Human papillomavirus (HPV) has been implicated in multiple cancers, but its significance in lung cancer has remained controversial. As the prevalence of HPV 16/18 infection was higher in lung adenocarcinoma among Taiwanese females, the aim of our study was to evaluate the clinical impact of HPV infections in lung adenocarcinoma. Two hundred and ten patients were enrolled to investigate the associations of HPV status in tumors with clinical characteristics as well as its impact on overall survival. The methods to assess HPV status were by immunohistochemistry for HPV L1 capsid protein and E6 protein and by nested polymerase chain reaction for HPV 16 and HPV 18. HPV infections were identified in 35.2% of patients, and associated with localized and smaller sized tumors (p 5 0.022 and p 5 0.002, respectively). Patients with HPV infections had a significantly better survival (p 5 0.023, by log-rank test) and a significantly reduced mortality risk after adjustments of age, tumor extent, epidermal growth factor receptor (EGFR) mutations status and treatments [adjusted hazard ratio 5 0.68, 95% confidence interval (CI) 5 0.49-0.96, p 5 0.026, by multivariate Cox proportional hazards models]. Specifically, patients with both HPV infections and EGFR mutations had the best survival outcome [1-year survival rate, 68.5% (95% CI 5 52.2-4.8%)]. Our findings indicate that HPV infections represent an independent prognostic factor for overall survival in patients with lung adenocarcinoma.Lung cancer is the leading cause of cancer death not only in the world but also in Taiwan. 1,2 Although cigarette smoking is the most important risk factor for lung carcinogenesis, accounting for approximately two-thirds of lung cancer patients, in Taiwan, one-third of lung cancer are never smokers. 3,4 This indicates that additional factors may play an important role in lung carcinogenesis.Epidermal growth factor receptor (EGFR) mutations in lung cancer are often found in adenocarcinoma, especially in never smokers. 5 Lung adenocarcinoma with EGFR mutations portends increased sensitivity of EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib. 6,7 However, it is still unclear what factors contribute to the acquisition of EGFR mutations for lung carcinogenesis.Human papillomavirus (HPV) has been identified to be a cause in the development of cervical cancer. 8 Viral E6 and E7 oncoproteins that inactivate tumor suppressor proteins p53 and retinoblastoma, respectively, are required for malignant transformation of cervical cancer cells. 9,10 HPV is also a recognized risk factor for squamous cell carcinoma of headand-neck cancer (HNSCC). 11,12 Clinical studies in stage III and IV HNSCC have demonstrated that patients with HPV infections have longer survival; therefore, HPV infections in HNSCC are considered to be a good prognostic factor. 13,14 The superior prognosis for HNSCC with HPV infections might be due to the increased sensitivity to chemotherapy and chemoradiation, but the mechanisms remain unclear.One Taiwanese study has rep...
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