HIV-Associated Malignancies: Unraveling Cancer Pathogenesis Through Medical Imaging, Biomarkers, Precision Medicine, and Vaccine Innovation

Abstract

Background: The introduction of effective antiretroviral therapy (ART) has transformed HIV infection into a chronic condition for many people living with HIV (PLWH), yet cancer remains an important source of morbidity and mortality. The malignancy spectrum is heterogeneous: risk is particularly elevated for tumors linked to oncogenic viruses and immune dysfunction, while selected non-AIDS-defining cancers also contribute to the contemporary burden. HIV-associated carcinogenesis is not explained by CD4 depletion alone; persistent viral co-infections, chronic inflammation, immune exhaustion, altered cytokine networks, and tumor-microenvironment effects interact over time. Objective: This narrative review integrates current evidence on HIV-associated malignancy biology with the clinical roles and limitations of medical imaging, tissue and circulating biomarkers, precision oncology, and vaccine-based prevention or treatment. It emphasizes the distinction between established clinical approaches and investigational strategies. Methods: A focused narrative synthesis was developed from peer-reviewed epidemiologic studies, mechanistic investigations, clinical trials, and authoritative scholarly reviews. Core themes included cancer-risk patterns in the ART era; KSHV-, EBV-, and HPV-associated oncogenesis; imaging for staging and response assessment; biomarker translation; treatment adaptation; and vaccine innovation. This is not a systematic review, and no formal risk-of-bias assessment or pooled analysis was performed. Results: Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin lymphoma, and HPV-associated anogenital cancers remain central to the HIV-cancer interface. Modern ART reduces several AIDS-defining cancer risks but does not eliminate risk, particularly when immune recovery is incomplete or oncogenic co-infections persist. FDG-PET/CT is useful in selected lymphoma contexts but is not cancer-specific; inflammatory and infectious processes may produce false-positive findings. Histopathology remains essential for diagnosis. Molecular characterization, circulating tumor DNA, immune profiling, and biomarker-guided treatment are promising, but validation and implementation remain uneven. Cancer vaccines have a clear preventive role for HPV and hepatitis B virus where indicated, while therapeutic cancer vaccines and HIV-directed immunization approaches remain investigational. Conclusion: Better outcomes require integrated HIV and oncology care, timely ART, prevention and screening, accurate tissue diagnosis, context-aware imaging, and evidence-calibrated use of molecular tools. Future research should prioritize prospective biomarker validation, equitable access to screening and treatment, representation of PLWH in trials, and mechanistically informed vaccine and immunotherapy studies.