Search

Background: Childhood obesity can have significant negative consequences for children's wellbeing and long-term health. Prior school-based interventions to prevent child overweight and obesity have shown limited effects, highlighting the necessity for comprehensive approaches addressing complex drivers of childhood obesity. "Generation Healthy Kids" (GHK) is a multi-setting, multi-component intervention to promote healthy weight development, health and wellbeing in Danish children aged 6-11 years. This protocol describes the GHK main trial, which is a cluster-randomized trial evaluating effectiveness and implementation of the GHK intervention., Methods: Twenty-four schools from the Capital, Zealand and Southern Denmark Regions are randomly allocated 1:1 to intervention or control. The intervention will run for two school years (18-20 months) from October 2023 to June 2025 and will include children in 1st-3rd grade (approx. n = 1,600). The intervention targets multiple settings, including families, schools, after-school clubs, and local communities. Within four focus areas-diet, physical activity, screen media use, and sleep habits-the intervention incorporates several fixed elements, including a school lunch program and three weekly sessions of physical activity at school. Furthermore, building on whole-systems thinking, the intervention encompasses co-created elements developed in collaboration with local stakeholders, e.g. municipalities, sports clubs and supermarkets. This part of the intervention emphasizes building local capacity and engagement to promote child health. Effectiveness data will be collected from participating children and families at baseline, and at the end of school year one (after 6-8 months) and school year two (after 18-20 months). The primary outcome is the change in fat mass, measured by air-displacement plethysmography, from baseline to end-of-study in the intervention group compared to the control group. This is supplemented with numerous secondary outcomes and other prespecified outcomes related to child health and wellbeing. Furthermore, thorough process evaluation will be performed., Discussion: GHK combines evidence-based intervention elements targeting multiple settings with a whole-systems approach focusing on capacity building and stakeholder involvement. This novel approach holds promise as an innovative way to promote child health and wellbeing and prevent childhood obesity., Trial Registration: ClinicalTrials.gov: NCT05940675 (registered on 4 July 2023)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Thomsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Overweight and obesity among children is a serious public health challenge worldwide which may lead to a range of negative physical, mental, and social consequences in childhood and later in life. There is a strong need for developing new innovative, integrated approaches and programs which can prevent overweight in children effectively and can be embedded into everyday practices. The Generation Healthy Kids intervention is a multi-component, multi-setting intervention aiming to promote healthy weight and well-being in children aged 6-11 years in Denmark. The present study investigates the feasibility and acceptability of 10 selected school-based intervention components and barriers and facilitators for implementation., Methods: A seven-week feasibility study was conducted in January to March 2023 among children in 1st and 2nd grade at a Danish public school, testing the multi-component intervention targeting children's meal-, physical activity-, sleep- and screen habits. Process evaluation data were collected using multiple methods (surveys, logbooks, evaluation sheets, registrations, counts, interviews, and observations) and data sources (parents, school staff, and school leader)., Results: Most intervention components were feasible to deliver at the school, but only four components were fully delivered as intended, while the remaining components to some or low degree were delivered as intended. Some components were found acceptable by all/nearly all children (e.g., 40 min of high intensity training three times a week), and others by some or few children (e.g., reusable water bottles and midmorning snack). Intervention activities for the parents and families were found acceptable by all/nearly all participating parents. Parents' acceptability of the intervention activities delivered to their children at school could not be assessed, as only few parents participated in surveys and none in interviews. School staff's acceptability of the intervention tasks they were asked to deliver varied but was overall relatively high. Facilitators and barriers for implementation of intervention components were identified at both individual-, school class-, and school level., Conclusions: The study underlines the importance of conducting feasibility studies as preparation for large trials. The findings will be used to refine intervention components, implementation strategies and data collection procedures before the Generation Healthy Kids main trial., Competing Interests: Declarations Ethics approval and consent to participate The study was performed in accordance with the Declaration of Helsinki and was approved by The Regional Committee on Health Research Ethics for Southern Denmark (reference number S-20220059). Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study investigates the incidence and clearance of cervical and anal high-risk human papillomavirus (hrHPV) infection in kidney transplant recipients (KTRs) compared to immunocompetent controls. During 2016-2017, we enrolled 125 female KTRs and 125 female controls. Liquid-based cervical and anal cytology samples collected at enrollment and follow-up were tested for human papillomavirus (HPV) DNA using the CLART HPV2 test. All participants answered a questionnaire on lifestyle and sexual behavior at both examinations. KTRs had an increased age-adjusted risk of incident cervical hrHPV infection compared to controls (hazard ratio [HR] = 3.6, 95% CI = 1.2-11.2). Probability of cervical hrHPV clearance at 18 months was lower among KTRs (8.3%) than controls (66.7%). There was no statistically significant difference in anal hrHPV incidence between KTRs and controls (HR = 0.9, 95% CI = 0.4-2.0). Clearance of anal hrHPV was similar between KTRs and controls at 18 months. During the total follow-up, a lower anal hrHPV clearance, although not statistically significant, was observed among KTRs (HR = 0.3, 95% CI = 0.06-1.2). KTRs had higher incidence of cervical hrHPV and lower probability of clearance, especially of cervical hrHPV infections, than controls. Our findings support that KTRs are at increased risk of HPV infection and point to the need for targeted HPV prevention strategies, such as cervical cancer screening., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Susanne K. Kjær has received a research grant outside this study through her affiliating institution from Merck. Jesper H. Bonde’s institution has received research funding or consumables at reduced prices or for free to support research from BD Diagnostics, GeneFirst, SelfScreen, Qiagen, Seegene, and Roche Diagnostics. Jesper H. Bonde has received honoraria for lectures from BD Diagnostics, MSD, and Hologic Ltd. Jesper H. Bonde is an appointed member of the National Danish Cervical Screening Committee by the Danish Health Authority. Linea Landgrebe Ring, Helle Kiellberg Larsen, Merete Hædersdal, Søren Schwartz Sørensen, Kirsten Frederiksen, and Louise Thirstrup Thomsen have no conflicts of interest to disclose., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to investigate high-risk human papillomavirus (hrHPV) prevalence according to socioeconomic and demographic characteristics in a Danish screening population., Methods: We used data from HPV SCREEN DENMARK, which was an implementation study embedded into the routine cervical cancer screening programme. During 2017-2020, women aged 30-59 years screened in the Region of Southern Denmark were offered HPV testing or cytology. In the HPV group, liquid-based cytology samples were tested for 14 hrHPV types. We obtained registry information on socioeconomic and demographic characteristics and used log-binomial regression to estimate the prevalence ratio (PR) of hrHPV in three age groups (30-39, 40-49, 50-59 years), adjusting for age and marital status., Results: We included 31,124 HPV unvaccinated women. In all age groups, the age-adjusted hrHPV prevalence was higher in women with basic versus higher education (e.g. age 30-39: 11.9% vs . 9.5%; PR age-adjusted =1.24; 95% confidence interval (CI): 1.02-1.50); women who were unemployed vs . employed (e.g. age 30-39: 11.6% vs . 10.4%; PR age-adjusted =1.11; 95% CI: 0.95-1.28); and in women with highest vs . lowest income (e.g. age 30-39: 11.6% vs . 9.5%, PR age-adjusted =1.18, 95% CI: 0.98-1.44). In models adjusted for marital status, these associations largely disappeared., Conclusions: We found slightly higher hrHPV prevalences in women with basic education, low income and unemployment. The differences largely disappeared when taking into account marital status as a potential proxy for sexual behaviour. Our findings support a need for targeted information on safe sexual practices and promoting socioeconomic equality in HPV vaccination and cervical cancer screening participation., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SKK has received research grants through her institution from Merck.

