Marianne Waldstrøm

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.

Six‐pattern p53 interpretation in 1293 vulvar squamous cell carcinomas: inter‐pathologist variation and pattern distribution according to p16 status

Aims Vulvar squamous cell carcinoma (VSCC) is classified into human papillomavirus (HPV)‐associated and HPV‐independent types, primarily using p16 immunohistochemistry, with p53 staining playing a complementary role since a subset of HPV‐independent VSCC is driven by TP53 mutations. We aimed to assess the robustness of the six‐pattern p53 classification by evaluating interobserver agreement and mapping pattern distribution in relation to p16 status. Methods We performed p53 immunohistochemistry on 1293 VSCC cases, comprising 832 p16‐negative and 461 p16‐positive cases. Eight pathologists independently evaluated p53, with each case assessed by two pathologists. Expression was classified as wild‐type (scattered or mid‐epithelial) or mutated (basal overexpression, parabasal/diffuse overexpression, absent or cytoplasmic). Interobserver agreement was measured using kappa statistics. Results Overall concordance across the six p53 patterns was 66.7%, increasing to 86.9% when dichotomized as wild‐type versus mutated. In the p16‐negative cases, concordance was 68.8% across all six patterns and 82.6% when dichotomized. Corresponding rates in the p16‐positive cases were 62.9% and 94.6%. Kappa values for pairwise assessments ranged from 0.44 to 0.73 (six‐pattern) and from 0.60 to 0.88 (dichotomized). After resolving discordant cases, 79.9% of p16‐negative cases showed a mutated pattern, and 20.1% were wild type (scattered). Among the p16‐positive cases, 93.1% exhibited a wild‐type pattern. Conclusions Findings support the clinical robustness of the six‐pattern p53 framework, as interobserver agreement was high and most discrepancies were unlikely to impact tumour classification. While p16 proved helpful in p53 interpretation, certain cases remained challenging due to p53 heterogeneity or ambiguous p16/p53 combinations indicating a need for additional molecular testing in such instances.