Background: Attention in the 2000s on the importance of mammographic density led us to study screening sensitivity, breast cancer incidence, and associations with risk factors by mammographic density in Danish breast cancer screening programs. Here, we summarise our approaches and findings. Methods: Dichotomized density codes: fatty, equal to BI-RADS density code 1 and part of 2, and other mixed/dense data from the 1990s—were available from two counties, and BI-RADS density codes from one region were available from 2012/13. Density data were linked with data on vital status, incident breast cancer, and potential risk factors. We calculated screening sensitivity by combining data on screen-detected and interval cancers. We used cohorts to study high density as a predictor of breast cancer risk; cross-sectional data to study the association between life style factors and density, adjusting for age and body mass index (BMI); and time trends to study the prevalence of high density across birth cohorts. Results: Sensitivity decreased with increasing density from 78% in women with BI-RADS 1 to 47% in those with BI-RADS 4. For women with mixed/dense compared with those with fatty breasts, the rate ratio of incident breast cancer was 2.45 (95% CI 2.14–2.81). The percentage of women with mixed/dense breasts decreased with age, but at a higher rate the later the women were born. Among users of postmenopausal hormone therapy, the percentage of women with mixed/dense breasts was higher than in non-users, but the patterns across birth cohorts were similar. The occurrence of mixed/dense breast at screening age decreased by a z-score unit of BMI at age 13—odds ratio (OR) 0.56 (95% CI 0.53–0.58)—and so did breast cancer risk and hazard ratio (HR) 0.92 (95% CI 0.84–1.00), but it changed to HR 1.01 (95% CI 0.93–1.11) when controlled for density. Age and BMI adjusted associations between life style factors and density were largely close to unity; physical activity OR 1.06 (95% CI 0.93–1.21); alcohol consumption OR 1.01 (95% CI 0.81–1.27); air pollution OR 0.96 (95% 0.93–1.01) per 20 μg/m³; and traffic noise OR 0.94 (95% CI 0.86–1.03) per 10 dB. Weak negative associations were seen for diabetes OR 0.61 (95% CI 0.40–0.92) and cigarette smoking OR 0.86 (95% CI 0.75–0.99), and a positive association was found with hormone therapy OR 1.24 (95% 1.14–1.35). Conclusion: Our data indicate that breast tissue in middle-aged women is highly dependent on childhood body constitution while adult life-style plays a modest role, underlying the need for a long-term perspective in primary prevention of breast cancer.

Early studies reported a 4‐ to 6‐fold risk of breast cancer between women with extremely dense and fatty breasts. As most early studies were case‐control studies, we took advantage of a population‐based screening program to study density and breast cancer incidence in a cohort design. In the Capital Region, Denmark, women aged 50 to 69 are invited to screening biennially. Women screened November 2012 to December 2017 were included, and classified by BI‐RADS density code, version 4, at first screen after recruitment. Women were followed up for incident breast cancer, including ductal carcinoma in situ (DCIS), to 2020 in nationwide pathology data. Rate ratios (RRs) and 95% confidence intervals (CI) were compared across density groups using Poisson‐regression. We included 189 609 women; 1 067 282 person‐years; and 4110 incident breast cancers/DCIS. Thirty‐three percent of women had BI‐RADS density code 1; 38% code 2; 24% code 3; 4.7% code 4; and missing 0.3%. Using women with BI‐RADS density code 1 as baseline; women with code 2 had RR 1.69 (95% CI 1.56‐1.84); women with code 3, RR 2.06 (95% CI 1.89‐2.25); and women with code 4, RR 2.37 (95% CI 1.05‐2.74). Results differed between observations accumulated during screening and above screening age. Our results indicated less difference in breast cancer risk across level of breast density than normally stated. Translated into absolute risk of breast cancer after age 50, we found a 6.2% risk for the one‐third of women with lowest density, and 14.7% for the 5% of women with highest density.

INTRODUCTION: We examined the association of long‐term exposure to air pollution and road traffic noise with dementia incidence in the Danish Nurse Cohort.METHODS: Female nurses were followed for dementia incidence (hospital contact or medication prescription) from 1993/1999 to 2020. Air pollution and road traffic noise levels were estimated at nurses’ residences, and their associations with dementia were examined using Cox regression models.RESULTS: Of 25,233 nurses 1409 developed dementia. Particulate matter with a diameter of ≤2.5 µm (PM_2.5) was associated with dementia incidence, after adjusting for lifestyle, socioeconomic status, and road traffic noise (hazard ratio [95% confidence interval] 1.35 [1.15–1.59] per interquartile range of 2.6 µg/m³). There was no association of PM2.5 with dementia in physically active nurses. Association with road traffic noise diminished after adjusting for PM₂.₅ (1.02 [0.93–1.11] per 7.6 dB).DISCUSSION: Long‐term exposure to air pollution increases risk of dementia, and physical activity may moderate this risk.Highlights: Long‐term exposure to air pollution was associated with increased risk of dementia among female nurses from the Danish Nurse Cohort. Association of air pollution with dementia was independent of road traffic noise. Association of road traffic noise with dementia diminished after adjusting for air pollution. Physical activity moderated adverse effects of air pollution on dementia.

