The prognostic value of DNA ploidy in a total population of uterine sarcomas.

BACKGROUND: The diagnosis of uterine sarcoma is associated with poor outcome for the patient and there is a need for reliable prognostic markers. Most previous studies on the prognostic value of DNA ploidy include few uterine sarcomas and report conflicting results. MATERIALS AND METHODS: We examined the prognostic value of DNA ploidy and its association with clinicopathological parameters and crude survival in a total population of 354 sarcoma. RESULTS: In univariate analyses, we observed significantly better crude survival for endometrial stromal sarcomas (ESS) and adenosarcoma (AS) patients with diploid as compared with nondiploid tumors, but not for patients with leiomyosarcomas (LMS). In Cox multivariate analyses, DNA ploidy was the only significant predictor of survival for patients with AS. In LMS, mitotic index (MI), tumor size, tumor extent and tumor margins, whereas for ESS, MI, tumor extent and tumor necrosis obtained independent significance of survival. DNA ploidy was a significant predictor of survival for LMS patients in Cox regression analyses when excluding MI. CONCLUSION: DNA ploidy might be useful as a prognostic marker in patients with LMS and AS.

CIN 2/3 and cervical cancer in an organised screening programme after an unsatisfactory or a normal Pap smear: a seven-year prospective study of the Norwegian population-based screening programme.

OBJECTIVES: To estimate the risk of cervical intraepithelial neoplasia (CIN) 2/3 and invasive cervical cancer (ICC) in an organised screening programme after an unsatisfactory or a normal Pap smear. SETTING: A seven-year prospective cohort study of the Norwegian population-based co-ordinated screening programme based on the actual diagnostic and screening procedures performed. Observations of 526,661 women with a normal index Pap smear and 21,405 women with an unsatisfactory index Pap smear were made during 3.26 million women-years. METHODS: The risk of being diagnosed with CIN 2/3 or ICC was calculated by logistic regression for the first two years of follow-up. The hazard of being diagnosed with CIN 2/3 or ICC for the women who were not diagnosed during the two first years was estimated by non-parametrical survival regression. RESULTS: After two years of follow-up, 0.2% of the women were diagnosed with CIN 2/3 and 0.01% with ICC after a normal Pap smear. An unsatisfactory Pap smear indicated a 1.6-4.0 times higher risk of harbouring a CIN 2/3 or ICC compared to women with a normal Pap smear. No increased risk of ICC was found during long-term follow-up for the 70% of the women with an unsatisfactory Pap smear who were returned to ordinary screening. Prior series of low-grade Pap smears followed by a normal Pap were associated with an increased risk of CIN 2/3 and ICC. CONCLUSIONS: An unsatisfactory Pap smear indicates a risk of harbouring CIN II/III or ICC. Repeated Pap smears are adequate as a follow-up of an unsatisfactory Pap smear. Women with repeated series of equivocal/LSIL Pap smears followed by a normal Pap should be considered at high risk.

The cervical cancer screening programme in Norway, 1992-2000: changes in Pap smear coverage and incidence of cervical cancer.

OBJECTIVES: Changes in the incidence of cervical cancer were studied to assess the impact of the Norwegian coordinated cervical cancer screening programme introduced in 1995. Attention was given as to whether recommendation letters sent to women without a screen in the previous 3 years could be an alternative to a conventional screening programme that invites women irrespectively of their spontaneous screening. SETTING: A population based, nationwide, screening programme in which women of 25 to 69 are recommended to have a conventional Pap smear every 3 years. METHODS: The impact of the screening programme was assessed indirectly by comparing trends in invasive cervical cancer, changes in coverage, and changes in interval between Pap smears in the 3 year period (1992-4) before screening with the two first screening rounds (1995-7 and 1998-2000). All Pap smears taken from women of all ages were included, a total of 4 744 967 Pap smears from more than 1.4 million women. Further, the impact was assessed directly by logistic regression by comparing the screening results of women recruited for the programme with women who had regularly had Pap smears. RESULTS: In the last 2 years studied, the incidence of invasive cancer was 22% lower than in the period before the programme. The proportion of women who had a Pap smear was higher after the implementation of the coordinated screening programme. The number of smears taken was less as the interval after a normal smear was greater. The newly recruited women had a threefold risk of having a high grade precursor and a 20-fold higher risk of cancer than the women who had had regular smears. CONCLUSIONS: The coordinated screening programme provides a low cost way of increasing the coverage of the female population, and consequently has reduced the rate of invasive cervical cancer.

Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study.

