Timo Hakulinen

Factors Affecting Operative and Excess Long-term Mortality in 935 Patients with Intracranial Meningioma

Between 1953 and 1980, a total of 935 patients underwent surgery for intracranial meningioma in the Department of Neurosurgery of the Helsinki University Hospital. The patients were followed up until death or the end of the year 1987. The cumulative observed survival rate was 91% at 3 months, 89% at 1 year, and 63% at 15 years. The relative survival rate, that is, the ratio of the the observed and the expected rates, was 91% at 3 months, 89% at 1 year, and 78% at 15 years. Significant risk factors for operative mortality (7%) for the 652 patients operated on from 1966 to 1980 were poor preoperative clinical condition, absence of epilepsy, old age, incomplete tumor removal, pulmonary embolism, and an intracranial hematoma requiring evacuation. For those 828 patients who survived the first postoperative year, the factors predicting an excess risk of death for up to 15 years were incomplete tumor removal, poor pre- and postoperative clinical condition, anaplasia of the tumor, and hyperostosis. Patients whose tumors were not completely removed had a 4.2-fold relative excess risk of death as compared with patients whose tumors were completely removed, and patients who had malignant tumors had a 4.6-fold risk as compared with those who had benign tumors.

Drinking water chlorination and cancer – a historical cohort study in Finland

Chlorinationof water richin organic material is knownto produce a complexmixture of organochlorine compounds, including mutagenic and carcinogenicsubstances. A historical cohort study of 621,431 persons living in 56 townsin Finland was conducted in order to assess the relation between historicalexposure to drinking water mutagenicity and cancer. Exposure to quantity ofmutagenicity was calculated on the basis of historical information of rawwater quality and water treatment practices using an empirical equationrelating mutagenicity and raw water pH, KMnO4 value andchlorine dose. Cancercases were derived fromthe population-based FinnishCancer Registryandfollow-up time in the study started in 1970. Age, gender, time period,social class, and urban residence were taken into account in Poissonregression analysis of the observed numbers of cases using expected numbersof cases standardized for age and gender as a basis. Excess risks werecalculated using a continuous variab le for mutagenicity for 3,000 net rev/lexposure representing an average exposure in a town using chlorinated surfacewater. After adjustment for con-founding, a statistically significant excessrisk was observed for women in cancers of the bladder (relative risk [RR] =1.48, 95 percent confidence interval [CI] = 1.01-2.18), rectum (RR = 1.38, CI= 1.03-1.85), esophagus (RR = 1.90, CI = 1.02-3.52), and breast (RR = 1.11,CI = 1.01-1.22). These results support the magnitude of excess risks forrectal and bladder cancers found in earlier epidemiologic studies onchlorination by-products and give additional information on exposure-responseconcerning the mutagenic compounds. Nevertheless, due to the public healthimportance of water chlorination, uncertainty related to the magnitude ofobserved risks, and the fact that excess risks were observed only for women,the results of the study should be interpreted withcaution.

Prospective seroepidemiological evidence that human papillomavirus type 16 infection is a risk factor for oesophageal squamous cell carcinoma

The genome of the major type of human papillomavirus that is associated with anogenital cancer, HPV16, is occasionally found in non-genital cancers, such as oesophageal cancer and various cancers of the head and neck,1 but it is not clear whether human papillomavirus infection is a measurable risk factor for these cancers. Since seropositivity for HPV16 capsids has documented specificity for HPV16 infection,2 serological testing can provide information on whether HPV16 infection is a risk factor for disease development. Previously we found that HPV16 capsid seropositivity was a risk factor for both cervical and anal cancers at odds ratios of 9.5 and 30.4 respectively.3 Therefore we designed a prospective study to assess whether HPV16 infection is also a risk factor for oesophageal or head and neck cancers. During 1968-72 the mobile clinic …

Prospective seroepidemiological study of role of human papillomavirus in non-cervical anogenital cancers

