a decreased risk of cancers of the lung (SIR 0.35, 95% CI 0.25-0.48), especially among endurance athletes (0.12, 0.01-0.41). This fits well with the low prevalence of smoking among the athletes. The SIR for kidney cancer was also significantly low (0.43, 0.16-0.93), possibly partly due to the better diet (more vegetables, less fat). Incidence of cancers not related to smoking was not reduced. None of the cancer sites showed a significant excess in the whole cohort but hurdlers had a significantly high relative risk of sarcomas of the bone and soft tissue which according to suggested causal mechanisms might be related e.g. to injuries during their active sport period. This as well as other observations without sound a priori hypotheses needs to be confirmed in more detailed analyses and in other data sets before final conclusions.

Adolescent↗
PubMed2000

Gynaecological infections as risk determinants of subsequent cervical neoplasia.

A longitudinal cohort study was carried out to determine whether gynaecological infections other than human papillomavirus (HPV) are also related to the subsequent increased risk of cervical neoplasia. The study comprised 19114 women attending the organized mass screening in Finland in 1985-1990 with cytologically detected HPV, Actinomyces, herpes simplex, Trichomonas vaginalis, or yeast. The women were followed-up for subsequent preinvasive lesions and invasive cancers until the end of 1994 by linkage to the nation-wide Cancer Registry. Standardized incidence ratios (SIR) with rates for the whole of Finland as reference and 95% confidence intervals (CI) were estimated. Trichomonas vaginalis and HPV were associated with a high relative risk of cervical cancer, SIR 6.4 (CI 3.7-10, preinvasive lesion and invasive cancer combined) and SIR 5.5 (CI 4.2 7.2, preinvasive lesion and invasive cancer combined), respectively. Herpes simplex was rarely detected, but the highest and statistically most significant point estimate was observed (SIR 12, CI 2.4-34, preinvasive lesion and invasive cancer combined). Neither Actinomyces nor yeast was associated with a significantly increased risk of cervical cancer. None of these results could be accounted for by the confounding effect of the other infections. Our results, based on a prospective design, lead us to propose that Trichomonas vaginalis and herpes simplex virus are also predictors for cervical neoplasia.

Adult↗
PubMed2000

Is the subsite distribution of laryngeal cancer related to smoking habits?

In Finland traditionally as many as two-thirds of laryngeal cancers have been considered to be supraglottic, while in other countries the majority are glottic. The Finnish observation is based on clinical series diagnosed and treated mainly before the 1960s. The aim of our study was to evaluate the present situation. This study consisted of 279 patients treated in Eastern Finland between 1975 and 1994 and included 145 (52%) glottic, 124 (44%) supraglottic and 10 (4%) subglottic tumours in 260 (93%) men and 19 (7%) women. During this study period, the proportion of glottic tumours remained stable in men but increased in women. The change in smoking habits seems to be the most important reason for the shift from supraglottic to glottic tumours.

Adult↗
PubMed2000

Attack rates of human papillomavirus type 16 and cervical neoplasia in primiparous women and field trial designs for HPV16 vaccination.

