Prognostic values of molecular subtypes and SWI/SNF protein expression in de-differentiated/undifferentiated endometrial carcinoma.

Aims: Classification and risk stratification of endometrial carcinoma (EC) has transitioned from histopathological features to molecular classification, e.g. the ProMisE classifier, identifying four prognostic subtypes: POLE mutant (POLEmut) with almost no recurrence or disease-specific death events, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP), with intermediate outcome and p53 abnormal (p53abn) with poor outcomes.

Serum CA125 levels in the context of ProMisE molecular classification provides pre-operative prognostic information that can direct endometrial cancer management.

Objective: Previous research suggests serum CA125 reflects extra-uterine disease in patients with endometrial carcinoma (EC). Our objective was to determine if CA125 can identify patients with extra-uterine and/or nodal metastases, the association of this biomarker with EC molecular subtype, and to explore an optimal cutoff in this context.

Methods: We assessed the association of CA125 levels with clinicopathologic and outcomes data on a cohort of 1107 molecularly classified EC.

Papillary and ductal patterns of mesonephric-like adenocarcinomas are often overlooked: a retrospective revaluation of over 1000 endometrial carcinomas.

Aims: Mesonephric-like adenocarcinoma (MLA) of the endometrium is often a diagnostic challenge, due to its morphological resemblance to other more common Müllerian neoplasms. This study aimed to retrospectively identify overlooked MLA in a large endometrial carcinoma cohort, using a combination of immunohistochemistry (IHC), morphology and KRAS sequencing.

Methods And Results: IHC was conducted on 1094 endometrial carcinomas, identifying 16 potential MLA cases based on GATA3+ and/or TTF1+ and ER- staining patterns, which subsequently underwent detailed histological review, KRAS sequencing and ProMisE molecular classification.

Hormonal biomarkers remain prognostically relevant within the molecular subgroups in endometrial cancer.

Objective: The prognostic relevance of hormonal biomarkers in endometrial cancer (EC) has been well-established. A refined three-tiered risk model for estrogen receptor (ER)/progesterone receptor (PR) expression was shown to improve prognostication. This has not been evaluated in relation to the molecular subgroups.

Assessing the impact of deep-learning assistance on the histopathological diagnosis of serous tubal intraepithelial carcinoma (STIC) in fallopian tubes.

In recent years, it has become clear that artificial intelligence (AI) models can achieve high accuracy in specific pathology-related tasks. An example is our deep-learning model, designed to automatically detect serous tubal intraepithelial carcinoma (STIC), the precursor lesion to high-grade serous ovarian carcinoma, found in the fallopian tube. However, the standalone performance of a model is insufficient to determine its value in the diagnostic setting.

University students' access and use of sexual and reproductive health services in Australia.

University attendance can lead to changes in sexual behaviour that place people at increased risk of negative sexual and reproductive health (SRH) experiences; however, relatively few studies have explored access to and use of SRH services by university students in Australia. A convenience sample of students ( = 4291) from five universities completed an online survey to examine barriers and facilitators to accessing SRH services. Descriptive statistics were used to analyse variations by gender, sexuality, and enrolment status.

Typing of Vulvar Squamous Cell Carcinoma: Why it is Important?

The classification of vulvar squamous cell carcinoma (VSCC), as in endometrial cancer, has shifted from the histology-based descriptors toward molecular-based identifiers. Recently, it has been reported that there are 3 genetically distinct and clinically significant subtypes of VSCC: HPV-associated VSCC, HPV-independent/p53 wild-type VSCC, and HPV-independent/p53-mutated VSCC. Each group has different prognostic implications as well as response to treatment, thus reinforcing the need for this 3-tier molecular classification.

Intersectional inequity in knowledge, attitude, and testing related to HIV in Ethiopia: People with multiple disadvantages are left behind.

