Showing papers by "Elsebeth Lynge published in 2016"

Mammographic density and structural features can individually and jointly contribute to breast cancer risk assessment in mammography screening: a case–control study

Abstract: Mammographic density is a well-established risk factor for breast cancer. We investigated the association between three different methods of measuring density or parenchymal pattern/texture on digitized film-based mammograms, and examined to what extent textural features independently and jointly with density can improve the ability to identify screening women at increased risk of breast cancer. The study included 121 cases and 259 age- and time matched controls based on a cohort of 14,736 women with negative screening mammograms from a population-based screening programme in Denmark in 2007 (followed until 31 December 2010). Mammograms were assessed using the Breast Imaging-Reporting and Data System (BI-RADS) density classification, Tabar’s classification on parenchymal patterns and a fully automated texture quantification technique. The individual and combined association with breast cancer was estimated using binary logistic regression to calculate Odds Ratios (ORs) and the area under the receiver operating characteristic (ROC) curves (AUCs). Cases showed significantly higher BI-RADS and texture scores on average than controls (p < 0.001). All three methods were individually able to segregate women into different risk groups showing significant ORs for BI-RADS D3 and D4 (OR: 2.37; 1.32–4.25 and 3.93; 1.88–8.20), Tabar’s PIII and PIV (OR: 3.23; 1.20–8.75 and 4.40; 2.31–8.38), and the highest quartile of the texture score (3.04; 1.63–5.67). AUCs for BI-RADS, Tabar and the texture scores (continuous) were 0.63 (0.57–0–69), 0.65 (0.59–0–71) and 0.63 (0.57–0–69), respectively. Combining two or more methods increased model fit in all combinations, demonstrating the highest AUC of 0.69 (0.63-0.74) when all three methods were combined (a significant increase from standard BI-RADS alone). Our findings suggest that the (relative) amount of fibroglandular tissue (density) and mammographic structural features (texture/parenchymal pattern) jointly can improve risk segregation of screening women, using information already available from normal screening routine, in respect to future personalized screening strategies.

Human Papillomavirus Assays and Cytology in Primary Cervical Screening of Women Aged 30 Years and Above

Abstract: In women aged ≥30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30–65 years in Copenhagen, Denmark. Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected more ≥CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more ≥CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results (positive test results without ≥CIN3) varied between 3.3% with cytology and 14.9% with cobas. All HPV assays led to significantly more false-positive tests, whereas compared to HC2 cobas and CLART were associated with a significantly higher and APTIMA with a significantly lower proportion. Detection of CIN1 was particularly increased for the three DNA assays. With APTIMA combined with cytological triage, about 20% more women were referred for colposcopy than with cytology screening. With the three DNA assays, the increase was ≥50%. The number of women with repeated testing was twice as high with APTIMA and almost five times as high with cobas compared to cytology. To our knowledge, Horizon was the only study set in routine practice that compared more than two HPV assays in the same women while also ascertaining the histological status of women with normal cytology/HPV-positive test results. HPV-based screening of Danish women aged 30–65 detected more high-grade CIN but decreased the screening specificity, and increased the demand for additional testing.

Cigarette smoking and mammographic density in the Danish Diet, Cancer and Health cohort

Abstract: Purpose Smoking before first childbirth increases breast cancer risk, but the biological mechanism remains unknown and may involve mammographic density (MD), one of the strongest biomarkers of breast cancer risk. We aimed to examine whether active smoking and passive smoking were associated with MD.

