Beneficial Effect of Consecutive Screening Mammography Examinations on Mortality from Breast Cancer: A Prospective Study.

Background Previously, the risk of death from breast cancer was analyzed for women participating versus those not participating in the last screening examination before breast cancer diagnosis. Consecutive attendance patterns may further refine estimates. Purpose To estimate the effect of participation in successive mammographic screening examinations on breast cancer mortality. Materials and Methods Participation data for Swedish women eligible for screening mammography in nine counties from 1992 to 2016 were linked with data from registries and regional cancer centers for breast cancer diagnosis, cause, and date of death (Uppsala University ethics committee registration number: 2017/147). Incidence-based breast cancer mortality was calculated by whether the women had participated in the most recent screening examination prior to diagnosis only (intermittent participants), the penultimate screening examination only (lapsed participants), both examinations (serial participants), or neither examination (serial nonparticipants). Rates were analyzed with Poisson regression. We also analyzed incidence of breast cancers proving fatal within 10 years. Results Data were available for a total average population of 549 091 women (average age, 58.9 years ± 6.7 [standard deviation]). The numbers of participants in the four groups were as follows: serial participants, 392 135; intermittent participants, 41 746; lapsed participants, 30 945; and serial nonparticipants, 84 265. Serial participants had a 49% lower risk of breast cancer mortality (relative risk [RR], 0.51; 95% CI: 0.48, 0.55; P < .001) and a 50% lower risk of death from breast cancer within 10 years of diagnosis (RR, 0.50; 95% CI: 0.46, 0.55; P < .001) than serial nonparticipants. Lapsed and intermittent participants had a smaller reduction. Serial participants had significantly lower risk of both outcomes than lapsed or intermittent participants. Analyses correcting for potential biases made little difference to the results. Conclusion Women participating in the last two breast cancer screening examinations prior to breast cancer diagnosis had the largest reduction in breast cancer death. Missing either one of the last two examinations conferred a significantly higher risk. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Stephen A. Feig in this issue.

Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women.

BACKGROUND: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death. METHODS: Among 549,091 women, covering approximately 30% of the Swedish screening-eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression. RESULTS: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51-0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66-0.84 [P < .001]). CONCLUSIONS: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.

Increasing participation in cervical screening by targeting long-term nonattenders: Randomized health services study.

High screening participation in the population is essential for optimal prevention of cervical cancer. Offering a high-risk human papillomavirus (HPV) self-test has previously been shown to increase participation. In this randomized health services study, we evaluated four strategies with regard to participation. Women who had not attended organized cervical screening in 10 years were eligible for inclusion. This group comprised 16,437 out of 413,487 resident women ages 33-60 (<4% of the screening target group). Among these 16,437 long-term nonattenders, 8,000 women were randomized to either (i) a HPV self-sampling kit sent directly; (ii) an invitation to order a HPV self-sampling kit using a new open source eHealth web application; (iii) an invitation to call a coordinating midwife with questions and concerns; or (iv) the standard annual renewed invitation letter with prebooked appointment time (routine practice). Overall participation, by arm, was (i) 18.7%; (ii) 10.7%; (iii) 1.9%; and (iv) 1.7%. The relative risk of participation in Arm 1 was 11.0 (95% CI 7.8-15.5), 6.3 (95% CI 4.4-8.9) in Arm 2 and 1.1 (95% CI 0.7-1.7) in Arm 3, compared to Arm 4. High-risk HPV prevalence among women who returned kits in study Arms 1 and 2 was 12.2%. In total, 63 women were directly referred to colposcopy from Arms 1 and 2; of which, 43 (68.3%) attended and 17 had a high-grade cervical lesion (CIN2+) in histology (39.5%). Targeting long-term nonattending women with sending or offering the opportunity to order self-sampling kits further increased the participation in an organized screening program.

Discontinuation of adjuvant hormone therapy among breast cancer patients not previously attending mammography screening.

