Screening and cervical cancer cure: population based cohort study.

OBJECTIVE: To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death. DESIGN: Nationwide population based cohort study. SETTING: Sweden. PARTICIPANTS: All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years. MAIN OUTCOME MEASURES: Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age, histopathological type, and FIGO (International Federation of Gynecology and Obstetrics) stage. RESULTS: In the screening ages, the cure proportion for women with screen detected invasive cancer was 92% (95% confidence interval 75% to 98%) and for symptomatic women was 66% (62% to 70%), a statistically significant difference in cure of 26% (16% to 36%). Among symptomatic women, the cure proportion was significantly higher for those who had been screened according to recommendations (interval cancers) than among those overdue for screening: difference in cure 14% (95% confidence interval 6% to 23%). Cure proportions were similar for all histopathological types except small cell carcinomas and were closely related to FIGO stage. A significantly higher cure proportion for screen detected cancers remained after adjustment for stage at diagnosis (difference 15%, 7% to 22%). CONCLUSIONS: Screening is associated with improved cure of cervical cancer. Confounding cannot be ruled out, but the effect was not attributable to lead time bias and was larger than what is reflected by down-staging. Evaluations of screening programmes should consider the assessment of cure proportions.

Genotyping of human papillomavirus in triaging of low-grade cervical cytology.

OBJECTIVE: The objective of the study was to evaluate whether typing of human papillomavirus (HPV) among women with low-grade cervical cytology can improve the ability to identify women with cervical cancer or cervical intraepithelial neoplasia grade III (CIN III or worse). STUDY DESIGN: A total of 1595 women with low-grade cervical cytology participating in a randomized implementation trial of HPV triaging using Hybrid Capture II were also HPV genotyped and CIN III or worse predictive values evaluated. RESULTS: HPV 16 was detected in 57% of cases with CIN III or worse but only among 24% of all tested women. Testing for the 3 HPV types with highest risk (HPV16/31/33) detected 77% of CIN III or worse, with 36% of women testing positive. Positivity for the other high-risk HPV types had a decreased risk for CIN III or worse. CONCLUSION: Different high-risk HPV types confer different risks for the presence of CIN III or worse, implying that HPV genotyping could be useful for the optimization of triaging strategies.

Randomized healthservices study of human papillomavirus-based management of low-grade cytological abnormalities.

Human papillomavirus (HPV)-based management of women with borderline atypical squamous cells of undetermined significance (ASCUS) or mildly abnormal cervical intraepithelial neoplasia (CINI) cervical cytology has been extensively studied in the research setting. We wished to assess safety and health care resource use of a real-life health care policy using HPV triaging. All 15 outpatient clinics involved in the organized population-based screening program in Stockholm, Sweden screening program were randomized to either continue with prior policy (colposcopy of all women with ASCUS/CINI) or to implement a policy with HPV triaging and colposcopy only of HPV-positive women. The trial enrolled the 3,319 women who were diagnosed with ASCUS (n = 1,335) or CINI (n = 1,984) in Stockholm during 17th March 2003 to 16th January 2006. Detection of high-grade cervical lesions (CINII+) and health care cost consumption was studied by registry linkages. The proportion of histopathology-verified CINII+ was similar for the two policies (395 of 1,752 women (22.5%; 95% Confidence interval [CI]: 20.6-24.6%) had CINII+ diagnosed with HPV triaging policy, 318 of 1,567 women (20.3%; 95%CI: 18.3-22.4%) had CINII+ with colposcopy policy). Sixty-four percent of women with ASCUS and 77% of women with CINI were HPV positive. HPV-positivity was age-dependent, with 81% of women below 35 years of age and 44% of women above 45 years of age testing HPV-positive. HPV triaging was cost-effective only above 35 years of age. In conclusion, a real-life randomized healthservices study of HPV triaging of women with ASCUS/CINI demonstrated similar detection of CINII+ as colposcopy of all women.

Risk of invasive cervical cancer in relation to clinical investigation and treatment after abnormal cytology: a population-based case-control study.

A substantial proportion of women with cervical cancer that have participated in cervical screening have a history of an abnormal cytology result. Our objective was to assess the impact of histological investigation and treatment of women with abnormal cytology on the subsequent risk of invasive cervical cancer. All invasive cervical cancer cases in Sweden 1999-2001 and five population-based control women per case were investigated. Clinical investigations and treatment were analysed in case women (N = 143) and control women (N = 176) below 67 with abnormal cytology results 0.5-6.5 years before the cases' diagnosis. Cervical cancer risk in relation to investigation [histology or not, punch biopsy, cervical curettage or cone/large loop excision of the transformation zone (LLETZ)], and treatment (treatment or not, excisional or ablative) was estimated as odds ratios (ORs) using logistic regression. Absence of histological assessment was associated with increased cancer risk, both after low-grade [OR 2.37; 95% confidence intervals (CI): 1.27-4.43] and high-grade squamous atypia (8.26; 2.37-28.8). Among women with histology, absence of treatment was associated with increased cancer risk (3.68; 1.53-8.84), also when biopsy showed low-grade atypia or normal findings (3.57; 1.18-10.8). Ablative therapy associated with increased risk compared with excisional (3.82; 1.01-14.4), and laser conisation associated with decreased risk compared with LLETZ (0.06; 0.01-0.36). In conclusion, low-grade as well as high-grade squamous atypical cytology results may warrant histological investigation, treatment reduced cancer risk even when histology was negative or showed low-grade atypia indicating a need for improvements in the diagnosis of high-grade lesions, and laser conisation was the most effective treatment.

