High-Risk Human Papillomavirus Infection in Lung Cancer: Mechanisms and Perspectives

Abstract

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.

The Role of Human Papilloma Virus (HPV) in Primary Lung Cancer Development: State of the Art and Future Perspectives

“…In light of the above-mentioned evidence [3,27,45], a similar mechanism, based on inflammation induced by air pollution [46], could explain the role of HPV in lung carcinogenesis among never-smoker patients, Figure 5.…”

“…In light of the above-mentioned evidence [3,27,45], a similar mechanism, based on inflammation induced by air pollution [46], could explain the role of HPV in lung carcinogenesis among never-smoker patients, Figure 5. A recent study revealed that 16% of NSCLC patients presented circulating HPV-DNA in peripheral blood [47] and abnormally expressed miRNAs in HPV-associated tumors [47].…”

“…Particularly for lung cancer, nine high-risk HPV genotypes were recently detected in patients with NSCLC, i.e., 16, 18, 31, 35, 45, 51, 52, 56, and 59 [26], and often multiple HPV types were concurrently observed in lung tissues [26]. The most frequently detected HPV genotypes were 16, 18, and 56 [27][28][29][30].…”

“…HPV-DNA was discovered not only in neoplastic lung cells [4][5][6]11,27] but also in human blood [6,11,27] and peripheral mononuclear cells [6]. The integrated form of HPV-DNA was identified in tissue samples of patients affected by NSCLC, while the episomal and mixed forms were identified in blood samples [26].…”

The microbiome in the pathogenesis of lung cancer

“…For example, human hepatitis B and C virus (HBV and HCV) infection increases the incidence of primary liver cancer; human papillomavirus (HPV) infection is associated with cervical and anal genital cancers; Epstein-Barr virus (EBV) is associated with the development of nasopharyngeal and lymphatic cancers; and Helicobacter pylori (HP) significantly increases the risk of gastric cancer. Similarly, emerging pathogens have been found that cause high-risk lung cancer, such as high-risk human papillomaviruses (HR-HPVs), cytomegalovirus, influenza virus, and measles virus (MV) [9][10][11][12]. In addition, accumulating studies have revealed the correlation of specific microbiota with lung cancer, such as Firmicutes, Proteobacteria, Actinobacteria, and Veillonella [13][14][15].…”