The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women

Lung cancer is the leading cause of cancer death in Taiwanese women since 1 982, High lung cancer mortality ratio of male:female in Taiwan (2:1) was ob served, although less than 10% of female lung cancer patients are smokers. Until now, the etiological factor remains unknown. We hypothesize that high -risk human papillomavirus (HPV) 16/18 may be associated with lung cancer d evelopment based on high prevalence of p53 negative immunostainings in fema le lung tumors compared with that of male lung tumors. In this study, 141 l ung cancer patients and 60 noncancer control subjects were enrolled to exam ine whether HPV 16/18 DNA existed in lung tumor and normal tissues by neste d PCR and in situ hybridization (ISH), respectively. The concordant detecti on of HPV 16 and 18 DNA between nested PCR and ISH method was 73 and 85.5%, respectively. Our data showed that 77 (54.6%) of 141 lung tumors had HPV 1 6/18 DNA compared with 16 (26.7%; P = 0.0005) of 60 noncancer control subje cts. In addition, ISH data showed that HPV 16/18 DNA was uniformly located in lung tumor cells, but not in the adjacent nontumor cells. When study sub jects were stratified by gender, age, and smoking status, nonsmoking female lung cancer patients who were older than 60 years old had significantly hi gh prevalence of HPV 16/18 infection. The odds ratio of HPV 16/18 infection of nonsmoking female lung cancer patients is much higher at 10.12 (95% con fidence interval, 3.88-26.38) compared with 1.98 (95% confidence interval, 0.84-4.76) of nonsmoking male lung cancer patients. This result strongly su ggests that HPV infection is associated with lung cancer development of non smoking female lung cancer patients. The high prevalence of HPV 16/18 infec tion may explain to a certain extent why Taiwanese women nonsmokers had a h igher lung cancer mortality rate.