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

Background: 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 C. pneumoniae and human papillomavirus (HPV) and the risk of lung cancer. Methods: 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. Results: 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 (OR = 2.33, 95% CI = 1.57–3.37, p < 0.001). Base on subgroup analysis, HPV infection rate was significantly higher in Asians (OR = 6.38, 95% CI = 2.33–17.46, p < 0.001), in tissues (OR = 5.04, 95% CI = 2.27–11.19, p < 0.001) and blood samples (OR = 1.40, 95% CI = 1.02–1.93, p = 0.04) of lung cancer patients but non-significantly lower in males (OR = 0.84, 95% CI = 0.57–1.22, p =0.35) and among lung cancer patients at clinical stage I-II (OR = 0.95, 95% CI = 0.61–1.49, p = 0.82). The overall pooled estimates from C. pneumoniae studies revealed that C. pneumoniae infection is a risk factor among lung cancer patients who are IgA seropositive (OR = 1.88, 95% CI = 1.30–2.70, p < 0.001) and IgG seropositive (OR = 1.50, 95% CI = 1.10–2.04, p = 0.010). All seronegative IgA (OR = 0.69, 95% CI = 0.42–1.16, p = 0.16) and IgG (OR = 0.66, 95% CI = 0.42–105, p = 0.08) titers are not associative risk factors to lung cancer. Conclusions: Immunoglobulin (IgA) and IgG seropositive titers of C. pneumoniae and lungs infected with HPV types 16 and 18 are potential risk factors associated with lung cancer