Overweight and obesity as risk factors for cervical cancer and detection of precancers among screened women: A nationwide, population-based cohort study.

OBJECTIVE: Obesity is a known risk factor for many types of cancer. However, there is no clear evidence whether overweight and obesity increases the risk of cervical cancer. We investigated the association between body mass index (BMI) and detection of squamous and glandular cervical cancer and precancer. METHODS: Based on the Medical Birth Registry, we conducted a nationwide cohort study in Denmark of 384,559 women with BMI ≥18.5 kg/m2 (pre-pregnancy BMI reported at the start of the pregnancy) having a cervical cytology screening at age 23-49 years within 5 years following the date of childbirth. The cohort was followed for 10 years from the first cervical cytology screening after the childbirth. We assessed absolute risks of cervical lesions according to BMI with the Aalen-Johansen estimator. We conducted Cox proportional hazards regression analyses to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses were adjusted for age, calendar year, parity, oral contraception use, HPV vaccination, smoking, country of origin, and education. RESULTS: Overweight and obesity were associated with higher rates of cervical cancer (HR = 1.24, 95% CI 1.04-1.49 and HR = 1.14, 95% CI 0.91-1.43, respectively) and lower rates of cervical precancer detection (HR = 0.88, 95% CI 0.84-0.92 and HR = 0.67, 95% CI 0.63-0.71, respectively). CONCLUSIONS: Higher than normal BMI was associated with higher incidence rates of cervical cancer and lower rates of precancer detection, emphasizing the importance of further research in possible mechanisms behind this association.

The influence of overweight and obesity on participation in cervical cancer screening: A systematic review and meta-analysis.

The prevalence of obesity is increasing worldwide. The incidence of cervical cancer has decreased after implementation of cervical cancer screening, however, obese women have higher risk of cervical cancer than women of normal weight. This might be caused by a lower participation rate in cervical cancer screening. The aim of this systematic review and meta-analysis was to examine the influence of overweight and obesity on adherence to cervical cancer screening recommendations. We conducted a thorough systematic literature search of electronic databases to identify studies examining screening participation among overweight and obese women compared to women of normal weight. Based on a random effect model, we calculated pooled odds ratios (OR) of screening participation with corresponding 95% confidence intervals (CI). I2 statistic was used to describe heterogeneity. A total of 32 papers were included. The pooled OR of screening participation was 0.94 (95%CI: 0.89-0.99) for overweight women and 0.79 (95%CI: 0.68-0.92) for obese women compared to women of normal weight. The heterogeneity was substantial (overweight: I2 = 89%; obese: I2 = 93%). The OR for screening adherence was 0.91 (95%CI: 0.80-1.05), 0.85 (95%CI: 0.70-1.03) and 0.67 (95%CI: 0.54-0.84) for women in obesity class I, II and III, respectively. The OR varied by geographical region and race. In conclusion, obese women are less likely to participate in cervical cancers screening compared to women of normal weight. In addition, the likelihood of adherence to screening recommendations decreases with increasing obesity class. This stresses the need for targeted intervention to increase screening adherence for overweight and obese women.

Women with obesity participate less in cervical cancer screening and are more likely to have unsatisfactory smears: Results from a nationwide Danish cohort study.

Some studies found an association between obesity and increased cervical cancer risk, but potential mechanisms are unknown. In this nationwide register-based cohort study, we investigated the association between overweight/obesity and cervical cancer screening participation and risk of unsatisfactory smears. The study population was identified in the Danish Medical Birth Registry. We included 342,526 women aged 23-49 years with pre-pregnancy body mass index (BMI) registered during 2004-2013. Screening participation and unsatisfactory smears during up to four years after child birth were identified in a nationwide pathology register. We used absolute risk regression to estimate the relative absolute risk (RAR) with 95% confidence intervals (CIs) of screening participation according to BMI, adjusted for age, calendar year, sociodemographic characteristics, parity and previous high-grade cervical intraepithelial neoplasia. Among those who were screened (n = 295,482), we used log-binomial regression to investigate the relative risk (RR) of an unsatisfactory smear according to BMI, adjusted for age, year, parity, oral contraceptive use and pathology department. A lower proportion of obese women (79.3%) than women of normal weight (85.8%) were screened, and obese women had lower adjusted probability of being screened than women of normal weight (RARadjusted = 0.94, 95% CI, 0.93-0.95). A higher proportion of obese women (2.4%) than women of normal weight (1.7%) had an unsatisfactory smear, and this association remained after adjustments (RRadjusted = 1.28, 95% CI, 1.19-1.38). In conclusion, women with obesity were less likely to participate in cervical cancer screening and more likely to have an unsatisfactory smear than women of normal weight.

