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Liver cancers give rise to a heavy burden on healthcare worldwide. Understanding the tumour microenvironment (TME) underpins the development of precision therapy. Single-cell RNA sequencing (scRNA-seq) technology has generated high-quality cell atlases of the TME, but its wider application faces enormous costs for various clinical circumstances. Fortunately, a variety of deconvolution algorithms can instead repurpose bulk RNA-seq data, alleviating the need for generating scRNA-seq datasets. In this study, we reviewed major public omics databases for relevance in this study and utilised eight RNA-seqs and one microarray dataset from clinical studies. To decipher the TME of liver cancer, we estimated the fractions of liver cell components by deconvoluting the samples with Cibersortx using three reference scRNA-seq atlases. We also confirmed that Cibersortx can accurately deconvolute cell types/subtypes of interest. Compared with non-tumorous liver, liver cancers showed multiple decreased cell types forming normal liver microarchitecture, as well as elevated cell types involved in fibrogenesis, abnormal angiogenesis, and disturbed immune responses. Survival analysis shows that the fractions of five cell types/subtypes significantly correlated with patient outcomes, indicating potential therapeutic targets. Therefore, deconvolution of bulk RNA-seq data with scRNA-seq atlas references can be a useful tool to help understand the TME.

Triage methods for cervical cancer detection show moderate accuracy and present considerable false-negative and false-positive result rates. A complementary diagnostic parameter could help improve the accuracy of identifying patients who need treatment. A pilot study was performed using a targeted proteomics approach with opportunistic ThinPrep samples obtained from women collected at the hospital’s outpatient clinic to determine the concentration levels of minichromosome maintenance-3 (MCM3) and envoplakin (EVPL) proteins. Forty samples with ‘negative for intraepithelial lesion or malignancy’ (NILM), 21 samples with ‘atypical squamous cells of undetermined significance’ (ASC-US), and 33 samples with ‘low-grade squamous intraepithelial lesion and worse’ (≥LSIL) were analyzed, using cytology and the patients’ histology reports. Highly accurate concordance was obtained for gold-standard-confirmed samples, demonstrating that the MCM3/EVPL ratio can discriminate between non-dysplastic and dysplastic samples. On that account, we propose that MCM3 and EVPL are promising candidate protein biomarkers for population-based cervical cancer screening.

Background Host-cell DNA methylation analysis can be used to triage women with high-risk human papillomavirus (HPV)-positive self-collected cervicovaginal samples, but current data are restricted to under-/never-screened women and referral populations. This study evaluated triage performance in women who were offered primary HPV self-sampling for cervical cancer screening. Methods Self-collected samples from 593 HPV-positive women who participated in a primary HPV self-sampling trial (IMPROVE study; NTR5078), were tested for the DNA methylation markers ASCL1 and LHX8 using quantitative multiplex methylation-specific PCR (qMSP). The diagnostic performance for CIN3 and cervical cancer (CIN3 + ) was evaluated and compared with that of paired HPV-positive clinician-collected cervical samples. Results Significantly higher methylation levels were found in HPV-positive self-collected samples of women with CIN3 + than control women with no evidence of disease (P values ASCL1/LHX8 yielded a sensitivity for CIN3 + detection of 73.3% (63/86; 95% CI 63.9–82.6%), with a corresponding specificity of 61.1% (310/507; 95% CI 56.9–65.4%). The relative sensitivity for detecting CIN3+ was 0.95 (95% CI 0.82–1.10) for self-collection versus clinician-collection, and the relative specificity was 0.82 (95% CI 0.75–0.90). Conclusions The ASCL1/LHX8 methylation marker panel constitutes a feasible direct triage method for the detection of CIN3 + in HPV-positive women participating in routine screening by self-sampling.

