Breast cancer is the most common cancer among South African women, yet the country has the lowest 5-year survival rate among the BRICS nations (Brazil, Russia, India, China, South Africa), at just 40%. Earlier diagnosis contributes to survival rates exceeding 90% in many high-income countries. We synthesised the evidence to identify barriers to early breast cancer diagnosis in South Africa and inform policy interventions.

A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.

OVID MEDLINE, Global Health, Health Management Information Consortium, Scopus and Web of Science were searched for studies published between 1 January 2015 and 31 March 2025.

We included English-language, peer-reviewed studies investigating patient-level, provider-level and/or health system-level barriers to early breast cancer diagnosis among adult women in South Africa. Barriers were classified using the WHO 2017 Guide to Cancer Early Diagnosis framework: (1) awareness and access to care; (2) clinical evaluation, diagnosis and staging and (3) access to treatment.

Two reviewers independently screened studies, extracted data and assessed risk of bias. Findings were synthesised narratively using the WHO framework.

22 studies (n=8518 participants; 5048 women with breast cancer) were included. Step 1 barriers included limited breast cancer knowledge and poor healthcare access, particularly among rural and less educated women. Step 2 barriers included multiple prediagnosis visits and inadequate diagnostic capacity, with delays of 28 days to over 12 months. Step 3 barriers included limited surgical and oncology services, requiring many rural patients to travel for treatment. One-stop clinics were associated with shorter diagnostic intervals.

Barriers to early diagnosis occur across the breast cancer pathway in South Africa. Community awareness, culturally grounded education, streamlined referral pathways and equitable investment in diagnostic and oncology services may significantly improve timely diagnosis and breast cancer outcomes.

CRD420261297178.

Lung squamous cell carcinoma is a subtype of non-small cell lung cancer (NSCLC) and its biological characteristics or treatment responses might differ from non-squamous NSCLC. Although neoadjuvant immunotherapy combined with chemotherapy has become the guideline-recommended treatment for resectable NSCLC, clinical benefits remain suboptimal as a substantial proportion of patients fail to achieve pathological complete response (pCR). Hence, we conduct a clinical study on QL1706 combined with chemotherapy for the neoadjuvant treatment of squamous NSCLC.

This is a phase II, multicentre, single-arm, prospective clinical trial. The study includes patients with stage II-IIIB squamous NSCLC who are eligible or potentially eligible for surgical resection. Enrolled patients receive the neoadjuvant treatment regimen consisting of three cycles of QL1706 (5 mg/kg, d1, Q3W) combined with platinum-doublet chemotherapy. The primary endpoint is the pCR rate. The secondary endpoints are major pathological response, clinical response rate, R0 resection rate, event-free survival, overall survival, safety and tolerability, feasibility of surgery and incidence rate of complications during the perioperative period or within 90 days after the surgery.

The study was approved by the ethics committee of Zhejiang Cancer Hospital on 29 May 2025 (IRB-2025-667). The current study protocol version is V.5.0. Patient enrollment has been ongoing since October 2025. The results of this study will be presented to peer-reviewed journals and scientific conferences.

ChiCTR2500104283.

Ovarian cancer is the leading cause of gynecological cancer death for women in the United States. Aging and obesity are known risk factors that increase incidence rate, severity, and metastatic progression of ovarian cancer. With aging and obesity, physiological changes occur including increased inflammation, altered metabolism, and, most notably, extracellular matrix (ECM) remodeling. Remodeling of the ECM is critical for accommodating adipocyte expansion in obesity and arises from accumulated modifications with aging. The already remodeled collagen under these host factors is driven by remodeling enzymes such as matrix metalloproteinases (MMPs). Of particular interest is membrane-bound MT1-MMP, which is required for invasion in metastatic ovarian cancer. MT1-MMP is responsible for the directed collagenolysis of the ECM, which is a barrier to metastatic growth. Because of metastatic dependence on MT1-MMP, there have been many attempts to inhibit this enzyme, but current therapies lack specificity and cause significant adverse side effects. Nonetheless, novel therapeutic interventions targeting MT1-MMP are promising to improve selectivity. In this chapter, we will highlight key pathways regulating MT1-MMP expression, impact on oncogenic phenotypes, and the mechanisms that aging and obesity use to further promote ECM remodeling and accelerate disease progression, while assessing past and future challenges to study and targeting MMPs for cancer treatment.