Intersectionality pinpoints intersecting factors that empower or oppress people with multiple (dis)advantageous conditions. This study examined intersectional inequity in knowledge, attitudes, and testing related to HIV among adults aged 15 to 49 years in Ethiopia. This study used nationally representative 2016 Ethiopian Demographic Health Survey data.

Improved Risk Prediction in Human Papillomavirus-Associated Endocervical Adenocarcinoma Through Assessment of Binary Silva Pattern-based Classification: An International Multicenter Retrospective Observational Study Led by the International Society of Gynecological Pathologists (ISGyP).

Endocervical adenocarcinomas (EACs) are a group of malignant neoplasms associated with diverse pathogenesis, morphology, and clinical behavior. As a component of the International Society of Gynecological Pathologists International Endocervical Adenocarcinoma Project, a large international retrospective cohort of EACs was generated in an effort to study potential clinicopathological features with prognostic significance that may guide treatment in these patients. In this study, we endeavored to develop a robust human papillomavirus (HPV)-associated EAC prognostic model for surgically treated International Federation of Gynecology and Obstetrics (FIGO) stage IA2 to IB3 adenocarcinomas incorporating patient age, lymphovascular space invasion (LVSI) status, FIGO stage, and pattern of invasion according to the Silva system (traditionally a 3-tier system).

Perceptions of nicotine vaping products among Australians living with HIV.

People living with HIV (PLHIV) are two to three times more likely to smoke tobacco compared to the general community. Evidence from the general population suggests that nicotine vaping products (NVPs) can be acceptable and effective smoking cessation aids, but there is limited evidence on the extent to which this is the case among PLHIV. This manuscript reports findings from the Tobacco Harm Reduction with Vaporised Nicotine (THRiVe) trial, a mixed-methods study investigating the feasibility of NVPs as smoking cessation aids among 29 PLHIV who smoked tobacco.

Learning generalizable AI models for multi-center histopathology image classification.

Investigation of histopathology slides by pathologists is an indispensable component of the routine diagnosis of cancer. Artificial intelligence (AI) has the potential to enhance diagnostic accuracy, improve efficiency, and patient outcomes in clinical pathology. However, variations in tissue preparation, staining protocols, and histopathology slide digitization could result in over-fitting of deep learning models when trained on the data from only one center, thereby underscoring the necessity to generalize deep learning networks for multi-center use.

Explaining inequity in knowledge, attitude, and services related to HIV/AIDS: a systematic review.

Background: Equitable service provision and coverage are important responses to end the threat of the HIV/AIDS pandemic. Understanding inequity supports policies and programmes to deliver tailored interventions. There is continuous evidence generation on inequity in HIV/AIDS services.

Practical guidance for assessing and reporting lymphovascular space invasion (LVSI) in endometrial carcinoma.

Lymphovascular space invasion (LVSI) is an important prognostic parameter in endometrial carcinoma (EC) and has gained increasing interest in recent years due to an expanding body of evidence of its independent prognostic value, especially when the presence of LVSI is quantified. A key strength of LVSI as a prognostic factor is that it can be detected on routine microscopic examination, without ancillary tests, and thus can be used in low-resource settings. A weakness, however, is the lack of uniformly applied criteria for assessment and quantification of LVSI, resulting in interobserver variation in diagnosis.

AI-based histopathology image analysis reveals a distinct subset of endometrial cancers.

Endometrial cancer (EC) has four molecular subtypes with strong prognostic value and therapeutic implications. The most common subtype (NSMP; No Specific Molecular Profile) is assigned after exclusion of the defining features of the other three molecular subtypes and includes patients with heterogeneous clinical outcomes. In this study, we employ artificial intelligence (AI)-powered histopathology image analysis to differentiate between p53abn and NSMP EC subtypes and consequently identify a sub-group of NSMP EC patients that has markedly inferior progression-free and disease-specific survival (termed 'p53abn-like NSMP'), in a discovery cohort of 368 patients and two independent validation cohorts of 290 and 614 from other centers.

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).

Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes.