Differential Detection of Human Papillomavirus Genotypes and Cervical Intraepithelial Neoplasia by Four Commercial Assays

Abstract: Laboratories now can choose from >100 human papillomavirus (HPV) assays for cervical screening. Our previous analysis based on the data from the Danish Horizon study, however, showed that four widely used assays, Hybrid Capture 2 (HC2), cobas, CLART, and Aptima, frequently do not detect the same HPV infections. Here, we determined the characteristics of the concordant samples (all four assays returning a positive HPV test result) and discordant samples (all other HPV-positive samples) in primary cervical screening at 30 to 65 years of age (n = 2,859) and in a concurrent referral population from the same catchment area (n = 885). HPV testing followed the manufacturers' protocols. Women with abnormal cytology were managed according to the routine recommendations. Cytology-normal/HPV-positive women were invited for repeated testing in 18 months. Screening history and histologically confirmed cervical intraepithelial neoplasia (CIN) in 2.5 years after the baseline testing were determined from the national pathology register. HPV-positive women undergoing primary screening having concordant samples were more likely to harbor high-risk infections and less likely to harbor only low-risk infections than women with discordant samples. Additionally, assay signal strengths were substantially higher in concordant samples. More than 80% of ≥CIN2 results were found for women with concordant samples, and no ≥CIN2 results were found when the infection was detected by only one assay. These patterns were similar in the referral population despite the younger age and higher number of HPV infections. HPV test result discordance identified a cluster of low-risk HPV infections that were hardly ever associated with high-grade CIN and, almost exclusively, represented false-positive screening findings.

Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays: split-sample study

Abstract: High-risk Human Papillomavirus (HPV) testing is replacing cytology in cervical cancer screening as it is more sensitive for preinvasive cervical lesions. However, the bottleneck of HPV testing is the many false positive test results (positive tests without cervical lesions). Here, we evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed no or limited frequency of cross-reactivity. In this independent study we evaluated the frequency of cross-reactivity for HC2, cobas, and APTIMA assays. Consecutive routine cervical screening samples from 5022 Danish women, including 2859 from women attending primary screening, were tested with the three evaluated DNA and mRNA HPV assays. Genotyping was undertaken using CLART HPV2 assay, individually detecting 35 genotypes. The presence or absence of cervical lesions was determined with histological examinations; women with abnormal cytology were managed as per routine recommendations; those with normal cytology and positive high-risk HPV test results were invited for repeated testing in 18 months. Cross-reactivity to low-risk genotypes was detected in 109 (2.2 %) out of 5022 samples on HC2, 62 (1.2 %) on cobas, and 35 (0.7 %) on APTIMA with only 10 of the samples cross-reacting on all 3 assays. None of the 35 genotypes was detected in 49 (1.0 %), 162 (3.2 %), and 56 (1.1 %) samples, respectively. In primary screening at age 30 to 65 years (n = 2859), samples of 72 (25 %) out of 289 with high-risk infections on HC2 and < CIN2 histology were due to cross-reactivity. On cobas, this was 106 (26 %) out of 415, and on APTIMA 48 (21 %) out of 224. Despite manufacturer claims, all three assays showed cross-reactivity. In primary cervical screening at age ≥30 years, cross-reactivity accounted for about one quarter of false positive test results regardless of the assay. Cross-reactivity should be addressed in EU tenders, as this primarily technical shortcoming imposes additional costs on the screening programmes.

Occupation and Risk of Bladder Cancer in Nordic Countries.

Abstract: Objective:The aim of this study was to describe the occupational variation in the incidence of kidney cancer in the Nordic population.Methods:The population comprised of 14.9 million individuals included in censuses between 1960 and 1990. Standardized incidence ratios (SIRs) were calculated for each

Colorectal cancer mortality 10 years after a single round of guaiac faecal occult blood test gFOBT screening: experiences from a Danish screening cohort

