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Article

Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma

  • Authors:
    • Hiromitsu Hatakeyama
    • Takatsugu Mizumachi
    • Tomohiro Sakashita
    • Satoshi Kano
    • Akihiro Homma
    • Satoshi Fukuda
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan
  • Pages: 2673-2679
    |
    Published online on: September 22, 2014
       https://doi.org/10.3892/or.2014.3509
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Abstract

High-risk human papillomavirus (HPV) infection is associated with carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC) and patients with HPV-positive tumors have a significantly favorable prognosis. However, the underlying mechanism of this favorable clinical outcome remains unclear. Epithelial-mesenchymal transition (EMT) causes aggressiveness of cancer cells and we investigated the expression of the EMT markers and analyzed their correlation with HPV status and prognosis in order to examine the treatment response of HPV-positive OPSCCs. A total of 79 patients with OPSCC were examined in the present study. All high-risk HPV infections were determined with the multiplex PCR kit from each formalin-fixed paraffin-embedded (FFPE) sample. We performed immunohistochemical staining for E-cadherin and vimentin. Expression of the markers was graded and we statistically analyzed the correlation between tumor, node, metastasis (TNM) stages and prognosis. High-risk HPV-positive tumors were detected in 23 cases. The five‑year survival rate in HPV-positive and -negative tumors was 82.7 and 48.3%, respectively. High E-cadherin expression rate in HPV-negative samples was 76.7% and 43.4% in HPV-positive samples (p=0.007). Vimentin expression did not show a difference between HPV-positive and -negative tumors. HPV-negative patients presented significantly greater heterogeneity of E-cadherin expression compared to HPV-positive patients (p=0.0349). HPV-positive OPSCCs originally lost their epithelial cell phenotype compared with HPV-negative tumors. Therefore, the paradoxical favorable prognosis of HPV-positive OPSCC may be due to the intratumor homogeneity in EMT.
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1 

Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar

2 

Kreimer AR, Clifford GM, Boyle P and Franceschi S: Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 14:467–475. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Lindel K, Beer KT, Laissue J, Greiner RH and Aebersold DM: Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer. 92:805–813. 2001. View Article : Google Scholar : PubMed/NCBI

4 

D’Souza G, Kreimer AR, Viscidi R, et al: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 356:1944–1956. 2007.PubMed/NCBI

5 

Kumar B, Cordell KG, Lee JS, et al: EGFR, p16, HPV titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol. 26:3128–3137. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Worden FP, Kumar B, Lee JS, et al: Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number. J Clin Oncol. 26:3138–3146. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Licitra L, Perrone F, Bossi P, et al: High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol. 24:5630–5636. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Weinberger PM, Yu Z, Haffty BG, et al: Molecular classification identifies a subset of human papillomavirus-associated oropharyngeal cancers with favorable prognosis. J Clin Oncol. 24:736–747. 2006. View Article : Google Scholar

9 

Fakhry C, Westra WH, Li S, et al: Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 100:261–269. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Mizumachi T, Kano S, Sakashita T, et al: Improved survival of Japanese patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma. Int J Clin Oncol. 18:824–828. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Westra WH: The morphologic profile of HPV-related head and neck squamous carcinoma: implications for diagnosis, prognosis, and clinical management. Head Neck Pathol. 6(Suppl 1): S48–S54. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Yilmaz M and Christofori G: EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 28:15–33. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Kalluri R: EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest. 119:1417–1419. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Hashimoto T, Soeno Y, Maeda G, et al: Progression of oral squamous cell carcinoma accompanied with reduced E-cadherin expression but not cadherin switch. PLoS One. 7:e478992012. View Article : Google Scholar : PubMed/NCBI

16 

Zhao Z, Ge J, Sun Y, et al: Is E-cadherin immunoexpression a prognostic factor for head and neck squamous cell carcinoma (HNSCC)? A systematic review and meta-analysis. Oral Oncol. 48:761–767. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Zeisberg M and Neilson EG: Biomarkers for epithelial-mesenchymal transitions. J Clin Invest. 119:1429–1437. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Nishiwaki M, Yamamoto T, Tone S, et al: Genotyping of human papillomaviruses by a novel one-step typing method with multiplex PCR and clinical applications. J Clin Microbiol. 46:1161–1168. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Olshan AF, Weissler MC, Pei H, et al: Alterations of the p16 gene in head and neck cancer: frequency and association with p53, PRAD-1 and HPV. Oncogene. 14:811–818. 1997. View Article : Google Scholar : PubMed/NCBI