Equity in HIV/AIDS services requires optimization of mainstreaming sectors in Ethiopia.

Background: Mainstreaming HIV and AIDS across sectors is crucial to close the disparities in service provision and coverage. However, evidence has shown that certain social groups are left behind in receiving HIV/AIDS services. The objective of this study was twofold: to understand the reasons behind the existing inequities and to explore challenges of equity in HIV/AIDS services in the Amhara region of Ethiopia.

Correction: Universality of universal health coverage: A scoping review.

[This corrects the article DOI: 10.1371/journal.pone.

VOLTA: an enVironment-aware cOntrastive ceLl represenTation leArning for histopathology.

In clinical oncology, many diagnostic tasks rely on the identification of cells in histopathology images. While supervised machine learning techniques necessitate the need for labels, providing manual cell annotations is time-consuming. In this paper, we propose a self-supervised framework (enVironment-aware cOntrastive cell represenTation learning: VOLTA) for cell representation learning in histopathology images using a technique that accounts for the cell's mutual relationship with its environment.

Targeted and Shallow Whole-Genome Sequencing Identifies Therapeutic Opportunities in p53abn Endometrial Cancers.

Purpose: Shallow whole-genome sequencing (sWGS) can detect copy-number (CN) aberrations. In high-grade serous ovarian cancer (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers to identify additional prognostic stratification and therapeutic opportunities.

A cross-sectional investigation of the factors associated with awareness of PEP and PrEP among Queensland university students.

Objective: University creates unique social environments for many young people that can result in behaviour changes that can impact sexual health-related risks and facilitate transmission of HIV. Little is known about HIV knowledge, risk, and awareness of pre-exposure prophylaxis/post-exposure prophylaxis (PrEP/PEP) among Australian university students.

Methods: A 2019 online survey distributed through Queensland universities, using active recruitment/snowball sampling.

Socioeconomic inequality in adults undertaking HIV testing over time in Ethiopia based on data from demographic and health surveys.

Introduction: HIV testing is the entry point to HIV prevention, care and treatment and needs continuous evaluation to understand whether all social groups have accessed services equally. Addressing disparities in HIV testing between social groups results in effective and efficient response against HIV prevention. Despite these benefits, there was no previous study on inequality and determinants over time in Ethiopia.

High concordance of molecular subtyping between pre-surgical biopsy and surgical resection specimen (matched-pair analysis) in patients with vulvar squamous cell carcinoma using p16- and p53-immunostaining.

Objective: Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen.

Methods: Matched-paired pre-surgical biopsies and subsequent resection specimen of 57 patients with VSCC were analysed for the immunohistochemical expression of p16 and p53 by performing a three-tiered molecular subtyping to test the accuracy rate.

Endometrial Carcinosarcomas are Almost Exclusively of p53abn Molecular Subtype After Exclusion of Mimics.

Our aim was to assess the molecular subtype(s) and perform a detailed morphologic review of tumors diagnosed as carcinosarcoma in a population-based cohort. Forty-one carcinosarcomas were identified from a cohort of 973 endometrial carcinomas diagnosed in 2016. We assessed immunostaining and sequencing data and undertook expert pathology reviews of these cases as well as all subsequently diagnosed (post-2016) carcinosarcomas of no specific molecular profile (NSMP) molecular subtype (n=3) from our institutions.

A tumor-restricted glycoform of podocalyxin is a highly selective marker of immunologically cold high-grade serous ovarian carcinoma.

Introduction: Targeted-immunotherapies such as antibody-drug conjugates (ADC), chimeric antigen receptor (CAR) T cells or bispecific T-cell engagers (eg, BiTE) all aim to improve cancer treatment by directly targeting cancer cells while sparing healthy tissues. Success of these therapies requires tumor antigens that are abundantly expressed and, ideally, tumor specific. The CD34-related stem cell sialomucin, podocalyxin (PODXL), is a promising target as it is overexpressed on a variety of tumor types and its expression is consistently linked to poor prognosis.