Human papillomavirus genotypes in penile cancers from Japanese patients and HPV-induced NF-κB activation

Senba,Masachika; Mori,Naoki; Wada,Akihiro; Fujita,Shuichi; Yasunami,Michio; Irie,Sumiko; Hayashi,Tomayoshi; Igawa,Tsukasa; Kanetake,Hiroshi; Takahara,Osamu; Toriyama,Kan

doi:10.3892/ol_00000047

Human papillomavirus genotypes in penile cancers from Japanese patients and HPV-induced NF-κB activation

Authors:
- Masachika Senba
- Naoki Mori
- Akihiro Wada
- Shuichi Fujita
- Michio Yasunami
- Sumiko Irie
- Tomayoshi Hayashi
- Tsukasa Igawa
- Hiroshi Kanetake
- Osamu Takahara
- Kan Toriyama
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Affiliations: Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan
Published online on: March 1, 2010 https://doi.org/10.3892/ol_00000047
Pages: 267-272

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Abstract

The causal relationship between chronic inflammation and cancer is widely accepted. Numerous investigations have identified nuclear factor-κB (NF-κB) as an important modulator in driving chronic inflammation to cancer. This study aimed to determine the prevalence of human papillomavirus (HPV) in penile cancer in Japanese patients and whether NF-κB is subsequently overexpressed in penile cancer. Thirty-four specimens of penile tissue (16 malignant and 18 benign cases) were examined to determine the association of HPV infection. An in situ hybridization (ISH) method was used to detect and localize HPV-DNA. A sensitive HPV polymerase chain reaction (PCR) procedure was used for the detection of HPV-DNA, and DNA sequencing was used to identify the HPV genotype. HPV-DNA was detected in 37.5 and 75% of cases of penile cancer, using ISH and PCR, respectively. Our efforts to detect HPV genotypes were unsuccessful as HPV-DNA could not be extracted from these materials. Using ISH, a prevalence of 68.2% of HPV infection was found in penile cancer in Kenyan patients in east Africa. In the present study, all 9 HPV-positive cases, (100%) were NF-κB-positive in the nucleus and/or cytoplasm. In contrast, of the 25 HPV-negative cases, 15 (60%) were NF-κB-positive in the nucleus and/or cytoplasm. Therefore, ISH is a method which is able to prove infection of a large quantity of HPV more effectively when compared with PCR. Thus, a large quantity of HPV infection leads to the activity of NF-κB. The most prevalent genotype was the HPV-22 found in 83.3% of the penile cancer cases. In addition, HPV-11 was found in 81.8% of the non-cancer cases. For cases with a high level of infection, the activity of NF-%B increased compared with those with a low level of HPV infection.