Vulvar cancer is rare, but causes substantial morbidity in affected patients. A subset of vulvar cancers is caused by high-risk human papillomavirus (hrHPV), which primarily exerts its oncogenic effect through upregulation of tumor suppressor protein p16. Tumors positive for both hrHPV and p16 (double positive) are assumed to be HPV-driven, but only few large studies have investigated the combined prevalence of hrHPV and p16 positivity in vulvar cancer over time. In this Danish cross-sectional study, we assessed the prevalence of p16 positivity and double positivity for hrHPV and p16 in a large sample of vulvar squamous cell carcinomas (VSCCs) diagnosed during 1990 to 2017. In a nationwide register, we identified VSCCs from 13 hospitals across Denmark, and collected archival tumor tissue for hrHPV testing with INNO-LiPA and immunohistochemical p16 staining. We calculated the prevalence of hrHPV, p16 positivity and double positivity according to time, age and histological subtype and evaluated time trends through estimated annual percentage changes. We included 1278 VSCCs. Overall, 35.0% (95% confidence interval [CI]: 32.4-37.6) were positive for p16 and 31.0% (95% CI: 28.4-33.5) were positive for both hrHPV and p16. The prevalence of p16 positivity and double positivity increased over time, both in women aged ≤59 and ≥60 years. The double positive prevalence was higher in nonkeratinizing (60.7%) and warty/basaloid VSCCs (67.5%) than in keratinizing (16.1%) and verrucous VSCCs (5.0%). These results indicate that approximately one-third of vulvar cancers were caused by hrHPV infection, supporting a substantial preventive potential of the HPV vaccine., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Introduction: Based on the experience from a Swedish biobank, we established a clinical cervical cytology biobank and adapted it to a Danish setting. The aim of the present study was to validate the biobank material regarding quality and quantity, to determine the usefulness of the material for future diagnostics and biomarker testing. Methods: Cervical cytology samples collected in ThinPrep were analyzed before and after biobanking using p16/ki-67 dual staining, a human papillomavirus (HPV) DNA test (Cobas), and a test for HPV messenger RNA (mRNA; Aptima). The concordance of the test results before and after biobanking was assessed. We also evaluated the morphology before and after biobanking and did additional tests on the biobanked material to qualify the usefulness of the material (library preparation for next-generation sequencing [NGS], reverse transcription-polymerase chain reaction [RT-PCR], and the Inno-Lipa HPV genotyping test). Results: For the Cobas HPV test, the concordance was 92% (122/133), and for the Inno-Lipa test (30 samples), it was 100%. For the Aptima assay, the concordance was a little lower, 84% (42/50). The morphology of the cell was well preserved, and the concordance of the p16/ki-67 dual staining was 88% (37/42). The functional tests showed that DNA-based NGS libraries (TST15 panel; Illumina) had good quality parameters. However, with the RT-PCR, 12% of the samples showed poor quality and a too low input amount for the analysis. Conclusion: The quality of the biobanked samples is high, and the material is suitable for testing of DNA, RNA, and protein. However, for testing of specific biomarkers, pilot studies are recommended to ensure sufficient input amount and quality of the material, especially for RNA-based studies.