Changes in Drinking Patterns, and Attitudes Toward and Knowledge About Alcohol Consumption During Pregnancy in a Population of Pregnant Danish Women.

BACKGROUND: In 1997, The Danish Health Authority recommended that "it is safest not to drink alcohol when you are pregnant," and in 1999 expanded recommendations. There are only a few studies evaluating the possible change of average alcohol consumption following changes in national recommendations, and no studies have been found comparing the changes in pregnant women's attitudes toward alcohol consumption during pregnancy. We aimed to evaluate the changes in drinking pattern, and knowledge about and attitudes toward alcohol consumption during pregnancy before and after the change of national recommendations. METHODS: This is a cross-sectional interview study with a representative sample of 1,418 woman attending antenatal care at the beginning of their second trimester in Aarhus, Denmark, in the year 2000, and a comparable sample of 439 pregnant women from 1998 in Aarhus. Participants were interviewed about their average alcohol consumption, binge drinking, and attitudes toward and knowledge about alcohol consumption during pregnancy. Data collection procedures and questions were identical for both samples. RESULTS: There were no differences between the 2 samples in terms of average alcohol consumption before (p = 0.19) and during (p = 0.45) pregnancy, and binge drinking in early pregnancy (p = 0.47). Attitudes toward and knowledge about alcohol in pregnancy did not change either (p > 0.5). Women's knowledge about guidelines was less precise in 2000 (p < 0.001). Worse knowledge was associated with younger age considering both samples (OR = 2.63, 95% CI: 1.63 to 4.26). Most pregnant women reported that they had not been informed or advised about alcohol consumption during pregnancy, but they would like to be advised by their healthcare professionals. CONCLUSIONS: After the changes in the national guidelines about alcohol consumption during pregnancy, there were no changes in behavior, attitudes, and knowledge of pregnant women. This would indicate that healthcare specialists should be encouraged to initiate a conversation about alcohol consumption during the first antenatal visit.

Perceived changes in knowledge and confidence of doctors and midwives after the completion of the Standardized Trainings in Obstetrical Emergencies.

BACKGROUND AND OBJECTIVES: There are only few training programs in obstetric emergencies currently in use and only some of them were evaluated with an adequate sample of participants. Therefore, we present the evaluation of the novel Standardized Trainings in Obstetrical Emergencies (STrObE), conducted in Lithuania. The aim of this study was to analyze whether participants' self-reported knowledge and confidence increased after the trainings, and whether the impact of the trainings was long-lasting. MATERIALS AND METHODS: Data was collected across the majority of hospitals providing secondary and tertiary obstetrical care in Lithuania in 2015. A total of 650 obstetricians-gynecologists and midwives attended the trainings; 388 (response rate 59.7%) of them filled in the initial questionnaire before the trainings, 252 (64.9%) immediately after, 160 (41.2%) 6 weeks after, and 160 (41.2%) 6 months after the trainings, which was the final sample for the analyses. Participants used a Likert-type scale to evaluate their knowledge and confidence about management of urgent obstetrical situations: vacuum-assisted vaginal delivery, shoulder dystocia, postpartum hemorrhage, preeclampsia/eclampsia, early preterm labor, and dystocia. We assessed how participants' self-reported knowledge and confidence changed after the trainings (compared to before the trainings) and how long the effect was retained for. RESULTS: The mean score of self-reported knowledge in obstetrical emergencies increased immediately after the trainings comparing to the scores before the trainings (P<0.001) and it did not differ further between the three time points after the trainings (i.e. immediately, 6 weeks, and 6 months; P>0.05). The same pattern was observed for self-reported confidence scores. The increase in self-reported knowledge and confidence after the trainings was stable. Moreover, the self-reported knowledge and confidence gains were greater for those participants with lower work experience, although benefit was seen across all experience levels. CONCLUSIONS: STrObE improved participants' self-reported knowledge and confidence and lasting positive effects were observed for at least 6 months after the initial trainings. Moreover, the trainings were more beneficial for those with lower work experience, although they benefited all the participants.

Prepregnancy Body Mass Index and Risk of Differentiated Thyroid Cancer: A Prospective Cohort Study of More than 440,000 Danish Women.

