1887

Journal of Medical Microbiology logo

Volume 68, Issue 3

Impact of HPV infection on gene expression and methylation in oral cancer patients Free

Abstract

Purpose. The current study aimed to examine the association between head and neck squamous cell carcinoma (HNSCC) and infection with different human papillomavirus virus (HPV) subtypes, including analysis of promoter methylation of several genes (APC, CDKN2A, MGMT, CDH1 and TIMP3) and the correlation with their mRNA expression in tumours and surgical margins.

Methodology. In 47 patients with a primary tumour of the oral cavity, HPV detection and identification of 33 subtypes was performed after previous DNA isolation using a GenoFlow HPV Array Test Kit.

Results. Fifteen patients (31.92 %) were HPV [+] and the following HPV types were detected: 16 (46.67 %), 18 (6.67 %) and 43/44 (40 %). This study is the first to describe HPV 43/44 subtypes in HNSCC in a Polish population. We noted no clinical significance of HPV [+] HNSCC compared to HPV [−], however, this differed among HPV subtypes. CDKN2A promoter methylation was more frequent in HPV-16/18 patients compared to HPV43/44 patients, but there was no difference in gene expression level between HPV [+] and [−] patients.

Conclusion. We detected HPV infection in 31.92 % of oral cancer cases. HPV 16, along with HPV 43/44, were the most frequent subtypes. Knowledge of HPV [+] HNSCC biology may be useful in establishing the prognosis and developing novel therapies in future.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): gene expression , HNSCC , HPV , oral cancer and promoter methylation
© 2019 The Authors
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000898
2019-01-09
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jmm/68/3/440.html?itemId=/content/journal/jmm/10.1099/jmm.0.000898&mimeType=html&fmt=ahah

