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HPV infection and p16 expression in carcinomas of the minor salivary glands

  • Head and Neck
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The correlation between p16 upregulation and high-risk HPV infection is well known in head and neck squamous cell cancer. However, no information is available on rare carcinomas of the minor salivary glands. We analyzed 38 samples of minor salivary gland malignancies. p16 expression was determined by immunohistochemistry, HPV DNA by using in situ hybridization to detect low (type 6 and 11) and high (type 16 and 18) risk HPV types. In 71% of samples p16 expression was found. Low-risk HPV DNA could not be detected in any of the samples, whereas high-risk HPV DNA was found in two samples of mucoepidermoid carcinoma, which also showed the highest immunoreactivity with p16. HPV infection does not seem to be a common event in minor salivary gland carcinoma. Upregulation of p16 is present in the majority of cases but only diffuse staining correlates with HPV 16 and 18 infections.

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  1. Conway MJ, Meyers C (2009) Replication and assembly of human papilloma viruses. J Dent Res 88:307–317

    Article  PubMed  CAS  Google Scholar 

  2. Pyeon D, Pearce SM, Lank SM, Ahlquist P, Lambert PF (2009) Establishment of human papillomavirus infection requires cell cycle progression. PLoS Pathog 5:e1000318

    Article  PubMed  Google Scholar 

  3. Rolfe M, Beer-Romero P, Glass S et al (1995) Reconstitution of p53-ubiquitinylation reactions from purified components: the role of human ubiquitin-conjugating enzyme UBC4 and E6-associated protein (E6AP). Proc Natl Acad Sci USA 92:3264–3268

    Article  PubMed  CAS  Google Scholar 

  4. Klingelhutz AJ, Foster SA, McDougall JK (1996) Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 380:79–82

    Article  PubMed  CAS  Google Scholar 

  5. Kiyono T, Foster SA, Koop JI, McDougall JK, Galloway DA, Klingelhutz AJ (1998) Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature 396:84–88

    Article  PubMed  CAS  Google Scholar 

  6. Merkley MA, Hildebrandt E, Podolsky RH et al (2009) Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes. Proteome Sci 7:29

    Article  PubMed  Google Scholar 

  7. Smeets SJ, Hesselink AT, Speel EJ et al (2007) A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 121:2465–2472

    Article  PubMed  CAS  Google Scholar 

  8. O’Regan EM, Toner ME, Finn SP et al (2008) p16(INK4A) genetic and epigenetic profiles differ in relation to age and site in head and neck squamous cell carcinomas. Hum Pathol 39:452–458

    Article  PubMed  Google Scholar 

  9. Hoffmann M, Ihloff AS, Görögh T et al (2010) p16(INK4a) overexpression predicts translational active human papillomavirus infection in tonsillar cancer. Int J Cancer 127:1595–1602

    Article  PubMed  CAS  Google Scholar 

  10. Ang KK, Harris J, Wheeler R et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35

    Article  PubMed  CAS  Google Scholar 

  11. Allen CT, Lewis JS, El-Mofty SK, Haughey BH, Nussenbaum B (2010) Human papillomavirus and oropharynx cancer: biology, detection and clinical implications. Laryngoscope 120:1756–1772

    Article  PubMed  Google Scholar 

  12. Speight P, Barrett A (2002) Salivary gland tumours. Oral Dis 8:229–240

    Article  PubMed  CAS  Google Scholar 

  13. Barnes L, Eveson JW, Reichart P, Sidransky D (2005) Pathology and genetics of head and neck tumours. In: World Health Organization classification of tumors, IARC Press, Lyon

  14. Vageli D, Sourvinos G, Ioannou M, Koukoulis GK, Spandidos DA (2007) High-risk human papillomavirus (HPV) in parotid lesions. Int J Biol Markers 22:239–244

    PubMed  CAS  Google Scholar 

  15. Atula T, Grénman R, Klemi P, Syrjänen S (1998) Human papillomavirus, Epstein-Barr virus, human herpesvirus 8 and human cytomegalovirus involvement in salivary gland tumours. Oral Oncol 34:391–395

    Article  PubMed  CAS  Google Scholar 

  16. Guo XL, Sun SZ, Wang WX, Wei FC, Yu HB, Ma BL (2007) Alterations of p16INK4a tumour suppressor gene in mucoepidermoid carcinoma of the salivary glands. Int J Oral Maxillofac Surg 36:350–353

    Article  PubMed  Google Scholar 

  17. Vékony H, Röser K, Löning T et al (2008) Deregulated expression of p16INK4a and p53 pathway members in benign and malignant myoepithelial tumours of the salivary glands. Histopathology 53:658–666

    Article  PubMed  Google Scholar 

  18. Birner P, Bachtiary B, Dreier B et al (2001) Signal-amplified colorimetric in situ hybridization for assessment of human papillomavirus infection in cervical lesions. Mod Pathol 14:702–709

    Article  PubMed  CAS  Google Scholar 

  19. Jaehne M, Roeser K, Jaekel T, Schepers JD, Albert N, Löning T (2005) Clinical and immunohistologic typing of salivary duct carcinoma: a report of 50 cases. Cancer 103:2526–2533

    Article  PubMed  Google Scholar 

  20. Etges A, Nunes FD, Ribeiro KC, Araújo VC (2004) Immunohistochemical expression of retinoblastoma pathway proteins in normal salivary glands and in salivary gland tumours. Oral Oncol 40:326–331

    Article  PubMed  CAS  Google Scholar 

  21. Schlecht NF, Brandwein-Gensler M, Nuovo GJ et al. (2011) A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer. Mod Pathol [Epub ahead of print]

  22. O’Neill CJ, McCluggage WG (2006) p16 expression in the female genital tract and its value in diagnosis. Adv Anat Pathol 13:8–15

    Article  PubMed  Google Scholar 

  23. Houghton O, Jamison J, Wilson R, Carson J, McCluggage WG (2010) p16 Immunoreactivity in unusual types of cervical adenocarcinoma does not reflect human papillomavirus infection. Histopathology 57:342–350

    Article  PubMed  Google Scholar 

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Correspondence to Dietmar Thurnher.

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Brunner, M., Koperek, O., Wrba, F. et al. HPV infection and p16 expression in carcinomas of the minor salivary glands. Eur Arch Otorhinolaryngol 269, 2265–2269 (2012).

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