Microbial biofilms are extremely organized groups of microorganisms entrenched in an extracellular polymeric substance (EPS) network which facilitates persistence, shielding against host immunity, and resistance to antimicrobial activity. Although traditionally related to chronic infections and complications in devices, recent evidence suggests that biofilms are also important in cancer formation and progression. Recent research has shown that microbial communities can be present in tumor micro-environment, and biofilms can be actively involved in carcinogenesis as opposed to being passive colonizers. In this chapter, a new association between biofilms and cancer is discussed through an understanding of their existence in various malignancies such as colorectal, oral, pancreatic, breast, gastric, lung, cervical, and liver cancers. The mechanisms of biofilms and tumor development are in detail discussed such as chronic inflammation, generation of genotoxic metabolites, immune modulation and destabilization of epithelial barriers. These mechanisms induce genomic instability, damage DNA, immunomodulation and the activation of oncogenic signaling pathways that promote the initiation and progression of tumors. Moreover, the chapter suggests the effect of biofilms on the tumor microenvironment, angiogenesis, metastasis, and cancer therapy resistance to chemotherapy, radiotherapy, and immunotherapy. Clinical implications are also discussed, and the problem includes difficulties in diagnosing, prognostic implications, and the effect of biofilm-related infections on patient outcomes. Although mounting evidence is obtained, the role of biofilms in oncology is under-recognized since it is challenging to detect, might be mistaken as contamination, and there is a lack of awareness in cancer research. The knowledge of the intricate relationships that exist between microbial biofilms and host tissues can provide fresh prospects to better diagnostics, specific antimicrobial therapy, and new treatment methods in cancers.

Large language models (LLMs) are increasingly being considered for clinical decision support, yet their safety in risk-based cervical screening management remains insufficiently characterized.

This study benchmarked the guideline concordance and safety-related performance of 3 LLMs in the initial American Society for Colposcopy and Cervical Pathology (ASCCP) risk-based management of abnormal cervical screening results, using a purposively constructed synthetic scenario set that oversamples complex and history-dependent decision nodes.

We developed 60 synthetic clinical scenarios reflecting initial abnormal screening management in immunocompetent, nonpregnant women aged 25 to 65 years using a predefined scenario coverage matrix. GPT-5.3, Gemini 3 Flash, and DeepSeek V3.2 were tested under 2 prompt conditions: Baseline Clinical Prompt and Guideline-Directed Prompt Package. Each scenario was run in 3 independent repetitions per model and prompt arm (1080 total observations). Responses were evaluated by 2 obstetrics and gynecology specialists, blinded to model and prompt-arm identity but not independent of gold-standard construction, using a prespecified rubric. The primary end point was the unsafe major error-free rate. Proportions are reported with CIs adjusted for within-scenario clustering, and generalized estimating equations were used for inferential comparisons.

Under the guideline-directed prompt package, the unsafe major error-free rate was 100% (95% CI 94%-100%) for GPT-5.3, 98.9% (95% CI 94%-99.8%) for Gemini 3 Flash, and 75% (95% CI 63.2%-84%) for DeepSeek V3.2. In the main-effects model, the guideline-directed prompt package was associated with higher odds of both unsafe major error-free performance (odds ratio [OR] 3.76, 95% CI 2.45-5.77; P<.001) and exact concordance (OR 8.27, 95% CI 4.14-16.52; P<.001). Error rates increased substantially with scenario complexity, rising from 3.1% in low-complexity to 29% in high-complexity scenarios. The most frequent error subtypes were undermanagement, genotype misinterpretation, and history neglect. Interrater agreement was almost perfect (weighted κ=0.839, 95% CI 0.811-0.867).

Safety-oriented benchmark performance in initial ASCCP risk-based management varied markedly by model, prompt condition, and scenario complexity. The guideline-directed prompt package was associated with improvement in both safety and guideline concordance, but even the best-performing model remained vulnerable in complex, history-dependent scenarios. LLMs may have value as clinician-supervised decision support tools, but these benchmark findings should not be interpreted as supporting autonomous clinical use in cervical screening management.

The expression of the HER2 oncogene has a specific prognostic and therapeutic objective in breast cancer care. Low gene expression, called HER2-low implies the possibility of being a candidate for targeted therapy. However, there is significant variability in its interpretation, hence the importance of emphasizing its proper identification and reporting.

To estimate the proportion of cases confirmed as HER2 1+ among biopsies previously reported as HER2 1+, and to describe their clinicopathological characteristics, as well as the interobserver agreement in their classification.

Observational, retrospective, and analytical study of cases previously diagnosed as HER2-negative score 1+, which were reviewed by 2 independent pathologists.