Background: High body mass index (BMI) has previously been associated with increased risk of differentiated thyroid cancer (DTC); however, only few studies have investigated the association with BMI in a large cohort assessed at a young age and with sufficient data on confounding factors. We assessed the association between excess body weight and the risk of DTC and papillary thyroid cancer (PTC) in a large cohort of young Danish women with substantial confounder control. Methods: We included all parous Danish women registered with a prepregnancy BMI ≥18.5 kg/m2 during 2004-2016 in the Danish Medical Birth Registry in the study population. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) with confidence intervals (CIs) of DTC according to BMI. In subanalyses, we investigated PTC as a separate group. Analyses were adjusted for calendar time, education, smoking status, benign thyroid disease (BTD), type II diabetes, parity, and oral contraceptive use. In addition, we examined the association with increasing BMI stratified for previous BTD. Results: A total of 443,403 women were included in the study population, and the median age at baseline was 30.0 years. Altogether, 463 women were diagnosed with DTC during follow-up. Excess body weight was associated with a higher rate of DTC (overweight, BMI 25-29.9 kg/m2: HR = 1.54; CI 1.25-1.90. Obese, BMI ≥30 kg/m2: HR = 1.32; CI 1.00-1.75) compared with normal weight. Results were similar in PTC. In addition, we found an increased rate of DTC with increasing BMI, when investigating BMI as a continuous variable per 5 kg/m2 increase (HR = 1.17; CI 1.07-1.27). The results were similar in women without previous BTD. Conclusions: Our study confirms that excess body weight is associated with an increased incidence of DTC and PTC in women.

Early adulthood overweight and obesity and risk of premenopausal ovarian cancer, and premenopausal breast cancer including receptor status: prospective cohort study of nearly 500,000 Danish women.

PURPOSE: To assess the association between higher-than-normal BMI and incidence of premenopausal ovarian and breast cancers. METHODS: This prospective cohort study included 461,646 women registered in the Danish Medical Birth Registry with self-reported early adulthood BMI ≥18.5 kg/m2, without a history of cancer. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CIs) of premenopausal epithelial ovarian cancer, breast cancer, estrogen receptor positive and negative, HER2 positive and negative breast cancers according to BMI. RESULTS: Compared with normal weight, obesity was associated with higher rates of premenopausal ovarian cancer (HR = 1.95, 95% CI 1.19-3.21) when adjusted for parity, use of hormonal contraception, family history of ovarian and/or breast cancer, other cancer, and calendar year. Obesity was associated with lower rates of premenopausal breast cancer (HR = 0.77, 95% CI 0.68-0.87) when adjusted for parity, use of hormonal contraception, family history of ovarian and/or breast cancer, any other cancer, calendar year, smoking, and highest achieved education. The associations were strongest with estrogen receptor positive premenopausal breast cancers. Results according to HER2 status were similar to overall results for premenopausal breast cancer. CONCLUSIONS: Obesity was associated with higher incidence of premenopausal ovarian cancer and lower incidence of premenopausal breast cancer.

Temporal Trends in Papillary and Follicular Thyroid Cancer Incidence from 1995 to 2019 in Adults in Denmark According to Education and Income.

Background: Thyroid cancer incidence has increased over the past decades. Differences in incidence trends have been observed depending on socioeconomic status. Here, we describe trends in the incidence of papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) in Denmark by level of education and income. Methods: All PTC and FTC cases registered in the Danish Cancer Registry from 1995 to 2019 were identified. Individual-level information on education and income was obtained from nationwide registries. We calculated age-standardized incidence rates according to sex, tumor size, education and income, and estimated incidence trends by average annual percentage change (AAPC) and corresponding confidence intervals [CIs] for the periods 1995 to 2004 and 2005 to 2019 by using Poisson regression models. Results: We identified 3454 cases of PTC and 972 cases of FTC. From 2005 to 2019 among women, the incidence of PTC increased across all levels of education (AAPCshort education = 12.5% [CI 9.8 to 15.3]; AAPCmedium education = 8.1% [CI 6.4 to 9.9]; AAPClong education = 7.3% [CI 5.4 to 9.2]). The same pattern was seen for income. The incidence of FTC increased in all levels of education (AAPCshort education = 10.5% [CI 5.8 to 15.4]; AAPCmedium education = 4.0% [CI 0.9 to 7.3]; AAPClong education = 4.3% [CI 0.6 to 8.1]), with the same pattern for income. Similar trends were observed among men, in both small (≤2 cm) and large (>2 cm) PTCs and from 1995 to 2004 in both sexes. Conclusions: Enhanced detection of thyroid cancer among all levels of education and income cannot be ruled out, and in addition, our results may suggest a true increase in the incidence of differentiated thyroid cancer.

