Head and Neck Pathology

, Volume 5, Issue 2, pp 108–116

Adenosquamous Carcinoma of the Head and Neck: Relationship to Human Papillomavirus and Review of the Literature

  • Ramya P. Masand
  • Samir K. El-Mofty
  • Xiao-Jun Ma
  • Yuling Luo
  • John J. Flanagan
  • James S. LewisJr.
Original Paper


Adenosquamous carcinoma (ADSC) of the head and neck is an aggressive variant of squamous cell carcinoma (SCC). Certain variants of head and neck SCC are human papillomavirus (HPV)-related and have better prognosis. The relationship of HPV to head and neck ADSC has not been investigated. We searched our files for the term “adenosquamous” and head and neck subsites and found cases from 1998 to 2009. The requisite histologic criteria were the presence of SCC combined with distinct gland formation and/or intracellular mucin. DNA in situ hybridization for high-risk HPV, RNA in situ hybridization for high risk HPV E6 and E7 transcripts, and immunohistochemistry for p16 and p53 were performed. The existing literature on ADSC was also reviewed. Of the 18 cases, eight were from the larynx and hypopharynx, four from the oral cavity, three from the oropharynx, and three from the nasal cavity. Three cases (16%) showed both high risk HPV E6 and E7 and p16 expression, one from the nasal cavity and two from the oropharynx. Both oropharyngeal carcinoma patients were alive and disease free at 34 and 103 months, respectively. ADSCs of the head and neck are a heterogeneous group of tumors. A small minority of cases harbor HPV and most of these, particularly those occurring at sites with known high prevalence of HPV, show active viral transcription with detectable E6 and E7 and overexpression of p16. The HPV-related oropharyngeal cases, though rare, appear to do very well clinically, while the remaining cohort of ADSC patients do quite poorly. Head and neck ADSC appears to be a mixed variant that can be further classified according to its HPV status.


