HPV infection and lung cancer

抄録

Lung cancer is the leading cause of cancer death in Taiwanese women since 1982. Cigarette smoking is considered to be the major cause of lung cancer, however more than 90% of female patients are nonsmokers. Therefore, different etiology may be expected in developing lung cancer in Taiwanese women. In the first case-control study indicated that human papillomavirus (HPV) 16/18 subtype was associated with lung cancer development in Taiwanese women nonsmokers, not in male smokers and nonsmokers. Here, we provide the following evidences to demonstrate that HPV16/18 is really involved in lung tumorigenesis. In the first, HPV16/18 E6 oncoprotein is indeed expressed in lung tumors, and p21^WAF1/CIP1 and Mdm2 mRNA expressions are reduced through p53 protein degraded by E6 oncoprotein in HPV-infected lung cancer cell lines which are successfully established from patients’ plural effusion. Secondly, the involvement of HPV infection in lung tumorigenesis may be partially through a concomitant increased expression of the autocrine and/or paracrine IL-6 and the downstream antiapoptic Mcl-1 in lung tumors and HPV-infected lung cancer cells. Thirdly, we evidence that hTERT transcription activated by HPV-16/18 E6 oncoprotein is required for HPV-infected lung tumorigenesis. Therefore, telomerase inhibitor may be chosen to be as a molecular targeting therapeutic in HPV-infected lung cancer. Collectively, these results provide the crucial data to evidence that HPV 16/18 infection is indeed involved in lung tumorigenesis, particularly in Taiwanese women nonsmokers.