351 cases were included, with a mean age of 59.56 years. The histological subtypes were invasive ductal carcinoma NOS (70.66%), histological grade 2 (56.92%), and SBR score 6 (41.82%), associated in 89.17% of cases with hormone receptor expression. There was agreement for the HER2-low diagnosis in 78.91% of cases, with a Cohen's kappa simple of 0.62, which is similar to some studies documented in the literature.

Agreement in the interpretation of HER2-low increases when it is performed by at least 2 pathologists; likewise, proper handling of surgical specimens in the pre-analytical phase is vital for optimal assessment, as this has a direct impact on current prognosis and treatment.

Minimally Invasive transCervical oEsophagectomy (MICE) is a novel technique with radical lymphadenectomy that avoids a transthoracic access, potentially preserving pleural integrity and obviating one lung ventilation, thereby reducing postoperative pulmonary complications. However, its advantages over conventional Transthoracic Minimally Invasive oEsophagectomy (TMIE) remain unclear. The objective of this study was to assess postoperative outcomes after TMIE and MICE. A retrospective cohort study was conducted including patients with resectable esophageal cancer (cT1-4aN0-3M0) who underwent esophagectomy at the Radboudumc, the Netherlands between 2020 and 2024. The primary outcome was the incidence of postoperative complications within 30 days. Inverse probability of treatment weighting (IPTW) was used to account for confounding between the groups. A total of 115 MICE and 172 TMIE patients were included. After IPTW, overall postoperative complications were more frequent after MICE (60.3% vs. 43.9%, RD: 16.4%, 95% CI: 3.3-29.4). This difference was predominantly driven by a higher incidence of recurrent laryngeal nerve palsy (RLNP) (MICE: 30.4% vs. TMIE: 0.0%). No statistical significant difference was observed in pulmonary complications (18.9% vs. 21.8%, RD: -2.9, 95% CI: -17.1 to 12.5) or anastomotic leakage (5.6% vs. 8.1%, RD: -2.4%, 95% CI: -11.5 to 7.3). Although overall postoperative complication rates were higher after MICE, this difference was mainly attributable to an increased incidence of mostly transient recurrent laryngeal nerve palsy, which is inevitably associated with the transcervical approach. Rates of pneumonia and anastomotic leakage were similar between MICE and TMIE. As these data include cases performed during the early experience with MICE, complication rates may improve as experience accumulates across surgical teams. These findings highlight the need for further evaluation and optimization of the MICE procedure prior to broader implementation.

Approximately 55 900 women are diagnosed with breast cancer in the UK each year, and around one in five develop lymphoedema following treatment. Breast, trunk and arm lymphoedema arise from disruption to shared lymphatic drainage pathways during axillary surgery and radiotherapy, yet the condition remains under-recognised and under-referred in many post-treatment care pathways and women can struggle to find appropriate bras to support their care needs.

This article explores why and where lymphoedema develops after breast cancer treatment, presents the patient experience of living with breast and trunk lymphoedema, and evaluates the clinical evidence for 3D micro-massage compression technology - specifically the Solidea® Silver Wave Skin Bra - as an adjunct to standard lymphoedema management.

This article combines a narrative review of current evidence on breast and trunk lymphoedema with first-person patient testimony and findings from a pilot audit of 21 women with breast and/or trunk lymphoedema following breast cancer treatment. Audit outcome measures included the clinician-completed Breast Symptom Assessment Score, the wearer-completed Self-Report Symptom Rating Scale, structured wearer feedback and qualitative telephone follow up at approximately 26 days and 11 weeks.

Women sometimes report a delay between symptom onset and receiving support, alongside difficulty sourcing an appropriate, comfortable bra; these issues are compounded further for those wearing a breast prosthesis. In the pilot audit, mean Breast Symptom Assessment Score reduced by 60% (from 5.8 to 2.3) over approximately 26 days, with moderate-to-severe swelling falling from 70% to 15%, breast hardness from 90% to 65%, and night-time discomfort from 85% to 45%. All 20 completing participants showed improvement, with 100% rating comfort as excellent or good; the lowest-rated domain in self-reported symptoms scales was degree of support, particularly among women with cup sizes above D.

Breast and trunk lymphoedema is common, chronic and profoundly life-limiting, with psychological and social impact that compounds the burden of breast cancer treatment. Proactive risk information, early referral and holistic support are essential.

3D micro-massage compression may support self-management alongside complete decongestive therapy, but clinicians should consider patient suitability and the current evidence gaps in larger-breasted women and other garment formats.

