Oncogenic human papillomavirus-associated nasopharyngeal carcinoma: an observational study of correlation with ethnicity, histological subtype and outcome in a UK population

Infectious Agents and Cancer - Tập 8 Số 1 - 2013
Max Robinson1, Yae-eun Suh2, Vinidh Paleri3, Debbie Devlin4, Bushra Ayaz4, Laura Pertl4, Selvam Thavaraj4
1Centre for Oral Health Research, School of Dental Sciences, Newcastle University, Newcastle upon Tyne, UK
2Head and Neck Oncology, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK
3Otolaryngology-Head and Neck Surgery, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK
4Clinical and Diagnostic Sciences, King’s College London Dental Institute, London, UK

Tóm tắt

Abstract Background Nasopharyngeal carcinoma (NPC) accounts for 0.6% of all cancers worldwide with the highest prevalence in South East Asia, Southern China and Northern Africa but the disease is uncommon in Europe with an annual incidence in this region of less than 1 per 100 000. Although the Epstein-Barr virus (EBV) is a well known causative agent in NPC, recent reports have implicated oncogenic Human Papillomavirus (HPV) in a subgroup of these tumours. The recent striking rise of oropharyngeal carcinoma has been attributed to HPV, but little is known about the prevalence and clinical significance of the virus in NPC. The aim of this study was to determine the prevalence of oncogenic HPV in NPC from tissue archives of two head and neck cancer centres in the UK. Methods Samples were available for 67 patients with clinically validated NPC. The detection of high-risk HPV was carried out by screening all cases for p16 using immunohistochemistry and HPV DNA by polymerase chain reaction (PCR) using GP5+/6+ primers. All cases with p16 over-expression or positive for HPV by PCR were then examined by high-risk HPV DNA in-situ hybridisation and genotype analysis by PCR. Results Eleven cases (11/67, 16.4%) showed concurrent over-expression of p16 and evidence of high-risk HPV DNA by in-situ hybridisation; the majority were HPV16 positive. Of these 11 cases, nine occurred in Whites and two in Blacks. Histologically, there were two keratinising squamous cell carcinoma and nine non-keratinising carcinomas (eight differentiated and one undifferentiated). None of the HPV-positive cases showed any co-infection with EBV. There was no statistically significant difference in overall survival outcome between patients with HPV-positive and HPV-negative NPC. Conclusion The results of this study show that oncogenic HPV is associated with a subgroup of NPCs and is more likely to occur in Whites. However, unlike oropharyngeal carcinoma there was no significant difference in overall survival between patients with HPV-positive and HPV-negative NPC.

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Tài liệu tham khảo

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.

Parkin DM, Muir CS: Cancer incidence in five continents. Comparability and quality of data. IARC Sci Publ. 1992, 120: 45-173.

Chang ET, Adami HO: The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2006, 15: 1765-1777. 10.1158/1055-9965.EPI-06-0353.

Price G, Roche M, Crowther R, Wright R: Profiles of Head and Neck Cancers in England: Incidence, Mortality and Survival.http://www.ncin.org.uk/publications/reports/,

Barnes L: Pathology and genetics of head and neck tumours. 2005, Lyon: IARC Press

Wei WI, Sham JS: Nasopharyngeal carcinoma. Lancet. 2005, 365: 2041-2054. 10.1016/S0140-6736(05)66698-6.

Giannoudis A, Ergazaki M, Segas J, Giotakis J, Adamopoulos G, Gorgoulis V, Spandidos DA: Detection of Epstein-Barr virus and human papillomavirus in nasopharyngeal carcinoma by the polymerase chain reaction technique. Cancer Lett. 1995, 89: 177-181. 10.1016/0304-3835(94)03667-8.

Rassekh CH, Rady PL, Arany I, Tyring SK, Knudsen S, Calhoun KH, Seikaly H, Bailey BJ: Combined Epstein-Barr virus and human papillomavirus infection in nasopharyngeal carcinoma. Laryngoscope. 1998, 108: 362-367. 10.1097/00005537-199803000-00010.

Punwaney R, Brandwein MS, Zhang DY, Urken ML, Cheng R, Park CS, Li HB, Li X: Human papillomavirus may be common within nasopharyngeal carcinoma of Caucasian Americans: investigation of Epstein-Barr virus and human papillomavirus in eastern and western nasopharyngeal carcinoma using ligation-dependent polymerase chain reaction. Head Neck. 1999, 21: 21-29. 10.1002/(SICI)1097-0347(199901)21:1<21::AID-HED3>3.0.CO;2-Z.

