Microbial infections as potential risk factors for lung cancer: Investigating the role of human papillomavirus and chlamydia pneumoniae

Abstract

<abstract><sec> <title>Background</title> <p>Lung cancer is the leading cause of cancer morbidity and mortality worldwide. Apart from tobacco smoke and dietary factors, microbial infections have been reported as the third leading cause of cancers globally. Deciphering the association between microbiome and lung cancer will provide potential biomarkers and novel insight in lung cancer progression. In this current study, we performed a meta-analysis to decipher the possible association between <italic>C. pneumoniae</italic> and human papillomavirus (HPV) and the risk of lung cancer.</p> </sec><sec> <title>Methods</title> <p>Literature search was conducted in most English and Chinese databases. Data were analyzed using CMA v.3.0 and RevMan v.5.3 software (Cochrane-Mantel-Haenszel method) by random-effects (DerSimonian and Laird) model.</p> </sec><sec> <title>Results</title> <p>The overall pooled estimates for HPV studies revealed that HPV infections in patients with lung cancer were significantly higher than those in the control group (<italic>OR</italic> = 2.33, 95% <italic>CI</italic> = 1.57–3.37, <italic>p</italic> < 0.001). Base on subgroup analysis, HPV infection rate was significantly higher in Asians (<italic>OR</italic> = 6.38, 95% <italic>CI</italic> = 2.33–17.46, <italic>p</italic> < 0.001), in tissues (<italic>OR</italic> = 5.04, 95% <italic>CI</italic> = 2.27–11.19, <italic>p</italic> < 0.001) and blood samples (<italic>OR</italic> = 1.40, 95% <italic>CI</italic> = 1.02–1.93, <italic>p</italic> = 0.04) of lung cancer patients but non-significantly lower in males (<italic>OR</italic> = 0.84, 95% <italic>CI</italic> = 0.57–1.22, <italic>p</italic> =0.35) and among lung cancer patients at clinical stage I-II (<italic>OR</italic> = 0.95, 95% <italic>CI</italic> = 0.61–1.49, <italic>p</italic> = 0.82). The overall pooled estimates from <italic>C. pneumoniae</italic> studies revealed that <italic>C. pneumoniae</italic> infection is a risk factor among lung cancer patients who are IgA seropositive (<italic>OR</italic> = 1.88, 95% <italic>CI</italic> = 1.30–2.70, <italic>p</italic> < 0.001) and IgG seropositive (<italic>OR</italic> = 1.50, 95% <italic>CI</italic> = 1.10–2.04, <italic>p</italic> = 0.010). All seronegative IgA (<italic>OR</italic> = 0.69, 95% <italic>CI</italic> = 0.42–1.16, <italic>p</italic> = 0.16) and IgG (<italic>OR</italic> = 0.66, 95% <italic>CI</italic> = 0.42–105, <italic>p</italic> = 0.08) titers are not associative risk factors to lung cancer.</p> </sec><sec> <title>Conclusions</title> <p>Immunoglobulin (IgA) and IgG seropositive titers of <italic>C. pneumoniae</italic> and lungs infected with HPV types 16 and 18 are potential risk factors associated with lung cancer.</p> </sec></abstract>

Dark under the Lamp: Neglected Biological Pollutants in the Environment Are Closely Linked to Lung Cancer

“…C. pneumoniae is a Gram-negative bacterium that is a common respiratory pathogen causing chronic and persistent respiratory infections [ 80 ]. Studies have shown that C. pneumoniae infection significantly increases the risk of lung cancer [ 23 , 81 , 82 , 83 , 84 ]. Although the mechanisms underlying C. pneumoniae -promoted lung cancer are still unknown, chronic inflammation caused by C. pneumoniae infection is inextricably linked to the development of lung cancer.…”

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

“…Other target proteins and genes regulated by E6/E7 are as follows: HIF-1α, VEGF, IL-6, IL-10, Mcl-1, Bcl-2, cIAP-2, EGFR, FHIT, hTERT, HER-2, ROS1, and AhR. The collective impact of these alterations generally enhances lung cell proliferation, angiogenesis, and cell immortalization [6,11,24]. In particular, hypoxia-inducible factor-1α (HIF-1α) protein accumulation and vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) expression promotes angiogenesis [24].…”

“…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].…”

“…Squamous cell carcinoma (44% of NSCLC cases in men and 25% in women) [1,2] stands as the lung cancer histology with the highest prevalence of HPV infection (up to 48.1%) [5,6,10,11]. This prevalence is often associated with smoking habits [5].…”

“…This prevalence is often associated with smoking habits [5]. In contrast, adenocarcinoma (28% of NSCLC cases in men and 42% in women) [1,2] demonstrates a reported HPV prevalence of 44.4% [5,6,10,11]. Adenocarcinoma is the main histotype found in non-smokers, displaying totally different molecular characteristics and expressing the highest number of driver mutations within the lung cancer landscape.…”