In Denmark, vaccination against human papillomavirus (HPV) has been implemented in the children's vaccination program (January 2009) and in multiple catch-up cohorts (October 2008 in girls 13-15 years and in August 2012 in women up to 27 years). In the present study we estimate incidence of cervical intraepithelial neoplasia grade 3 (CIN3), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (AC) during 2000-2019. All cases of CIN3 and AIS were identified from the nationwide Pathology Data Bank, while SCC and AC were identified from the Danish Cancer Registry. We calculated age-standardized incidence rates and estimated annual percentage change (EAPC) with corresponding 95% confidence interval (CI) for the periods before vaccination implementation (2000-2005), early after implementation of childhood HPV vaccination and the first catch-up vaccination program (2006-2012), and after implementation of the second catch-up program (2013-2019). For CIN3 and AIS, age-specific incidence rates and EAPCs were calculated. An increasing age-standardized incidence was observed before introduction of HPV vaccination (2000-2005) for CIN3 [EAPC CIN3 : 3.0 (95% CI 1.7 to 4.3)] and AIS [EAPC AIS : 3.5 (95% CI 0.7 to 6.4)]. In the most recent period (2013-2019), following implementation of the second catch-up program, a decrease was observed for both CIN3 [EAPC CIN3 : -6.5 (95% CI -8.3 to -4.8)], AIS [EAPC AIS : -8.7 (95% CI -12.3 to -5.1)] and for SCC [EAPC SCC : -3.9 (95% CI -7.5 to -0.2)]. In this study we document a decrease in the incidence of CIN3, AIS and SCC in the period after implementation of multi-cohort HPV vaccination in Denmark., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Kidney transplant recipients (KTRs) have increased risk of human papillomavirus (HPV)-related cancers, including cervical and anal cancer. In this cross-sectional clinical study, we investigated the prevalence of cervical high-risk HPV (hrHPV) and low-risk (lrHPV), risk factors for cervical hrHPV infection, and the prevalence of cervical and anal hrHPV co-infection in KTRs and immunocompetent controls., Methods: During 2016-2017, we recruited 125 female KTRs and 125 female immunocompetent controls from one dermatology department (KTRs and controls) and five nephrology departments (KTRs) in Denmark. Liquid-based cervical and anal cytology samples were tested for HPV DNA using the INNO-LiPA test and participants answered a questionnaire on lifestyle. Odds ratios (ORs) were estimated using logistic regression, adjusting for age, lifetime sexual partners, smoking, and (in models concerning anal HPV) receptive anal sex., Results: KTRs had higher prevalence of cervical hrHPV than controls (35.5% vs. 18.2; OR adjusted = 2.9, 95% CI, 1.5-5.5). In contrast, the prevalence of lrHPV was similar in KTRs and controls (25.6% vs. 23.1; OR adjusted = 1.2, 95% CI, 0.7-2.3). KTRs were more likely than controls to have cervical and anal hrHPV co-infection (27.3% vs. 6.6%, OR adjusted = 6.3, 95% CI, 2.7-15.0)., Conclusions: Female KTRs had high prevalence of cervical hrHPV, and co-infection with anal and cervical hrHPV was common. Our results underline that KTRs are an important target group for preventive efforts against HPV-related diseases., (© 2023 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

Objective: A substantial proportion of vulvar cancers are caused by high-risk human papillomavirus (hrHPV), but hrHPV prevalence in vulvar cancer has mainly been investigated in smaller studies which did not evaluate time trends. Our aim was to assess hrHPV prevalence in >1300 Danish vulvar cancers diagnosed during 1990-2017, including changes in hrHPV prevalence over time., Methods: In a nationwide pathology register, we identified women diagnosed with vulvar cancer at thirteen hospitals from all Danish regions. Archival tumor tissue was collected from local repositories and, upon pathology review, sent to a central laboratory for HPV testing using INNO-LiPA. We calculated hrHPV prevalence according to time, age and histology, and evaluated the overall and age-specific estimated annual percentage change (EAPC)., Results: We included 1308 vulvar cancer cases, with a median age of 72 years at diagnosis. The overall hrHPV prevalence was 52.0% (95% CI: 49.3-54.7). HPV types 16/18 were found in 39.6% of cases, whereas nine-valent HPV (9vHPV) vaccine types 16, 18, 31, 33, 45, 52, and 58 were found in 50.8%. The hrHPV prevalence showed an increasing trend over time, with an EAPC of 0.35% (95% CI: 0.00-0.71). The hrHPV prevalence was higher in younger women throughout the study period, and increasing trends over time were seen in both older (age ≥ 60) and younger (age < 60) women. The hrHPV prevalence was higher in non-keratinizing (71.0%) and warty/basaloid (78.0%) carcinomas than in keratinizing (39.4%) and verrucous (36.4%) carcinomas., Conclusions: Our results indicate that the 9vHPV vaccine could potentially prevent a substantial proportion of vulvar cancers in Denmark., Competing Interests: Declaration of Competing Interest SKK has previously received lecture fee from Merck and research grant through her affiliating institution from Merck. No other authors report any potential conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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 (RAR adjusted  = 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 (RR adjusted  = 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of human papillomavirus (HPV) related cancers such as anal squamous cell carcinoma. However, risk of non-malignant HPV infection has never been systematically studied in IBD. This study aims to assess the risk of genital warts (GW) in IBD patients., Methods: Using the Danish nationwide registries, we identified 49,163 patients with IBD between 1996 and 2018 and matched them to 491,665 individuals from the general population by age, sex, and HPV immunisation. Cumulative incidence rates for GW in IBD and non-IBD patients were calculated by age. Cox proportional regression analysis was used to calculate hazard ratios (HR) for GW in IBD compared to matched population and in Crohn's disease (CD) compared to ulcerative colitis (UC). We undertook subgroup analysis for risk of GW by sex, year of IBD diagnosis, contraceptive exposure and IBD treatment exposure., Results: The fully adjusted HR for GW in IBD patients compared to the matched non-IBD population was 1.33 (95% CI: 1.19-1.49) and 1.13 (95% CI: 1.01, 1.27) in CD as compared to UC. This increased risk was particularly observed in female (HR: 1.54, 95% CI: 1.33-1.79) over male (HR: 1.14, 95% CI: 0.97-1.34) IBD patients, but was also found across all periods of diagnosis with IBD, regardless of contraceptive treatment exposure, and also seen in IBD patients who had never been exposed to immunosuppressive treatment (HR: 1.33, 95% CI: 1.19-1.49)., Conclusion: In this nationwide, population-representative cohort study, we observed a 33% increased risk of GW in patients with IBD compared to the matched population and a 13% increased risk of GW in CD compared with UC. This risk was particularly increased in female over male IBD patients and seen independent of IBD treatment exposure., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Cervical cancer