Pär Sparén

Survival trend after invasive cervical cancer diagnosis in Sweden before and after cytologic screening : 1960-1984

Background. Cytologic screening can reduce mortality from cervical cancer by detection and removal of premalignant lesions. Conceivably, mortality is further reduced because more women with invasive disease are diagnosed at an earlier. curable stage. This hypothesis can be assessed in Sweden, where population‐based screening programs were introduced successively over about a decade starting in 1964.

Trends in tumour characteristics and survival of malignant melanoma 1960-84: a population-based study in Sweden.

In Sweden, improvement in survival rates of patients with cutaneous malignant melanoma has counteracted the increase in incidence to produce a moderate rise in mortality. Our aim was to determine the possible impact of drift in diagnostic criteria, earlier diagnosis and changing biological features of the tumours upon trends in survival. We studied a stratified sample of 528 patients diagnosed between 1960 and 1984 in a strictly defined geographical region. No evidence of drift in diagnostic criteria was found. The proportion of patients with invasion level Clark II increased from 3.2% in 1960-64 to 22.5% in 1980-84, the proportion of thin melanomas (< or = 0.75 mm) increased from 9.4% to 31.5% and the tumour thickness decreased significantly between each 5 year period of diagnosis. These changes are most likely the results of earlier diagnosis. However, changes in tumour characteristics have occurred, since the proportion of superficially spreading malignant melanoma increased from 35% in 1960-64 to 51% in 1980-84 and the proportion of acral lentiginous melanoma decreased from 11% to 2%. The proportion of nodular melanomas remained fairly constant. The proportion of tumours with lymphocytic reaction did not change, whereas those with histological regression increased slightly. Proportional hazards analyses showed a significantly lower survival in patients diagnosed in 1960-64 but no apparent trend after 1965. This finding remained after adjustment for all studied clinical and histopathological factors which point towards changes in unmeasured biological features of the disease.

Efficiency of organised and opportunistic cytological screening for cancer in situ of the cervix

Cervical cancer incidence and mortality can be reduced by removal of precursor lesions detected at cytological screening. Organised screening, i.e. regular invitation of defined target groups, is generally considered more effective than opportunistic screening. The latter method however, is predominant in most settings. There is no scientific basis for advocating one type of screening or the other. Our aim was to compare the two types and to analyse their efficiency. We analysed 466,275 smears taken in an open cohort of 118,890 women during 1969-88. A computerised database permitted standardised classification of all smears and complete ascertainment of cancer in situ through record linkage. The number of in situ cancers detected per 1000 smears, the detection ratio, was used as an outcome measure both in univariate analyses and in multivariate logistic regression models. Cancer in situ was detected in 1076 women in the study cohort, with a detection ratio of 3.0 at organised and 2.1 at opportunistic screening, yielding an unadjusted odds ratio of 0.69 (95% CI 0.61-0.79). After adjustment for age and time period, the probability of detecting cancer in situ was around 25% higher with opportunistic than with organised screening (OR = 1.26; 95% CI 1.09-1.46). This difference in favour of opportunistic screening was most pronounced in the first 10 year period and disappeared during the last decade. The difference in efficiency between organised and opportunistic screening in the detection of cancer in situ was slight, if any. The dogma that organised screening is significantly more efficient than the opportunistic type needs reconsideration.Cervical cancer incidence and mortality can be reduced by removal of precursor lesions detected at cytological screening. Organised screening, i.e. regular invitation of defined target groups, is generally considered more effective than opportunistic screening. The latter method however, is predominant in most settings. There is no scientific basis for advocating one type of screening or the other. Our aim was to compare the two types and to analyse their efficiency. We analysed 466,275 smears taken in an open cohort of 118,890 women during 1969-88. A computerised database permitted standardised classification of all smears and complete ascertainment of cancer in situ through record linkage. The number of in situ cancers detected per 1000 smears, the detection ratio, was used as an outcome measure both in univariate analyses and in multivariate logistic regression models. Cancer in situ was detected in 1076 women in the study cohort, with a detection ratio of 3.0 at organised and 2.1 at opportunistic screening, yielding an unadjusted odds ratio of 0.69 (95% CI 0.61-0.79). After adjustment for age and time period, the probability of detecting cancer in situ was around 25% higher with opportunistic than with organised screening (OR = 1.26; 95% CI 1.09-1.46). This difference in favour of opportunistic screening was most pronounced in the first 10 year period and disappeared during the last decade. The difference in efficiency between organised and opportunistic screening in the detection of cancer in situ was slight, if any. The dogma that organised screening is significantly more efficient than the opportunistic type needs reconsideration.

