Kirsten Marie Jochumsen

A Sensitive and Transparent Method for Tumor-Informed Detection of Circulating Tumor DNA in Ovarian Cancer Using Whole-Genome Sequencing

Circulating tumor DNA (ctDNA) is a biomarker that could potentially improve the survival rate of ovarian cancer (OC), e.g., by monitoring treatment response and early relapse detection. However, an optimal method for ctDNA analysis in OC remains to be established. We developed a method for tumor-informed single-nucleotide variant detection of ctDNA in OC using whole-genome sequencing. Tumor and plasma samples obtained at the time of diagnosis from 10 patients with OC were included. The tested method involved applying basic filters with different cut-offs of read depth, allelic depth, and variant allele frequency of tumor and normal DNA. In addition, we applied a new filtering approach using plasma samples from the other included OC patients (the plasma pool) for specific removal of artefacts. The basic filters with varying cut-offs showed minor improvement in signal-to-noise ratio (S2N). However, the addition of the plasma pool filter resulted in a considerable ctDNA signal improvement, indicated by both S2N and z-score. This study demonstrates a promising method for ctDNA detection in OC patients using a tumor-informed approach for whole-genome sequencing. Despite the limited number of patients involved, the results suggest a significant potential of the method for ctDNA signal detection in patients with OC.

Cervical cancer incidence in Denmark: Disentangling determinants of time trend

AbstractCervical 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.