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Significant association of high-risk human papillomavirus (HPV) but not of p53 polymorphisms with oral squamous cell carcinomas in Malaysia

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Abstract

Purpose

The purpose of this study was to evaluate the role of HPV and p53 polymorphisms in oral squamous cell carcinomas (OSCC) affecting Malaysian population.

Methods

We analysed frozen samples from 105 OSCC as well as 105 oral specimens derived from healthy individuals. PCR assays targeting two regions of the virus were used. PCR amplification for the analysis of p53 codon 72 arginine/proline alleles was carried out in a separate reaction.

Results

HPV DNA was detected in 51.4% OSCC samples, while 24.8% controls were found to be HPV positive. HPV was found to be significantly associated with OSCC (P < 0.001, OR = 4.3 after adjustment for habits) when compared to controls. High-risk HPV was found to be significantly associated with OSCC cases (P < 0.05). Demographic profiles of age, gender, race and habits were not associated with HPV presence in cases and controls. However, significantly less HPV positivity was seen in poorly differentiated compared to well-differentiated OSCCs. No significant association was found between HPV positivity and p53 polymorphisms in cases and control groups. Additionally, we found no association of codon 72 polymorphism with oral cancer.

Conclusions

This study indicates that high-risk HPV infection is one of the contributing factors for OSCCs. HPV 16 was the predominant type found in Malaysian patients with OSCC. Further, we did not find any association between p53 codon 72 polymorphism and HPV infection or between the p53 polymorphism and the risk of oral cancer.

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References

  • Agorastos T, Masouridou S, Lambropoulos AF, Chrisafi S, Miliaras D, Pantazis K, Constantinides TC, Kotsis A, Bontis I (2004) P53 codon 72 polymorphism and correlation with ovarian and endometrial cancer in Greek women. Eur J Cancer Prev 13:277–280

    Article  CAS  PubMed  Google Scholar 

  • Ammatuna P, Giovannelli L, Giambelluca D, Mancuso S, Rubino E, Colletti P, Mazzola G, Belfiore P, Lima R (2000) Presence of human papillomavirus and Epstein-Barr virus in the cervix of women infected with the human immunodeficiency virus. J Med Virol 62:410–415

    Article  CAS  PubMed  Google Scholar 

  • Andl T, Kahn T, Pfuhl A, Nicola T, Erber R, Conradt C, Klein W, Helbig M, Dietz A, Weidauer H, Bosch FX (1998) Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control. Cancer Res 58:5–13

    CAS  PubMed  Google Scholar 

  • Badaracco G, Venuti A, Morello R, Muller A, Marcante ML (2000) Human papillomavirus in head and neck carcinomas: prevalence, physical status and relationship with clinical/pathological parameters. Anticancer Res 20:1301–1305

    CAS  PubMed  Google Scholar 

  • Baez A, Almodovar JI, Cantor A, Celestin F, Cruz-Cruz L, Fonseca S, Trinidad-Pinedo J, Vega W (2004) High frequency of HPV16-associated head and neck squamous cell carcinoma in the Puerto Rican population. Head Neck 26:778–784

    Article  PubMed  Google Scholar 

  • Beckman G, Birgander R, Sjalander A, Saha N, Holmberg PA, Kivela A, Beckman L (1994) Is p53 polymorphism maintained by natural selection? Hum Hered 44:266–270

    Article  CAS  PubMed  Google Scholar 

  • Buchman VL, Chumakov PM, Ninkina NN, Samarina OP, Georgiev GP (1988) A variation in the structure of the protein-coding region of the human p53 gene. Gene 70:245–252

    Article  CAS  PubMed  Google Scholar 

  • Chang KW, Chang CS, Lai KS, Chou MJ, Choo KB (1989) High prevalence of human papillomavirus infection and possible association with betel quid chewing and smoking in oral epidermoid carcinomas in Taiwan. J Med Virol 28:57–61

    Article  CAS  PubMed  Google Scholar 

  • Chang JY, Lin MC, Chiang CP (2003) High-risk human papillomaviruses may have an important role in non-oral habits-associated oral squamous cell carcinomas in Taiwan. Am J Clin Pathol 120:909–916

    Article  PubMed  Google Scholar 

  • Cheah PL, Looi LM, Ng MH, Sivanesaratnam V (2002) Telomerase activation and human papillomavirus infection in invasive uterine cervical carcinoma in a set of Malaysian patients. J Clin Pathol 55:22–26

