Jennifer L. Butt

Prognostic Relevance of Molecular Classification in Endometrial Cancer: Insights From a South African Cohort

PURPOSE Geographical and racial diversity may influence endometrial cancer (EC) prognosis, yet its impact remains underexplored. In South Africa (SA), the rising incidence of EC underscores the need to investigate potential biologic differences. Molecular classification of EC offers valuable prognostic insights that could help address disparities and improve care. This study evaluated the prevalence and prognostic significance of molecular subtypes in a South African high-intermediate and high-risk EC cohort. MATERIALS AND METHODS We included 133 patients with high-intermediate and high-risk EC diagnosed in SA between January 2017 and December 2021. Clinical, demographic (including self-identified race), and follow-up data were collected. Central pathology review assessed histotype, grade, lymphovascular space invasion, and International Federation of Gynecology and Obstetrics 2009 stage. Molecular subtyping followed the WHO 2020 algorithm using targeted next-generation sequencing and immunohistochemistry for p53, mismatch repair (MMR) proteins, and ER. Shallow whole-genome sequencing (sWGS) assessed genome-wide copy number alterations. RESULTS Among 131 patients with complete molecular classification, the most common subtype was p53-abnormal (p53abn, n = 71; 54.2%), followed by MMR-deficient (MMRd, n = 30; 22.9%), no specific molecular profile (NSMP, n = 21; 16.0%), and POLE -ultramutated ( POLE mut, n = 9; 6.9%). Nonendometrioid EC (NEEC) predominated (n = 82; 61.7%). High-grade endometrioid EC and NEEC were more frequent in non-White patients ( P = .030). Molecular subtypes were significantly associated with overall recurrence ( P = .029), with no recurrences in POLE mut ECs and the worst outcomes in p53abn ECs. sWGS revealed higher CN burdens in p53abn ECs, with recurrent focal alterations involving CCNE1 amplification and RB1 loss. CONCLUSION To our knowledge, this study is the first to demonstrate the prognostic value of EC molecular classification in a South African cohort. These findings support the global relevance of molecular EC subtyping. The urgent need for access to molecular diagnostics or cost-effective alternatives in resource-limited settings is highlighted.

The impact of concurrent HIV-infection on women with vulvar cancer: Comparison of clinical characteristics and outcome

Background HPV-related vulvar cancer is increasing in prevalence, especially in women living with HIV. Treatment of vulva cancer is based on evidence from HPV-independent cancers, which affect older women. The impact of HIV on vulvar cancer characteristics and treatment outcomes needs to be elucidated. Patients and Methods A retrospective observational study compared the clinical characteristics, treatment, and outcomes of 92 HIV-positive and 131 HIV-negative women with vulvar cancer at our institution. Using descriptive statistics, HIV-positive and negative patients were compared and Cox regression models were tested for differences in mortality and recurrence. Results HIV-positive patients were 20 years younger than HIV-negative patients ( p < 0.001). More than 50% of patients presented with advanced stage cancer, however this was independent of HIV-status. Although HIV infection was associated with poorer survival ( p = 0.022); rates of cure ( p = 0.933) and recurrence rates ( p = 0.8) were similar in HIV-positive and negative women. Conclusions Vulvar cancer occurs at a much younger age in women living with HIV. Awareness among HIV-positive women and health care providers would lead to diagnosis of vulvar cancer at an earlier stage. Treatment protocols for HPV-related vulvar cancer should not be altered due to HIV status and should take into consideration the young age of the patients.