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Background: For cervical cancer (CC), the implementation of preventive strategies has the potential to make CC occurrence and death largely avoidable. To better understand the factors possibly responsible for the barriers to HPV vaccination and screening, we aimed to examine possible differences in biological and social parameters as well as screening adherence between women with and women without a prior CC diagnosis and according to disease stage. Methods: Through the Danish Cancer Registry (DCR), women diagnosed with CC in Denmark between 1987 and 2016 were included. These were age- and residence-matched in a 1:5 ratio with controls from the general female population. The study population was sub grouped into a low-stage subpopulation with women with early-stage CC and matched controls and a high-stage subpopulation with women with late-stage CC and matched controls. Biological and social parameters were compared within the subpopulations as well as between low- and high-stage cases. For part of the study population, screening attendance was examined to compare differences in adherence. Results: Overall, we found that the risk of CC is significantly increased in socially disadvantaged women and not least non-attenders in screening. Interestingly, the high-stage subpopulation was significantly older than the low-stage subpopulation (pp-values all Conclusions:Older women, socially disadvantaged women, and non-attenders in screening are particularly vulnerable in terms of developing CC, especially high-stage disease. Therefore, improvements in the participating rate in screening as well as a revision of the current screening guidelines are needed.

At present, human papillomavirus (HPV) testing is replacing morphology-based cytology as the primary tool for cervical cancer screening in several countries. However, the HPV assays approved for screening lack detection for all but one of the possibly carcinogenic HPV types and do not genotype all included HPV types. This study demonstrates the use of a targeted HPV next generation sequencing (NGS) panel to detect and genotype all 25 carcinogenic, probably carcinogenic, and possibly carcinogenic HPV types as well as the low-risk types HPV6 and HPV11. The panel was validated using a cohort of 93 paired liquid-based cytology samples (general practitioner (GP)-collected cervical samples and cervico-vaginal self-samples (SS)). Overall, the targeted panel had a sensitivity (GP = 97.7%, SS = 92.1%) and specificity (GP = 98.0%, SS = 96.4%) similar to the commercial HPV assays, Cobas® 4800 HPV DNA test (Roche) and CLART® HPV4S assay (GENOMICA). Interestingly, of the samples that tested positive with the NGS panel, three (6.4%) of the GP-collected samples and four (9.1%) of the self-samples tested positive exclusively for HPV types only included in the NGS panel. Thus, targeted HPV sequencing has great potential to improve the HPV screening programs since, as shown here, it can identify additional HPV positive cases, cases with HPV integration, variants in the HPV genome, and which HPV type is dominant in multi-infected cases.