    CAS  PubMed  Google Scholar 

  • D’Costa J, Saranath D, Dedhia P, Sanghvi V, Mehta AR (1998) Detection of HPV-16 genome in human oral cancers and potentially malignant lesions from India. Oral Oncol 34:413–420

    Article  PubMed  Google Scholar 

  • Dahlstrom KR, Adler-Storthz K, Etzel CJ, Liu Z, Dillon L, El-Naggar AK, Spitz MR, Schiller JT, Wei Q, Sturgis EM (2003) Human papillomavirus type 16 infection and squamous cell carcinoma of the head and neck in never-smokers: a matched pair analysis. Clin Cancer Res 9:2620–2626

    PubMed  Google Scholar 

  • de Roda Husman AM, Walboomers JM, van den Brule AJ, Meijer CJ, Snijders PJ (1995) The use of general primers GP5 and GP6 elongated at their 3’ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 76(Pt 4):1057–1062

    Article  PubMed  Google Scholar 

  • de Villiers E-M, Fauquet C, Broker TR, Bernard H-U, zur Hausen H (2004) Classification of papillomaviruses. Virology 324:17–27

    Article  PubMed  Google Scholar 

  • Dumont P, Leu JI, Della Pietra AC, George DL 3rd, Murphy M (2003) The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 33:357–365

    Article  CAS  PubMed  Google Scholar 

  • Elamin F, Steingrimsdottir H, Wanakulasuriya S, Johnson N, Tavassoli M (1998) Prevalence of human papillomavirus infection in premalignant and malignant lesions of the oral cavity in U.K. subjects: a novel method of detection. Oral Oncol 34:191–197

    Article  CAS  PubMed  Google Scholar 

  • Enwonwu CO, Meeks VI (1995) Bionutrition and oral cancer in humans. Crit Rev Oral Biol Med 6:5–17

    Article  CAS  PubMed  Google Scholar 

  • Fouret P, Martin F, Flahault A, Saint-Guily JL (1995) Human papillomavirus infection in the malignant and premalignant head and neck epithelium. Diagn Mol Pathol 4:122–127

    Article  CAS  PubMed  Google Scholar 

  • Giannoudis A, Graham DA, Southern SA, Herrington CS (1999) p53 codon 72 ARG/PRO polymorphism is not related to HPV type or lesion grade in low- and high-grade squamous intra-epithelial lesions and invasive squamous carcinoma of the cervix. Int J Cancer 83:66–69

    Article  CAS  PubMed  Google Scholar 

  • Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE et al (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:709–720

    Article  CAS  PubMed  Google Scholar 

  • Giovannelli L, Campisi G, Lama A, Giambalvo O, Osborn J, Margiotta V, Ammatuna P (2002) Human papillomavirus DNA in oral mucosal lesions. J Infect Dis 185:833–836

    Article  CAS  PubMed  Google Scholar 

  • Ha PK, Califano JA (2004) The role of human papillomavirus in oral carcinogenesis. Crit Rev Oral Biol Med 15:188–196

    Article  PubMed  Google Scholar 

  • Hiyama T, Tanaka S, Kitadai Y, Ito M, Sumii M, Yoshihara M, Shimamoto F, Haruma K, Chayama K (2002) p53 Codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis. Int J Cancer 100:304–308

    Article  CAS  PubMed  Google Scholar 

  • Ibieta BR, Lizano M, Fras-Mendivil M, Barrera JL, Carrillo A, Ma Ruz-Godoy L, Mohar A (2005) Human papilloma virus in oral squamous cell carcinoma in a Mexican population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99:311–315

    Article  PubMed  Google Scholar 

  • Ikenberg H, Sauerbrei W, Schottmuller U, Spitz C, Pfleiderer A (1994) Human papillomavirus DNA in cervical carcinoma—correlation with clinical data and influence on prognosis. Int J Cancer 59:322–326

    Article  CAS  PubMed  Google Scholar 

  • Ji X, Neumann AS, Sturgis EM, Adler-Storthz K, Dahlstrom KR, Schiller JT, Wei Q, Li G (2008) p53 codon 72 polymorphism associated with risk of human papillomavirus-associated squamous cell carcinoma of the oropharynx in never-smokers. Carcinogenesis 29:875–879

    Article  CAS  PubMed  Google Scholar 

  • Jin X, Wu X, Roth JA, Amos CI, King TM, Branch C, Honn SE, Spitz MR (1995) Higher lung cancer risk for younger African-Americans with the Pro/Pro p53 genotype. Carcinogenesis 16:2205–2208

