Endometrial adenocarcinoma in women with HIV infection: pathogenesis, diagnosis, and interdisciplinary management strategies

The advent of combination antiretroviral therapy (ART) has profoundly modified the oncologic landscape in people living with HIV (PLWH), shifting the burden from AIDS-defining malignancies towards non-AIDS-defining cancers. Against this background, endometrial adenocarcinoma in women living with HIV is gaining clinical relevance as a hormone dependent solid tumour in which classical metabolic and reproductive risk factors intersect with HIV related immune dysfunction and chronic inflammation. The aim. To summarise recent evidence on the epidemiology, risk factors, morphologic and molecular features of endometrial adenocarcinoma in women living with HIV, and on the impact of immune status and ART on disease course and outcomes. Material and methods. A focused search of PubMed, Scopus and Web of Science was performed for 2021–2025 using combinations of the terms «endometrial cancer», «endometrial carcinoma», «HIV infection», «women living with HIV», «nonAIDS-defining cancers», «molecular classification», and «tumor immune microenvironment». Original studies, meta-analyses, systematic reviews and international guidelines were included. Results and discussion. As PLWH age and life expectancy improves under effective ART, the incidence of hormone driven solid tumours, including endometrial adenocarcinoma, is increasing. In women with HIV, endometrial cancer risk is shaped by the combination of traditional determinants (obesity, metabolic syndrome, unopposed estrogen exposure, late menopause) and HIV-specific factors (prolonged immunosuppression, low nadir CD4⁺ count, high historical viral load, chronic immune activation). Contemporary data support the applicability of the four-tier molecular classification (POLE-mut, MMRd, p53abn, NSMP) and ESGO/ESTRO/ESP and FIGO-based integrated risk models to this population, although dedicated validation is lacking. Emerging studies highlight the role of the tumour immune microenvironment, the frequency of MMRd and high tumour mutational burden as prognostic and predictive markers for immune checkpoint inhibitors in selected patients. Conclusions. Endometrial adenocarcinoma in women living with HIV represents an emerging clinicopathologic challenge that requires coordinated management by infectious disease specialists, gynaecologic oncologists and pathologists. Prospective, HIV-focused multicentre studies are needed to refine risk estimates, validate molecularly informed prognostic models and develop tailored strategies for screening, treatment and long-term surveillance in this high risk group.

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