BACKGROUND: Identification of human papillomavirus type 16 (HPV16) as the major risk factor for cervical neoplasia, and mass production of DNA free HPV capsids have paved the way to preventive vaccination trials. Design of such trials requires reliable attack rate data. OBJECTIVE: Determination of (1) HPV16 and (2) cervical neoplasia attack rates in primiparous women. Estimation of actuarial sample sizes for HPV16 vaccination phase IV trials. DESIGN: A longitudinal cohort study. METHODS: Population based Finnish Maternity Cohort (FMC) and Finnish Cancer Registry (FCR) were linked for the identification of two cohorts of primiparous women: (1) a random subsample of the FMC: 1656 women with two pregnancies between 1983-9 or 1990-6 and living in the Helsinki metropolitan area, and (2) all 72,791 primiparous women living in the same area during 1983-94. Attack rate for persistent HPV16 infection (1) was estimated in 1279 seronegative women by proportion of seroconversions between the first and the second pregnancy. Comparable 10 year cumulative incidence rate (CR) of cervical intraepithelial neoplasia grade III and cervical cancer (CIN III+) (2) was estimated based on cases registered at the FCR during 1991-4. RESULTS: The HPV16 attack rates were 13.8% (< 18 years), 7.0% (18-19 years), 2.3% (21 years), 2.4% (23 years), and 4.5% (< 25 years). Number of vaccinees required for a 5 year efficacy trial with persistent HPV16 infection as the end point ranged between 1000 and 3900, assuming 80% power, 90%-70% vaccine efficacy (VE), and misclassification. The CRs of CIN III+ were 0.33% (< 18 years), 0.44% (18-19 years), 0.21% (20-24 years), and 0.28% (< 25 years). Number of vaccinees required for a 10 year efficacy trial with HPV16 positive CIN III+ as the end point was 15,000 assuming 80% power, 90% VE, and 75% aetiological fraction of CIN III+ for HPV16. CONCLUSIONS: The attack rates of HPV16 and CIN III+ identify primiparous women under 25 years of age among target populations for postnatal HPV vaccination at phase II/III trials.

Adolescent↗
PubMed2000

Second cancers among long-term survivors of Hodgkin's disease diagnosed in childhood and adolescence.

PURPOSE: To quantify the risk of second cancers among long-term survivors of Hodgkin's disease (HD) diagnosed before 21 years of age and to explore sex-, age-, and site-related differences. PATIENTS AND METHODS: We analyzed data from 5,925 pediatric HD patients, including 2,646 10-year and 755 20-year survivors, who were reported to 16 population-based cancer registries in North America and Europe between 1935 and 1994. RESULTS: A total of 157 solid tumors (observed/expected ratio [O/E] = 7.0; 95% confidence interval [CI], 5.9 to 8.2.) and 26 acute leukemias (O/E = 27.4; 95% CI, 17.9 to 40. 2) were reported. Risk of solid tumors remained significantly increased among 20-year survivors (O/E = 6.6, observed [O] = 40, cumulative risk = 6.5%) and persisted for 25 years (O/E = 4.6, O = 15, cumulative risk = 11.7%). Temporal trends for cancers of thyroid, female breast, bone/connective tissue, stomach, and esophagus were consistent with the late effects of radiotherapy. Greater than 50-fold increased risks were observed for tumors of the thyroid and respiratory tract (one lung and one pleura) among children treated before age 10. At older ages (10 to 16 years), the largest number of second cancers occurred in the digestive tract (O/E = 19.3) and breast (O/E = 22.9). Risk of solid tumors increased with decreasing age at HD on a relative but not absolute scale. CONCLUSION: Children and adolescents treated for HD experience significantly increased risks of second cancers at various sites for 2 to 3 decades. Although our results reflect the late effects of past therapeutic modalities, they underscore the importance of lifelong follow-up of pediatric HD patients given early, more aggressive treatments.

Adolescent↗
PubMed2000

Hemangioblastomas of the retina: impact of von Hippel-Lindau disease.