screening is offered free-of-charge to women aged 23-64 years in Denmark. Immigrants participate less in screening than Danish-born women, but little is known about their participation in follow-up after abnormal screening results. In this registry-based cohort study, we examined the likelihood of timely follow-up after an abnormal cervical cytology in immigrants from different countries and regions compared with Danish-born women. In nationwide registers, we identified women aged 23-64 years with high-grade (n = 74,335) or low-grade (n = 174,038) abnormal cytology during 1997-2017. Timely follow-up was defined as a new examination within six months for high-grade and 18 months for low-grade abnormalities. We calculated the probability of timely follow-up by country and region of origin and estimated odds ratios (ORs) of timely follow-up between immigrants and Danish-born women. The proportions with timely follow-up after high-grade abnormalities ranged from 90.6%-95.1% in immigrants from different countries or regions, compared with 95.5% in Danish-born women. For low-grade abnormalities, follow-up ranged from 75.2%-92.8% in immigrants, compared with 90.6% in Danish-born women. Women from Sub-Saharan Africa had low probability of timely follow-up after both high-grade (90.9%) and low-grade (75.2%) abnormalities. The differences between immigrants and Danish-born women remained when adjusting for age, year, income, employment and marital status. In conclusion, immigrants from most countries and regions were slightly less likely than Danish-born women to receive timely follow-up after abnormal cervical cytology, also after adjusting for socioeconomic differences. Efforts should be made to improve follow-up of abnormal screening results in immigrant groups with low attendance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Human papillomavirus (HPV) testing as the primary cervical cancer screening method is implemented in several countries. We report data from the first round of a large Danish pilot implementation of HPV-based screening. Our aim was to compare colposcopy referrals, detection of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer, and positive predictive value (PPV) of colposcopy referral in HPV vs cytology-based screening., Material and Methods: From May 2017 to October 2018, women aged 30-59 years attending cervical cancer screening in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark were screened by primary HPV testing (n = 16 067) or primary cytology (n = 23 981) depending on municipality of residence. In the HPV group, women with HPV16/18, or other high-risk HPV types and abnormal cytology, were referred to immediate colposcopy. Women with other high-risk HPV types and normal cytology were invited for repeat screening with HPV test and cytology after 12 months. From a nationwide pathology register, we obtained information on screening results and subsequent histological diagnoses during up to 2.9 years after the first screen. PPVs included diagnoses within 1 year after referral., Results: In the HPV group, 3.7% were referred to immediate colposcopy and 2.8% were referred at the 12-month repeat screening. The total referral to colposcopy was higher in the HPV (6.6%) than cytology group (2.1%) (age-adjusted relative referral = 3.05, 95% confidence interval [CI] 2.75-3.38). The detection of CIN3+ was higher in the HPV (1.5%) than the cytology group (0.8%) (age-adjusted relative detection = 1.88, 95% CI 1.56-2.28). The probability of CIN3 + among women referred to colposcopy (= PPV) was lower in the HPV (21.1%; 95% CI 18.7%-23.7%) than the cytology group (34.6%; 95% CI 30.7%-38.9%). In the HPV group, the PPV was lower among women referred at repeat screening (12.1%) than among women referred immediately (27.8%)., Conclusions: Compared with cytology-based screening, HPV-based screening provided a 90% increased CIN3+ detection at the cost of a threefold increase in colposcopy referrals, when considering complete data from the prevalence round. Our findings support implementation of HPV-based screening in Denmark, but modifications of screening algorithms may be warranted to decrease unnecessary colposcopy referrals., (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To describe trends in incidence of high-grade vaginal intraepithelial neoplasia (VaIN) and vaginal squamous cell carcinoma (SCC) in Denmark. For vaginal SCC, we also examine 5-year relative survival and mortality., Methods: All high-grade VaIN cases diagnosed 1997-2017 and vaginal SCCs during 1978-2017 were identified in two high-quality nationwide registers. Age-standardized incidence rates and average annual percentage change (AAPC) were assessed. For vaginal SCC, 5-year relative survival was calculated, and Cox regression was applied to study the effect of selected characteristics on mortality., Results: Altogether, 831 cases of high-grade VaIN and 721 vaginal SCCs were identified. The age-standardized incidence rate of high-grade VaIN showed no clear trend over time. However, when we stratified by age and divided the study period according to HPV vaccine licensure in Denmark (2006), the incidence of high-grade VaIN decreased significantly by 15.6% per year (95% CI: -23.2, -7.3%) after 2007 onwards among the youngest women (<30 years). For vaginal SCC, the incidence decreased from 0.5 (1978-1982) to 0.3 (2013-2017) per 100,000 woman-years. The 5-year relative survival improved over time and was 67.9% (95% CI: 54.9, 84.1%) in the most recent time period. Mortality was significantly associated with calendar year, age, and stage at diagnosis., Conclusions: The overall incidence of high-grade VaIN showed no clear trend over time, but a significant decline was observed in women younger than 30 years after HPV vaccine licensure. The incidence of vaginal SCC was reduced by approximately 50% and survival after vaginal SCC improved over time., Competing Interests: Declaration of competing interest Susanne K. Kjaer has previously received speaking and advisory board fees from Merck, and research grant through her institution from Merck. Hanna Kristina Bertoli, Louise Baandrup, Gitte Lerche Aalborg, Alexander K. Kjaer and Louise T. Thomsen report no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 (RR adjusted , 0.97; 95% CI, 0.64-1.48), overweight (RR adjusted , 0.98, 95% CI, 0.82-1.17), or obese (RR adjusted , 0.93; 95% CI, 0.63-1.36) compared with women of normal weight. The risk of hrHPV persistence was similar in overweight (RR adjusted , 0.98; 95% CI, 0.71-1.34) and obese (RR adjusted , 1.00; 95% CI, 0.56-1.79) women compared with women of normal weight, whereas underweight women had a lower risk (RR adjusted , 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