Abstract Objective: To evaluate the association between infection with the major oncogenic types of human papillomavirus and the risk of developing non-cervical anogenital cancers in a cohort followed up prospectively. Design: Data from two large serum banks to which about 700 000 people had donated serum samples were followed up for a mean of 8 years. People who developed non-cervical anogenital cancers during follow up were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Within this cohort a nested case-control study was conducted based on the serological diagnosis of infection with human papillomavirus types 16, 18, and 33. Subjects: 81 cases and 240 controls matched for sex, age, and storage time of serum samples. Main outcome measures: Odds ratios of developing non-cervical anogenital cancers in presence of IgG antibodies to specific micro-organisms. Results: Subjects seropositive for human papillomavirus type 16 had an increased risk of developing non-cervical anogenital cancers (odds ratio 3.1 (95% confidence interval 1.4 to 6.9)). Subjects seropositive for type 33 also had an increased risk (odds ratio 2.8 (1.0 to 8.3)) but not significantly after adjustment for infection with type 16. Seropositivity for human papillomavirus type 16 was associated with an increased risk of developing vulvar and vaginal cancers (odds ratio 4.5 (1.1 to 22)) and a strongly increased risk of developing preinvasive vulvar and vaginal lesions (odds ratio ∞ (3.8 to ∞)). Seropositivity for human papillomavirus type 18 increased the risk of developing preinvasive lesions (odds ratio 12 (1.2 to 590)). High, but non-significant odds ratios for types 16 and 33 were seen for penile cancers. Conclusions: This study provides prospective seroepidemiological evidence that infection with human papillomavirus type 16 confers an increased risk of developing non-cervical genital cancers, particularly vulvar and vaginal cancers. Key messages Human papillomavirus has emerged as a leading infectious cause of human cancer, notably cervical and other anogenital cancers, but prospective epidemiological evidence of causality is lacking This study used six million person years of follow up to investigate the relation between seropositivity for human papillomavirus and the development of non-cervical anogenital cancers Infection with human papillomavirus type 16 increases the risk of developing non-cervical genital cancers, particularly vulvar and vaginal cancers Infection with human papillomavirus type 16 should be considered in future intervention strategies for cervical and other genital cancers

Long-term survival of 1986 patients with intracranial meningioma diagnosed from 1953 to 1984 in Finland. Comparison of the observed and expected survival rates in a population-based series

Intracranial meningioma was diagnosed and histologically verified in 1986 patients, 597 men and 1389 women, between 1953 and 1984 in Finland. The closing date of this survival study was December 31, 1987, and the follow‐up was complete. Meningiomas, usually slowly growing and surgically curable benign tumors, caused considerable short‐term mortality, with a relative survival rate (RSR) of 83% at 1 year, and slight but continual long‐term mortality, with RSR of 71% at 15 years. From 1979 to 1984, when computed tomography (CT) was available, the mortality at 3 months for the patients who had surgical procedures was 2% in those younger than 45 years and 10% in those older than 64 years; patients who did not have operations had 1‐year mortality of 61%. The short‐term and long‐term excess mortalities are associated significantly with old age, no surgical procedure, and the period of diagnosis; the long‐term excess mortality also is associated with male gender.

Drinking water mutagenicity and leukemia, lymphomas, and cancers of the liver, pancreas, and soft tissue

The acid, mutagenic compounds present in chlorinated drinking water have caused concern about the potential cancer risk of drinking-water mutagenicity. In this study, past exposure to drinking water mutagenicity was assessed for the years 1955 and 1970 in 56 Finnish municipalities, using the historical information on water quality and treatment. Cases of leukemia, lymphomas, and cancers of the liver, pancreas, and soft tissue were derived from the Finnish Cancer Registry for two periods: 1966-1976 and 1977-1989. Relative risk was estimated in an additive Poisson regression model, adjusting for age, gender, social class, urbanity, and time period. In an ordinary municipality that was supplied with mutagenic drinking water (3,000 net rev/l), the observed exposure-response relationship indicated a relative risk of 1.1-1.3 for lymphomas and 1.1-1.2 for pancreatic cancer, compared with municipalities in which nonmutagenic drinking water was consumed.