4vHPV vaccination has been tested in randomized controlled trials under almost ideal conditions, and studies of real‐life use have compared outcome between vaccinated and unvaccinated women from the same birth cohort and mostly before screening age. Here we present the first—to our knowledge—evaluation of the impact of the 4vHPV vaccination in real life without selection bias in the reported data. The study has been carried out by comparing the results after first cervical screening between an HPV‐vaccinated and an unvaccinated birth cohort, consisting of women born in Denmark in 1993 and 1983, respectively. Cytology data covering an 8‐year period, from the age of 15 (age of HPV‐vaccination) to age 23 (age of invitation to first cervical screening), were retrieved from the Danish National Pathology Register. Abnormal cytology, defined as atypical squamous cell of undetermined significance and worse (ASCUS+) was detected in 9.4% of women born in 1993 as compared with 9.0% of women born in 1983; RR = 1.04 (95% CI 0.96–1.12), p = .29. Detection of high‐grade squamous intraepithelial lesion (HSIL) was statistically significantly lower in the 1993 than in the 1983 cohort, RR = 0.6 (95% CI 0.5–0.7), p < .0001, while the opposite pattern was seen for ASCUS RR = 1.4 (95% CI 1.2–1.6), p < .0001. The decrease in HSIL means that more women can be spared referral for colposcopy and biopsy. The increase of ASCUS could be explained by transition from conventional to liquid‐based cytology, but this observation requires further monitoring.

BACKGROUND: Danish women vaccinated with the 4-valent human papillomavirus (HPV) vaccine (HPV types: 6/11/16/18) at age 14 in 2008 reached screening age in 2017, allowing assessment of long-term effects on prevalence, persistence and incidence of HPV infections. AIM: To examine the HPV status of cervical samples over time among women vaccinated as girls. METHODS: Between February 2017 and February 2024, residual material from cytology-analysed samples collected through the ‘Trial23’ study, part of the national screening programme, was tested for HPV16/18 and non-vaccine high-risk (HR) HPV types. Prevalence in first, second and third samples, and persistence and incidence between samples were calculated. RESULTS: Over 7 years, 8,659 women provided at least one sample, 5,835 at least two and 2,461 at least three. In 7,800 vaccinated women, HPV16/18 prevalence was 0.4% (95% confidence interval (CI): 0.2–0.5), 0.3% (95% CI: 0.1–0.4) and 0.2% (95% CI: 0.0–0.4) in three consecutive samples. Prevalence of non-vaccine HR HPV was 32% (95% CI: 31–33), 28% (95% CI: 27–29) and 31% (95% CI: 29–33). Persistence of HPV16/18 and non-vaccine HPV among vaccinated women was 40% and 53%. In adjusted analyses comparing vaccinated vs unvaccinated women, incidence was significantly lower for HPV16/18 (adjusted relative risk (aRR) < 0.10) while incidence of non-vaccine HR HPV types was higher (aRR: 1.66; 95% CI: 1.12–2.45). No significant difference was observed for persistence. CONCLUSION: Our study provides real-world evidence of stable protection against HPV16/18 infections in women vaccinated as girls. Less intensive screening seems reasonable until women vaccinated with the 9-valent vaccine reach screening age, when screening should be reconsidered.

Rationale: Air pollution is a major risk factor for chronic cardiorespiratory diseases, affecting the immune and respiratory systems’ functionality, but epidemiological evidence in respiratory infections remains sparse. Objectives: We aimed to assess the association of long-term exposure to ambient air pollution with the risk of developing new and recurrent acute lower respiratory infections (ALRIs), characterized by persistently severe symptoms necessitating hospital contact, and identify the potential susceptible populations by socioeconomic status, smoking, physical activity status, overweight, and comorbidity with chronic lung disease. Methods: We followed 23,912 female nurses from the Danish Nurse Cohort (age >44 yr) from baseline (1993 or 1999) until 2018 for incident and recurrent ALRIs defined by hospital contact (inpatient, outpatient, and emergency room) data from the National Patient Register. Residential annual mean concentrations of fine particulate matter, nitrogen dioxide (NO2), and black carbon were modeled using the Danish Eulerian Hemispheric Model/Urban Background Model/Air Geographic Information System. We used marginal Cox models with time-varying exposures to assess the association of 3-year running mean air pollution level with incident and recurrent ALRIs and examined effect modification by age, socioeconomic status, smoking, physical activity, body mass index, and comorbidity with asthma or chronic obstructive pulmonary disease (COPD). Results: During a 21.3-year mean follow-up, 4,746 ALRIs were observed, of which 2,553 were incident. We observed strong positive associations of all three pollutants with incident ALRIs, with hazard ratios and 95% confidence intervals of 1.19 (1.08–1.31) per 2.5 μg/m3 for fine particulate matter, 1.17 (1.11–1.24) per 8.0 μg/m3 for NO2, and 1.09 (1.05–1.12) per 0.3 μg/m3 for black carbon, and slightly stronger associations with recurrent ALRIs. Associations were strongest in patients with COPD and nurses with low physical activity. Conclusions: Long-term exposure to air pollution at low levels was associated with risks of new and recurrent ALRIs, with patients with COPD and physically inactive subjects most vulnerable.