# Molecular factors associated with lung cancer in people living with HIV

## TL;DR

People with HIV are more likely to develop lung cancer due to immune issues, inflammation, and HIV-related factors that promote tumor growth.

## Contribution

The paper identifies molecular mechanisms by which HIV contributes to lung cancer development in people living with HIV.

## Key findings

- HIV proteins like Tat, gp120, and Nef contribute to cancer by affecting cell cycle and immune evasion.
- Persistent HIV reservoirs in the lungs cause immune dysregulation and promote tumor growth.
- HIV integration disrupts tumor suppressor genes like PTEN and silences regulators like P16INK4a.

## Abstract

Lung cancer is the most common Non-AIDS-Defining Cancer (NADC) and a leading cause of cancer-related death in People Living With HIV (PLWH). Despite antiretroviral therapy, PLWH are at higher risk of developing cancer compared to the general population. This increased susceptibility reflects a combination of immunosuppression, chronic inflammation, smoking, and direct oncogenic effects of HIV proteins. Tat, gp120, and Nef modulate cell cycle control, apoptosis, epithelial-mesenchymal transition, angiogenesis, and immune evasion. Persistent HIV reservoirs in lung tissue (mainly effector memory CD4⁺ T-cells and alveolar macrophages) sustain local immune dysregulation. Extracellular vesicles carrying viral proteins or nucleic acids activate oncogenic pathways, while HIV integration disrupts tumor suppressor genes such as PTEN and induces epigenetic silencing of regulators like P16INK4a. These alterations, together with oxidative stress, promote a pro-tumorigenic microenvironment. A deeper understanding of these mechanisms may enable early biomarker identification and the design of targeted preventive and therapeutic strategies for lung cancer in PLWH.