Trends in incidence and survival from anal cancer and incidence of high-grade anal intraepithelial neoplasia in Denmark.

OBJECTIVE: The aim of the current study was to assess temporal trends in incidence of anal squamous cell carcinomas (SCC) and high-grade anal intraepithelial lesions (AIN2/3), and estimate survival from anal cancer and factors related to 5-year mortality in Denmark. METHODS: We analyzed anal SCC and AIN2/3 cases in the period of 1998-2018 from the Danish Cancer Register and the Danish Registry of Pathology, respectively. Overall, period, gender, and histology specific age-standardized incidence rates, average annual percentage change (AAPC), and 5-year relative survival were estimated. Cox proportional hazards models were applied to evaluate the effect on 5-year mortality of period, age, gender, and stage of disease. RESULTS: Altogether 2580 anal cancers and 871 AIN2/3 were identified. The AIN2/3 incidence increased for women 1998-2007 (AAPC: 3.5% (95% CI -0.7, 8.0)) and then tended to decrease during 2008-2018(AAPC: -5.2% (95% CI -9.6, -0.6)). A similar pattern was observed for men, although at a lower incidence with the decrease starting later (2008-2012) and the trend not reaching statistical significance. The anal SCC incidence increased over the whole study period for both women and men (women AAPC: 4.0% (95% CI 3.2%, 4.9%) and men AAPC: 3.6% (95% CI 2.3%, 4.9%)). The relative survival improved over time (from 61% to 72%). Being older and male was associated with a higher risk of dying within 5 years. CONCLUSIONS: There is a need to focus attention on anal cancer and its precursor lesions, as the cancer incidence continues to increase. Actions could include screening and gender-neutral HPV vaccination.

Trends in rectal cancer incidence, relative survival, and mortality in Denmark during 1978-2018.

OBJECTIVE: Rectal cancer is common in developed countries, though incidence varies globally. We assessed time trends in incidence, relative survival and mortality in Denmark. METHODS: Rectal cancer cases ( N = 50 461) diagnosed in 1978-2018 were identified in the Danish Cancer Registry. We calculated age-standardized incidence rates, overall and according to sex and age. Average annual percentage changes (AAPC) were estimated using Poisson regression. We estimated 5-year relative survival and evaluated the effect of age, calendar year of diagnosis, sex and stage of disease on mortality using the Cox proportional hazards model. RESULTS: The incidence of rectal cancer tended to decrease in all age groups and both sexes during 1978-1997, but increased since 1998, more in men (AAPC = 2.05%; 95% CI,1.80; 2.31) than in women (AAPC = 0.99%; 95% CI,0.68; 1.30). It increased in men until 79 years and in women up to 59 years. Mortality decreased over time when adjusting for age, stage and sex. Overall, men had the highest 5-year mortality after adjusting for age, calendar period and stage. Five-year relative survival improved (1978-2018) for all stages. Initially, the overall 5-year relative survival tended to be better for women, but in recent years, it has been similar in both sexes. CONCLUSION: Incidence of rectal cancer increased in the last two decades, most markedly in women 59 years and younger. Mortality decreased when adjusting for age and stage. Relative survival improved over time more for men than for women, so in recent years, it has been virtually identical in men and women.

Prognostic value of high-risk human papillomavirus DNA and p16INK4a immunohistochemistry in patients with anal cancer: An individual patient data meta-analysis.