    Article  CAS  PubMed  Google Scholar 

  • Katiyar S, Thelma BK, Murthy NS, Hedau S, Jain N, Gopalkrishna V, Husain SA, Das BC (2003) Polymorphism of the p53 codon 72 Arg/Pro and the risk of HPV type 16/18-associated cervical and oral cancer in India. Mol Cell Biochem 252:117–124

    Article  CAS  PubMed  Google Scholar 

  • Manos MM, Ting Y, Wright DK, Lewis AJ, Broker TR, Wolinski SM (1989) Use of polymerase chain reaction amplification for the detection of genital human papillomaviruses. Cancer Cells 7:209–214

    CAS  Google Scholar 

  • Miller CS, Johnstone BM (2001) Human papillomavirus as a risk factor for oral squamous cell carcinoma: a meta-analysis, 1982–1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 91:622–635

    Article  CAS  PubMed  Google Scholar 

  • Minaguchi T, Kanamori Y, Matsushima M, Yoshikawa H, Taketani Y, Nakamura Y (1998) No evidence of correlation between polymorphism at codon 72 of p53 and risk of cervical cancer in Japanese patients with human papillomavirus 16/18 infection. Cancer Res 58:4585–4586

    CAS  PubMed  Google Scholar 

  • Nishikawa A, Fujimoto T, Akutagawa N, Iwasaki M, Takeuchi M, Fujinaga K, Kudo R (2000) p53 Polymorphism (codon-72) has no correlation with the development and the clinical features of cervical cancer. Int J Gynecol Cancer 10:402–407

    Article  PubMed  Google Scholar 

  • Ostwald C, Muller P, Barten M, Rutsatz K, Sonnenburg M, Milde-Langosch K, Loning T (1994) Human papillomavirus DNA in oral squamous cell carcinomas and normal mucosa. J Oral Pathol Med 23:220–225

    Article  CAS  PubMed  Google Scholar 

  • Perrone F, Mariani L, Pastore E, Orsenigo M, Suardi S, Marcomini B, DaRiva L, Licitra L, Carbone A, Pierotti MA, Pilotti S (2007) p53 codon 72 polymorphisms in human papillomavirus-negative and human papillomavirus-positive squamous cell carcinomas of the oropharynx. Cancer 109:2461–2465

    Article  CAS  PubMed  Google Scholar 

  • Pim D, Banks L (2004) p53 polymorphic variants at codon 72 exert different effects on cell cycle progression. Int J Cancer 108:196–199

    Article  CAS  PubMed  Google Scholar 

  • Rosenthal AN, Ryan A, Al-Jehani RM, Storey A, Harwood CA, Jacobs IJ (1998) p53 codon 72 polymorphism and risk of cervical cancer in UK. Lancet 352:871–872

    Article  CAS  PubMed  Google Scholar 

  • Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N (1992) Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. 1985. Biotechnology 24:476–480

    CAS  PubMed  Google Scholar 

  • Saini R, Shen TH, Othman NH, Santhanam J, Othman N, Tang TH (2007) Evaluation of polymerase chain reaction (PCR) method and hybrid capture II (HCII) assay for the detection of human papillomavirus in cervical scrapings. Med J Malaysia 62:206–209

    CAS  PubMed  Google Scholar 

  • Scheckenbach K, Lieven O, Gotte K, Bockmuhl U, Zotz R, Bier H, Balz V (2004) p53 codon 72 polymorphic variants, loss of allele-specific transcription, and human papilloma virus 16 and/or 18 E6 messenger RNA expression in squamous cell carcinomas of the head and neck. Cancer Epidemiol Biomarkers Prev 13:1805–1809

    CAS  PubMed  Google Scholar 

  • Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM (1990) The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129–1136

    Article  CAS  PubMed  Google Scholar 

  • Scully C, Bedi R (2000) Ethnicity and oral cancer. Lancet Oncol 1:37–42

    Article  CAS  PubMed  Google Scholar 

  • Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F, Breuer J, Leigh IM, Matlashewski G, Banks L (1998) Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 393:229–234

    Article  CAS  PubMed  Google Scholar 

  • Summersgill KF, Smith EM, Kirchner HL, Haugen TH, Turek LP (2000) p53 polymorphism, human papillomavirus infection in the oral cavity, and oral cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90:334–339

    Article  CAS  PubMed  Google Scholar 

  • Syrjanen S (2005) Human papillomavirus (HPV) in head and neck cancer. J Clin Virol 32(Suppl 1):S59–S66

    Article  PubMed  Google Scholar 

  • Thomas M, Kalita A, Labrecque S, Pim D, Banks L, Matlashewski G (1999) Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol 19:1092–1100

