Long-term risk of cervical cancer following conization of cervical intraepithelial neoplasia grade 3-A Danish nationwide cohort study.

Using nationwide Danish registries we examined the long-term risk of cervical cancer in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (including adenocarcinoma in situ (AIS)) on the cone compared to women with a normal cytology test. Initially, we identified women born 1918-1990, who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. From the Pathology Data Bank information on CIN3 on the cone, margins status, histological type of CIN3 and cervical cytology results was extracted. Cox proportional hazard model was used to estimate the relative risk of subsequent cervical cancer. We included 59,464 women with CIN3 on the cone and 1,918,508 women with a normal cytology test. Overall, women diagnosed with CIN3 had a higher risk of subsequent cervical cancer compared to women with normal cytology (HR = 2.06; 95%CI: 1.81-2.35). Analyses according to time since conization showed elevated risks in all time periods, and 25 years or more after conization the relative risk was significantly increased (HR = 2.56; 95%CI: 1.37-4.77). Twenty years or more after conization, also women with negative margins had an increased relative risk (HR = 2.49; 95%CI: 1.12-5.57). In addition, the long-term relative risk of cervical cancer varied with the different histological types of CIN3 and was highest for AIS (HR = 7.50; 95%CI: 1.87-30.01, 10-14 years after conization). In conclusion, women diagnosed with CIN3 on the cone have a long-lasting increased risk of cervical cancer even when the margins on the cone are negative.

Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia: A Danish Nationwide Cohort Study.

BACKGROUND: High-risk human papillomavirus (HPV) is essential for developing high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) and has also been associated with noncervical anogenital cancers. However, limited knowledge exists about the long-term risk for anal, vulvar, and vaginal cancer following CIN2 or CIN3 diagnosis. METHODS: In a nationwide cohort study, we followed nearly 2.8 million women born in 1918-1990 who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. The cohort was linked to multiple nationwide registers to obtain information on cancer diagnoses and confounders. Follow-up started when the women reached 18 years, date of immigration, or January 1978, and continued until emigration, death, December 31, 2012, or the date of first diagnosis of anogenital or rectal cancer. RESULTS: Women with a history of CIN2 or CIN3 had higher risks for subsequent anal, vulvar, and vaginal cancer than women with no such history. The relative risks were higher for CIN3 than CIN2. No excess risk was found for rectal cancer. Analyses in which time since first CIN3 was taken into account showed increased relative risks for anal [HR = 4.8; 95% confidence interval (CI), 3.3-7.0], vulvar (HR = 3.2; 95% CI, 2.0-5.3), and vaginal (HR = 5.5; 95% CI, 2.4-12.3) cancers ≥25 years after CIN3 diagnosis. CONCLUSION: Women with a history of CIN2 or CIN3 have a long-term increased relative risk for developing anal, vulvar, and vaginal cancer due to an impaired ability to control a persistent HPV infection. IMPACT: This finding adds to our understanding of the relation between HPV infection and noncervical anogenital cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1090-7. ©2016 AACR.

Alcohol intake in pregnancy increases the child's risk of atopic dermatitis. the COPSAC prospective birth cohort study of a high risk population.

BACKGROUND: Atopic dermatitis has increased four-fold over the recent decades in developed countries, indicating that changes in environmental factors associated with lifestyle may play an important role in this epidemic. It has been proposed that alcohol consumption may be one contributing risk factor in this development. OBJECTIVE: To analyze the impact of alcohol intake during pregnancy on the development of atopic dermatitis during the first 7 years of life. METHOD: The COPSAC cohort is a prospective, longitudinal, birth cohort study of 411 children born to mothers with a history of asthma, followed up for 7 years with scheduled visits every 6 months as well as visits for acute exacerbations of atopic dermatitis. Risk of atopic dermatitis from any alcohol consumption during pregnancy was analyzed as time-to-diagnosis and adjusted for known risk factors. RESULTS: 177 of 411 children developed atopic dermatitis before age 7 years. We found a significant effect of alcohol intake during pregnancy on atopic dermatitis development (HR 1.44, 95% CI 1.05-1.99 p=0.024). This conclusion was unaffected after adjustment for smoking, mother's education and mother's atopic dermatitis. LIMITATIONS: The selection of a high-risk cohort, with all mothers suffering from asthma, and all children having a gestational age above 35 weeks with no congenital abnormality, systemic illness, or history of mechanical ventilation or lower airway infection. CONCLUSION: Alcohol intake by pregnant women with a history of asthma, is significantly associated with an increased risk for the child for developing atopic dermatitis during the first 7 years of life.

Obesity, inflammation and metabolic syndrome in Danish adolescents.

AIM: To describe biomarkers of inflammation and markers related to the metabolic syndrome (MS) in healthy obese Danish adolescent and compare to a normal-weight group. METHODS: Fifty-one obese and 30 normal-weight adolescents (12-15 years) were included. Anthropometry and blood pressure were measured, and blood was sampled. RESULTS: Obese adolescents had significantly higher blood pressure, insulin, homeostasis model assessment of insulin resistance, C-peptide, total cholesterol, low-density lipoprotein cholesterol (LDL), triglyceride, C-reactive protein (CRP), interleukin-6 and tumour necrosis factor alpha and lower high-density lipoprotein cholesterol values, compared with normal-weight adolescents, whereas there were no differences between the groups for glucose, free fatty acids or faecal calprotectin. Within the obese group insulin, low-density lipoprotein cholesterol, and CRP were positively associated with body mass index (BMI) Z-scores. The MS was present in 14% of obese adolescents. CRP was positively associated with most anthropometric measures within the obese group, and in multiple linear regression analysis both BMI Z-score and the sum of skin folds explained a considerable part (R(2) = 0.421) of the variation in CRP. CONCLUSION: Otherwise healthy Danish obese adolescents had marked low-grade inflammation, elevated biomarkers of the MS and high prevalence of the MS.