BACKGROUND: Breast cancer patients who have not previously attended mammography screening may be more likely to discontinue adjuvant hormone therapy and therefore have a worse disease prognosis. METHODS: We conducted a population-based cohort study using data from Stockholm Mammography Screening Program, Stockholm-Gotland Breast Cancer Register, Swedish Prescribed Drug Register, and Swedish Cause of Death Register. Women in Stockholm who were diagnosed with breast cancer between 2001 and 2008 were followed until December 31, 2015. Non-participants of mammography screening were defined as women who, prior to their breast cancer diagnosis, were invited for mammography screening but did not attend. RESULTS: Of the 5098 eligible breast cancer patients, 4156 were defined as screening participants and 942 as non-participants. Compared with mammography screening participants, non-participants were more likely to discontinue adjuvant hormone therapy, with an adjusted hazard ratio (HR) of 1.30 (95% CIs, 1.11 to 1.53). Breast cancer patients not participating in mammography screening were also more likely to have worse disease-free survival, even after adjusting for tumor characteristics and other covariates (adjusted HR 1.22 (95% CIs, 1.05 to 1.42 for a breast cancer event). CONCLUSIONS: Targeted interventions to prevent discontinuation of adjuvant hormone therapy are needed to improve breast cancer outcomes among women not attending mammography screening.

Overdiagnosis in the population-based organized breast cancer screening program estimated by a non-homogeneous multi-state model: a cohort study using individual data with long-term follow-up.

BACKGROUND: Overdiagnosis, defined as the detection of a cancer that would not become clinically apparent in a woman's lifetime without screening, has become a growing concern. Similar underlying risk of breast cancer in the screened and control groups is a prerequisite for unbiased estimates of overdiagnosis, but a contemporary control group is usually not available in organized screening programs. METHODS: We estimated the frequency of overdiagnosis of breast cancer due to screening in women 50-69 years old by using individual screening data from the population-based organized screening program in Stockholm County 1989-2014. A hidden Markov model with four latent states and three observed states was constructed to estimate the natural progression of breast cancer and the test sensitivity. Piecewise transition rates were used to consider the time-varying transition rates. The expected number of detected non-progressive breast cancer cases was calculated. RESULTS: During the study period, 2,333,153 invitations were sent out; on average, the participation rate in the screening program was 72.7% and the average recall rate was 2.48%. In total, 14,648 invasive breast cancer cases were diagnosed; among the 8305 screen-detected cases, the expected number of non-progressive breast cancer cases was 35.9, which is equivalent to 0.43% (95% confidence interval (CI) 0.10%-2.2%) overdiagnosis. The corresponding estimates for the prevalent and subsequent rounds were 15.6 (0.87%, 95% CI 0.20%-4.3%) and 20.3 (0.31%, 95% CI 0.07%-1.6%), respectively. The likelihood ratio test showed that the non-homogeneous model fitted the data better than an age-homogeneous model (P <0.001). CONCLUSIONS: Our findings suggest that overdiagnosis in the organized biennial mammographic screening for women 50-69 in Stockholm County is a minor phenomenon. The frequency of overdiagnosis in the prevalent screening round was higher than that in subsequent rounds. The non-homogeneous model performed better than the simpler, traditional homogeneous model.

Long-term prognostic implications of risk factors associated with tumor size: a case study of women regularly attending screening.

BACKGROUND: Breast cancer prognosis is strongly associated with tumor size at diagnosis. We aimed to identify factors associated with diagnosis of large (> 2 cm) compared to small tumors, and to examine implications for long-term prognosis. METHODS: We examined 2012 women with invasive breast cancer, of whom 1466 had screen-detected and 546 interval cancers that were incident between 2001 and 2008 in a population-based screening cohort, and followed them to 31 December 2015. Body mass index (BMI) was ascertained after diagnosis at the time of study enrollment during 2009. PD was measured based on the contralateral mammogram within 3 years before diagnosis. We used multiple logistic regression modeling to examine the association between tumor size and body mass index (BMI), mammographic percent density (PD), or hormonal and genetic risk factors. Associations between the identified risk factors and, in turn, the outcomes of local recurrence, distant metastases, and death (153 events in total) in women with breast cancer were examined using Cox regression. Analyses were carried out according to mode of detection. RESULTS: BMI and PD were the only factors associated with tumor size at diagnosis. For BMI (≥25 vs. < 25 kg/m2), the multiple adjusted odds ratios (OR) were 1.37 (95% CI 1.02-1.83) and 2.12 (95% CI 1.41-3.18), for screen-detected and interval cancers, respectively. For PD (≥20 vs. < 20%), the corresponding ORs were 1.72 (95% CI 1.29-2.30) and 0.60 (95% CI 0.40-0.90). Among women with interval cancers, those with high BMI had worse prognosis than women with low BMI (hazard ratio 1.70; 95% CI 1.04-2.77), but PD was not associated with the hazard rate. Among screen-detected cancers, neither BMI nor PD was associated with the hazard rate. CONCLUSIONS: In conclusion, high BMI was associated with the risk of having a tumor larger than 2 cm at diagnosis. Among women with interval cancer, high BMI was associated with worse prognosis. We believe that women with high BMI should be especially encouraged to attend screening.