High participation in cervical cancer screening is essential for an effective screening program. In this population-based study, we investigated associations between general health, lifestyle and sexual behavior, and non-participation in cervical cancer screening in Denmark. During 2011-2012, a random sample of women aged 18-45 years from the general female population were invited to participate in a survey regarding health, lifestyle and sexual habits. Altogether 18,631 women responded (response rate: 75.1%), of whom 14,271 women aged 23-45 years were included in this analysis. Information on screening participation within four years after response, and data on sociodemographic characteristics, was obtained from nationwide registers. Logistic regression was used to calculate odds ratios (ORs) for non-participation, crude and adjusted for sociodemographic characteristics. Overall, 13.9% of the women were not screened during follow-up. The odds of non-participation was increased in women who were overweight (OR adj.  = 1.20; 95% CI, 1.06-1.35), obese (OR adj.  = 1.46; 95% CI, 1.27-1.67), perceived themselves as much too fat (OR adj.  = 1.50; 95% CI, 1.29-1.74), had poor self-perceived health (OR adj.  = 1.22; 95% CI, 1.03-1.45) or smoked daily (OR adj.  = 1.81; 95% CI, 1.61-2.03). Conversely, women with previous genital warts or other sexually transmitted infections, and young women with ≥10 lifetime sexual partners or ≥2 new recent partners, had decreased odds of non-participation. In conclusion, obesity, poor self-perceived health and daily smoking were associated with lower participation in cervical cancer screening. Interventions targeting these groups are needed., Competing Interests: Declaration of competing interest SKK has previously received speakers and advisory board fee from Merck and a research grant through her research institution from Merck. The remaining authors report no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess the incidence of vulvar high-grade precancerous lesions and cancer in Denmark during 1997-2018., Methods: We identified incident vulvar cancer cases in the Danish Cancer Registry and incident cases of vulvar precancerous lesions in the Danish Pathology Register. We calculated age-standardized incidence rates of vulvar squamous cell carcinoma (VSCC), non-SCC and precancerous lesions, and age-specific incidence rates of VSCC and precancerous lesions. Incidence trends were evaluated using linear Poisson regression to estimate the average annual percentage change (AAPC). For vulvar precancerous lesions, trends were evaluated in the period before (1997-2007) and after (2008-2018) implementation of HPV vaccination., Results: In the 22-year study period, the age-standardized incidence rate of VSCC increased from 1.23 (1997-1998) to 1.98 per 100,000 (2017-2018), corresponding to an average yearly increase of 2.95% (95%CI: 2.15-3.75). The incidence of non-SCC increased only slightly. Overall, the incidence of vulvar precancerous lesions increased (AAPC = 2.38%; 95%CI: 1.75-3.02). After implementation of HPV vaccination, the incidence of vulvar precancerous lesions decreased significantly in women aged <20 (AAPC = -22.10% (95%CI: -35.27 to -6.26)) and 20-29 years (AAPC = -6.57, 95% CI: -10.63 to -2.33), whereas the incidence increased in the majority of age groups ≥50 years., Conclusions: Overall, the incidence of VSCC and vulvar precancerous lesions increased during 1997-2018. However, after introduction of HPV vaccination, the incidence of vulvar precancerous lesions decreased among women aged <20 and 20-29 years, pointing towards a possible effect of HPV vaccination in this group. This development should be followed in the future., Competing Interests: Declaration of competing interest SKK has previously received lecture and scientific advisory board fee from Merck and a research grant through her institution from Merck. The other authors report no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: All cervical cancers and some vulvar, vaginal and anal cancers are caused by high-risk human papillomavirus (hrHPV). However, little is known about the association between cervical HPV infection and subsequent intraepithelial neoplasia and cancer at other anogenital sites. In this prospective cohort study, we estimated the risk of vulvar, vaginal and anal intraepithelial neoplasia grade 2/3 or cancer (VIN2+, VaIN2+, AIN2+) according to cervical hrHPV status., Methods: Liquid-based cervical cytology samples were collected from 40,399 women screened against cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested for hrHPV using Hybrid Capture 2 (HC2) and genotyped using INNO-LiPA. We linked the cohort with Danish nationwide registries to identify cases of VIN2+, VaIN2+ and AIN2+ during up to 15 years of follow-up. We estimated age-adjusted hazard ratios (HRs) using Cox regression and cumulative incidences using Aalen-Johansen's estimator., Results: Women with cervical HPV16 infection had increased hazard of VIN2+ (HR = 2.6; 95% confidence interval [CI], 1.2-5.5), VaIN2+ (HR = 23.5; 95% CI, 6.8-81.6) and AIN2+ (HR = 3.7; 95% CI, 1.1-12.2) compared with HC2 negative women. Women with other hrHPV types than HPV16 also had increased hazard of VaIN2+ (HR = 7.1; 95% CI, 2.3-22.3) and a borderline statistically significantly increased risk of AIN2+ (HR = 2.2; 95% CI, 0.9-4.9) compared with HC2 negative women. The 10-year cumulative incidences of VIN2+, VaIN2+ and AIN2+ in women with cervical HPV16 were 0.3% (95% CI, 0.2%-0.7%), 0.2% (95% CI, 0.1%-0.5%) and 0.1% (95 CI, 0.0%-0.4%)., Conclusions: Cervical HPV16 infection is associated with increased risk of VIN2+, VaIN2+ and AIN2+., Competing Interests: Declaration of competing interest Susanne K. Kjær has received speaker's and advisory board fees from Merck, and unrestricted research grant through her institution from Merck. Thomas Iftner has received lecture fees and research grants through his institution from Hologic GmbH and Becton Dickinson GmbH. Hanna Kristina Bertoli, Louise T. Thomsen and Christian Dehlendorff report no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In this registry-based cohort study, we estimated the risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer in renal transplant recipients (RTRs) compared to a nontransplanted comparison cohort. We identified all first-time RTRs in Denmark during 1990-2015 in a nationwide nephrology register. For each RTR, we randomly selected 50 age- and sex-matched non-RTRs from the background population. The study population was followed for diagnoses of cervical, vaginal, vulvar, penile and anal intraepithelial neoplasia grades 2-3 (IN2/3) and cancer for up to 27 years. We estimated hazard ratios (HRs) of anogenital IN2/3 and cancer in RTRs vs. non-RTRs by Cox regression separately for men and women using age as underlying timescale, adjusting for income, education, HPV vaccination and immunocompromising conditions. We included 4,261 RTRs and 213,673 non-RTRs. RTRs had increased hazard of cervical (HR = 2.1, 95% CI: 1.7-2.8), vaginal (HR = 35.0, 95% CI: 13.9-87.7), vulvar (HR = 16.4, 95% CI: 10.4-25.8), penile (HR = 21.9, 95% CI: 11.1-43.5) and anal (women: HR = 51.1, 95% CI: 28.0-93.1; men: HR = 39.0, 95% CI: 16.7-91.1) IN2/3. The HRs of anogenital cancers were also increased at most sites. The HR of anogenital IN2/3 in female RTRs tended to be higher during graft function than during dialysis. In female RTRs aged <40 years at transplantation, 10-15% had cervical IN2/3 and 5-12% had vaginal/vulvar/anal IN2/3 within 20 years after transplantation, compared to 4-8 and 0.2-0.4%, respectively, of female non-RTRs. In conclusion, RTRs had substantially higher risk of HPV-related anogenital premalignancies and cancer than non-RTRs., (© 2019 UICC.)