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1	Zur Hausen H: Papillomaviruses in the causation of human cancers – a brief historical account. Virology. 44:219–224. 2009.
2	Senba M, Mori N and Wada A: Oncogenesis of and the link between inflammation and cancer due to human papillomavirus (HPV) infectionand the development of vaccine control strategies. Cancer Res J. 2:307–338. 2009.
3	Smith JS, Herrero R, Bosetti C, et al: Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer. J Natl Cancer Inst. 94:1604–1613. 2002. View Article : Google Scholar : PubMed/NCBI
4	Smith JS, Munoz N, Herrero R, et al: Evidence for Chlamydia trachomatis as a human papillomavirus cofactor in the etiology of invasive cervical cancer in Brazil and the Philippines. J Infect Dis. 185:324–331. 2002.
5	Lu H, Ouyang W and Huang C: Inflammation, a key event in cancer development. Mol Cancer Res. 4:221–233. 2006. View Article : Google Scholar : PubMed/NCBI
6	Hussain SP and Harris CC: Inflammation and cancer: an ancient link with novel potentials. Int J Cancer. 121:2373–2380. 2007. View Article : Google Scholar : PubMed/NCBI
7	Karin M and Greten FR: NF-κB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 5:749–759. 2005.
8	Karin M: Nuclear factor-κB in cancer development and progression. Nature. 441:431–436. 2006.
9	Schottenfeld D and Beebe-Dimmer J: Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin. 56:69–83. 2006. View Article : Google Scholar : PubMed/NCBI
10	Kleter B, Doorn LJ, Schegget J, et al: Novel short-fragment PCR assay for highly sensitive broad-spectrum detection of anogenital human papillomaviruses. Am J Pathol. 135:1731–1739. 1998. View Article : Google Scholar : PubMed/NCBI
11	Picconi MA, Ejian AM, Distefano AL, et al: Human papillomavirus (HPV) DNA in penile carcinomas in Argentina: analysis of primary tumors and lymph nodes. J Med Virol. 61:65–69. 2000. View Article : Google Scholar : PubMed/NCBI
12	Senba M, Kumatori A, Fujita S, et al: The prevalence of human papilomavirus genotypes in penile cancers from northern Thailand. J Med Virol. 78:1341–1346. 2006. View Article : Google Scholar : PubMed/NCBI
13	Sarkar FH, Miles BJ, Plieth DH and Crissman JD: Detection of human papillomavirus in squamous neoplasm of the penis. J Urol. 147:389–392. 1992.PubMed/NCBI
14	Tornesello ML, Buonaguro FM, Beth-Giraldo E, Kyalwazi SK and Giraldo G: Human papillomavirus (HPV) DNA in penile carcinomas and two cell lines from high-incidence area for genital cancers in Africa. Int J Cancer. 51:587–592. 1992. View Article : Google Scholar : PubMed/NCBI
15	Senba M, Buziba N, Mori N, Wada A, Irie S and Toriyama K: Detection of human papillomavirus and cellular regulators p16^INK4a, p53, and NF-κB in penile cancer cases in Kenya. Acta Virol. 53:43–48. 2009. View Article : Google Scholar : PubMed/NCBI
16	Cupp MR, Malek RS, Goellner JR, Smith TF and Espy MJ: The detection of human papillomavirus deoxyribonucleic acid in intraepithelial, in situ, verrucous and invasive carcinoma of the penis. J Urol. 154:1024–1029. 1995. View Article : Google Scholar : PubMed/NCBI
17	Tornesello ML, Duraturo ML, Losito S, et al: Human papillomavirus genotypes and HPV 16 variants in penile carcinoma. Int J Cancer. 122:132–137. 2008. View Article : Google Scholar : PubMed/NCBI
18	Rubin MA, Kleter B, Zhou M, et al: Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol. 159:1211–1218. 2001. View Article : Google Scholar
19	Cubilla AL, Reuter VE, Gregoire L, et al: Basaloid squamous cell carcinoma: a distinctive human papilloma virus-related penile neoplasm. A report of 20 cases. Am J Surg Pathol. 22:755–761. 1998. View Article : Google Scholar : PubMed/NCBI
20	Gross G and Pfister H: Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasia and in genital warts. Med Microbiol Immunol. 193:35–44. 2004. View Article : Google Scholar : PubMed/NCBI
21	Gregoire L, Cubilla AL, Reuter VE, Haas GP and Lancaster WD: Preferential association of human papillomavirus with high-grade histological variants of penile invasive squamous cell carcinoma. J Natl Cancer Inst. 87:1705–1709. 1995. View Article : Google Scholar : PubMed/NCBI
22	Kiriakidis S, Andreakos E, Monaco C, Foxwell B, Feldmann M and Paleolog E: VEGF expression in human macrophages is NF-κB-dependent: studies using adenoviruses expressing the endogenous NF-κB inhibitor IκBα and kinase-defective form of the IκB kinase 2. J Cell Sci. 116:665–674. 2003.
23	Nees M, Geoghegan JM, Hyman T, Frank S, Miller L and Woodworth CD: Papillomavirus type 16 oncogenes downregulate expression of interferon-responsive genes and upregulate proliferation-associated and NF-κB-responsive genes in cervical keratinocytes. J Virol. 75:4283–4296. 2001.PubMed/NCBI
24	Spitkovsky D, Hehner SP, Hofmann TG, Moller A and Schmitz ML: The human papillomavirus oncoprotein E7 attenuates NF-κB activation by targeting IκB kinase complex. J Biol Chem. 277:25576–25582. 2002.PubMed/NCBI
25	Havard L, Delvenne P, Frare P, Boniver J and Giannini SL: Differential production of cytokines and activation of NF-κB in HPV transformed keratinocytes. Virology. 298:271–285. 2002.
26	Havard L, Rahmouni S, Boniver J and Delvenne P: High levels of p105 (NFκB1) and p100 (NFκB2) proteins in HPV 16-transformed keratinocytes: role of E6 and E7 oncoproteins. Virology. 331:357–366. 2005.
27	Mishra A, Bharti AC, Varghese P, Saluja D and Das BC: Differential expression and activation of NF-κB family proteins during oral carcinogenesis: role of high risk human papillomavirus infection. Int J Cancer. 119:2840–2850. 2006.
28	James MA, Lee JH and Klingelhutz AJ: Human papillomavirus type 16 E6 activates NF-κB, induces cIAP-2 expression and protects against apoptosis in a PDZ binding motif-dependent manner. J Virol. 80:5301–5307. 2006.