Time from breast cancer diagnosis to therapeutic surgery and breast cancer prognosis: A population-based cohort study.

Theoretically, time from breast cancer diagnosis to therapeutic surgery should affect survival. However, it is unclear whether this holds true in a modern healthcare setting in which breast cancer surgery is carried out within weeks to months of diagnosis. This is a population- and register-based study of all women diagnosed with invasive breast cancer in the Stockholm-Gotland healthcare region in Sweden, 2001-2008, and who were initially operated. Follow-up of vital status ended 2014. 7,017 women were included in analysis. Our main outcome was overall survival. Main analyses were carried out using Cox proportional hazards models. We adjusted for likely confounders and stratified on mode of detection, tumor size and lymph node metastasis. We found that a longer interval between date of morphological diagnosis and therapeutic surgery was associated with a poorer prognosis. Assuming a linear association, the hazard rate of death from all causes increased by 1.011 (95% CI 1.006-1.017) per day. Comparing, for example, surgery 6 weeks after diagnosis to surgery 3 weeks after diagnosis, thereby confers a 1.26-fold increased hazard rate. The increase in hazard rate associated with surgical delay was strongest in women with largest tumors. Whilst there was a clear association between delays and survival in women without lymph node metastasis, the association may be attenuated in subgroups with increasing number of lymph node metastases. We found no evidence of an interaction between time to surgery and mode of detection. In conclusion, unwarranted delays to primary treatment of breast cancer should be avoided.

Longitudinal fluctuation in mammographic percent density differentiates between interval and screen-detected breast cancer.

Interval breast cancer (IC) has a more aggressive phenotype and higher mortality than screen-detected cancer (SDC). In this case-case study, we investigated whether the size of longitudinal fluctuations in mammographic percent density (PD fluctuation) was associated with the ratio of IC versus SDC among screened women with breast cancer. The primary study population consisted of 1,414 postmenopausal breast cancer cases, and the validation population of 1,241 cases. We calculated PD fluctuation as the quadratic mean of deviations between actual PD and the long-term trend estimated by a mixed effects model. In a logistic regression model we examined the association between PD fluctuation and IC versus SDC including adjustments for PD at last screening, age at diagnosis, BMI and hormone replacement therapy. All statistical tests were two-sided. There were 385 IC and 1,029 SDC in the primary study population, with PD fluctuations of 0.44 and 0.41 respectively (p = 0.0309). After adjustments, PD fluctuation was associated with an increased ratio of IC versus SDC, with an estimated per-standard deviation odds ratio of 1.17 (95% CI = 1.03-1.33), compared to 1.19 (95% CI = 1.04-1.38) in the validation population. In screened women with breast cancer, high fluctuation in mammographic percent density was associated with an increased ratio of IC versus SDC. Whether this is entirely related to a reduced mammographic detectability or to a biological phenotype promoting faster tumor growth remains to be elucidated.

Novel mammographic image features differentiate between interval and screen-detected breast cancer: a case-case study.

BACKGROUND: Interval breast cancers are often diagnosed at a more advanced stage than screen-detected cancers. Our aim was to identify features in screening mammograms of the normal breast that would differentiate between future interval cancers and screen-detected cancers, and to understand how each feature affects tumor detectability. METHODS: From a population-based cohort of invasive breast cancer cases in Stockholm-Gotland, Sweden, diagnosed from 2001 to 2008, we analyzed the contralateral mammogram at the preceding negative screening of 394 interval cancer cases and 1009 screen-detected cancers. We examined 32 different image features in digitized film mammograms, based on three alternative dense area identification methods, by a set of logistic regression models adjusted for percent density with interval cancer versus screen-detected cancer as the outcome. Features were forward-selected into a multiple logistic regression model adjusted for mammographic percent density, age, BMI and use of hormone replacement therapy. The associations of the identified features were assessed also in a sample from an independent cohort. RESULTS: Two image features, 'skewness of the intensity gradient' and 'eccentricity', were associated with the risk of interval compared with screen-detected cancer. For the first feature, the per-standard deviation odds ratios were 1.32 (95 % CI: 1.12 to 1.56) and 1.21 (95 % CI: 1.04 to 1.41) in the primary and validation cohort respectively. For the second feature, they were 1.20 (95 % CI: 1.04 to 1.39) and 1.17 (95%CI: 0.98 to 1.39) respectively. The first feature was associated with the tumor size at screen detection, while the second feature was associated with the tumor size at interval detection. CONCLUSIONS: We identified two novel mammographic features in screening mammograms of the normal breast that differentiated between future interval cancers and screen-detected cancers. We present a starting point for further research into features beyond percent density that might be relevant for interval cancer, and suggest ways to use this information to improve screening.