Improved control of invasive cervical cancer in Sweden over six decades by earlier clinical detection and better treatment.

PURPOSEnCancer of the cervix uteri can be controlled by cytologic screening for the detection of precursor lesions, but such intervention remains unrealistic in many countries in which this cancer is common. The possibility of reducing mortality by earlier clinical detection, followed by basic therapy, has never been properly assessed.nnnPATIENTS AND METHODSnWe compiled records of incident cases of invasive cancer of the cervix diagnosed in a defined area of Sweden from 1930 through 1990. In a cohort of 6,044 women, we analyzed temporal trends in incidence and survival by clinical stage and age at diagnosis. Generalized proportional hazards models were used to study several factors simultaneously and quantify the overall reduction in mortality.nnnRESULTSnFor each successive stage at diagnosis, the overall risk of dying increased 2.5-fold (95% confidence interval [CI], 2.4 to 2.7). From 1930, a marked improvement in stage distribution was accompanied by increasing survival rates in stages I and II disease. These changes largely took place before the introduction of screening and external-beam radiation. The 10-year relative survival rate increased from 33% in the 1930s to approximately 55% in the 1950s and thereafter.nnnCONCLUSIONnImprovements in public and professional awareness of cervical cancer resulted in diagnoses at earlier clinical stages. The rate of cure in early stages improved when basic local treatment was introduced, but only little of the progress was attributable to the introduction of more advanced treatment technologies. These findings offer considerable hope for a substantial reduction in the mortality of cervical cancer without cytologic screening, even in countries with limited resources.

Increasing cancer risk in younger birth cohorts in Sweden

There is controversy about cancer mortality trends; some analyses show increasing mortality, but others suggest that rates are falling in the youngest age groups. We have investigated trends in cancer incidence in the whole of Sweden for the period 1958 to 1987. 837,085 cancer cases were registered during the period studied. Incidence rate patterns were studied by age-period-cohort modelling. The risk of cancer was higher for people born during the 1950s than for those born in 1873-82; for women the risk was doubled and for men it was trebled. Although the rate of increase slowed, it showed no sign of levelling off in the youngest birth cohorts. The frequency of smoking-related cancers increased greatly in both sexes, but such tumours could explain only part of the rise in total cancer. These trends predict a continuing rise in the incidence rate of cancer, and suggest a worrying pattern of increasing population exposure to carcinogenic influences.

Trends in mortality rates from malignant melanoma in Sweden 1953-1987 and forecasts up to 2007.

To monitor mortality rates from malignant melanoma we analysed all patients in Sweden (6,324) who died of malignant melanoma in 1953 through 1987. Age-standardised rates per 10(5) increased from 1.1 to 4.0 in men and from 1.0 to 2.6 in women. The average annual increase levelled off in men from 4.6% during 1953-1967 to 2.0% in 1978-1987; and in women from 3.7% to 0%. Multivariate analyses showed that the change in rates for men was mainly due to a birth-cohort effect, whereas in women the rates changed similarly in all age-groups in accordance with a time-period effect. The risk of dying of malignant melanoma increased in men for birth cohorts up to 1932, whereas in women the rise continued for cohorts born as late as 1947. The best-fitted multivariate models were extrapolated to the year 2007, among men a slight increase in mortality rates seemed likely, whereas among women the rates will probably remain unchanged.

