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      The Prevalence of Human Papillomavirus Infection in Korean Non-Small Cell Lung Cancer Patients

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          Abstract

          Human papillomavirus (HPV) infection is a co-carcinogen of lung cancer and contributes to its pathogenesis. To evaluate the prevalence of HPV infection, polymerase chain reaction (PCR) was employed to detect HPV 16, 18, and 33 DNA in tumor tissues of 112 patients with non-small cell lung cancer (NSCLC) who underwent curative surgery from Jan. 1995 to Dec. 1998 at Severance Hospital, Seoul, Korea. The patients consisted of 90 men and 22 women. Nineteen patients were under 50 years old (17%), and 92 patients (82%) were smokers. Fifty-three patients had adenocarcinomas, while 59 patients had non-adenocarcinomas. Early stage (I and II) cancer was found in 64 patients (57.1%) and advanced stage (III and IV) found in 48 (42.9%). The prevalence of HPV 16, 18, and 33 were 12 (10.7%), 11 (9.8%), and 37 (33.0%), respectively. Smoking status, sex, and histologic type were not statistically different in the presence of HPV DNA. The presence of HPV 16 was more common in younger patients and HPV 18 was more common in advanced stage patients. This study showed that the prevalence rate of HPV 16 and 18 infections in NSCLC tissue was low, suggesting HPV 16 and 18 infections played a limited role in lung carcinogenesis of Koreans. However, the higher prevalence of HPV 33 infections in Korean lung cancer patients compared to other Asian and Western countries may be important and warrants further investigation.

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          Most cited references37

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          Association of human papillomavirus types 16 and 18 E6 proteins with p53.

          Human papillomavirus type 16 (HPV-16) is a DNA tumor virus that is associated with human anogenital cancers and encodes two transforming proteins, E6 and E7. The E7 protein has been shown to bind to the retinoblastoma tumor suppressor gene product, pRB. This study shows that the E6 protein of HPV-16 is capable of binding to the cellular p53 protein. The ability of the E6 proteins from different human papillomaviruses to form complexes with p53 was assayed and found to correlate with the in vivo clinical behavior and the in vitro transforming activity of these different papillomaviruses. The wild-type p53 protein has tumor suppressor properties and has also been found in association with large T antigen and the E1B 55-kilodalton protein in cells transformed by SV40 and by adenovirus type 5, respectively, providing further evidence that the human papillomaviruses, the adenoviruses, and SV40 may effect similar cellular pathways in transformation.
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            Role of a p53 polymorphism in the development of human papillomavirus-associated cancer.

            The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.
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              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 1982. High lung cancer mortality ratio of male:female in Taiwan (2:1) was observed, 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 development based on high prevalence of p53 negative immunostainings in female lung tumors compared with that of male lung tumors. In this study, 141 lung cancer patients and 60 noncancer control subjects were enrolled to examine whether HPV 16/18 DNA existed in lung tumor and normal tissues by nested PCR and in situ hybridization (ISH), respectively. The concordant detection 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 16/18 DNA compared with 16 (26.7%; P = 0.0005) of 60 noncancer control subjects. 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 subjects were stratified by gender, age, and smoking status, nonsmoking female lung cancer patients who were older than 60 years old had significantly high 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% confidence 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 suggests that HPV infection is associated with lung cancer development of nonsmoking female lung cancer patients. The high prevalence of HPV 16/18 infection may explain to a certain extent why Taiwanese women nonsmokers had a higher lung cancer mortality rate.
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                Author and article information

                Journal
                Yonsei Med J
                YMJ
                Yonsei Medical Journal
                Yonsei University College of Medicine
                0513-5796
                1976-2437
                28 February 2007
                20 February 2007
                : 48
                : 1
                : 69-77
                Affiliations
                [1 ]Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
                [2 ]Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.
                [3 ]Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
                [4 ]The Institute of Chest Diseases, Yonsei University College of Medicine, Seoul, Korea.
                [5 ]Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
                [6 ]Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, Korea.
                [7 ]Department of Internal Medicine, Ewha Women's University College of Medicine, Seoul, Korea.
                Author notes
                Reprint address: requests to Dr. Se Kyu Kim, Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. Tel: 82-2-2228-1954, Fax: 82-2-393-6884, sekyukim@ 123456yumc.yonsei.ac.kr
                Article
                10.3349/ymj.2007.48.1.69
                2628003
                17326248
                f895b7f6-c993-4b94-8737-4f9faa9fe8d5
                Copyright © 2007 The Yonsei University College of Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 March 2006
                : 25 July 2006
                Categories
                Original Article

                Medicine
                human papillomavirus,polymerase chain reaction,carcinogenesis,non-small cell lung carcinoma

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