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

Cervical cancer is a preventable disease. Nevertheless, stagnation has been seen in incidence rates also in countries with well‐functioning healthcare. On this basis, we investigated associations between control interventions and changes in cervical cancer incidence in Denmark from 2009 to 2022. Data on human papillomavirus (HPV)‐vaccination were retrieved from Staten's Serum Institute; on screening recommendations from Danish Health Authority, on screening performance from Danish Quality Database for Cervical Screening; and on cervical cancer incidence from Nordcan and Danish Cancer Register. We reported coverage with HPV vaccination (1+ dose); coverage with cervical cell samples; number of women with primary HPV tests; proportion of non‐normal cell samples without timely follow‐up; number of conizations; and cervical cancer incidence rates. In 2022, all women aged ≤29 had been offered childhood HPV vaccination with coverage of 80%–90%. By 2020–2022, the cervical cancer incidence rate in women aged 20–29 was 3 per 100,000; at level of disease elimination. In 2017, women aged 70+ were offered a one‐time HPV screening, and by 2020–2022, the old‐age peak in cervical cancer incidence had largely disappeared. From 2009 to 2022, proportion of non‐normal cell samples without timely follow‐up decreased from 20% to 10%, and conventional cytology was largely replaced by SurePath liquid‐based cytology; these factors could explain the steady decrease in cervical cancer incidence rate. Implementation of primary HPV screening in women aged 30–59 in 2021 was reflected in a, probably temporary, increase in the 2022 cervical cancer incidence rate. In conclusion, combined interventions with childhood HPV vaccination; one‐time HPV screening of elderly women; and better management of screening broke previous stagnation in cervical cancer incidence rate.

The case of a 56-year-old woman with a fibroid uterus who developed utero-cutaneous fistula is presented. The woman was para 0, had an unremarkable medical history, and had no prior diagnosis of a gynecologic pathology, no operative interventions involving the uterine wall or any other risk factor for fistula. Abdominal examination revealed an abdominal mass with overlying deep, purulent ulceration. 18F-FDG PET/CT scan was consistent with uterine leiomyoma, but a differential diagnosis of sarcoma was considered due to the presence of the fistula, patchy increased FDG uptake of the tumor and several mildly enlarged lymph nodes bilaterally in the inguinal and iliac region. Hysterectomy with bilateral salpingo-oophorectomy was performed. Histological diagnosis was of leiomyoma with focal bizarre atypia, degenerative and metaplastic changes and utero-cutaneous fistula. To the best of our knowledge, this is the first case report describing a benign leiomyoma forming a fistula between the uterus and abdominal surface.

Background: Ovarian cancer remains the most lethal gynecological cancer, primarily due to its asymptomatic nature in early stages and consequent late diagnosis. Early detection improves survival, but current biomarkers lack sensitivity and specificity. Cell-free DNA (cfDNA) released from tumor cells captures tumor-associated epigenetic alterations and represents a promising source for minimally invasive biomarkers. Among these, aberrant DNA methylation occurs early in tumorigenesis and may reflect underlying disease biology. This study aimed to investigate genome-wide cfDNA methylation profiles in patients with ovarian cancer, benign ovarian conditions, and healthy controls to identify cancer-associated methylation patterns that may inform future biomarker development. Results: We performed genome-wide cfDNA methylation profiling using cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) on plasma samples from 40 patients with high-grade serous ovarian carcinoma, 38 patients with benign ovarian conditions, and 38 healthy postmenopausal women. A total of 536 differentially methylated regions (DMRs) were identified between ovarian cancer and controls (n = 76), with 97% showing hypermethylation in ovarian cancer. DMRs were enriched in CpG islands and gene bodies and depleted in repetitive elements, consistent with known cancer-associated methylation patterns. Fifteen genes showed robust hypermethylation across analyses. These genes exhibited methylation across intronic, exonic, and upstream regulatory regions. Separate comparisons of ovarian cancer to each control group (benign and healthy) supported the reproducibility of these findings. Gene Ontology enrichment analysis revealed enrichment in gland development, embryonic morphogenesis, and endocrine regulation, suggesting biological relevance to ovarian tumorigenesis. Conclusions: This study identifies consistent cfDNA hypermethylation patterns in ovarian cancer, affecting genes involved in developmental regulation and hormone-related processes. Our findings underscore the potential of cfMeDIP-seq for detecting tumor-specific methylation signatures in plasma and highlight these 15 hypermethylated genes as biologically relevant targets for future studies on cfDNA methylation in ovarian cancer.

