SLC7A11 Expression Is Up-Regulated in HPV- and Tobacco-Associated Lung Cancer.

High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical, anogenital, and a subset of oropharyngeal cancers. In addition, HR-HPVs have been detected in lung carcinomas worldwide, even though the role of these viruses in this type of cancer is not fully understood. This study evaluated the presence of HPV in a cohort of 204 lung cancer cases by multiplex polymerase chain reaction (PCR)-Luminex. In addition, we used transcriptomic approaches to characterize the HPV-associated gene expression profile in the context of tobacco-smoke-associated lung cancer. HPV16 was detected in 8/204 lung carcinomas (4.0%). Through a significance analysis of microarrays (SAM) analysis, we found that the solute carrier family 7-member 11 (SLC7A11/xCT) gene (an antiporter that mediates the uptake of extracellular cystine) is up-regulated in tobacco-smoke- and HPV-associated lung cancers. In addition, SLC7A11 up-regulation correlates with both HR-HPV16 E6/E7 expression and tobacco smoke exposure in lung epithelial cells. Furthermore, we found decreased survival in HPV/SLC7A11-positive patients with lung cancer when compared to HPV/SLC7A11-negative cases. Thus, this study suggests that SLC7A11 up-regulation is associated with both HPV-positive and tobacco-smoke-associated lung carcinomas, with a potential association with clinical prognosis.