References

  1. Majchrzak E, Szybiak B, Wegner A, Pienkowski P, Pazdrowski J et al. Oral cavity and oropharyngeal squamous cell carcinoma in young adults: a review of the literature. Radiol Oncol 2014; 48:1–10 [View Article][PubMed]
     [Google Scholar]
  2. Marur S, D’Souza G, Westra WH, Forastiere AA, Head H-A et al. A virus-related cancer epidemic – A review of epidemiology, biology, virus detection and issues in management. Lancet Oncol 2010; 11:781–789
     [Google Scholar]
  3. Ndiaye C, Mena M, Alemany L, Arbyn M, Castellsagué X et al. HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. Lancet Oncol 2014; 15:1319–1331 [View Article][PubMed]
     [Google Scholar]
  4. Hübbers CU, Akgül B. HPV and cancer of the oral cavity. Virulence 2015; 6:244–248 [View Article][PubMed]
     [Google Scholar]
  5. Rampias T, Sasaki C, Psyrri A. Molecular mechanisms of HPV induced carcinogenesis in head and neck. Oral Oncol 2014; 50:356–363 [View Article][PubMed]
     [Google Scholar]
  6. WHO TNM classification of carcinomas of the oral cavity. http://screening.iarc.fr/atlasoralclassiftnm.php#reference accessed 19 September 2018
  7. Strzelczyk JK, Krakowczyk Ł, Owczarek AJ. Aberrant DNA methylation of the p16, APC, MGMT, TIMP3 and CDH1 gene promoters in tumours and the surgical margins of patients with oral cavity cancer. J Cancer 2018; 9:1896–1904 [View Article][PubMed]
     [Google Scholar]
  8. Strzelczyk JK, Gołąbek K, Krakowczyk Ł, Owczarek AJ. Expression profiles of MGMT, p16, and APC genes in tumor and matching surgical margin from patients with oral squamous cell carcinoma. Acta Biochim Pol 2016; 63:505–509 [View Article][PubMed]
     [Google Scholar]
  9. Strzelczyk JK, Krakowczyk Ł, Gołąbek K, Owczarek AJ. Expression profiles of selected genes in tumors and matched surgical margins in oral cavity cancer: do we have to pay attention to the molecular analysis of the surgical margins?. Adv Clin Exp Med 2018; 27:833–840 [View Article][PubMed]
     [Google Scholar]
  10. Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma. J Clin Oncol 2015; 33:3235–3242 [View Article][PubMed]
     [Google Scholar]
  11. Chung CH, Bagheri A, D'Souza G. Epidemiology of oral human papillomavirus infection. Oral Oncol 2014; 50:364–369 [View Article][PubMed]
     [Google Scholar]
  12. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011; 29:4294–4301 [View Article][PubMed]
     [Google Scholar]
  13. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006; 118:3030–3044 [View Article][PubMed]
     [Google Scholar]
  14. Rivera-Peña B, Ruíz-Fullana FJ, Vélez-Reyes GL, Rodriguez-Benitez RJ, Marcos-Martínez MJ et al. HPV-16 infection modifies overall survival of puerto rican HNSCC patients. Infect Agent Cancer 2016; 11:47 [View Article][PubMed]
     [Google Scholar]
  15. Marques-Silva L, Farias LC, Fraga CA, de Oliveira MV, Cardos CM et al. HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients. Oncol Lett 2012; 3:945–949 [View Article][PubMed]
     [Google Scholar]
  16. Ljøkjel B, Haave H, Lybak S, Aarstad HH, Karlsdottir A et al. The impact of HPV infection, smoking history, age and operability of the patient on disease-specific survival in a geographically defined cohort of patients with oropharyngeal squamous cell carcinoma. Acta Otolaryngol 2014; 134:964–973 [View Article][PubMed]
     [Google Scholar]
  17. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363:24–35 [View Article][PubMed]
     [Google Scholar]
  18. Polz-Gruszka D, Morshed K, Stec A, Polz-Dacewicz M. Prevalence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) in oral and oropharyngeal squamous cell carcinoma in south-eastern Poland. Infect Agent Cancer 2015; 10:37 [View Article][PubMed]
     [Google Scholar]
  19. Rautava J, Kuuskoski J, Syrjänen K, Grenman R, Syrjänen S. HPV genotypes and their prognostic significance in head and neck squamous cell carcinomas. J Clin Virol 2012; 53:116–120 [View Article][PubMed]
     [Google Scholar]
  20. Blioumi E, Chatzidimitriou D, Pazartzi C, Katopodi T, Tzimagiorgis G et al. Detection and typing of human papillomaviruses (HPV) in malignant, dysplastic, nondysplastic and normal oral epithelium by nested polymerase chain reaction, immunohistochemistry and transitional electron microscopy in patients of northern Greece. Oral Oncol 2014; 50:840–847 [View Article][PubMed]
     [Google Scholar]
  21. Szostek S, Klimek M, Zawilinska B, Kosz-Vnenchak M. Genotype-specific human papillomavirus detection in cervical smears. Acta Biochim Pol 2008; 55:687–692[PubMed]
     [Google Scholar]
  22. Soto D, Song C, McLaughlin-Drubin ME. Epigenetic alterations in human papillomavirus-associated cancers. Viruses 2017; 9:248 [View Article][PubMed]
     [Google Scholar]
  23. Hong S, Dutta A, Laimins LA. The acetyltransferase Tip60 is a critical regulator of the differentiation-dependent amplification of human papillomaviruses. J Virol 2015; 89:4668–4675 [View Article][PubMed]
     [Google Scholar]
  24. Avvakumov N, Torchia J, Mymryk JS. Interaction of the HPV E7 proteins with the pCAF acetyltransferase. Oncogene 2003; 22:3833–3841 [View Article][PubMed]
     [Google Scholar]
  25. Mclaughlin-Drubin ME, Crum CP, Münger K. Human papillomavirus E7 oncoprotein induces KDM6A and KDM6B histone demethylase expression and causes epigenetic reprogramming. Proc Natl Acad Sci USA 2011; 108:2130–2135 [View Article][PubMed]
     [Google Scholar]