Breast Cancer Screening Program in Stockholm County, Sweden - Aspects of Organization and Quality Assurance.

The population-based breast cancer screening program in Stockholm County was initiated in 1989. The program follows the recommendations issued by the Swedish Board of Health and Welfare, and is in agreement with guidelines from the European Commission. Individual data is available for all women in Stockholm County aged 40-69 years since initiation of the program in 1989. The participation rate exceeds 70%, the recall rate averages 3%, and the detection rate is 0.5%. The introduction of the breast cancer screening program in Stockholm County has reduced breast cancer mortality by 29% and among participants by 52%. The breast screening program is well organized and functioning, and well adapted to its purpose. Follow-up ensures a good quality process with the aim of reducing breast cancer mortality.

A pooled analysis of interval cancer rates in six European countries.

The objective of this study was to assess detection rates and interval breast cancer (IC) rates from eight programmes in the European Breast Cancer Screening Network. A common data collection protocol was used to explore differences in IC rates among programmes and discuss their potential determinants. Pooled analysis was used to describe IC rates by age, compliance in screening, recall rate, screening detection (SD) rate and expected breast cancer incidence. Participation in screening averaged 77.9% (range 42.6-88.7%), recall rate 5.4% (range 3.3-17.7%) in the initial and 3.4% (range 1.8-8.9%) in the subsequent screening rounds, and SD rate was 60.4 (range 41.6-91) per 10 000 women in initial and 38.5 (range 31.3-62.6) in subsequent screens. IC rate during first 12 months after screening was 5.9 (range 2.1-7.3) per 10 000 women screened negative and 12.6 (range 6.3-15) in the second year of the interval. IC comprised 28% of the IC and SD cancers. The ratio between IC rate and expected incidence was 0.29 for the first 12 months and 0.63 for the 13-24 months period. Sensitivity was higher for the ages 60-69 years and for initial tests than subsequent tests. There were distinct differences in the IC rates between programmes. The results of this study reveal large variations in screening sensitivity and performance. Pooled evaluation of some process indicators within the European breast cancer screening programmes proved to be feasible and is likely to be useful for the future, particularly if it is performed regularly and extensively.

Risk of invasive cervical cancer in relation to management of abnormal Pap smear results.

OBJECTIVE: We sought to evaluate the management of women with abnormal cytology in terms of subsequent risk of invasive cervical cancer. STUDY DESIGN: The screening histories of all invasive cervical cancer cases diagnosed in Sweden 1999-2001 and of 5 population-based controls per case were reviewed. In all, 159 patients and 258 control subjects aged < 67 years had an abnormal smear result 0.5-6.5 years prior to cancer diagnosis. The cervical cancer risk was estimated in relation to management by calculating odds ratios. RESULTS: Histologic assessment of low-grade squamous abnormalities strongly reduced the risk compared to repeated cytology (odds ratio, 0.46; 95% confidence interval, 0.24-0.89). Delaying histologic assessment was also associated with a higher risk (odds ratio, 5.65; 95% confidence interval, 1.39-23.05). After high-grade squamous atypia, absence of any cytologic or histologic specimen was a major determinant of cancer risk (odds ratio, 12.52; 95% confidence interval, 1.42-infinitive). CONCLUSION: For adequate protection against invasive cervical cancer, further assessment with histology must be recommended also for women with low-grade squamous abnormalities.

Temporal trends in the use of adjuvant systemic therapy in breast cancer: a population based study in Sweden 1976-2005.

