Mechanistic Underpinnings of Lung Cancer Initiation in Patients With Human Immunodeficiency Virus Infection

Lung cancer is the leading cause of cancer related death in the United States. A proven risk factor for the development and progression of lung cancer is human immunodeficiency virus (HIV). HIV persists within the lung in alveolar macrophages and bronchial epithelial cells, reducing mucociliary function and decreasing epithelial integrity. This persistence yields chronic inflammation by way of matrix metalloproteinases, which causes pulmonary injury. Over time, this progresses to pulmonary disease and allows for the development of superimposed pulmonary infections and chronic inflammatory states. This injury is a risk factor for the development of dysplasia, and chronic pulmonary disease and infections further increase the risk for developing lung cancer. HIV persistence and chronic inflammation also lead to CD8+ T cell exhaustion and alterations to macrophages and dendritic cells that blunt the physiologic anti-tumor response. As such, HIV infection promotes initial dysplasia and allows for progression on pre-invasive lesions to frank malignancy. The purpose of this review is to highlight this under-appreciated risk factor and summarize the biologic and immunologic role of HIV in lung cancer initiation and progression. Further research regarding risk reduction and surveillance in this population and the potential increased role of immunotherapy is warranted.