Is mammography screening history a predictor of future breast cancer risk?

Inspired by the model by Walter and Day for risk of cervical cancer following negative screens, one might hypothesize that women in a mammography screening programme with a certain number of negative screens had a lower remaining breast cancer risk than that of women in general. We studied whether number of negative screens was a predictor for a low remaining breast cancer risk in women participating in the mammography screening programmes in Stockholm, Copenhagen and Funen. Data were collected from the mammography screening programmes in Stockholm, Sweden (1989-2012), Copenhagen, Denmark (1991-2009) and Funen, Denmark (1993-2009), and linked to the respective cancer registries. We calculated cumulative hazard rates for breast cancer in women in cohorts defined by age at entry and number of negative screens for the maximum follow-up period in each screening centre. For all centres and cohorts, the cumulative hazard were parallel for all number of negative screens, from after the time, when the women were scheduled to be invited for the next screen. This means that the remaining breast cancer risk is similar no matter how many negative screens a woman have had. Number of negative screens was not a predictor of a low remaining breast cancer risk in women participating in the mammography screening programmes in Stockholm, Sweden, Copenhagen and Funen, Denmark. The history of previous negative screens is therefore not suitable for personalisation of mammography screening.

A simple way to measure the burden of interval cancers in breast cancer screening.

BACKGROUND: The sensitivity of a mammography program is normally evaluated by comparing the interval cancer rate to the expected breast cancer incidence without screening, i.e. the proportional interval cancer rate (PICR). The expected breast cancer incidence in absence of screening is, however, difficult to estimate when a program has been running for some time. As an alternative to the PICR we propose the interval cancer ratio ICR=intervalcancersintervalcancers+screendetectedcancers. We validated this simple measure by comparing it with the traditionally used PICR. METHOD: We undertook a systematic review and included studies: 1) covering a service screening program, 2) women aged 50-69 years, 3) observed data, 4) interval cancers, women screened, or interval cancer rate, screen detected cases, or screen detection rate, and 5) estimated breast cancer incidence rate of background population. This resulted in 5 papers describing 12 mammography screening programs. RESULTS: Covering initial screens only, the ICR varied from 0.10 to 0.28 while the PICR varied from 0.22 to 0.51. For subsequent screens only, the ICR varied from 0.22 to 0.37 and the PICR from 0.28 to 0.51. There was a strong positive correlation between the ICR and the PICR for initial screens (r = 0.81), but less so for subsequent screens (r = 0.65). CONCLUSION: This alternate measure seems to capture the burden of interval cancers just as well as the traditional PICR, without need for the increasingly difficult estimation of background incidence, making it a more accessible tool when evaluating mammography screening program performance.

Interventions to improve cervical cancer screening uptake amongst young women: a systematic review.

OBJECTIVES: In view of declining screening uptake in young women, this review aims to summarise the available evidence relating to interventions designed to increase cervical screening uptake amongst women aged ≤ 35 years. METHODS: Electronic databases were searched and further articles located by manual searches. Study designs employing a valid comparison group and including women aged ≤ 35 years published through 2012 were considered. Data was extracted on the uptake from either screening programme statistics or as reported by the study subjects. A narrative synthesis was undertaken for each category of interventions identified. RESULTS: Ninety-two records were screened with 36 articles retrieved for further assessment. Four studies met the inclusion criteria, two of which evaluated more than one intervention. One of the studies evaluated the use of a modified invitation letter and reported no significant increase in uptake compared to a standard invitation. Three studies investigated the use of a reminder letter, with two reporting a positive effect on screening uptake in women aged 24-34. Three studies were included which supported the use of physician and telephone reminders. One study on HPV self-sampling reported a positive effect when compared with a reminder letter. CONCLUSIONS: There is a lack of randomised controlled trials designed to specifically address falling cervical screening uptake in amongst young women. Cervical screening programmes need to look beyond the use of invitation/reminders letters in this group of women to develop interventions which attempt to overcome as many barriers to uptake as possible.

