Aim To 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. Methods Lung 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 without EGFR mutations. The EGFR mutation 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 to EGFR mutation, smoking status, and sex. A meta-analysis of available data about HPV infection in non-small cell lung cancer was performed. Results More frequent HCMV, EBV, HPV16, and HPV18 infections were observed in lung adenocarcinoma samples with EGFR mutations than in samples without these mutations. Coinfection of the investigated viruses was observed only in lung adenocarcinoma samples with mutated EGFR . In the group with EGFR mutations, smoking was significantly associated with HPV16 infection. The meta-analysis showed that non-small cell lung cancer patients with EGFR mutations had a higher odds of HPV infection. Conclusion HCMV, EBV, and high-risk HPV infections are more frequent in EGFR -mutated lung adenocarcinomas, which indicates a possible viral impact on the etiology of this lung cancer subtype.

MicroRNAs are a class of small non-coding RNA molecules that regulate gene expression on post-transcriptional level. Their biogenesis consists of a complex series of sequential processes, and they regulate expression of many genes involved in all cellular processes. Their function is essential for maintaining the homeostasis of a single cell; therefore, their aberrant expression contributes to development and progression of many diseases, especially malignant tumors and viral infections. Moreover, they can be associated with certain states of a specific disease, obtained in the least invasive manner for patients and analyzed with basic molecular methods used in clinical laboratories. Because of this, they have a promising potential to become very useful biomarkers and potential tools in personalized medicine approaches. In this review, miRNAs biogenesis, significance in cancer and infectious diseases, and current available test and methods for their detection are summarized.

Non-small cell lung cancer (NSCLC) molecular biomarker testing is obligatory for determining therapy. The aim of this study was to compare immunocytochemistry (ICC) results of NSCLC predictive biomarkers between bronchoscopic and non-bronchoscopic type of cytology samples. This study included archive records of 1109 predictive ICC results (ALK, ROS1, and PD-L1). The ICC was done on bronchoscopic, and non-bronchoscopic NSCLC samples prepared as cytological smears and cytospins, using Dako EnVisionTM FLEX detection visualization system. The ALK, ROS1, and PD-L1 distribution between bronchoscopic and non-bronchoscopic samples was analysed. The future perspective of cytology in precision medicine was reconsidered. The obtained positive results of ALK, ROS1, and PD-L1 ICC were in concordance with the previously observed range. There was no statistically significant difference in ALK, ROS1, and PD-L1 ICC distribution between the bronchoscopic and non-bronchoscopic groups of samples (p=0.730). The comparison of PD-L1 expression, and, separately PD-L1 ≥50% expression, between two groups of samples showed no statistically significant difference (p=0.236; p=0.436). Bronchoscopic and non-bronchoscopic samples prepared as cytological smears and cytospins are a suitable, but underutilized resource for ALK, ROS1, and PD-L1 biomarker analysis. The implementation of optimized predictive immunocytochemistry assays to provide rapid and reliable results for limited tumour samples is necessary.