20 

Braakhuis BJ, Snijders PJ, Keune WJ, et al: Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst. 96:998–1006. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Haraf DJ, Nodzenski E, Brachman D, et al: Human papilloma virus and p53 in head and neck cancer: clinical correlates and survival. Clin Cancer Res. 2:755–762. 1996.PubMed/NCBI

22 

Perrone F, Suardi S, Pastore E, et al: Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma. Clin Cancer Res. 12:6643–6651. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Kessis TD, Slebos RJ, Nelson WG, et al: Human papillomavirus 16 E6 expression disrupts the p53-mediated cellular response to DNA damage. Proc Natl Acad Sci USA. 90:3988–3992. 1993. View Article : Google Scholar : PubMed/NCBI

24 

Koch WM, Lango M, Sewell D, Zahurak M and Sidransky D: Head and neck cancer in nonsmokers: a distinct clinical and molecular entity. Laryngoscope. 109:1544–1551. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Nijkamp MM, Span PN, Hoogsteen IJ, van der Kogel AJ, Kaanders JH and Bussink J: Expression of E-cadherin and vimentin correlates with metastasis formation in head and neck squamous cell carcinoma patients. Radiother Oncol. 99:344–348. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Andrews NA, Jones AS, Helliwell TR and Kinsella AR: Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases. Br J Cancer. 75:1474–1480. 1997. View Article : Google Scholar : PubMed/NCBI

27 

Baumann JL, Cohen S, Evjen AN, et al: Human papillomavirus in early laryngeal carcinoma. Laryngoscope. 119:1531–1537. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Kreimer AR, Alberg AJ, Daniel R, et al: Oral human papillomavirus infection in adults is associated with sexual behavior and HIV serostatus. J Infect Dis. 189:686–698. 2004. View Article : Google Scholar : PubMed/NCBI

29 

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

30 

Vessey CJ, Wilding J, Folarin N, et al: Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma. J Pathol. 176:151–159. 1995. View Article : Google Scholar : PubMed/NCBI

31 

Matthews K, Leong CM, Baxter L, et al: Depletion of Langerhans cells in human papillomavirus type 16-infected skin is associated with E6-mediated down regulation of E-cadherin. J Virol. 77:8378–8385. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Jung YS, Kato I and Kim HR: A novel function of HPV16-E6/E7 in epithelial-mesenchymal transition. Biochem Biophys Res Commun. 435:339–344. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Gerlinger M, Rowan AJ, Horswell S, et al: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 366:883–892. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Mroz EA and Rocco JW: MATH, a novel measure of intratumor genetic heterogeneity, is high in poor-outcome classes of head and neck squamous cell carcinoma. Oral Oncol. 49:211–215. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Mroz EA and Rocco JW: Gene expression analysis as a tool in early-stage oral cancer management. J Clin Oncol. 30:4053–4055. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Hatakeyama H, Mizumachi T, Sakashita T, Kano S, Homma A and Fukuda S: Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma. Oncol Rep 32: 2673-2679, 2014.
APA
Hatakeyama, H., Mizumachi, T., Sakashita, T., Kano, S., Homma, A., & Fukuda, S. (2014). Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma. Oncology Reports, 32, 2673-2679. https://doi.org/10.3892/or.2014.3509
MLA
Hatakeyama, H., Mizumachi, T., Sakashita, T., Kano, S., Homma, A., Fukuda, S."Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma". Oncology Reports 32.6 (2014): 2673-2679.
Chicago
Hatakeyama, H., Mizumachi, T., Sakashita, T., Kano, S., Homma, A., Fukuda, S."Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma". Oncology Reports 32, no. 6 (2014): 2673-2679. https://doi.org/10.3892/or.2014.3509
Copy and paste a formatted citation
x
Spandidos Publications style
Hatakeyama H, Mizumachi T, Sakashita T, Kano S, Homma A and Fukuda S: Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma. Oncol Rep 32: 2673-2679, 2014.
APA
Hatakeyama, H., Mizumachi, T., Sakashita, T., Kano, S., Homma, A., & Fukuda, S. (2014). Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma. Oncology Reports, 32, 2673-2679. https://doi.org/10.3892/or.2014.3509
MLA
Hatakeyama, H., Mizumachi, T., Sakashita, T., Kano, S., Homma, A., Fukuda, S."Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma". Oncology Reports 32.6 (2014): 2673-2679.
Chicago
Hatakeyama, H., Mizumachi, T., Sakashita, T., Kano, S., Homma, A., Fukuda, S."Epithelial-mesenchymal transition in human papillomavirus‑positive and -negative oropharyngeal squamous cell carcinoma". Oncology Reports 32, no. 6 (2014): 2673-2679. https://doi.org/10.3892/or.2014.3509
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