Adenosquamous carcinoma Human papillomavirus Head and neck p16 p53 


  1. 1.
    Cardesa A, Zidar N, Alos L. Adenosquamous carcinoma. In: Barnes L, Eveson J, Reichart P, Sidransky D, editors. Pathology and genetics head and neck tumours. Lyon: IARC Press; 2005. p. 130–1.Google Scholar
  2. 2.
    Slootweg PJ, Richardson M. Squamous cell carcinoma of the upper aerodigestive system. In: Gnepp DR, editor. Diagnostic surgical pathology of the head and neck. Philadelphia: Saunders Elsevier; 2009. p. 88–91.Google Scholar
  3. 3.
    Damiani JM, Damiani KK, Hauck K, et al. Mucoepidermoid-adenosquamous carcinoma of the larynx and hypopharynx: a report of 21 cases and a review of the literature. Otolaryngol Head Neck Surg. 1981;89(2):235–43.PubMedGoogle Scholar
  4. 4.
    Gerughty RM, Hennigar GR, Brown FM. Adenosquamous carcinoma of the nasal, oral and laryngeal cavities. A clinicopathologic survey of ten cases. Cancer. 1968;22(6):1140–55.PubMedCrossRefGoogle Scholar
  5. 5.
    Chernock RD, El-Mofty SK, Parvin CA, Lewis JS Jr, Chernock RD. HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: utility of microscopic features in predicting patient outcome. Head and Neck Pathol. 2009;3(3):186–94.CrossRefGoogle Scholar
  6. 6.
    El-Mofty SK, Patil S. Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):339–45.PubMedCrossRefGoogle Scholar
  7. 7.
    Chernock RD, Lewis JS Jr, Zhang Q, et al. Human papillomavirus-positive basaloid squamous cell carcinomas of the upper aerodigestive tract: a distinct clinicopathologic and molecular subtype of basaloid squamous cell carcinoma. Hum Pathol. 2010;41(7):1016–23.PubMedCrossRefGoogle Scholar
  8. 8.
    Begum S, Westra WH. Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol. 2008;32(7):1044–50.PubMedCrossRefGoogle Scholar
  9. 9.
    Jo VY, Mills SE, Stoler MH, et al. Papillary squamous cell carcinoma of the head and neck: frequent association with human papillomavirus infection and invasive carcinoma. Am J Surg Pathol. 2009;33(11):1720–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Singhi AD, Stelow EB, Mills SE, et al. Lymphoepithelial-like carcinoma of the oropharynx: a morphologic variant of HPV-related head and neck carcinoma. Am J Surg Pathol. 2010;34(6):800–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Lewis JS Jr, Thorstad WL, Chernock RD, et al. p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010;34(8):1088–96.PubMedCrossRefGoogle Scholar
  12. 12.
    Adelstein DJ, Ridge JA, Gillison ML, et al. Head and neck squamous cell cancer and the human papillomavirus: summary of a National cancer institute state of the science meeting, November 9–10, 2008, Washington, DC. Head and Neck. 2009;31(11):1393–422.PubMedCrossRefGoogle Scholar
  13. 13.
    Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.PubMedCrossRefGoogle Scholar
  14. 14.
    Syrjanen S. Human papillomavirus (HPV) in head and neck cancer. J Clin Virol. 2005;32(Suppl 1):S59–66.PubMedCrossRefGoogle Scholar
  15. 15.
    Rischin D, Young RJ, Fisher R, 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(27):4142–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Chung CH, Gillison ML. Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res. 2009;15(22):6758–62.PubMedCrossRefGoogle Scholar
  17. 17.
    Shi W, Kato H, Perez-Ordonez B, et al. Comparative prognositc value of HPV16 E6 mRNA compared with in situ hybridization for human oropharyngeal squamous carcinoma. J Clin Oncol. 2009;27(36):6213–21.Google Scholar
  18. 18.
    Westra W. The changing face of head and neck cancer in the twenty-first Century: the impact of HPV on the epidemiology and pathology of oral cancer. Head and Neck Pathol. 2009;3:78–81.CrossRefGoogle Scholar
  19. 19.
    Strati K, Pitot HC, Lambert PF. Identification of biomarkers that distinguish human papillomavirus (HPV)-positive versus HPV-negative head and neck cancers in a mouse model. Proc Natl Acad Sci USA. 2006;103(38):14152–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Hafkamp HC, Manni JJ, Haesevoets A, et al. Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas. Int J Cancer. 2008;122(12):2656–64.PubMedCrossRefGoogle Scholar
  21. 21.
    Kim SH, Koo BS, Kang S, et al. HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c-myc during tumor formation. Int J Cancer. 2007;120(7):1418–25.PubMedCrossRefGoogle Scholar
  22. 22.
    Klussmann JP, Gultekin E, Weissenborn SJ, et al. Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus. Am J Pathol. 2003;162(3):747–53.PubMedCrossRefGoogle Scholar
  23. 23.
    El-Mofty SK, Lu DW. Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the palatine tonsil and not the oral cavity, in young patients: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol. 2003;27(11):1463–70.PubMedCrossRefGoogle Scholar
  24. 24.
    Yoshida T, Sano T, Oyama T, et al. Prevalence, viral load, and physical status of HPV 16 and 18 in cervical adenosquamous carcinoma. Virchows Arch. 2009;455(3):253–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Cruz I, Snijders PJ, Van Houten V, et al. Specific p53 immunostaining patterns are associated with smoking habits in patients with oral squamous cell carcinomas. J Clin Pathol. 2002;55(11):834–40.PubMedCrossRefGoogle Scholar