    CAS  PubMed  Google Scholar 

  • Tieben LM, ter Schegget J, Minnaar RP, Bouwes Bavinck JN, Berkhout RJ, Vermeer BJ, Jebbink MF, Smits HL (1993) Detection of cutaneous and genital HPV types in clinical samples by PCR using consensus primers. J Virol Methods 42:265–279

    Article  CAS  PubMed  Google Scholar 

  • Tsai MH, Lin CD, Hsieh YY, Chang FC, Tsai FJ, Chen WC, Tsai CH (2002) Prognostic significance of the proline form of p53 codon 72 polymorphism in nasopharyngeal carcinoma. Laryngoscope 112:116–119

    Article  CAS  PubMed  Google Scholar 

  • Wilczynski SP, Bergen S, Walker J, Liao SY, Pearlman LF (1988) Human papillomaviruses and cervical cancer: analysis of histopathologic features associated with different viral types. Hum Pathol 19:697–704

    Article  CAS  PubMed  Google Scholar 

  • Wilczynski SP, Lin BT, Xie Y, Paz IB (1998) Detection of human papillomavirus DNA and oncoprotein overexpression are associated with distinct morphological patterns of tonsillar squamous cell carcinoma. Am J Pathol 152:145–156

    CAS  PubMed  Google Scholar 

  • Zain RB, Ikeda N, Gupta PC, Warnakulasuriya S, van Wyk CW, Shrestha P, Axell T (1999) Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25–27, 1996. J Oral Pathol Med 28:1–4

    Article  CAS  PubMed  Google Scholar 

  • Zehbe I, Voglino G, Wilander E, Delius H, Marongiu A, Edler L, Klimek F, Andersson S, Tommasino M (2001) p53 codon 72 polymorphism and various human papillomavirus 16 E6 genotypes are risk factors for cervical cancer development. Cancer Res 61:608–611

    CAS  PubMed  Google Scholar 

  • zur Hausen H (1996) Papillomavirus infections—a major cause of human cancers. Biochim Biophys Acta 1288:55–78

    Google Scholar 

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Acknowledgments

The authors would like to thank Prof E. M. deVilliers for providing the plasmids of HPV 6, 11, 16 and 18, Dr Micheal Favre for providing the plasmid of HPV 33 and Dr Lorincz for providing the plasmid of HPV 31, 38 and 51 which were used in this study. This study was supported by “Science fund” provided by MOSTI, Grant No- 305/PPSG/6113208.

Conflict of interest statement

Dr Tang Thean Hock is currently working in Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, Penang. He was an employee in Institute for Research in Molecular Medicine (INFORMM), Health Campus, Universiti Sains Malaysia, Kelantan, when the study was conducted. The authors declare that they have no Conflict of interests.

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Author notes

  1. Thean-Hock Tang

    Present address: Infectious Disease Cluster (IDC), Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, Bertam, 13200, Penang, Malaysia

Authors and Affiliations

  1. School of Dental Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia

    Rajan Saini, Deepti Saini & Abdul Rashid Ismail

  2. Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia

    Thean-Hock Tang

  3. Oral Cancer Research and Coordinating Centre, University of Malaya, Kuala Lumpur, Malaysia

    Rosnah Binti Zain

  4. Oral Cancer Research Team, Cancer Research Initiatives Foundation (CARIF), 2nd Floor Outpatient Centre, Sime Darby Medical Centre, 47500, Subang Jaya, Selangor, Malaysia

    Sok Ching Cheong

  5. Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia

    Kamarul Imran Musa

  6. Department of Oral and Maxillofacial Surgery, Hospital Tengku Ampuan Rahimah, Ministry of Health Malaysia, Klang, Malaysia

    Mannil Thomas Abraham

  7. Department of Oral Maxillofacial Surgery, Hospital Kuala Lumpur, Ministry of Health Malaysia, Kuala Lumpur, Malaysia

    Wan Mahadzir Wan Mustafa

  8. Department of Biomedical Sciences, Faculty of Allied Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Jacinta Santhanam

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  1. Rajan Saini
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Correspondence to Rajan Saini.

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Saini, R., Tang, TH., Zain, R.B. et al. Significant association of high-risk human papillomavirus (HPV) but not of p53 polymorphisms with oral squamous cell carcinomas in Malaysia. J Cancer Res Clin Oncol 137, 311–320 (2011). https://doi.org/10.1007/s00432-010-0886-8

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  • DOI: https://doi.org/10.1007/s00432-010-0886-8

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