A simple non‐linear model in incidence prediction

A simple model is proposed for incidence prediction. The model is non-linear in parameters but linear in time, following models in environmental cancer epidemiology. Assuming a Poisson distribution for the age and period specific numbers of incident cases approximate confidence and prediction intervals are calculated. The major advantage of this model over current models is that age-specific predictions can be made with greater accuracy. The model also preserves in the period of prediction the age pattern of incidence rates existing in the data. It may be fitted with any package which includes an iteratively reweighted least squares algorithm, for example GLIM. Cancer incidence predictions for the Stockholm-Gotland Oncological Region in Sweden are presented as an example.

A population‐based study on the incidence and survival rates of 3857 glioma patients diagnosed from 1953 to 1984

Intracranial glioma was diagnosed during the patients life and histologically verified in 3857 patients between 1953 and 1984 in Finland. Their survival up to the end of 1987 was analyzed, the follow‐up being complete. The treatment was by operation in 1193 cases, radiation in 459 cases, both operation and radiation in 1486 cases, and neither operation nor radiation in 719 cases. The 1‐year, 5‐year, 10‐year, and 15‐year cumulative relative survival rates were 0.53, 0.29, 0.20, and 0.18, respectively. The newborn to 14‐year‐olds lost 56% of their life expectancy; the 15‐year‐olds to 44‐year‐olds, 71%; the 45‐year‐olds to 64‐year‐olds, 88%; and the 65‐year‐olds to 99‐year‐olds, 91%. According to the model with the best fit in regression analysis the prognosis was significantly better among young, recently diagnosed patients who had undergone both operation and radiation.

Substantial variation in therapy for colorectal cancer across Europe: EUROCARE analysis of cancer registry data for 1987

To provide a quantitative description of the treatments applied to malignant colorectal cancer across Europe, we analysed all cases (11,333) of colorectal cancer registered in 1987 by 15 Cancer Registries in eight European countries. In a third of cancer registries, therapy was known for all cases, in the others 1-15% of registrations lacked treatment information. Eighty per cent of all patients received surgical resection, ranging from 58% (Estonia) to 92% (Tarn). The proportion of resections decreased with advancing age (85-73% for colon cancer; 85-70% for rectal cancer for < 65 years to > 74 years, respectively). Only 4% of colon cancer patients received adjuvant or palliative chemotherapy, range 1-12%. Sixteen per cent of rectal cancer patients received radiotherapy with great inter-registry variability (1-43%). Since the proportion of surgically resected patients correlated positively with the 5-year relative survival probability reported by the recently published EUROCARE study, this may be part of the explanation for the major differences in survival for these cancers among different European populations. The most likely determinant of this correlation is stage at diagnosis, but, quality of, and access to surgery, as well as access to endoscopy, may differ among countries and registry areas, and these may also contribute to inter-country survival differences.

Do morphology and stage explain the inferior lung cancer survival in Denmark

Danish lung cancer patients diagnosed during 1983-1987 experienced 5-yr relative survival rates 2-7% inferior to patients in the other Nordic countries, despite the similarity of cancer registration and healthcare systems in the Nordic countries. Is the inferior relative survival in Denmark due to differences in morphology or stage of lung cancers? The present study compared in detail the survival of 92,719 patients diagnosed with lung cancer during 1978-1992 in Denmark, Finland, and Norway. In particular, differences in morphology and extent of disease were studied. A poor survival rate for small cell anaplastic lung carcinoma compared with all other morphologies was confirmed. However, this could not explain the relative survival differences observed between countries. Extent of disease was the most important predictor of survival. Part of the observed survival differences could be explained by a less favourable stage distribution in Denmark, combined with a slightly lower relative survival rate for those with metastatic disease. Differences in treatment are unlikely to explain the findings, although delays in diagnosing and treating patients in Denmark compared with neighbouring countries could partially explain the lower patient survival in Denmark. In conclusion, the main factor in the lower survival rate in Denmark is unfavourable stage distribution.