PURPOSE: To assess the prevalence of von Hippel-Lindau (VHL) disease and prognosis of vision in patients with retinal hemangioblastomas (HBs). METHODS: Thirty-six consecutive patients with retinal HBs were treated at Helsinki University Hospital between 1974 and 1998. Detailed neurologic, ophthalmologic, and radiologic examinations; pedigree; mutation analyses; and collection of all relevant clinical, imaging, operative, and autopsy data were performed to identify VHL. RESULTS: The median follow-up time was 10 years. No patient was lost to follow-up. There were three patient groups: 1) 11 patients with clinically definite VHL; 2) 10 patients with clinically suspected VHL with more than one retinal HB (5/10) or visceral cysts (5/10), but with no family history, no detected germ-line mutations, and no VHL-related neoplasms; and 3) 15 patients without VHL with a single retinal HB but no other data suggestive of VHL. In the 11 patients with definite VHL, retinal HBs were detected at a median age of 27 years versus 40 years in the 15 non-VHL patients, and 21 of the 22 eyes were affected. Two VHL patients were totally blind at the end of follow-up compared with one legally blind patient with suspected VHL, but none of the non-VHL patients was blind. The clinical appearance of HBs did not differ among the patient groups. CONCLUSIONS: The prevalence of VHL among patients with retinal HBs was 30% to 58% (11-21 of 36). Visual prognosis was more favorable in non-VHL than VHL patients. All patients with retinal HB should undergo thorough VHL exclusion.

Adolescent↗
PubMed2000

Risk of cervical cancer subsequent to a positive screening cytology: follow-up study in Finland.

BACKGROUND: The purpose of the study was to estimate subsequent incidence of cervical cancer among women with positive cytology followed by negative histology. METHODS: This was a longitudinal cohort study involving about 80,000 women with class II, III, IV or V cytology at the organized mass screening in Finland in 1971 1990. Follow-up through the Finnish Cancer Registry started from the fifth month following the initial screening and ended on December 31, 1995. RESULTS: Standardized incidence ratios (SIR) of invasive cervical cancer varied from 2.2 (class II) to 19 (class V), and SIRs of preinvasive lesion varied from 3.0 (class II) to 20 (class V) compared to the risk among the total Finnish female population of same age and calendar period. The relative risk was greatest during first years of follow-up for both preinvasive and invasive cervical lesions, and it remained significantly high over 5 years of follow-up. For women with class II cytology there were peaks in relative risk in the years of subsequent rescreenings. CONCLUSION: Women with positive cytology have a high relative risk of cervical cancer even when excluding the cancers found at screening; the high relative risk is persistent for more than 5 years, and therefore these women should be kept under close surveillance and repeated smears should be taken with relatively short intervals.

Adult↗
PubMed2000

A genetic epidemiological study of hereditary prostate cancer (HPC) in Finland: frequent HPCX linkage in families with late-onset disease.

Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPC1 at 1q24-q25 (OMIM #601518) and HPCX at Xq27-q28 (OMIM #300147). Genetically homogeneous populations, such as that of Finland, and distinct subsets of families may help to minimize the genetic heterogeneity that complicates the genetic dissection of complex traits. Here, the role of the HPC1, and HPCX loci in a series of Finnish prostate cancer families was studied, especially in subgroups of families defined by age, number of affected cases, and the mode of disease transmission. DNA samples were collected from 57 Finnish HPC families with at least two living prostate cancer patients. Linkage analysis was carried out with 39 microsatellite markers for the HPC1 region and 22 markers for the HPCX region. The maximum two-point LOD score for the HPCX was 2.05 (marker DXS1205, at theta = 0.14), whereas HPC1 LOD scores were all negative. In HOMOG3R analyses, significant evidence of heterogeneity was observed. Subgroup analyses performed to explore the nature of this heterogeneity indicated that families with no male-to-male (NMM) transmission and a late age of diagnosis (>65 years) accounted for most of the HPCX-linked cases. The maximum HPCX LOD score in this subgroup was 3.12 (theta = 0.001). Nonparametric sibling pair analyses gave a peak LOD score of 3.04 (P < 0.000093) for the NMM transmission subgroup. No subgroup showed any positivity for HPC1. This study suggests that the HPCX-linked prostate cancer families represent a distinct subgroup characterized by NMM transmission of disease and late age of diagnosis.

Age of Onset↗
PubMed1999

Genetic predisposition, environment and cancer incidence: a nationwide twin study in Finland, 1976-1995.