The introduction of prophylactic HPV vaccination has significantly reduced vaccine-type HPV infections and is reshaping the landscape of cervical cancer prevention. As vaccinated cohorts enter screening age, understanding the genotype-specific risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) is critical for adapting screening strategies. To compare HPV genotype-specific detection rates of histologically confirmed CIN2+ between vaccinated and unvaccinated women in Denmark's Trial23 cohort, with over seven years of follow-up. This population-based cohort study included 15,668 women born in 1994 who were offered HPV vaccination with the 4-valent vaccine in 2008 and entered Danish screening age in 2017 In our cohort, 95 % were vaccinated and 5 % were unvaccinated. The primary endpoints of this study were HPV-type-specific incident CIN2+ cases. The first histological biopsy sample diagnosed with CIN2+ in 2017-2023 was retrieved for HPV genotyping with the Seegene Allplex HPV28. Cox proportional hazards models estimated hazard ratios (HRs) for CIN2+ outcomes by hierarchically grouped HPV genotypes. Among vaccinated women, the incidence of CIN2+ was 5.3 per 1000 person-years, compared to 12.1 per 1000 person-years in unvaccinated women (HR: 0.44; 95 % CI: 0.34-0.57). Vaccination was associated with a 95 % reduction in HPV16/18-related CIN2+ (HR: 0.05; 95 % CI: 0.03-0.09). A similar, but non-significant, trend of a 32 % risk of CIN2+ for HPV31/33/45/52/58 was found, with an adjusted HR of 0.68 (95 % CI: 0.43-1.09). For CIN2+ associated with other high-risk HPV types, the HR was 0.70 (95 % CI 0.35-1.37). HPV16/18 vaccination reduced the risk of HPV16/18-related CIN2+ lesions, but a substantial burden remained from non-vaccine high-risk types. The substantial protection against HPV16/18-related CIN2+ and the consequential shift in HPV genotype distribution of CIN2+ among vaccinated women underline the need for adaptation of screening strategies.

Introduction: Up to 39% of women in Denmark do not participate regularly in the cervical cancer screening program and initiatives to increase participation are called upon. The primary aim of this study was to describe previous screening history and characteristics of women attending screening in a walk‐in clinic. Furthermore, we wanted to investigate barriers to cervical cancer screening.Material and methods: We designed a walk‐in clinic that was open 2 days a week from 16.00 to 19.00 h, located in the Departments of Gynecology in the two main hospitals of the North Denmark Region. The main purpose of the clinic was cervical cancer screening and the study period was 5 months. Women who were not eligible for screening or had other health complaints were referred to their general practitioner. The women included in the study, filled out a questionnaire regarding educational and occupational status; their screening history was registered using data from the Danish Pathology Register.Results: During the study period, 255 women visited the walk‐in clinic. The final study population consisted of 249 women who met the inclusion criteria. Age range of participants was 23–77 years, with a median age of 45 years. The majority of the participants were currently employed (81%) or students (10%), the remaining being retired (5%) or unemployed (4%). Screening history showed that 138 (55.4%) of the women were on time for the screening or delayed less than 6 months compared to their recommended screening interval. Sixty‐one women (24.5%) were delayed >6 months but <2 years. Fifty women (20.1%) were classified as non‐attenders, with more than a 2‐year delay in their screening. In the group of non‐attenders, eight women had never been screened. Of the remaining 42 women, the median time since last screening was 8.2 years (range 5.0–25.3 years).Conclusions: Women attending the walk‐in clinic tended to be primarily actively working or students (91%). All age groups in the screening population were represented. Screening history showed that 44.6% had not followed the recommended screening program.