Detection of Human Papillomavirus DNA, E6/E7 Messenger RNA, and p16INK4a in Lung Cancer: A Systematic Review and Meta-analysis

Abstract Background The etiologic link between human papillomavirus (HPV) and lung cancer is still controversial. Methods PubMed and Cochrane databases were searched from inception to December 2020 to identify studies on the infection of HPV in lung cancer. We calculated the attributable proportion of HPV in lung cancer by pooling the infection of cases positive for both HPV DNA and biomarkers of carcinogenesis that may be induced by HPV (E6/E7 messenger RNA or p16INK4a). Results A total of 117 studies, comprising data of 12 616 lung cancer cases from 22 countries across 5 continents, were included. The overall HPV DNA positivity in primary lung cancer cases worldwide was 16.4% (95% confidence interval, 12.7%–20.5%). HPV DNA positivity of lung cancer varied significantly by pathological type and geographic region. Notably, the expression rate of p16INK4a is significantly higher than the positivity of HPV DNA and of HPV E6/E7 mRNA (P < .05). The estimate of HPV attributable proportion defined by expression of E6/E7 mRNA was 0 and of p16INK4a was 7.3%. Conclusions The data in this systematic review is robust enough to contradict the possible participation of HPV in lung cancer carcinogenesis. Prophylactic vaccines targeting HPV cannot have the potential to prevent lung cancer. Human papillomavirus (HPV) DNA positivity of lung cancer varied significantly by pathological type and geographic region. However, a lack of correlation between HPV DNA positivity and E6/E7 mRNA or p16INK4a expression contradicts the possible participation of HPV in lung cancer carcinogenesis.