Twin studies integrate genetic and environmental (including physical environment and life-style) information by comparing monozygotic and dizygotic twins for the occurrence of disease. Our objectives were to compare cancer incidence in twins with national rates and to estimate both the probability that co-twins of affected twins may develop cancer and the importance of genetic predisposition and environment in cancer development. The nationwide record linkage of the Finnish Twin Cohort Study, the Finnish Cancer Registry and the Central Population Register allowed the follow-up of 12,941 same-sexed twin pairs for incident primary cancers from 1976 to 1995. Zygosity was determined by use of a validated questionnaire in 1975. Methods included calculation of standardized incidence ratios and concordances and fitting of structural equation models. A total of 1,613 malignant neoplasms occurred in the cohort. The overall cancer incidence among twins resembled that among the general population. Monozygotic co-twins of affected twins were at 50% higher risk than were dizygotic co-twins. Based on genetic modeling, inherited genetic factors accounted for 18% (95% confidence interval 4-32%) of the liability in inter-individual variation in the risk of overall cancer, while non-genetic factors shared by twins accounted for 7% (0-16%) and unique environmental factors for 75% (65-85%). Our results appear to exclude a contribution greater than one-third for genetic predisposition in the development of cancer in the general population, thus pointing to the earlier confirmed substantial role of environment.

Adult↗
PubMed1999

Effect of organised screening on cervical cancer incidence and mortality in Finland, 1963-1995: recent increase in cervical cancer incidence.

A nation-wide screening programme for cervical cancer started in Finland gradually from 1963 onwards. By the beginning of the 1990s, there had been a decrease of 80% both in the age-adjusted incidence of and mortality from cervical cancer. To describe the recent patterns in cervical cancer incidence and mortality and evaluate their differentials in relation with the organised screening activities, we have updated the material on the cervical cancer incidence and mortality as well as mass-screening activities up to the year 1995. Based on the files of the Finnish Cancer Registry, there is a striking increase of about 60% in the incidence of cervical cancer during the last 4 years of the study period among women below 55 years of age. The mortality rates are still decreasing. There is no overall decrease over recent years in the coverage of the programme invitations or smears taken. Incidence of invasive cancer and of moderate and severe dysplasia as detected in mass screening have increased. As to the interpretation, changes in the risk factors, such as in sexual behaviour and smoking habits, over the decades might partly explain increasing trends in cervical cancer incidence. As the change in incidence was relatively abrupt, inadequacies or changes in the effectiveness in the screening programme, particularly among young women, may also have contributed. Expanding the coverage of and attendance in the pap-screening programme among women in young target ages would still be effective. Increasing emphasis on quality assessment in screening is also needed.

Adult↗
PubMed1999

The cost-effectiveness of nationwide breast carcinoma screening in Finland, 1987-1992.

BACKGROUND: The aim of this study was to evaluate the cost-effectiveness, from a societal perspective, of the Finnish nationwide breast carcinoma screening program. METHODS: The effects were measured in life-years saved from 1987 to 2020, using data from the nationwide program to the end of 1992. A total of 90,000 women ages 50-59 were invited for screening during the years 1987-89. The total number of participants screened was 76,000. The screening interval was 24 months, with follow-up to the end of 1992. From the beginning of 1993, the estimation model used parameters based on published studies and national cancer statistics. Data on health care and non-health care costs and time costs were obtained from internal accounts of screening units, published studies, national statistics, health market sources, and a questionnaire completed by a sample of 1400 screening attendees. The discount rate, the annual rate of time preference over future costs and life-years saved, was 3%. The main outcome measure was the cost per life-year saved. RESULTS: The estimated number of life-years of life saved was 578, of which 8% occurred 1987-1992. The estimated life-years saved per 1000 screenings was 3.2. The total costs were $11 million in U.S. dollars, i.e., $14.3 million per 100,000 participants. CONCLUSIONS: The cost of breast carcinoma mammographic screening per life-year saved was $18,955 in the base case, ranging from $15,502 to $40,308 according to the different models used in analysis.

Breast Neoplasms↗