Abstract: Background In Denmark, colorectal cancer (CRC) is the third most frequent cancer. Randomised trials have shown that guaiac faecal occult blood test (gFOBT) screening can reduce CRC mortality, but a recent large randomised study from Finland did not find any effect. A feasibility study was carried out in Denmark in 2005–2006 where residents aged 50–74 years in 2 Danish counties were invited once to participate in gFOBT screening. We used the unique Danish registers to assess the impact of gFOBT screening in this group on CRC incidence and mortality. Methods In this cohort study, we followed a group comprising 166 277 individuals invited to screening and a reference group comprising the remaining 1 240 348 Danes of the same age. We linked the Danish population and health service registers to obtain information about colonoscopies, polypectomies, incident CRC and cause of death. Results After a median follow-up time of 8.9 years, the CRC mortality was significantly lower in the screening group than in the reference group with an adjusted HR (aHR) of 0.92 (95% CI 0.86 to 0.99), while the aHR for all-cause mortality was 0.95 (95% CI 0.94 to 0.96). For screening participants, the aHR for CRC mortality and all-cause mortality was 0.72 (0.64 to 0.80) and 0.59 (0.57 to 0.60), respectively. Conclusions About 10 years after a single round of gFOBT screening, we found a significant 8% deficit in CRC mortality in the screening group compared with other Danes. We found almost the same deficit in all-cause mortality, and on this basis, it is not possible to conclude that one screening round had an effect on CRC mortality. Our study indicated that close monitoring of the outcome of CRC screening is warranted.

P032 Occupational solvent exposure and risk of bladder cancer in the nordic countries

Abstract: Introduction Bladder cancer risk is suggested to vary between occupational categories. We assessed the occupational variation in incidence of bladder cancer and relationship with chemical solvent exposures in the Nordic countries. Methods The study is based on Nordic Occupational Cancer Study (NOCCA). Data consist of 14.9 million individuals of age 30 to 64 years from the Nordic countries who participated in one or more population censuses since 1960 and were followed up for 45 years. During the follow-up 148,669 cases of bladder cancer were detected. Standardised incidence ratio with 95% of confidence interval (CI) was used to describe the variation in bladder cancer risk in comparison to the national average. Quantitative estimates of solvents exposure for 113,343 bladder cancer cases and 566,715 population controls were assigned using Nordic job exposure matrix. Hazard ratios (HR) and 95% CI: for each solvent was estimated using conditional logistic regression. Results Highest statistically significant risks were observed among tobacco workers (SIR 1.57, 95% CI: 1.24–1.96), chimney sweeps (1.48, 1.21–1.80), waiters (1.43, 1.33–1.53), hairdressers, seamen, printers, plumbers. Significant decreased risks were observed among farmers (0.70, 0.68–0.71) and forestry workers (0.74, 0.70–0.78). Significantly increasing trends in SIR over the years were observed among drivers and launderers. The occupational risk associated with the chemical solvent at highest exposure levels (>90th percentile of the exposed persons) were aliphatic and alicyclic hydrocarbon solvent (HR 1.08, 95% CI: 1.00–1.23), benzene (1.16, 1.04–1.31), toluene (1.20, 1.00–1.38) and trichloroethylene (1.23, 1.12–1.40). Conclusion Occupation is evidently associated with bladder cancer risk. Part of that variation appears to be attributable to solvent exposures.

Consequences of a false-positive mammography result: drug consumption before and after screening.

Abstract: Background Previous research showed women experiencing false-positive mammograms to have greater anxiety about breast cancer than women with normal mammograms. To elucidate psychological effects of false-positive mammograms, we studied impact on drug intake. Methods We calculated the ratio of drug use for women with false-positive versus women with normal mammograms, before and after the event, using population-based registers, 1997-2006. The ratio of the ratios (RRR) assessed the impact. Results Before the test, 40.3% of women from the false-positive group versus 36.2% from the normal group used anxiolytic and antidepressant drugs. There was no difference in use of beta blockers. Hormone therapy was used more frequently by the false-positive, 36.6% versus 28.7%. The proportion of women using anxiolytic and antidepressant drugs increased with 19% from the before to the after period in the false-positive group, and with 16% in the normal group, resulting in an RRR of 1.02 (95% CI 0.92-1.14). RRR was 1.03 for beta blockers, 0.97 for hormone therapy. Conclusion(s) Drugs used to mitigate mood disorders were used more frequently by women with false-positive than by women with normal mammograms already before the screening event, while the changes from before to after screening were similar for both groups. The results point to the importance of control for potential selection in studies of screening effects.