ObjectiveTo assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme.DesignAll individuals that participated in 2017 and 2018 with a negative FIT and were eligible for CRC screening in 2019 and 2020 were included using individual-level data. Multivariable logistic regression analyses were used to assess the association between either the different time periods (ie, ‘before’, ‘during’ and ‘after’ the first COVID-19 wave) or the invitation interval on screen-detected and interval CRCs.ResultsPositive predictive value for advanced neoplasia (AN) was slightly lowerduring(OR=0.91) andafter(OR=0.95) the first COVID-19 wave, but no significant difference was observed for the different invitation intervals. Out of all individuals that previously tested negative, 84 (0.004%) had an interval CRC beyond the 24 months since their last invitation. The time period of invitation as well as the extended invitation interval was not associated with detection rates for AN and interval CRC rate.ConclusionThe impact of the first COVID-19 wave on screening yield was modest. A very small proportion of the FIT negatives had an interval CRC possibly due to an extended interval, which potentially could have been prevented if they had received the invitation earlier. Nonetheless, no increase in interval CRC rate was observed, indicating that an extended invitation interval up to 30 months had no negative impact on the performance of the CRC screening programme and a modest extension of the invitation interval seems an appropriate intervention.

Background Surgical treatment for high-grade cervical intraepithelial neoplasia (CIN) may affect future fertility and pregnancy outcomes, therefore alternative therapies are desirable. Objectives To determine the efficacy of topical imiquimod in treatment of high-grade CIN (defined as regression CIN 1 or less), and to determine the clearance rate of high-risk human papillomavirus (hr-HPV), compared to surgical treatment and placebo. Search strategy Cohort studies and trials up to July 2022 were searched with the terms imiquimod, cervical dysplasia, and HPV. Selection criteria Studies evaluating the efficacy of imiquimod in CIN lesions. Data collection and analysis The study followed the PRISMA checklist. Meta-analysis was conducted to determine the efficacy of imiquimod treatment. Main results Five studies involving 463 women with high-grade CIN were included. Imiquimod was associated with histological regression to CIN1 or less in 55% of cases versus 29% for placebo, and 93% for surgical treatment. Imiquimod-treated women had a greater odds ratio of histological regression to CIN1 or less than placebo-treated women (ORs 4.17, 95% CI 2.03-8.54). In comparison to imiquimod, surgical treatment had an odds ratio of 14.81 (95% CI 6.59-33.27) for histological regression to CIN1 or less. The hr-HPV clearance rate was 53.4% after imiquimod treatment and 66% after surgical treatment (ORs 1.53, 95% CI 0.62-23.77). Conclusions: Histological regression is higher in imiquimod treatment than placebo. Surgical treatment, which is currently the golden standard, shows a higher regression rate than imiquimod. Future studies should focus on patient selection and further development of alternative treatments.

The World Health Organization launched a campaign on elimination of cervical cancer on November 17th 2020. In this article the authors give an overview of HPV-related cancer in The Netherlands and stress that HPV-vaccinations for boys and girls and screening for women is of utmost importance to eliminated cervical cancer in The Netherlands and the benefit for boys to avoid HPV related cancer themselves. They state that HPV vaccinations are efficient and safe. All Health Workers should counsel boys and girls and their parents toward HPV-vaccination for all.

We studied harms related to cervical cancer screening and management of screen-positive women in the United States (US) and the Netherlands. We utilised data from four US integrated health care systems (SEARCH), the US National Health Interview Survey, New Mexico state, the Netherlands national histopathology registry, and included studies on adverse health effects of cervical screening. We compared the number of Papanicolaou (Pap) smear tests, abnormal test results, punch biopsies, treatments, health problems (anxiety, pain, bleeding, and discharge), and preterm births associated with excisional treatments. Results were age-standardized to the 2007 US population. Based on SEARCH, an estimated 36 million Pap tests were performed in 2007 for 91 million US women aged 21–65 years, leading to 2.3 million abnormal Pap tests, 1.5 million punch biopsies, 0.3 million treatments for precancerous lesions, 5 thousand preterm births, and over 8 million health problems. Under Netherlands screening practice, fewer Pap tests (58%), abnormal test results (64%), punch biopsies (75%), treatment procedures (40%), preterm births (60%), and health problems (63%) would have occurred. The SEARCH data did not differ much from other US data for 2007 or from more recent data up to 2013. Thus compared with the less intensive screening practice in the Netherlands, US practice of cervical cancer screening may have resulted in two- to three-fold higher harms, while the effects on cervical cancer incidence and mortality are similar. The results are also of high relevance in making recommendations for HPV screening. Systematic collection of harms data is needed for monitoring and for better incorporation of harms in making screening recommendations.