BACKGROUND: High-risk human papillomavirus (hrHPV) types represent the aetiological agents in a major proportion of anal squamous cell carcinomas (ASCC). Several studies have suggested a prognostic relevance of HPV-related markers, particularly hrHPV DNA and p16INK4a (p16) protein expression, in patients with ASCC. However, broader evaluation of these prognostic marker candidates has been hampered by small cohort sizes and heterogeneous survival data among the individual studies. We conducted an individual patient data (IPD) meta-analysis to determine the prognostic value of hrHPV DNA and p16 in patients with ASCC while controlling for major clinical and tumour covariates. PATIENTS AND METHODS: A systematic literature search was conducted to identify all published studies analysing p16 alone or in combination with hrHPV DNA and reporting survival data in patients with ASCC. Clinical and tumour-related IPD were requested from authors of potentially eligible studies. Survival analyses were performed with a proportional hazard Cox model stratified by study and adjusted for relevant covariates. The study-specific hazard ratios (HRs) for the exposures were pooled using a random-effects model. Kaplan-Meier curves from different studies were pooled per exposure group and weighted by the study's total sample size. RESULTS: Seven studies providing IPD from 693 patients with ASCC could be included in the meta-analysis. Seventy-six percent of patients were p16+/hrHPV DNA+, whereas 11% were negative for both markers. A discordant marker status was observed in 13% of cases. Patients with p16+/hrHPV DNA+ ASCC showed significantly superior overall survival (OS) compared with patients with p16-/hrHPV DNA- tumours (pooled adjusted HR = 0.26 [95% confidence interval {CI}, 0.14-0.50]) with pooled three-year OS rates of 86% (95% CI, 82-90%) versus 39% (95% CI, 24-54%). Patients with discordant p16 and hrHPV DNA status showed intermediate three-year OS rates (75% [95% CI, 56-86%] for p16+/hrHPV DNA- and 55% [95% CI, 35-71%] for p16-/hrHPV DNA+ ASCC). CONCLUSION: This first IPD meta-analysis controlling for confounding variables shows that patients with p16+/hrHPV DNA+ ASCC have a significantly better survival than patients with p16-/hrHPV DNA- tumours.

The role of body mass index in incidence and persistence of cervical human papillomavirus infection.

PURPOSE: This study aimed to assess the association between body mass index and incident or persistent cervical high-risk human papillomavirus (hrHPV) infection. METHODS: This cohort study included 6809 women from the general Danish population who participated in two clinical visits (in 1991-1993 and in 1993-1995). Height and weight were measured by nurses, lifestyle data were obtained by structured interviews, and cervical cytology samples were obtained for hrHPV DNA testing. We conducted log-binomial regression to estimate risk ratios (RRs) with 95% confidence intervals (CIs) of incident and type-specific persistent hrHPV infection according to body mass index, adjusting for age, education, smoking, and the number of sexual partners in the past year. RESULTS: We found no increased risk of incident hrHPV infection in women who were underweight (RRadjusted, 0.97; 95% CI, 0.64-1.48), overweight (RRadjusted, 0.98, 95% CI, 0.82-1.17), or obese (RRadjusted, 0.93; 95% CI, 0.63-1.36) compared with women of normal weight. The risk of hrHPV persistence was similar in overweight (RRadjusted, 0.98; 95% CI, 0.71-1.34) and obese (RRadjusted, 1.00; 95% CI, 0.56-1.79) women compared with women of normal weight, whereas underweight women had a lower risk (RRadjusted, 0.32; 95% CI, 0.11-0.95). CONCLUSIONS: Overweight and obesity were not associated with HPV incidence or persistence when adjusting for sexual behavior.

Prognostic Significance of HPV DNA and p16INK4a in Anal Cancer: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis of observational studies evaluating survival in patients with anal cancer, according to human papillomavirus (HPV) DNA, p16INK4a, and combined HPV DNA/p16INK4a status. We systematically searched PubMed, EMBASE, and Cochrane Library databases to identify studies published in English until July 25, 2018, directly providing or allowing estimation of survival of patients with anal cancer according to the presence of HPV DNA and/or overexpression of p16INK4a We estimated pooled HRs and 95% confidence intervals (CI) for overall survival (OS) using a random-effects model. We included 16 studies, comprising 1,724 patients with anal cancer tested for HPV DNA (65% positive), and 567 patients tested for p16INK4a (87% positive). The pooled HR for OS was 0.54 (95% CI, 0.33-0.89) for HPV DNA positive versus negative, 0.37 (95% CI, 0.24-0.57) for p16INK4a positive versus negative, and 0.36 (95% CI, 0.22-0.58) for HPV DNA positive/p16INK4a positive versus HPV DNA positive/p16INK4a negative patients with anal cancer. Patients with HPV DNA or p16INK4a positive anal cancer have significantly better OS compared with HPV DNA or p16INK4a negative. This points to the possible value of HPV DNA and/or p16INK4a testing when planning the management and follow-up strategy for patients diagnosed with anal cancer.