Objective: In Denmark, human papillomavirus (HPV) vaccination has been offered at age of 12 to girls born in 1996 and later. In this cohort study, we examined routine HPV vaccination uptake in immigrants and descendants from different countries and regions compared with native Danes, including the influence of socioeconomic characteristics and potential changes in uptake by birth cohort., Methods: In nationwide registers, we identified all girls born in 1996-2003 (n = 260 251) and obtained information on country of origin, HPV vaccinations and parents' income and employment. Vaccination was defined as receiving ≥1 dose within 2 years after eligibility for routine vaccination. Odds ratios (ORs) were estimated by logistic regression separately for birth cohorts 1996-2000 and 2001-2003., Results: Uptake in immigrants and descendants varied by country and region of origin. Overall, immigrants had lower uptake than native Danes, in birth cohorts 1996-2000 [79% vs. 93%, OR = 0.31; 95% confidence interval (CI), 0.29-0.34] and 2001-2003 (63% vs. 73%, OR = 0.60; 95% CI, 0.54-0.66). Descendants had lower uptake than native Danes in cohorts 1996-2000 (89% vs. 93%, OR = 0.65; 95% CI, 0.60-0.68), but higher uptake in cohorts 2001-2003 (76% vs. 73%, OR = 1.15; 95% CI, 1.08-1.21). Most associations were attenuated, but not entirely explained, when adjusting for socioeconomic characteristics., Conclusion: HPV vaccination uptake varied by country and region. Most immigrants had lower uptake than native Danes, and in most groups, this was not fully explained by socioeconomic differences. Patterns in descendants were mixed. Interventions to increase uptake should be tailored to specific groups of immigrants/descendants.

Objective: To assess the prevalence and type distribution of oral human papillomavirus (HPV) among renal transplant recipients (RTRs) and healthy controls and to examine risk factors for oral HPV among RTRs., Materials and Methods: During 2016-2017 we recruited 250 RTRs and 250 controls. Oral samples were tested for HPV DNA with INNO-LiPA HPV Genotyping Extra II. All participants answered a questionnaire on lifestyle and sexual behaviour, and characteristics of RTRs were obtained from medical files. We assessed prevalence and type distribution of oral HPV. Using logistic regression, the risk of oral HPV and risk factors for oral HPV among RTRs were estimated as odds ratios (OR) with 95% confidence intervals (CI)., Results: Overall, 30 RTRs (12.1%) and 26 controls (10.4%) were oral HPV positive (OR = 1.14; 95% CI: 0.64-2.05). Female RTRs tended to have a higher oral HPV prevalence than controls (OR = 1.73; 95% CI: 0.63-4.77), while no difference was observed among men. HPV51 was the commonest genotype. Sexual behaviour tended to be associated with oral HPV among RTRs., Conclusions: There was no overall difference in oral HPV prevalence between RTRs and controls, but female RTRs tended to have a higher prevalence of oral HPV than controls., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Introduction: The optimal clinical management of women diagnosed with low-grade squamous intraepithelial lesions (LSIL) during cervical cancer screening remains unclear. In this prospective cohort study, we compared the clinical performance of two human papillomavirus (HPV) mRNA tests for triage of women with LSIL in Denmark., Material and Methods: In a nationwide pathology register, we identified women aged 23-65 years with LSIL during 2008-2012. We included women tested for HPV mRNA with the PreTect HPV Proofer test for five high-risk HPV types (n = 2176) or the Aptima assay for 14 high-risk HPV types (n = 426). Subsequent histological diagnoses of cervical intraepithelial neoplasia grades 2, 3 or cancer (CIN2+) were identified in the register. We calculated the sensitivity and specificity for CIN2+ at 18 and 36 months of follow up, and the cumulative incidence of CIN2+ among women testing positive and negative, overall and by age (23-29, 30-39, 40-65 years)., Results: The proportion of women with a positive mRNA test at baseline was higher in women tested with Aptima (66.7%) than in women tested with Proofer (42.8%). After 18 months, Aptima had higher sensitivity for CIN2+ than Proofer (98% [95% CI 94% to 100%] vs 85% [95% CI 82% to 88%]), whereas Proofer showed higher specificity than Aptima (67% [95% CI 64% to 70%]) vs (40% [95% CI 33% to 46%]). Aptima had particularly low specificity in women aged <40 years (23-29: 19% [95% CI 5% to 36%]; 30-39: 10% [95% CI 0% to 33%]). The 36-month cumulative incidence of CIN2+ was higher in Proofer positive (54.3% [95% CI 50.9% to 57.8%]) than in Aptima positive women (37.6% [95% CI 31.2% to 44.8%]). In women with a negative mRNA test, the 36-month cumulative incidences of CIN2+ were 13.1% (95% CI 10.8% to 15.8%) and 5.9% (95% CI 1.7% to 19.0%) for Proofer and Aptima, respectively., Conclusions: In women with LSIL, Aptima had high sensitivity for CIN2+, but low specificity, especially in women aged <40 years. The Proofer test may be useful to limit immediate colposcopy referrals in younger women with LSIL, but given its low sensitivity and negative predictive value, Proofer negative women must be followed with repeat cytology., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: Sexual behavior at the population level impacts on public health. Recent representative sexual behavior data are lacking., Material and Methods: Cross-sectional surveys in 2005 and 2012 on women age 18-45 years randomly selected from the general population in Denmark (n = 40 804), Norway (n = 30 331) and Sweden (n = 32 114)., Results: Median (interquartile range) age at first intercourse was 16 (15-18) years in Denmark, 17 (16-18) years in Norway, and 17 (15-18) years in Sweden. Women in the most recent birth cohort had sexual debut at the lowest age, and were most likely to have sexual debut before the legal age of consent. Proportions with debut age ≤14 years among women born 1989-1994 vs 1971-1976, odds ratio (95% confidence interval) were: 18.4% vs 10.9%, 1.95 (1.74-2.18) in Denmark, 12.9% vs 6.3%, 2.38 (2.01-2.82) in Norway, 17.8% vs 11.4%, 1.75 (1.55-1.98) in Sweden. Median (interquartile range) number of lifetime sexual partners was 6 (3-10) in Denmark, 5 (2-10) in Norway, and 6 (3-11) in Sweden. The proportion of women reporting >10 sexual partners was also highest in the most recent survey. The percentage with odds ratio (95% confidence interval) in 2012 vs 2005 surveys were: 24.9% vs 22.8%, 1.13 (1.07-1.18) for Denmark; 23.8% vs 19.8%, 1.27 (1.19-1.34) for Norway; and 28.3% vs 23.8%, 1.31 (1.24-1.38) for Sweden. Similarly, the proportion of women reporting ever having had a sexually transmitted infection among women age <30 years were: 29.4% vs 26.4%, 1.21 (1.13-1.31) in Denmark, 28.9% vs 25.0%, 1.20 (1.10-1.31) in Norway, and 29.4% vs 22.2%, 1.45 (1.33-1.58) in Sweden., Conclusions: Scandinavian women reported lower age at first intercourse in younger birth cohorts. Moreover, they reported more lifetime sexual partners and a higher prevalence of ever having a sexually transmitted infection in 2012 than in 2005. Our findings may inform the interpretation of trends in outcomes associated with sexual health, and public health policies., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

