Association between expression of human papillomavirus 16/18 E6 oncoprotein and survival in patients with stage I non-small cell lung cancer

The clinical significance of HPV-16/18 E6 oncoprotein expression in non-small cell lung cancer (NSCLC) is not fully known. A study was undertaken to investigate the association between expression of human papillomavirus 16/18 E6 oncoprotein and survival in patients with stage I NSCLC. We analyzed a series of 217 patients with stage I NSCLC for the presence of HPV-16/18 E6 oncoprotein by immunohistochemistry. HPV-16 E6 oncoprotein was expressed in 49 (22.6%) patients and HPV-18 E6 oncoprotein was expressed in 31 (14.3%) patients. Statistical analysis revealed that the prevalence of expression of HPV-16 and HPV-18 E6 oncoproteins was significantly high in female patients, nonsmokers and patients with adenocarcinoma. The adjusted odds ratio for expression of HPV-16 E6 oncoprotein in female patients was 2.275 [95% confidence interval (CI), 0.999-5.179] and that in patients with adenocarcinoma was 2.320 (95% CI, 1.029-5.232). These ratios were significantly higher than those in male patients and patients with squamous cell carcinoma. Interestingly, we found that the 17 patients who expressed HPV-16 and HPV-18 E6 oncoprotein had a higher 5-year cumulate survival rate (72.2%) than the 154 patients who did not express both oncoproteins (48.3%); the difference was significant (p=0.055). Expression of HPV-16/18 E6 oncoprotein in stage I NSCLC may play an important role in female adenocarcinoma patients and survival benefits in patients who expressed HPV-16 and HPV-18 E6 oncoprotein.