Routine Fecal Occult Blood Screening and Colorectal Cancer Mortality in Sweden.

Importance: Population-based colorectal cancer (CRC) screening programs are implemented worldwide, but there are difficulties evaluating their effectiveness. The magnitude of routine CRC screening effectiveness regarding cancer-specific mortality is unclear. Objective: To evaluate cancer-specific mortality associated with early vs late or no invitation for routine CRC screening using fecal occult blood testing. Design, Setting, and Participants: This prospective cohort study was performed in the region of Stockholm-Gotland, Sweden, between January 1, 2008, and December 31, 2021. All individuals of the target population of screening born from 1938 to 1954 were included. Data were analyzed from December 12, 2022, to June 25, 2023. Exposures: Individuals were invited early (2008-2012), late (2013-2015), or not at all to screening with biennial guaiac-based fecal occult blood test. The early invitation group was considered the exposure group and the late or no invitation group was considered the control group. Main Outcomes and Measures: The main outcome was cancer-specific mortality, defined as CRC registered in the Cancer Register with CRC as underlying cause of death in the Cause of Death Register. Excess mortality was calculated as all-cause deaths among the individuals with CRC subtracted from the expected number of deaths had they not had CRC. Poisson regression analysis based on deaths and person-years was used to estimated mortality rate ratio (RR) with 95% CIs, adjusted for follow-up years and attained age. Results: In total, 379 448 individuals (193 436 [51.0%] female) were invited for CRC screening, including 203 670 individuals in the exposure group and 175 778 in the control group. The mean screening participation rate was 63.3%, and there was a maximum of 14 years follow-up. There were 834 CRC deaths in 2 190 589 person-years in the exposure group, compared with 889 CRC deaths in 2 249 939 person-years in the control group. Individuals who underwent early CRC screening had reduced adjusted risk of CRC mortality (RR, 0.86; 95% CI, 0.78-0.95) and excess mortality (RR, 0.84; 95% CI, 0.75-0.93). Conclusions and Relevance: This prospective cohort study of routine screening with fecal occult blood testing found a 14% decrease in CRC mortality associated with screening. The true association of screening with reduced mortality is expected to be higher due to some coexistence of testing in the control group and CRC deaths diagnosed more than 2 years after screening.

Mammographic density and survival in interval breast cancers.

INTRODUCTION: Mammographic density (MD) is the strongest risk factor for breast cancer. It is also strongly associated with interval cancers (ICs) due to decreased screening sensitivity and possibly by also giving rise to more aggressive tumors. With this information as background, we compared survival in interval and screen-detected cancers, taking MD into consideration. METHODS: The patients were postmenopausal women ages 50 to 74 years who were diagnosed with breast cancer in Sweden between 1993 and 1995. A total of 1,115 women with screen-detected cancers and 285 with ICs had available mammograms. Cox proportional hazards models were used to compare breast cancer-specific survival between interval and screen-detected cancers stratified on MD. RESULTS: Hazard rates for breast cancer-specific survival were approximately three times higher in ICs than in screen-detected cancers, independent of MD. After adjustment for tumor size, a proxy for time to diagnosis, ICs in nondense breasts still had a statistically significantly increased hazard rate compared to screen-detected cancers in nondense breasts (5-yr survival hazard ratio (HR) 2.43, P = 0.001). In dense breasts, however, there was no longer evidence of a difference in survival between ICs and screen-detected cancers (5-yr survival HR 1.41, P = 0.486). CONCLUSIONS: In nondense breasts, ICs seem to be truly more aggressive than screen-detected cancers. In dense breasts, the poorer prognosis of ICs compared to that of screen-detected cancers may be attributable at least partially to later detection. However, to the best of our knowledge, this study is the first to investigate these relationships, and further studies are warranted to confirm our results.

Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial.