BACKGROUND: Both adjuvant therapy and mammography screening can decrease breast cancer mortality and there is a need of knowing to what extent those two modalities are used in the population. Screening coverage is well documented but there is a scarcity of population-based data on use of systemic adjuvant treatment. AIM: To describe the introduction, and trends in the use of adjuvant systemic therapy for breast cancer in two of six public health regions in Sweden. MATERIAL & METHODS: Population-based data on use of adjuvant therapy were available from databases with documented high quality and high coverage data for Stockholm (1976-2005) and North Sweden (1980-2003, and 2005). RESULTS: The use of systemic treatment was infrequent before the late 1980s in both regions, but increased during the 1990s. In 2005, the proportion of operable breast cancer patients treated with adjuvant endocrine therapy in the ages 40-59 was around 60 to 80%. The proportion adjuvant chemotherapy was less than 15% for the ages 70-74. For the north region the use of endocrine therapy increased successively over time, with an exception for age group 40-49 were a more rapidly increase occurred in the late 1990s. In Stockholm the increment was higher and more rapidly. There was no clear difference in chemotherapy use between the regions, and the use increased from the mid 1980s in age group 40-49, and in the early 1990s for women aged 50-59. In age group's 60-69 and 70-74 the use was relatively infrequent. CONCLUSIONS: Trends in, and levels of the use of adjuvant systemic therapy for breast cancer varied over time in the two study regions, particularly for endocrine therapy. We consider that the differences between the regions mainly reflect different interpretations of new scientific evidence. We stress the importance of a good documentation of all new treatment protocols.

Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden.

BACKGROUND: The effectiveness of cervical cancer screening programs differs widely in different populations. The reasons for these differences are unclear. Routine and comprehensive audits have been proposed as an ethically required component of screening. We performed a nationwide audit of the effectiveness of the Swedish cervical cancer screening program. METHODS: We identified all invasive cervical cancer cases that were diagnosed in Sweden from January 1, 1999, through December 31, 2001, and had been reported to the Swedish Cancer Registry (n = 1230 cases). We verified the diagnoses by histopathologic rereview and matched each case subject to five (population-based) age-matched control subjects who were identified from the National Population Register. The Pap smear screening histories for case and control subjects were reviewed for a 6-year period using the National Cervical Cancer Screening Register, which contains data on essentially all relevant cytological and histological diagnoses in Sweden. Odds ratios (ORs), and their 95% confidence intervals (CIs), of cervical cancer according to screening history were calculated in conditional logistic regression models. All statistical tests were two-sided. RESULTS: Women who had not had a Pap smear within the recommended screening interval had higher risk of cervical cancer than women who had been screened (OR = 2.52, 95% CI = 2.19 to 2.91). This risk was similarly increased for all age groups (P(homogeneity) = .96). The risk for non-squamous cell cervical cancers (OR = 1.59, 95% CI = 1.20 to 2.11) was also increased. Women who had not had a Pap smear within the recommended screening interval had a particularly high risk of advanced cancers (OR = 4.82, 95% CI = 3.61 to 6.44). Among women who had been screened within the recommended interval, those with abnormal Pap smears had a higher risk of cervical cancer than those with normal smears (OR = 7.55, 95% CI = 5.88 to 9.69) and constituted 11.5% of all women with cervical cancer. CONCLUSIONS: Nonadherence to screening intervals was the major reason for cervical cancer morbidity. The screening program was equally effective for women of all ages and was also effective against non-squamous cancers.

Breast cancer incidence and mortality in the Nordic capitals, 1970-1998. Trends related to mammography screening programmes.

The aim of the present study was to relate the time trends in breast cancer incidence and mortality to the introduction of mammography screening in the Nordic capitals. Helsinki offered screening to women aged 50-59 starting in 1986. The other three capitals offered screening to women aged 50-69 starting in 1989 in Stockholm, 1991 in Copenhagen, and 1996 in Oslo. Prevalence peaks in breast cancer incidence depended on the age groups covered by the screening, the length of the implementation of screening, and the extent of background opportunistic screening. No mortality reduction following the introduction of screening was visible after seven to 12 years of screening in any of the three capitals where significant effects of the screening on the breast cancer mortality had already been demonstrated by using other analytical methods for the evaluation. No visible effect on mortality reduction was expected in Oslo due to too short an observation period. The study showed that the population-based breast cancer mortality trend is too crude a measure to detect the effect of screening on breast cancer mortality during the first years after the start of a programme.

Pattern of participation in a cohort aged 50-60 years at first invitation to the service-screening programme with mammography in Stockholm county, Sweden.

BACKGROUND: Mammography screening can only be effective if a high proportion of the invited women attend. The aim of the present study was to search for patterns of participation in women who were invited to five consecutive rounds in a large screening programme. METHOD: Stockholm service-screening programme started 1989 and invites women between 50 and 69 years of age to mammography with 2 years interval. 64,852 women were eligible for an invitation to all five rounds during a 10-year period and were included in the study. RESULTS: More than 50% attended at all five rounds, and more than 70% at least four rounds. Only 8.5% were permanent non-participants. Women who attended at the first invitation round were more likely to attend also at subsequent rounds. CONCLUSIONS: It is possible to reach a high participation also in a large urban screening programme, but it seems that the invitation and examination at first round are most important in order to get a high compliance. Women who come at first round are more likely to come back for routine screening at a majority of subsequent rounds.