Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. While molecular profiling particularly EGFR mutation analysis has transformed therapeutic approaches, the role of viral oncogenesis, such as human papillomavirus (HPV) infection and Epstein-Barr virus (EBV), in NSCLC is less well understood. In this study, we investigated the clinical relevance of HPV/EBV infection and EGFR mutations in NSCLC.

This retrospective study analyzed tumor tissues from 93 patients with NSCLC, as well as lung tissues from 10 normal adjacent samples. HPV-DNA detection and genotyping were performed using PCR-based methods, alongside EBV-DNA analysis. EGFR mutations were assessed via exon-specific PCR amplification. Associations between HPV/EGFR status and clinicopathological parameters were evaluated, and Kaplan–Meier survival analysis was used to assess overall survival (OS) according to molecular profiles.

HPV-DNA was detected in 31.2% of NSCLC tumors, while EBV-DNA was identified in 2.15%, with no positivity in normal adjacent tissues. HPV 16 was the most prevalent genotype, especially among adenocarcinoma (AC) cases. EGFR mutations were found in 20.4% of patients, predominantly in AC, with exon 19 deletions and L858R mutations being the most common. While HPV status showed no significant correlation with most clinical features, a strong inverse association was observed with surgical operability (p < 0.001). Survival analyses revealed that HPV-positive patients had shorter OS compared to HPV-negative counterparts. Patients with EGFR mutations exhibited longer OS, particularly in the HPV-negative subgroup, while the HPV-positive/EGFR-wild type group had the poorest outcomes.

This study demonstrates distinct prevalence patterns and prognostic implications of HPV infection and EGFR mutations in NSCLC. EGFR-mutant status correlated with improved survival, while HPV positivity was associated with inoperable disease and poorer outcomes. Further validation in larger cohorts is needed before clinical application.

Not applicable.