BACKGROUND: Screening for colorectal cancer is done with lower gastrointestinal endoscopy or stool-based tests. There is little evidence from randomised trials to show primary colonoscopy reduces mortality in colorectal cancer. We aimed to investigate the effect of screening with once-only colonoscopy or two rounds of faecal immunochemical test screening on colorectal cancer mortality and incidence. METHODS: We did a randomised controlled trial in Sweden (SCREESCO). Residents in 18 of 21 regions who were age 60 years in the year of randomisation were identified from a population register maintained by the Swedish Tax Agency. A statistician with no further involvement in the trial used a randomised block method to assign individuals to once-only colonoscopy, two rounds of faecal immunochemical testing (OC-Sensor; 2 years apart), or a control group (no intervention; standard diagnostic pathways), in a ratio of 1:6 for colonoscopy versus control and 1:2 for faecal immunochemical testing versus control. Masking was not possible due to the nature of the trial. The primary endpoints of the trial are colorectal cancer mortality and colorectal cancer incidence. Here, we report preliminary participation rates, baseline findings, and adverse events from March, 2014, to December, 2020, in the two intervention groups after completion of recruitment and screening, up to the completion of the second faecal immunochemical testing round. Analyses were done in the intention-to-screen population, defined as all individuals who were randomly assigned to the respective study group. This study is registered with ClinicalTrials.gov, NCT02078804. FINDINGS: Between March 1, 2014, and Dec 31, 2020, 278 280 people were included in the study; 31 140 were assigned to the colonoscopy group, 60 300 to the faecal immunochemical test group, and 186 840 to the control group. 10 679 (35·1%) of 30 400 people who received an invitation for colonoscopy participated. 33 383 (55·5%) of 60 137 people who received a postal faecal immunochemical test participated. In the intention-to-screen analysis, colorectal cancer was detected in 49 (0·16%) of 31 140 people in the colonoscopy group versus 121 (0·20%) of 60 300 in the faecal immunochemical test group (relative risk [RR] 0·78, 95% CI 0·56-1·09). Advanced adenomas were detected in 637 (2·05%) people in the colonoscopy group and 968 (1·61%) in the faecal immunochemical test group (RR 1·27, 95% CI 1·15-1·41). Colonoscopy detected more right-sided advanced adenomas than faecal immunochemical testing. There were two perforations and 15 major bleeds in 16 555 colonoscopies. No intervention-related deaths occurred. INTERPRETATION: The diagnostic yield and the low number of adverse events indicate that the design from this trial, both for once-only colonoscopy and faecal immunochemical test screening, could be transferred to a population-based screening service if a benefit in disease-specific mortality is subsequently shown. FUNDING: Swedish regions, County Council, Regional Cancer Center Mellansverige, Swedish Cancer Society, Aleris Research and Development Fund, Eiken Chemical.

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.

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.

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.

How can young women be encouraged to attend cervical cancer screening? Suggestions from face-to-face and internet focus group discussions with 30-year-old women in Stockholm, Sweden.

BACKGROUND: cervical cancer screening (CCS) using Pap-smears has been carried out for decades and is still an essential tool for secondary cancer prevention. Focus has traditionally been on what hinders women's attendance, instead of researching this issue from a positive standpoint, i.e. what factors encourage women to take a Pap-smear? In this article, we therefore explore issues that 30-year-old women have addressed as encouraging CCS attendance, with particular focus on aspects susceptible to intervention. MATERIAL AND METHODS: through the population-based cervical cancer screening (PCCSP) registry in Stockholm, Sweden, a stratified random sampling technique was used to recruit women from the same birth cohort with varied CCS histories and results. Nine face-to-face focus groups discussions (FGDs) and 30 internet-based FGDs were conducted with a total of 138 women aged 30. Qualitative analysis was inspired by interpretative description, to generate clinically relevant and useful data. RESULTS: in general, these women expressed positive views about the PCCSP as an existing service, regardless of screening history. They described a wide range of factors encompassing the entire screening trajectory from invitation through follow-up which could motivate young women to CCS participation, including social marketing. Many of the suggestions related to individualization of the PCCSP, as well as a need to understand the relationship between human papilloma virus (HPV) and cervical cancer. DISCUSSION: [corrected these results are discussed in terms of the inherent tension between population-based public health initiatives and individually-oriented health care provision. Many suggestions given are already incorporated into the existing Stockholm-Gotland screening program, although this information may not reach women who need it. New research should test whether systematic information on HPV may provide a missing link in motivating young women to attend CCS, and which of their suggestions can serve to increase CCS participation.

Early detection of breast cancer rectifies inequality of breast cancer outcomes.

OBJECTIVES: To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome. METHODS: We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression. RESULTS: All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range. CONCLUSIONS: Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.