In this nationwide register-based cohort study, we examined cervical cancer screening participation among immigrants in Denmark by country and region of origin. Furthermore, we assessed whether differences in screening participation between immigrants and Danish-born women were explained by sociodemographic or health-related characteristics, and examined predictors of participation among immigrants. Using high-quality registries, we identified women invited for cervical cancer screening during 2008-2009 and retrieved individual-level data on sociodemographic-, health- and immigration-related characteristics. A total of 610,907 women were followed for up to 2.9 years after screening invitation. We estimated the probability of participation using the Aalen-Johansen estimator and the hazard ratios (HRs) of participation using Cox regression. The probability of participation within follow-up was 74.5% (95% CI, 74.4%-74.6%) in Danish-born women; 61.2% (95% CI, 60.4%-62.1%) in Western immigrants; and 61.3% (95% CI, 60.9%-61.8%) in non-Western immigrants. Participation in immigrants varied by region of origin from 44.3% (95% CI, 41.4%-47.4%) in immigrants from North America, New Zealand and Australia to 67.8% (95% CI, 65.4%-70.3%) in immigrants from South- and Central America. Substantial variation was seen between specific countries of origin. Differences in participation between immigrants and Danish-born women were not explained by sociodemographic or health-related characteristics. Predictors of low participation in immigrants included lower income, unemployment, being unmarried, having a history of schizophrenia or other psychoses, and ≤5 years' stay in Denmark. In conclusion, cervical cancer screening participation in immigrants varied by region and country of origin, but all immigrant groups had lower participation than Danish-born women., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Genital warts (GWs) are a risk factor for subsequent human papillomavirus (HPV)-related anogenital cancers. In this register-based, prospective cohort study, we estimated the risk of GWs in renal transplant recipients (RTRs) compared with a nontransplanted cohort. In a nationwide database, we identified first-time RTRs in Denmark during 1996 to 2015. For each RTR, 50 age- and sex-matched nontransplanted individuals were selected from the population registry. Information on GWs, sociodemographic characteristics, HPV vaccination, and other causes of immunosuppression was retrieved from registries. We estimated the cumulative incidence of GWs and used Cox regression to estimate hazard ratios (HR) of GWs in RTRs vs non-RTRs. We included 3268 RTRs and 162 910 non-RTRs without GWs 1 year before baseline. RTRs had higher hazard of GWs than non-RTRs (HR = 3.30; 95% confidence interval, 2.76-3.93, adjusted for sex, age, education, and income). The increased hazard of GWs compared with non-RTRs was more pronounced in female than in male RTRs. Although not statistically significant, the hazard tended to be higher in RTRs with functioning grafts compared with RTRs on dialysis after graft failure. The hazard of GWs was increased <1 year after transplantation and remained increased during ≥10 years. In conclusion, RTRs had substantially higher risk of GWs than non-RTRs., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Offering human papillomavirus-based self-sampling to nonparticipants in routine cervical cancer screening can increase screening participation. However, little is known about characteristics of women who accept self-sampling. In this population-based study, we investigated determinants for participation in self-sampling among Danish nonattenders to routine cervical cancer screening. Methods: During 2014 to 2015, a random sample of screening nonparticipants ages 27 to 65 years living in the Capital Region of Denmark were invited for self-sampling. Of 21,314 eligible women, 4,743 participated in self-sampling. Information on sociodemographic characteristics and mental and physical health of all the women was obtained from nationwide registries, and 3,707 women completed a questionnaire on lifestyle, sexual behavior, and reasons for nonparticipation in routine screening. We used logistic regression to estimate ORs for participation in self-sampling, crude, and adjusted for sociodemographic characteristics. Results: Basic education [OR adjusted = 0.79; 95% confidence interval (CI), 0.72-0.88], low income (OR adjusted = 0.66; 95% CI, 0.59-0.73), origin from a nonwestern country (OR adjusted = 0.43; 95% CI, 0.38-0.48), and being unmarried (OR adjusted = 0.66; 95% CI, 0.61-0.72) were associated with lower self-sampling participation. Long-term unscreened women (OR adjusted = 0.49; 95% CI, 0.45-0.53), women with prior schizophrenia or other psychoses (OR adjusted = 0.62; 95% CI, 0.48-0.80), women with poor self-perceived health (OR adjusted = 0.42; 95% CI, 0.25-0.69), and women who perceived screening as unnecessary (OR adjusted = 0.54; 95% CI, 0.37-0.80) or irrelevant (OR adjusted = 0.81; 95% CI, 0.78-0.96) were less likely to self-sample. Conclusions: Certain population groups, including women with low socioeconomic position or of nonwestern origin, were less likely to participate in self-sampling. Impact: Targeted approaches may be needed to increase screening participation in these groups. Cancer Epidemiol Biomarkers Prev; 27(11); 1342-51. ©2018 AACR., (©2018 American Association for Cancer Research.)