Sub-Saharan Africa carries a disproportionate burden of HIV-associated malignancies. The contemporary tumour spectrum in the dolutegravir (DTG) era remains incompletely characterised in East African routine HIV-care settings. The immunovirological context at the time of cancer or benign tumor diagnosis is similarly under-described. We sought to describe the spectrum, malignant fraction, and immunovirological correlates of neoplasms diagnosed at a specialised HIV centre in Kampala, Uganda.

We conducted a retrospective, cross-sectional analysis of 219 tumour records identified within the longitudinal clinical cohort of people living with HIV (PLHIV) in continuous care at Mildmay Hospital, contributed by 216 individual patients (three of whom each had two separate tumour diagnoses on different dates) between November 2017 and January 2026. Tumours were classified by ICD-10 disease group and malignancy status (benign/malignant). Bivariate associations with malignancy status were tested using χ² or Fisher exact tests for categorical variables and Mann-Whitney U tests for continuous variables (two-sided α = 0.05), with Benjamini-Hochberg false discovery rate (FDR) correction applied across each panel of comparisons given the number of variables tested. Crude odds ratios (OR) with 95% confidence intervals (CI) were computed for dichotomous comparisons. A sensitivity analysis restricted to one tumour record per patient (n = 216) was performed to assess the influence of the three patients with two records each.

The cohort had a median age of 47 years (IQR 39-54) and was 127/219 (58.0%) female. Overall, 138/219 tumours (63.0%) were malignant. Kaposi sarcoma (KS) was the most frequently registered malignancy (n = 65; 47.1% of all malignant tumours; 29.7% of the full cohort). Among 155 records with viral load data, 133 (85.8%) were virally suppressed at tumour diagnosis, yet 70/133 (52.6%) of those suppressed records were malignant. Advanced WHO clinical stage (III/IV) at ART initiation was associated with malignant diagnosis (OR 3.51, 95% CI 1.54-8.81; FDR-adjusted p = 0.003). Median CD4 at ART initiation was lower among malignant compared with benign tumour records (147 vs 476 cells/µL; FDR-adjusted p = 0.001), and median ART duration before diagnosis was shorter (37 vs 101 months; FDR-adjusted p < 0.001). Restricting the analysis to KS versus other malignancies only (n = 138), KS patients had lower CD4 at ART initiation (136 vs 171 cells/µL, p = 0.079) and markedly shorter ART duration before diagnosis (4 vs 63 months, p < 0.001) than patients with other malignancies. All associations were materially unchanged in the patient-level sensitivity analysis.

HIV-associated tumours in this Ugandan cohort remain predominantly malignant and are dominated by KS despite high viral suppression rates. Malignancy clusters among patients with low pre-ART CD4 counts, advanced WHO stage, and short ART duration, though these are unadjusted, hypothesis-generating comparisons rather than evidence of causal or temporal gradients. These data establish the analytic platform for a prospective HIV-oncology cohort at Mildmay Hospital and Mildmay Research Centre and inform context-appropriate cancer screening priorities.

Immune checkpoint inhibitors benefit only a subset of patients with urothelial carcinoma, and bulk biomarkers may not capture spatially organized stromal and vascular programs that restrict immune access. We performed a retrospective public multi-cohort transcriptomic study to examine whether a cancer-associated fibroblast (CAF)/TGF-beta/endothelial barrier direction is associated with immune exclusion and checkpoint resistance in bladder cancer. GSE171351 was used for spatial discovery, GSE319536 for external spatial recurrence testing, TCGA-BLCA for prognosis-oriented support, and IMvigor210, GSE176307 and GSE328930/DUTRENEO for treatment-response projection. In the four-section discovery cohort, rank-5 non-negative matrix factorization separated an E2 barrier-enriched program from an E4 hypoxic epithelial program, although component assignment was strongly associated with section identity. The external cohort reproduced the direct CAF/TGF-beta/endothelial barrier direction in 22 of 22 sections but did not reproduce E2/E4 mutual exclusivity: projected E2 and E4 were positively correlated (rho = 0.928). In IMvigor210, top-quartile E2-high tumors showed suggestive, but not statistically conclusive, evidence of anti-PD-L1 non-response after full biologic covariate adjustment (OR=2.57, 95% CI 1.00-6.64, p = 0.051; delta AUC = 0.009). A prespecified heuristic barrier-exclusion score was associated with non-response in exploratory fixed- and random-effects summaries (OR=1.52, 95% CI 1.20-1.92), including a sensitivity analysis excluding GSE328930. These results identify a recurrent barrier direction rather than a universal two-niche architecture and support a hypothesis-generating mechanism-to-translation framework that requires prospective spatial and pathology-level validation.