Abstract

A subset of human papillomaviruses (HPVs), so-called high-risk (HR)-HPVs are the causal agents of cervical, anogenital and a group of head and neck carcinomas. Additionally, HR-HPVs have been detected in extragenital tumors including in lung cancer, though their role in this heterogeneous group of malignancies remains controversial. In this review, we address the epidemiological and experimental studies regarding the role of HR-HPV in lung cancer, worldwide, and we propose potential mechanisms. The evidence suggests that HR-HPVs are involved in the development of a variable subset of lung carcinomas in both smoker and non-smoker subjects. Lung cancer is a very prevalent and heterogeneous group of malignancies, and most of them are etiologically associated with tobacco smoking. However, viral infections have been detected in lung carcinomas, with high-risk human papillomaviruses (HR-HPVs) being among them. The role of HR-HPVs in lung cancer has been considered to be controversial. This issue is due to the highly variable presence of this virus in lung carcinomas worldwide, and the low viral load frequently that is detected. In this review, we address the epidemiological and mechanistic findings regarding the role of HR-HPVs in lung cancer. Some mechanisms of HR-HPV-mediated lung carcinogenesis have been proposed, including (i) HPV works as an independent carcinogen in non-smoker subjects; (ii) HPV cooperates with carcinogenic compounds present in tobacco smoke; (iii) HPV promotes initial alterations being after cleared by the immune system through a "hit and run" mechanism. Additional research is warranted to clarify the role of HPV in lung cancer.