Trends in breast cancer incidence in Sweden 1958-1988 by time period and birth cohort

Statistics from the Swedish National Cancer Registry based on all 110,658 cases of invasive breast cancer during the 31-year period 1958-1988 were analysed. Age-specific incidence rates increased over successive calendar periods. The average annual increase in the age-standardised incidence rate was 1.3%, with the greatest percentage changes among the youngest age groups. During the latter half of the study period, the rates of increase tended to diminish in the youngest age groups and even reversed significantly among women from 75 years of age. In analyses using age-period-cohort models, the best fit of the cancer incidence data was found for the full model which simultaneously considered the effects of age, period and cohort. Cohort effects were found to be more important than period effects, in terms of model fit. These effects emerged as a seemingly consistent, and in a logarithmic scale, fairly linear increase in the relative risk of breast cancer incidence with a 3-fold elevation in women born in the 1950s relative to those born in the 1880s. It is concluded that the rising breast cancer incidence in Sweden is explained chiefly by birth cohort effects, which indicate persistent secular changes in largely unknown risk factors associated with life style. We could not in the present data see any clear evidence for an adverse effect of contraceptive or replacement sex steroids on breast cancer incidence.

Trends in Childhood and Adolescent Cancer Survival in Sweden 1960 Through 1984

The temporal changes in childhood and adolescent cancer survival in Sweden 1960-1984 were analyzed. Complete follow-up through 1986 of 6,262 patients younger than 20 years at diagnosis revealed that the overall 5-year survival rates increased from 36.1 to 65.7% in males and from 43.6 to 73.6% in females. The temporal trends differed markedly between age groups and tumour sites and types. Over the study period, 5-years, survival for testicular cancer increased from 46.9 to 87.2%, kidney cancer, predominantly Wilms tumour from 35.5 to 77.1% (with a higher rate of 89.1% in 1975-1979), Hodgkins disease from 61.2 to 91.9%, non-Hodgkins lymphoma from 32.5 to 76.6%, and all leukemias from 8.9 to 58.7%. Only a moderate improvement was noted for tumours of the bone, muscle and connective tissue, and survival rates for tumours of the nervous system remained largely unchanged. Our data reflect the remarkable therapeutic improvements that have occurred for cancer in the young and indicate that these improvements have rapidly become available in Sweden.

Biochemical evidence for a mature phenotype in morphologically poorly differentiated neuroblastomas with a favourable outcome

Neuroblastoma is an embryonal tumour of the sympathetic nervous system with marked heterogeneity in terms of histological maturity and clinical course. A previous study revealed that high tumour levels of the csrc protein, particularly its neuronal isoform (pp60csrcN), correlated with favourable outcome. To test whether this feature reflects a higher degree of neuronal maturation in these tumours, an extended series (47 consecutive neuroblastomas and 10 ganglioneuromas) were analysed for levels of csrc protein isoforms, neuron-specific enolase, and synaptophysin. Immunoblotting and radioimmunoassay techniques were employed. The results were compared with conventional histological signs of neuronal maturation. High pp60csrcN levels were specific for prognostically favourable neuroblastomas and correlated with high neuronal marker levels. However, signs of histological maturation correlated poorly with these parameters. It is therefore concluded that low stage tumours are highly differentiated in biochemical terms despite their frequently immature histology. Furthermore, the clinical usefulness of these biochemical parameters as prognostic markers was compared with established parameters in a multivariate analysis. Stage 4 disease, MYCN amplification, and age above 18 months at diagnosis was the most powerful combination of variables found for predicting a poor outcome. As expected, none of the neuronal differentiation markers investigated could add to the prediction of aggressive disease when compared with this model. However, high expression of pp60csrcN appeared to be useful in predicting long-term survival in high stage infant neuroblastoma.