Mirzamani N, Salehian P, Farhadi M, Tehran EA: Detection of EBV and HPV in nasopharyngeal carcinoma by in situ hybridization. Exp Mol Pathol. 2006, 81: 231-234. 10.1016/j.yexmp.2006.04.006.

Maxwell JH, Kumar B, Feng FY, McHugh JB, Cordell KG, Eisbruch A, Worden FP, Wolf GT, Prince ME, Moyer JS: HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans. Head Neck. 2010, 32: 562-567.

Lo EJ, Bell D, Woo JS, Li G, Hanna EY, El-Naggar AK, Sturgis EM: Human papillomavirus and WHO type I nasopharyngeal carcinoma. Laryngoscope. 2010, 120: 1990-1997. 10.1002/lary.21089.

Laantri N, Attaleb M, Kandil M, Naji F, Mouttaki T, Dardari R, Belghmi K, Benchakroun N, El Mzibri M, Khyatti M: Human papillomavirus detection in moroccan patients with nasopharyngeal carcinoma. Infect Agent Cancer. 2011, 6: 3-10.1186/1750-9378-6-3.

Singhi AD, Califano J, Westra WH: High-risk human papillomavirus in nasopharyngeal carcinoma. Head Neck. 2012, 34: 213-218. 10.1002/hed.21714.

Shah SM, Drage MG, Lichtman AH, Haddad RI: Metastatic human papillomavirus-positive nasopharyngeal carcinoma with an unusual pattern of aggressive hematogenous spread. J Clin Oncol. 2012, 30: e321-323. 10.1200/JCO.2012.42.3566.

Lin Z, Khong B, Kwok S, Cao H, West RB, Le QT, Kong CS: Human papillomavirus 16 detected in nasopharyngeal carcinomas in Caucasian Americans but not in endemic Southern Chinese patients. Head Neck. 2013, 10.1002/hed.23362. Epud ahead of print

Chaturvedi AK: Epidemiology and clinical aspects of HPV in head and neck cancers. Head Neck Pathol. 2012, 6 (Suppl 1): S16-24.

Jordan RC, Lingen MW, Perez-Ordonez B, He X, Pickard R, Koluder M, Jiang B, Wakely P, Xiao W, Gillison ML: Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol. 2012, 36: 945-954. 10.1097/PAS.0b013e318253a2d1.

Isayeva T, Li Y, Maswahu D, Brandwein-Gensler M: Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review. Head Neck Pathol. 2012, 6 (Suppl 1): S104-120.

Smeets SJ, Hesselink AT, Speel EJ, Haesevoets A, Snijders PJ, Pawlita M, Meijer CJ, Braakhuis BJ, Leemans CR, Brakenhoff RH: A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer. 2007, 121: 2465-2472. 10.1002/ijc.22980.

Thavaraj S, Stokes A, Guerra E, Bible J, Halligan E, Long A, Okpokam A, Sloan P, Odell E, Robinson M: Evaluation of human papillomavirus testing for squamous cell carcinoma of the tonsil in clinical practice. J Clin Pathol. 2011, 64: 308-312. 10.1136/jcp.2010.088450.

Schache AG, Liloglou T, Risk JM, Filia A, Jones TM, Sheard J, Woolgar JA, Helliwell TR, Triantafyllou A, Robinson M: Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination. Clin Cancer Res. 2011, 17: 6262-6271. 10.1158/1078-0432.CCR-11-0388.

Lopes V, Murray P, Williams H, Woodman C, Watkinson J, Robinson M: Squamous cell carcinoma of the oral cavity rarely harbours oncogenic human papillomavirus. Oral Oncol. 2011, 47: 698-701. 10.1016/j.oraloncology.2011.04.022.

Carlson D, Barnes L, Chan J, Ellis G, Harrison L, Hunt J, Richardson M, Seethala R, Shah J, Thompson LDR: Protocol for the Examination of Specimens From Patients With Carcinomas of the Pharynx.http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Pharynx_12protocol.pdf,

Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA: Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988, 239: 487-491. 10.1126/science.2448875.

Jacobs MV, Snijders PJ, van den Brule AJ, Helmerhorst TJ, Meijer CJ, Walboomers JM: A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol. 1997, 35: 791-795.

White JS, Weissfeld JL, Ragin CC, Rossie KM, Martin CL, Shuster M, Ishwad CS, Law JC, Myers EN, Johnson JT, Gollin SM: The influence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines. Oral Oncol. 2007, 43: 701-712. 10.1016/j.oraloncology.2006.09.001.

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Infectious Agents and Cancer

Tập 8 Số 1

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