Human Cytomegalovirus in EGFR‐Mutated and Wild‐Type Lung Adenocarcinoma: Detection in Cytological Smears and Associated Peripheral Immune Response

ABSTRACT Background Human cytomegalovirus (HCMV) has been proposed as a potential risk factor in lung cancer. This study aimed to investigate the relationship between the presence of HCMV in tumor cells and the immune response to HCMV in the peripheral blood of patients with EGFR‐mutated and EGFR wild‐type lung adenocarcinoma. Methods DNA was extracted from 102 May‐Grünwald‐Giemsa–stained cytological smears (51 EGFR‐mutated and 51 EGFR wild‐type). HCMV presence in tumor cells was assessed by PCR targeting viral genes MIE and gB . The immune response to HCMV was evaluated in 80 corresponding peripheral blood samples using the QuantiFERON‐CMV ELISA test. Statistical analysis was performed using the chi‐square test, with significance p < 0.05. Results HCMV MIE gene was detected in eight (15.7%) EGFR‐mutated and one (2.0%) EGFR wild‐type smear. The HCMV gB gene was identified in four (7.8%) EGFR wild‐type smears and none of the EGFR‐mutated smears. Immune response to HCMV was observed in 18 (62.1%) EGFR‐mutated and 26 (50.9%) EGFR wild‐type patients. Among those with detectable HCMV MIE , an immune response was found in two EGFR‐mutated and one EGFR‐negative patient. Among smears positive for HCMV gB , immune response was detected in three EGFR wild‐type cases. One EGFR wild‐type case showed no immune response despite the presence of HCMV gB . Conclusion No clear association was observed between HCMV in lung adenocarcinoma cells and the immune response to HCMV in peripheral blood, regardless of EGFR gene mutation status.