Cervical cancer occurs most often in under-screened women. In this nationwide register study, we described differences in sociodemographic characteristics between passive and active non-participants and examined socio-demographic characteristics, reproductive history, and mental and physical health as potential determinants for passive non-participation compared with participation in the Danish cervical cancer screening program. Screening history in women aged 23-49 years invited for cervical cancer screening in 2008-2009 was retrieved from the Danish Pathology Databank with information about dates of invitation and unsubscription. We identified participants (n = 402,984), active non-participants (n = 10,251) and passive non-participants (n = 63,435) within four years following baseline invitation and retrieved data about the study population from high-quality registries. We examined differences in socio-demographic characteristics of passive and active non-participants, and used multiple logistic regression analyses to identify potential determinants of passive non-participation. We found that active and passive non-participants differed in relation to socio-demography. When compared with screening participants, the odds of passive non-participation was increased in women who originated from less developed countries; were unmarried; had basic education or low income; had four or more children; smoked during pregnancy; had multiple induced abortions; or had a history of obesity, intoxicant abuse or schizophrenia or other psychoses. In conclusion, in this nationwide, prospective, population-based study, differences in socio-demographic characteristics between passive and active non-participants were found. Furthermore, sociodemography, reproductive history, and mental and physical health were determinants for passive non-participation. Addressing inequalities in screening attendance may help to further decrease the incidence of and mortality from cervical cancer., (Copyright © 2018. Published by Elsevier Inc.)

In this prospective cohort study, we estimated the long-term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high-risk human papillomavirus (hrHPV) genotype and semi-quantitative viral load at baseline among 33,288 women aged 14-90 years with normal baseline cytology. During 2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women with single hrHPV infections. The cohort was followed in a nationwide pathology register for up to 11.5 years. In women aged ≥30 years at baseline, the 8-year absolute risk for CIN3+ following baseline detection of HPV16 was 21.8% (95% confidence interval [CI]: 18.0-25.6%). The corresponding risks for HPV18, HPV31, HPV33, and other hrHPV types, respectively, were 12.8% (95% CI: 7.6-18.0%), 11.3% (95% CI: 7.7-14.9%), 12.9% (95% CI: 7.0-18.8%) and 3.9% (95% CI: 2.7-5.2%). Similar absolute risk estimates were observed in women aged <30 years. Higher HPV16-viral load was associated with increased risk of CIN3+ (hazard ratio = 1.34, 95% CI: 1.10-1.64, per 10-fold increase in viral load). A similar trend, although statistically nonsignificant, was found for viral load of HPV18. The 8-year absolute risk of CIN3+ in women with HPV16-viral load ≥100.0 pg/ml was 30.2% (95% CI: 21.9-38.6%). Our results support that hrHPV genotyping during cervical cancer screening may help identify women at highest risk of CIN3+., (© 2014 UICC.)

Objectives: Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in women with prevalent HPV infection and in a subgroup of women with persistent HPV infection., Methods: Participants in this population-based cohort study underwent a structured interview, including history of CT infection, and subsequently cervical exfoliated cells were obtained for HPV DNA and CT DNA testing. Women with high-risk HPV DNA infection and no prevalent cervical disease constituted the overall study population (n=1390). A subgroup of women with persistent HPV infection (n=320) was also identified. All women were passively followed for development of cervical lesions in the national Pathology Data Bank. HRs and 95% CIs for CIN3+ during follow-up (up to 19 years) were estimated in an accelerated failure time model., Results: Women who reported more than one CT infection had a statistically significantly increased risk of CIN3+ (high-risk HPV-positive, HR=2.51, 95% CI 1.44 to 4.37) (persistent HPV infection, HR=3.65, 95% CI 1.53 to 8.70). We found no association between CT DNA and subsequent risk of CIN3+ among women who were HPV-positive or had a persistent HPV infection at baseline., Conclusions: Repeated CT infections increased the risk of CIN3+ among women with prevalent as well as persistent high-risk HPV infection., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To assess whether recipients and non-recipients of the human papillomavirus (HPV) vaccine subsequently differ in terms of sexual risk taking behaviour., Design: Cross-sectional survey. Sequential analyses constructed from self-reported age at vaccination, age at first intercourse and age at response., Setting: A random selection of women aged 18-46 years living in Denmark, Norway and Sweden in 2011-2012, eligible for opportunistic or organized catch-up HPV vaccination., Participants: A total of 3805 women reported to have received the HPV vaccine and 40,247 reported not to have received it. Among vaccinees, 1539 received the HPV vaccine before or at the same age as sexual debut, of which 476 and 1063 were eligible for organized catch-up and opportunistic vaccination, respectively., Main Outcome Measures: Self-reported sexual behaviour, compared by hazard ratios and odds ratios for women who received the HPV vaccine before or at the same age as sexual debut versus women who did not receive the HPV vaccine., Results: HPV vaccination did not result in younger age at first intercourse. Women who received the HPV vaccine before or at the same age as sexual debut did not have more sexual partners than did non-vaccinees. Non-use of contraception during first intercourse was more common among non-vaccinees than among HPV vaccinees. The results were similar for organized catch-up and opportunistic vaccinees., Conclusion: Women who received the HPV vaccine before or at the same age as sexual debut did not subsequently engage more in sexual risk taking behaviour than women who did not receive the HPV vaccine., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test., Methods: In this prospective cohort study, consecutive liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up to 10.5 years for development of CIN 3 or worse., Results: The 8-year absolute risk of CIN 3 or worse was 1.1% (95% confidence interval [CI] 1.0-1.3%) for HPV-negative women; 1.7% (0.8-2.6%) for low-risk HPV-positive women without concurrent high-risk HPV; 17.4% (16.4-18.5%) for high-risk HPV-positive women without concurrent low-risk HPV; and 15.9% (13.5-18.3%) for women with concurrent high-risk and low-risk HPV. The 8-year absolute risk of CIN 3 or worse after a negative high-risk HPV test (irrespective of low-risk HPV status) was lower than after a normal cytology result among women aged younger than 30 years (3.5% [95% CI, 2.9-4.0%] compared with 6.9% [6.2-7.5%], P<.001) and women aged 30 years or older (0.7% [95% CI, 0.6-0.9%] compared with 1.8% [95% CI, 1.6-2.0%], P<.001)., Conclusion: A negative high-risk HPV test provides greater long-term reassurance against CIN 3 or worse than normal cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types., Level of Evidence: II.