AimTo assess the frequency of human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and high-risk types of human papillomavirus (HPV16 and HPV18) infections in lung adenocarcinoma samples.MethodsLung adenocarcinoma cytological smears and their DNA isolates were obtained from patients hospitalized at the Department for Lung Diseases Jordanovac, Zagreb, in 2016 and 2017. Overall, 67 lung adenocarcinoma samples were examined: 34 with epidermal growth factor receptor gene (EGFR) mutations and 33 withoutEGFRmutations. TheEGFRmutation status and virus presence were assessed with a polymerase chain reaction, and random samples were additionally tested for EBV with Sanger sequencing. HCMV, EBV, HPV16, and HPV18 infections were evaluated in relation toEGFRmutation, smoking status, and sex. A meta-analysis of available data about HPV infection in non-small cell lung cancer was performed.ResultsMore frequent HCMV, EBV, HPV16, and HPV18 infections were observed in lung adenocarcinoma samples withEGFRmutations than in samples without these mutations. Coinfection of the investigated viruses was observed only in lung adenocarcinoma samples with mutatedEGFR. In the group withEGFRmutations, smoking was significantly associated with HPV16 infection. The meta-analysis showed that non-small cell lung cancer patients withEGFRmutations had a higher odds of HPV infection.ConclusionHCMV, EBV, and high-risk HPV infections are more frequent inEGFR-mutated lung adenocarcinomas, which indicates a possible viral impact on the etiology of this lung cancer subtype.