Human papillomavirus has emerged as the leading infectious cause of cervical and other anogenital cancers. We have studied the relation between human papillomavirus infection and the subsequent risk of anal and perianal skin cancer. A case-cohort study within two large Nordic serum banks to which about 760 000 individuals had donated serum samples was performed. Subjects who developed anal and perianal skin cancer during follow up (median time of 10 years) were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Twenty-eight cases and 1500 controls were analysed for the presence of IgG antibodies to HPV 16, 18, 33 or 73, and odds ratios of developing anal and perianal skin cancer were calculated. There was an increased risk of developing anal and perianal skin cancer among subjects seropositive for HPV 16 (OR=3.0; 95%CI=1.1-8.2) and HPV 18 (OR=4.4; 95%CI=1.1-17). The highest risks were seen for HPV 16 seropositive patients above the age of 45 years at serum sampling and for patients with a lag time of less than 10 years. This study provides prospective epidemiological evidence of an association between infection with HPV 16 and 18 and anal and perianal skin cancer.

Interval cancers in the Norwegian breast cancer screening program: frequency, characteristics and use of HRT.

Breast cancers diagnosed between screening examinations among women who attend a breast cancer screening program are defined as interval cancers. The Norwegian Breast Cancer Screening Program started as a pilot project in 1996, and data from the first 2-year interval are available. Our study quantifies interval cancers in the pilot project and explores characteristics and factors that may be associated with interval cancer. Interval cancers in the screening population were identified through the Cancer Registry of Norway. The frequency of invasive interval cancer was calculated as cases per 10,000 screened and as observed/expected ratio. Characteristics of the interval cancers were compared to screening-detected and clinical cancers. Breast density was assessed in a blinded review of 3 categories of screening mammograms. Information on hormone replacement therapy (HRT) use was collected from a questionnaire. The frequency of invasive interval cancers was 18.2 (15.9-20.7) per 10,000 screened and the observed/expected ratio was 0.49 (0.43-0.56). The frequency in the second year of the interval was higher than reported from other programs. The median tumor size of the interval cancers was 19.5 mm and 44.0% of the patients had affected axillary lymph nodes. The interval cancer cases had higher proportions of dense breasts and reported use of HRT compared to screen normal and screening-detected cases. The reported frequency of interval cancers is similar to comparable programs. The interval cancers differed significantly from the cancers detected in the first screening round and were more similar to clinical cancers. Interval cancer was associated with dense breasts and use of HRT. Screening programs must keep these associations in focus.

[Physical activity and breast cancer]. / Fysisk aktivitet og brystkreft.

BACKGROUND: Physical activity may affect hormonal concentrations that may have bearing on the risk of breast cancer. The aim of this study was to investigate whether physical activity affects this risk. MATERIAL AND METHODS: All women aged 51-60 invited over an eight-week period in 1997 to a pilot breast cancer screening in Norway were also invited to participate in this study (n = 10,513). Information was collected by questionnaire about intensity and duration of physical activity from the age of ten up to the present, in five-year intervals. The activity was converted to scores of Metabolic Equivalent Task (MET). RESULTS: 74% og those invited attended the screening; 76% og those attending also took part in this study. A total of 2,300 of women gave adequate information about physical activity; only 12 of them had breast cancer. Those with cancer reported less physical activity compared to the controls. Physical activity corresponding to > or = 15 MET/week at age 10-24 reduced the risk of breast cancer at age 51-60 significantly (OR = 0.2; CI 0.0-0.9). INTERPRETATION: The small number of breast cancer cases limits the validity of the results, though the data indicate that physical activity of > or = 15 MET/week at age 10-24 may reduce the risk of breast cancer at age 51-60.

Mammography screening in Norway: results from the first screening round in four counties and cost-effectiveness of a modeled nationwide screening.

OBJECTIVE: To evaluate whether the results of the first screening round in the Norwegian Breast Cancer Screening Program predict future mortality reduction and to explore the cost-effectiveness of the program. METHODS: The results of surrogate measures were calculated and compared with the targets. A cost-effectiveness analysis was performed assuming a nationwide program starting in 1996 with an attendance rate of 80% and a mortality reduction of 30%. RESULTS: The attendance rate was 79.5% and the detection rate was 0.67%. The proportion of invasive tumors smaller than 15 mm was 53.1%, and 21.7% of the patients who underwent axillary surgery had lymphatic metastasis. The C/E ratios were found to be 3750 US dollars (USD) per year of life saved and 86,045 USD per life saved. CONCLUSION: The results of the first screening round will lead to a mortality reduction of at least 30%. The cost-effectiveness analysis shows that it is possible to run a highly cost-efficient screening program in Norway.

Histopathologic subtyping of cervical adenocarcinoma reveals increasing incidence rates of endometrioid tumors in all age groups: a population based study with review of all nonsquamous cervical carcinomas in Norway from 1966 to 1970, 1976 to 1980, and 1986 to 1990.

