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Lung Cancer. 2014 Jan;83(1):8-13. doi: 10.1016/j.lungcan.2013.10.002. Epub 2013 Oct 31.

Human papilloma virus in non-small cell lung cancer in never smokers: a systematic review of the literature.

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Department of Medical Oncology, Izumi Municipal Hospital, Osaka, Japan. Electronic address:
Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Aichi, Japan.
Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan.
Department of Internal Medicine, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai, Osaka, Japan.
Department of Respiratory Medicine, Kinki Central Hospital, Itami, Hyogo, Japan.
Department of Medical Oncology, Kinki University School of Medicine, Osakasayama, Osaka, Japan.
Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA, United States.
Department of Internal Medicine, Koyo Hospital, Wakayama, Japan.


Non-small cell lung cancer (NSCLC) in never smokers has emerged as a global public health issue. The cause is still unclear, and few studies have focused on the prevalence of human papillomavirus (HPV) in the never smokers. We performed a systematic search of PubMed for articles of HPV infection in human subjects with NSCLC up to September 2012. Although smoking status was not fully reported in all studies, we contacted the authors by e-mail to supplement this information. Differences in the distribution of patients with and without HPV infection were tested with the Chi squared test. We identified 46 eligible articles, including 23 from Asian countries (N=2337 NSCLC cases), 19 from European countries (N=1553) and 4 from North and South America (N=160). The HPV prevalence was 28.1% (95% confidence interval (CI) 26.6-30.3%), 8.4% (95% CI 7.1-9.9%) and 21.3% (95% CI 15.2-28.4%), respectively. Eleven studies from East Asia (N=1110) and 4 from Europe (N=569) provided information on smoking status. The number of never smoker was 392 patients (33.9%) in East Asia and 54 patients (14.8%) in Europe. The HPV prevalence in East Asian countries was similar between never and ever smokers (33.9% vs 39.2%, P=0.080). Based on the literature confirming the presence of HPV in lung cancer in never smokers, the virus plays a role in carcinogenesis in the disease. There were different patterns of HPV prevalence between Asian and European countries in the never smokers as well as in ever smokers.


Epidemiology; Geographic differences; Human papillomavirus; Never smoker; Non-small cell lung cancer; Polymerase chain reaction; Systematic review

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