Background: In human papillomavirus (HPV)-induced carcinogenesis, the arginine (Arg) allele of the TP53 codon 72 polymorphism binds more efficiently to the HPV E6 oncoprotein than the proline (Pro) allele. We investigated the physical status of HPV-16 DNA and the TP53 codon 72 polymorphism in oropharyngeal squamous cell carcinoma (OPSCC). Methods: Tumor samples from 70 p16-positive OPSCC patients were tested for HPV-16 physical status by examining the E2 and E6 open reading frames. The TP53 codon 72 polymorphism was screened by direct sequencing. Results: Of 70 patients, 53 were E6 positive, 29 had integrated forms of HPV-16 DNA, and 24 had mixed or episomal forms. Furthermore, 44 carried the Arg/Arg or Arg/Pro genotype, 3 carried the Pro/Pro genotype, and in 6 patients we were unable to obtain sequencing data. Conclusions: HPV-16 physical status was heterogeneous in our OPSCC patients. Most OPSCC patients had the TP53 Arg/Arg or Arg/Pro genotype.

1.
Ang KK, Harris J, Wheeler R, et al: Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010;363:24-35.
2.
Gillison ML, D'Souza G, Westra W, et al: Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 2008;100:407-420.
3.
D'Souza G, Kreimer AR, Viscidi R, et al: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 2007;356:1944-1956.
4.
Zandberg DP, Bhargava R, Badin S, Cullen KJ: The role of human papillomavirus in nongenital cancers. CA Cancer J Clin 2013;63:57-81.
5.
Saito Y, Ebihara Y, Ushiku T, et al: Negative human papillomavirus status and excessive alcohol consumption are significant risk factors for second primary malignancies in Japanese patients with oropharyngeal carcinoma. Jpn J Clin Oncol 2014;44:564-569.
6.
Hama T, Tokumaru Y, Fujii M, et al: Prevalence of human papillomavirus in oropharyngeal cancer: a multicenter study in Japan. Oncology 2014;87:173-182.
7.
Worsham MJ, Stephen JK, Chen KM, et al: Improved survival with HPV among African Americans with oropharyngeal cancer. Clin Cancer Res 2013;19:2486-2492.
8.
Munger K, Phelps WC, Bubb V, Howley PM, Schlegel R: The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol 1989;63:4417-4421.
9.
Pett MR, Alazawi WO, Roberts I, et al: Acquisition of high-level chromosomal instability is associated with integration of human papillomavirus type 16 in cervical keratinocytes. Cancer Res 2004;64:1359-1368.
10.
Kim SH, Koo BS, Kang S, et al: HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c-myc during tumor formation. Int J Cancer 2007;120:1418-1425.
11.
Akagi K, Li J, Broutian TR, et al: Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res 2014;24:185-199.
12.
Beckman G, Birgander R, Själander A, et al: Is p53 polymorphism maintained by natural selection? Hum Hered 1994;44:266-270.
13.
Kawajiri K, Nakachi K, Imai K, Watanabe J, Hayashi S: Germ line polymorphisms of p53 and CYP1A1 genes involved in human lung cancer. Carcinogenesis 1993;14:1085-1089.
14.
Perrone F, Mariani L, Pastore E, et al: p53 codon 72 polymorphisms in human papillomavirus-negative and human papillomavirus-positive squamous cell carcinomas of the oropharynx. Cancer 2007;109:2461-2465.
15.
Saito Y, Yoshida M, Ushiku T, et al: Prognostic value of p16 expression and alcohol consumption in Japanese patients with oropharyngeal squamous cell carcinoma. Cancer 2013;119:2005-2011.
16.
Ueda Y, Enomoto T, Miyatake T, et al: Analysis of clonality and HPV infection in benign, hyperplastic, premalignant, and malignant lesions of the vulvar mucosa. Am J Clin Pathol 2004;122:266-274.
17.
Gillison ML, Broutian T, Pickard RK, et al: Prevalence of oral HPV infection in the United States, 2009-2010. JAMA 2012;307:693-703.
18.
Woodman CB, Collins SI, Young LS: The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer 2007;7:11-22.
19.
Parfenov M, Pedamallu CS, Gehlenborg N, et al: Characterization of HPV and host genome interactions in primary head and neck cancers. Proc Natl Acad Sci USA 2014;111:15544-15549.
20.
Storey A, Thomas M, Kalita A, et al: Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 1998;393:229-234.
21.
Klug SJ, Ressing M, Koenig J, et al: TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. Lancet Oncol 2009;10:772-784.
22.
Wang JJ, Zheng Y, Sun L, et al: TP53 codon 72 polymorphism and colorectal cancer susceptibility: a meta-analysis. Mol Biol Rep 2011;38:4847-4853.
23.
Yu H, Huang YJ, Liu Z, et al: Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck. Mol Carcinog 2011;50:697-706.
24.
Wang Z, Sturgis EM, Guo W, et al: Association of combined p73 and p53 genetic variants with tumor HPV16-positive oropharyngeal cancer. PLoS One 2012;7:e35522.
25.
Zeng XT, Luo W, Geng PL, et al: Association between the TP53 codon 72 polymorphism and risk of oral squamous cell carcinoma in Asians: a meta-analysis. BMC Cancer 2014;14:469.
26.
Ward MJ, Mellows T, Harris S, et al: Staging and treatment of oropharyngeal cancer in the human papillomavirus era. Head Neck 2014, DOI: 10.1002/hed.23697.
27.
Spector ME, Chinn SB, Bellile E, et al: Matted nodes predict distant metastasis in advanced stage III/IV oropharyngeal squamous cell carcinoma. Head Neck 2014, DOI: 10.1002/hed.23882.
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