BACKGROUND: The effect of histopathologic review and subclassification on incidence rates for nonsquamous cell carcinoma (non-SCC) of the uterine cervix in the Norwegian population was evaluated. METHODS: All non-SCC from three 5-year periods (1966-70, 1976-80, and 1986-90) were reviewed, classified, and graded. RESULTS: Incidence rates were 1.2, 1.2, and 1.7 per 100,000 for adenocarcinoma and 0.1, 0.3, and 0.5 per 100,000 for other carcinomas in the three periods. Adenocarcinomas increased in all age groups, most markedly in women younger than 35 years. Incidence rates for both major subgroups of endocervical (EC) and endometrioid (EM) carcinomas increased for women younger than 55 years. After 1976-80, the incidence rate for EC, but not for EM, decreased in women older than 55 years. Endometrioid carcinoma became the dominant histologic subtype in 1986-90. Shifts toward lower clinical stages and younger age were found for EC, EM, and carcinoma not otherwise specified (NOS). Patients with NOS, clear cell, serous, or glassy cell/undifferentiated carcinoma were older, and their disease was diagnosed at higher stages. Distribution of International Federation of Gynecology and Obstetrics (FIGO) stages was: Stage I: 62%; Stage II: 21%; Stage III: 12%; and Stage IV: 5%. Distribution of histologic subgroups was: EC:, 24%; EM: 21%; NOS: 16%; clear cell: 7%; adenosquamous: 7%; small cell: 6%; serous: 4%; undifferentiated: 3%; and villoglandular carcinoma: 2%. Other subgroups were seen only sporadically. CONCLUSIONS: Incidence rates of non-SCC of the uterine cervix are increasing in Norway. Improvements in diagnostic procedures may explain shifts toward lower stage and age of patients but not the observed differences between histologic subgroups.

Ductal carcinoma in situ of the breast--a review of diagnosis, treatment and outcome in a hospital-based Norwegian series.

Between 1980 and 1994, 71 women with histologically proven ductal carcinoma in situ (DCIS) were diagnosed at Ullevål Hospital; bilateral tumours were found in two patients. Surgical treatment was mastectomy (42 lesions) or local excision (31 lesions). Median follow-up time was 7.2 years. Ten patients experienced a local recurrence, seven of which were invasive carcinomas. The actuarial 5-year local recurrence rate was 22% after local excision. A multivariate analysis found that tumour size was the only factor that predicted local recurrence after local excision. An analysis of relative survival in a nation-wide material of 832 DCIS patients in the period 1980 to 1994 demonstrates that relative survival after a DCIS diagnosis is almost 100%, irrespective of surgical treatment of the initial lesion.

[A pilot project with mammography--results from the first screening round]. / Prøveprosjekt med mammografi--resultater fra første undersøkelsesrunde.

BACKGROUND: Organised mammography screening can reduce mortality from breast cancer. A pilot project for organised mammography screening was started in four Norwegian counties in 1995/1996. This paper evaluates the results from the first screening round with focus on early indicators predicting future mortality reduction. MATERIALS AND METHODS: All women aged 50-69 were offered two-view mammography biennially. The screening examinations were performed in dedicated screening units, and the mammograms were read at breast diagnostic centres located in university hospitals. All test results and information about diagnostic procedures and treatment were reported to The Cancer Registry of Norway and registered in a central screening database. This database was essential in order to monitor and evaluate the pilot project. RESULTS: 79.5% of the invited women accepted and about 127,000 women were examined. The detection rate was 6.7 cancers per 1,000 women screened. 53.1% of the invasive tumours were less than 15 mm; about one fifth of the patients had axillary lymph node metastasis. INTERPRETATION: The obtained results met the predefined aims. Thus a future mortality reduction of at least 30% is expected. The parliamentary decision on expanding the pilot project to a nationwide programme seems well founded.

[Cost-effectiveness of mammography screening in Norway]. / Samfunnsøkonomisk lønnsomhet av mammografiscreening i Norge.

Since January 1996, mammography screening every second year has been offered to women aged 50 to 69 in four counties in Norway. As an input to the evaluation of the programme, medical authorities commissioned an analysis of the cost-efficacy of screening. The results are presented in this paper. This study of the screening in the City of Oslo is based on registration of time used on various procedure, data for all procedure performed, and financial accounting data. The result have been recalculated for a simulated nation-wide project. Only costs up to the time of diagnosis (malignant/benign) have been included. The total cost of the Oslo programme 1996/97 was NOK 12.1 m (USD 1.6 m). Cost per women examined was NOK 395 and per cancer detected NOK 57,639. Cost per life saved was estimated at NOK 680,000, per year-of-life saved NOK 30,000. Based on accounting data only, comparisons could be made between counties. Costs in other counties were between 39 and 73% higher than in Oslo. Using an estimate of a 40% higher costs nation-wide, we find that the total cost of one year of nation-wide (population 4.5 m) screening would amount to NOK 83 m, cost per life saved to NOK 950,000, and per year-of-life saved to NOK 41,000. Estimated cost per life saved by traffic safety measures has been NOK 10 m. On this basis, mammography screening in Norway seems to be a highly cost-effective measure.

