Ralf L. O. van de Laar

Unraveling Differences in Molecular Mechanisms and Immunological Contrasts between Squamous Cell Carcinoma and Adenocarcinoma of the Cervix

This study aims to refine our understanding of the inherent heterogeneity in cervical cancer by exploring differential gene expression profiles, immune cell infiltration dynamics, and implicated signaling pathways in the two predominant histological types of cervix carcinoma, Squamous Cell Carcinoma (SCC) and Adenocarcinoma (ADC). Targeted gene expression data that were previously generated from samples of primary cervical cancer were re-analyzed. The samples were grouped based on their histopathology, comparing SCC to ADC. Each tumor in the study was confirmed to be high risk human papilloma virus (hrHPV) positive. A total of 21 cervical cancer samples were included, with 11 cases of SCC and 10 of ADC. Data analysis revealed a total of 26 differentially expressed genes, with 19 genes being overexpressed in SCC compared to ADC (Benjamini–Hochberg (BH)-adjusted p-value < 0.05). Importantly, the immune checkpoint markers CD274 and CTLA4 demonstrated significantly higher expression in SCC compared to ADC. In addition, SCC showed a higher infiltration of immune cells, including B and T cells, and cytotoxic cells. Higher activation of a variety of pathways was found in SCC samples including cytotoxicity, interferon signaling, metabolic stress, lymphoid compartment, hypoxia, PI3k-AKT, hedgehog signaling and Notch signaling pathways. Our findings show distinctive gene expression patterns, signaling pathway activations, and trends in immune cell infiltration between SCC and ADC in cervical cancer. This study underscores the heterogeneity within primary cervical cancer, emphasizing the potential benefits of subdividing these tumours based on histological and molecular differences.

High acceptability of point‐of‐care HIV testing at the colposcopy outpatient clinic in hospitals in the Netherlands

AbstractObjectiveCervical cancer and its precursor are labeled as HIV indicator conditions, justifying the recommendation of HIV testing for all patients. This study aimed to assess the acceptance and patients' and gynecologists' perceptions on HIV testing in patients with cervical dysplasia at the colposcopy outpatient clinic in hospitals in the Netherlands.MethodsA cross‐sectional study was conducted between May 2021 and February 2023 to implement point‐of‐care HIV testing in five hospitals in the Rotterdam region, the Netherlands. We included patients aged 18 years and older, without documented HIV, presenting with cervical dysplasia. The primary outcome was the HIV test acceptance rate. Secondary outcomes were the HIV positivity rate and the association between dysplasia severity and test acceptance. We also assessed patients' and gynecologists' perspectives on this testing strategy with a questionnaire.ResultsOf 563 patients, 523 accepted HIV testing, resulting in a test acceptance rate of 92.9% (95% confidence interval, 90.45%–94.88%). Testing rates were consistent among participating hospitals (91.6%–100.0%) None of the patients tested positive for HIV. Severity of dysplasia was not associated with test acceptance (P = 0.768). Most patients (n = 500, 96.0%) reported good or higher experience with this testing strategy. The main barriers for gynecologists to offer HIV testing were lack of time (n = 22, 33.9%) and fear to offend a patient (n = 7, 12.5%). Less than half (n = 19, 39.3%) of gynecologists believed an HIV test should be offered to all patients with cervical dysplasia.ConclusionPoint‐of‐care HIV testing at colposcopy outpatient clinics was well accepted by patients. The data indicate that the primary barrier lies with the physicians to offer such testing.