The association between human papillomavirus presence and epidermal growth factor receptor mutations in Asian patients with non-small cell lung cancer

Hengrui Liang, Zhenkui Pan, Xiuyu Cai, Wei Wang, Chengye Guo, Jiaxi He, Yuehan Chen, Zhichao Liu, Bo Wang, Jianxing He, Wenhua Liang, on behalf of AME Lung Cancer Cooperative Group


Background: The etiology of non-small cell lung cancer (NSCLC) in non-smoker patients remains largely unknown. It has been widely proved that human papillomavirus (HPV) participates in the development of various cancers. Epidermal growth factor receptor (EGFR) mutation patients represent a large portion of non-smokers with NSCLC. We performed this meta-analysis to determine whether HPV infection in NSCLC tissue is associated with EGFR mutations compared with HPV negative controls.
Methods: Online databases were searched up to June 30th 2017. We included studies in which HPV detection was based on polymerase chain reaction (PCR) methods. Random effects model was used in data synthesis and the relative effects were presented as odds ratio (OR) with 95% confidence intervals (CIs).
Results: Finally, four eligible studies with a total of 498 patients from Asian countries were identified and included. The general EFGR mutation positive rate was 38.2% among all patients, and the HPV DNA detection rate (HPV subtype being involved: 16, 18, 33 and 58) was 35.3%. The presence of EGFR mutation was significantly higher in HPV-positive patients compared with HPV-negative controls (52% vs. 31%; OR =2.41, 95% CI: 1.21 to 4.77; P=0.012), with moderate heterogeneity among studies (I2=59%; P=0.062).
Conclusions: Our results suggest that HPV infection is associated with EGFR mutations in NSCLC, at least in Asian populations. Further efforts should be made on exploring the potential mechanism and the prognostic character of HPV/EGFR positive NSCLC patient.