Breast cancer in Norway 1970-1993: a population-based study on incidence, mortality and survival.

The incidence, mortality and survival of breast cancer patients from 1970 to 1993 were studied using data from the Cancer Registry of Norway. The age-adjusted incidence rate increased from 62.0 to 76.9 per 100,000 person-years during the period, and more than 2000 cases are now registered annually. The increase tends to be highest in the age group below 40 years. The increase is mainly found in cases with localized tumours at the time of diagnosis. The mortality rate has been almost unchanged in the period; the age adjusted mortality rate is 27.0 per 100,000 person-years at the end of the study period. The 5-year overall survival has increased among cases with axillary lymph node metastases at the time of diagnosis; the other stages show only little improvement.

[Mass screening for cervical cancer. Experiences after 25 years of voluntary screening and 2 years of organized screening]. / Masseundersøkelsen for livmorhalskreft. Erfaringer etter 25 år med villscreening og to års organisert screening.

In 1990 the Norwegian Ministry of Health and Social Services initiated an organised screening programme for cervical cancer, the main goal of which is to reduce the incidence of and mortality from cervical cancer in Norway. All women aged between 25-69 years are offered screening every third year. In the first three years of the programme, all voluntary screening was reported to The Cancer Registry of Norway. This showed that a high number of smear tests were carried out on young women, against a low rate of smear tests on older women. Since January 1995 invitations have been sent to all women aged between 25-69 years, where there is no record of a smear test having been done in the last three years. Results so far show that the number of women who have had a smear test done in the last three years is increasing in the older age groups. A total of 2.6 million smears have been recorded. Approximately 90% of the smears were normal, only 1.7% showing signs of dysplasia. All pathological smears will be followed up with a reminder either from the laboratories or The Cancer Registry.

Uterine sarcomas in Norway 1956-1992: incidence, survival and mortality.

A total of 1042 patients diagnosed with uterine sarcoma were reported to The Cancer Registry of Norway from 1956 to 1992. In the present study long-term trends in incidence, survival and mortality were analysed. To evaluate the effect of the introduction of chemotherapy in the treatment of this disease, special attention was paid to the time periods 1971-1975 and 1983-1987. The reporting system is based on pathology reports, clinical records and death certificates. Histological type, diagnostic period, clinical stage and age were included in the study. The analysis of survival was based on 5-year relative survival. Both the incidence and mortality rate of uterine sarcomas in Norway doubled in the time period 1956-1992, mainly due to an increase of carcinosarcomas. The overall annual incidence rate in 1987-1992 was 1.7 per 100000 females in the population per year, accounting for 9.7% of all uterine corpus malignancies. In 1990-1992, 26% of the mortality due to uterine corpus malignancies was caused by sarcoma. No change in 5-year survival was seen after the introduction of chemotherapy in the treatment of the disease (P = 0.35). Stage (P < 0.001) and age (P < 0.001) were both important prognostic factors. Patients with an endometrial stromal sarcoma (P < 0.001) had a more favourable prognosis than those with other histological types.

Mass screening for cervical cancer in Norway: evaluation of the pilot project.

The Norwegian Department of Health and Social Affairs initiated a national screening program for cervical cancer in 1990, with all women aged 25 to 70 years to be offered cervical screening every three years. During the first three years of the program (November 1991-October 1994), all spontaneous cervical cytology in Norway was recorded at the Norwegian Cancer Registry. In addition, women in the counties of Vestfold and Sør-Trøndelag were invited individually to be screened. The aim of the present study was principally to evaluate the organization aspects of a nationwide, population-based screening program for cervical cancer in Norway. Special attention was paid to the coverage, the attendance rate, and the cytologic findings in the two-county study area. A total of 1,581,379 Pap smears were recorded from November 1991 to October 1994. Most smears were taken from women under age 30 years (31.7 percent). About 25 percent of the women aged 25 to 29 years had more than one normal smear. In the study area, a coverage of about 71 percent in the age group 25 to 69 years was achieved. The pilot project also has shown that it is possible to recruit elderly women into screening. However, no difference was noted between the study and the reference area with regard to findings per smear of precursor lesions (CIN 3, modified SNOMED coding system). The experiences from three years of recording and the implementation of the pilot project have provided useful guidelines for the national screening which began in January 1995.