  26. 26.
    Keelawat S, Liu CZ, Roehm PC, et al. Adenosquamous carcinoma of the upper aerodigestive tract: a clinicopathologic study of 12 cases and review of the literature. Am J Otolaryngol. 2002;23(3):160–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Sheahan P, Toner M, Timon CV. Clinicopathological features of head and neck adenosquamous carcinoma. ORL J Otorhinolaryngol Relat Spec. 2005;67(1):10–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Martinez-Madrigal F, Baden E, Casiraghi O, et al. Oral and pharyngeal adenosquamous carcinoma. A report of four cases with immunohistochemical studies. Eur Arch Otorhinolaryngol. 1991;248(5):255–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Abdelsayed RA, Sangueza OP, Newhouse RF, et al. Adenosquamous carcinoma: a case report with immunohistochemical evaluation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85(2):173–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Alos L, Castillo M, Nadal A, et al. Adenosquamous carcinoma of the head and neck: criteria for diagnosis in a study of 12 cases. Histopathology. 2004;44(6):570–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Ferlito A. A pathologic and clinical study of adenosquamous carcinoma of the larynx. Report of four cases and review of the literature. Acta Otorhinolaryngol Belg. 1976;30(4):379–89.PubMedGoogle Scholar
  32. 32.
    Fujino K, Ito J, Kanaji M, et al. Adenosquamous carcinoma of the larynx. Am J Otolaryngol. 1995;16(2):115–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Izumi K, Nakajima T, Maeda T, et al. Adenosquamous carcinoma of the tongue: report of a case with histochemical, immunohistochemical, and ultrastructural study and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85(2):178–84.PubMedCrossRefGoogle Scholar
  34. 34.
    Aden KK, Niehans G, Adams GL, et al. Adenosquamous carcinoma of the larynx and hypopharynx with five new case presentations. Trans Am Laryngol Assoc. 1988;216–21.Google Scholar
  35. 35.
    Leung KL, Yang KY, Chen CJ. Adenosquamous carcinoma of the buccal mucosa: a case report. Taiwan J Oral Maxillofac Surg. 2009;20:19–28.Google Scholar
  36. 36.
    Minic AJ, Stajcic Z. Adenosquamous carcinoma of the inferior turbinate: a case report. J Oral Maxillofac Surg. 1994;52(7):764–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Napier SS, Gormely JS, Newlands C, et al. Adenosquamous carcinoma. A rare neoplasm with an aggressive course. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995;79(5):607–11.PubMedCrossRefGoogle Scholar
  38. 38.
    Sanderson RJ, Rivron RP, Wallace WA. Adenosquamous carcinoma of the hypopharynx. J Laryngol Otol. 1991;105(8):678–80.PubMedCrossRefGoogle Scholar
  39. 39.
    Scully C, Porter SR, Speight PM, et al. Adenosquamous carcinoma of the mouth: a rare variant of squamous cell carcinoma. Int J Oral Maxillofac Surg. 1999;28(2):125–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Sheahan P, Fitzgibbon J, Lee G, et al. Adenosquamous carcinoma of the tongue in a 22 years old female: report of a case with immunohistochemistry. Eur Arch Otorhinolaryngol. 2003;260(9):509–12.PubMedCrossRefGoogle Scholar
  41. 41.
    Siar CH, Ng KH. Adenosquamous carcinoma of the floor of the mouth and lower alveolus: a radiation-induced lesion? Oral Surg Oral Med Oral Pathol. 1987;63(2):216–20.PubMedCrossRefGoogle Scholar
  42. 42.
    Li X, Di B, Shang Y, et al. Clinicopathologic risk factors for distant metastases from head and neck squamous cell carcinomas. Eur J Surg Oncol. 2009;35(12):1348–53.PubMedGoogle Scholar
  43. 43.
    Al-Othman MO, Morris CG, Hinerman RW, et al. Distant metastases after definitive radiotherapy for squamous cell carcinoma of the head and neck. Head Neck. 2003;25(8):629–33.PubMedCrossRefGoogle Scholar
  44. 44.
    Skarsgard DP, Groome PA, Mackillop WJ, et al. Cancers of the upper aerodigestive tract in Ontario, Canada, and the United States. Cancer. 2000;88(7):1728–38.PubMedCrossRefGoogle Scholar
  45. 45.
    Ogura K, Ishi K, Matsumoto T, et al. Human papillomavirus localization in cervical adenocarcinoma and adenosquamous carcinoma using in situ polymerase chain reaction: review of the literature of human papillomavirus detection in these carcinomas. Pathol Int. 2006;56(6):301–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Tsuhako K, Nakazato I, Hirayasu T, et al. Human papillomavirus DNA in adenosquamous carcinoma of the lung. J Clin Pathol. 1998;51(10):741–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ramya P. Masand
    • 1
  • Samir K. El-Mofty
    • 1
  • Xiao-Jun Ma
    • 2
  • Yuling Luo
    • 2
  • John J. Flanagan
    • 2
  • James S. LewisJr.
    • 1
  1. 1.Department of Pathology and ImmunologyWashington University School of MedicineSt. LouisUSA
  2. 2.Advanced Cell Diagnostics, Inc.HaywardUSA

Personalised recommendations