  26. Rayess H, Wang MB, Srivatsan ES. Cellular senescence and tumor suppressor gene p16. Int J Cancer 2012; 130:1715–1725 [View Article][PubMed]
     [Google Scholar]
  27. Li J, Poi MJ, Tsai MD. Regulatory mechanisms of tumor suppressor P16(INK4A) and their relevance to cancer. Biochemistry 2011; 50:5566–5582 [View Article][PubMed]
     [Google Scholar]
  28. Kumar B, Cordell KG, Lee JS, Worden FP, Prince ME 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 2008; 26:3128–3137 [View Article][PubMed]
     [Google Scholar]
  29. Wittekindt C, Gültekin E, Weissenborn SJ, Dienes HP, Pfister HJ et al. Expression of p16 protein is associated with human papillomavirus status in tonsillar carcinomas and has implications on survival. Adv Otorhinolaryngol 2005; 62:72–80 [View Article][PubMed]
     [Google Scholar]
  30. Fonseca-Silva T, Farias LC, Cardoso CM, Souza LR, Carvalho Fraga CA et al. Analysis of p16(CDKN2A) methylation and HPV-16 infection in oral mucosal dysplasia. Pathobiology 2012; 79:94–100 [View Article][PubMed]
     [Google Scholar]
  31. Sinha P, Bahadur S, Thakar A, Matta A, Macha M et al. Significance of promoter hypermethylation of p16 gene for margin assessment in carcinoma tongue. Head Neck 2009; 31:1423–1430 [View Article][PubMed]
     [Google Scholar]
  32. Coordes A, Lenz K, Qian X, Lenarz M, Kaufmann AM et al. Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status. Eur Arch Otorhinolaryngol 2016; 273:2157–2169 [View Article][PubMed]
     [Google Scholar]
  33. Rischin D, Young RJ, Fisher R, Fox SB, Le QT et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol 2010; 28:4142–4148 [View Article][PubMed]
     [Google Scholar]
  34. Posner MR, Lorch JH, Goloubeva O, Tan M, Schumaker LM et al. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann Oncol 2011; 22:1071–1077 [View Article]
     [Google Scholar]
  35. Biron VL, Mohamed A, Hendzel MJ, Alan Underhill D, Seikaly H. Epigenetic differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinomas. J Otolaryngol Head Neck Surg 2012; 41 Suppl 1:65–70 [View Article][PubMed]
     [Google Scholar]
  36. Toupance S, Brassart B, Rabenoelina F, Ghoneim C, Vallar L et al. Elastin-derived peptides increase invasive capacities of lung cancer cells by post-transcriptional regulation of MMP-2 and uPA. Clin Exp Metastasis 2012; 29:511–522 [View Article][PubMed]
     [Google Scholar]
  37. Qi JH, Ebrahem Q, Moore N, Murphy G, Claesson-Welsh L et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med 2003; 9:407–415 [View Article][PubMed]
     [Google Scholar]
  38. Weiss D, Basel T, Sachse F, Braeuninger A, Rudack C. Promoter methylation of cyclin A1 is associated with human papillomavirus 16 induced head and neck squamous cell carcinoma independently of p53 mutation. Mol Carcinog 2011; 50:680–688 [View Article][PubMed]
     [Google Scholar]
  39. Han XG, Li Y, Mo HM, Li K, Lin D et al. TIMP3 regulates osteosarcoma cell migration, invasion, and chemotherapeutic resistances. Tumour Biol 2016; 37:8857–8867 [View Article][PubMed]
     [Google Scholar]
  40. Birkedal-Hansen B, Pavelic ZP, Gluckman JL, Stambrook P, Li YQ et al. MMP and TIMP gene expression in head and neck squamous cell carcinomas and adjacent tissues. Oral Dis 2000; 6:376–382[PubMed]
     [Google Scholar]
  41. Su CW, Su BF, Chiang WL, Yang SF, Chen MK et al. Plasma levels of the tissue inhibitor matrix metalloproteinase-3 as a potential biomarker in oral cancer progression. Int J Med Sci 2017; 14:37–44 [View Article][PubMed]
     [Google Scholar]
  42. Adissu HA, Mckerlie C, di Grappa M, Waterhouse P, Xu Q et al. Timp3 loss accelerates tumour invasion and increases prostate inflammation in a mouse model of prostate cancer. Prostate 2015; 75:1831–1843 [View Article][PubMed]
     [Google Scholar]
  43. Shen B, Jiang Y, Chen YR, Zheng HC, Zeng W et al. Expression and inhibitory role of TIMP-3 in hepatocellular carcinoma. Oncol Rep 2016; 36:494–502 [View Article][PubMed]
     [Google Scholar]
  44. Wu DW, Tsai LH, Chen PM, Lee MC, Wang L et al. Loss of TIMP-3 promotes tumor invasion via elevated IL-6 production and predicts poor survival and relapse in HPV-infected non-small cell lung cancer. Am J Pathol 2012; 181:1796–2602 [View Article][PubMed]
     [Google Scholar]
  45. Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA 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 2008; 100:261–269 [View Article][PubMed]
     [Google Scholar]
  46. De Schutter H, Geeraerts H, Verbeken E, Nuyts S. Promoter methylation of TIMP3 and CDH1 predicts better outcome in head and neck squamous cell carcinoma treated by radiotherapy only. Oncol Rep 2009; 21:507–513[PubMed]
     [Google Scholar]
  47. Lim Y, Wan Y, Vagenas D, Ovchinnikov DA, Perry CF et al. Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers. BMC Cancer 2016; 16:749 [View Article][PubMed]
     [Google Scholar]
  48. St Guily JL, Jacquard AC, Prétet JL, Haesebaert J, Beby-Defaux A et al. Human papillomavirus genotype distribution in oropharynx and oral cavity cancer in France–The EDiTH VI study. J Clin Virol 2011; 51:100–104 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000898
Loading
Impact of HPV infection on gene expression and methylation in oral cancer patients
J. Med. Microbiol. 68, 440 (2019); https://doi.org/10.1099/jmm.0.000898
/content/journal/jmm/10.1099/jmm.0.000898
/content/journal/jmm/10.1099/jmm.0.000898
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error