Skip to main content
SpringerLink
Log in

The Morphologic Profile of HPV-Related Head and Neck Squamous Carcinoma: Implications for Diagnosis, Prognosis, and Clinical Management

  • Invited Review
  • Published:
Head and Neck Pathology Aims and scope Submit manuscript

Abstract

Much recent attention has highlighted a subset of head and neck squamous cell carcinomas (HNSCCs) related to the human papillomavirus (HPV) that is characterized by an epidemiologic, demographic, and clinical profile that deviates from the profile of conventional non-HPV-related HNSCC. Lost in the dash to develop and implement diagnostic assays to detect the presence of HPV in HNSCCs is the unpretentious observation that these HPV-HNSCCs are also distinctive with respect to their microscopic appearance, and that an awareness of these characteristic morphologic features can facilitate the diagnosis of HPV-related HNSCC (HPV-HNSCC). This review will delineate the microscopic appearance of HPV-HNSCC, spotlight ways in which the misinterpretation of these microscopic features can lead to diagnostic confusion, and provide recommendations for appropriate terminology when diagnosing HPV-HNSCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Gillison ML, Koch WM, Spafford M, et al. Causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709–20.

    Article  PubMed  CAS  Google Scholar 

  2. 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, D.C. Head Neck. 2009;31:1393–422.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. 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. Natl Cancer Inst. 2008;100:261–9.

    Article  CAS  Google Scholar 

  5. Begum S, Cao D, Gillison ML, et al. Tissue distribution of HPV 16 DNA integration in patients with tonsillar carcinoma as visualized by HPV 16 in situ hybridization and p16 immunohistochemistry. Clin Caner Res. 2005;11:5694–9.

    Article  CAS  Google Scholar 

  6. Singhi AD, Stelow EB, Mills SE, Westra WH. Lymphoepithelial-like carcinoma of the oropharynx: a morphologic variant of HPV-related head and neck carcinoma. Am J Surg Pathol. 2010;34:800–5.

    Article  PubMed  Google Scholar 

  7. El-Mofty SK, Lu DW. Prevalence of high-risk human papillomavirus DNA in nonkeratinizing (cylindrical cell) carcinoma of the sinonasal tract: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol. 2005;29:1367–72.

    Article  PubMed  Google Scholar 

  8. Pai SI, Westra WH. Molecular pathology of head and neck cancer: implications for diagnosis, prognosis and treatment of patients with head and neck squamous cell carcinoma. Annual Rev Pathol. 2009;4:49–70.

    Article  CAS  Google Scholar 

  9. Chernock RD, El-Mofty SK, Thorstad WL, et al. HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: utility of microscopic features in predicting patient outcome. Head Neck Pathol. 2009;3:186–94.

    Article  PubMed  Google Scholar 

  10. Scantlebury JB, Zhang Q, Thorstad WL, et al. Anaplastic nuclei and tumor cell multinucleation are strong predictors of poorer survival in nonkeratinizing oropharyngeal squamous cell carcinoma. Mod Pathol. 2011;282–3A.

  11. 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;32:1044–50.

    Article  PubMed  Google Scholar 

  12. Bishop JA, Westra WH. Human papillomas virus-related small cell carcinoma of the oropharynx. Am J Surg Pathol. 2011;35:1679–84.

    Article  PubMed  Google Scholar 

  13. Westra WH. The changing face of head and neck cancer in the 21st century: the impact of HPV on the epidemiology and pathology of oral cancer. Head Neck Pathol. 2009;3:78–81.

    Article  PubMed  Google Scholar 

  14. Wenig BM, Barnes L, Carlson DL et al. Protocol for the examination of specimens from patients with carcinomas of the pharynx. Based on AJCC/UICCTNM. 7th ed. College of American Pathologists. Available from URL: http://www.cap.org.

  15. Begum S, Gillison ML, Ansari-Lari MA, Shah K, Westra WH. Detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin. Clin Cancer Res. 2003;15:6469–75.

    Google Scholar 

  16. Goldenberg D, Khan Z, Westra WH, et al. Cystic lymph node metastasis in patients with head and neck cancer: an HPV-related phenomenon. Head Neck. 2008;39:898–903.

    Article  Google Scholar 

  17. Bishop JA, Illei PB, Gabrielson E, Westra WH. HPV analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma. Am J Surg Pathol. 2012;36:142–8.

    Article  PubMed  Google Scholar 

  18. Weichert W, Schewe C, Denkert C, et al. Molecular HPV typing as a diagnostic tool to discriminate primary from metastatic squamous cell carcinoma of the lung. Am J Surg Pathol. 2009;33:513–20.

    Article  PubMed  Google Scholar 

  19. El Naggar A, Westra WH. Immunohistochemical detection P16 expression as a surrogate marker for HPV related oropharyngeal carcinoma: a guide for interpretative relevance and consistency. Head Neck. 2011. doi:10.1002/hed.21974.

Download references

Author information

Authors and Affiliations

  1. Departments of Pathology, Oncology, and Otolaryngology, Head and Neck Surgery, The Johns Hopkins Medical Institutions, 401 N. Broadway, Weinberg 2242, Baltimore, MD, 21231, USA

    William H. Westra

Authors
  1. William H. Westra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William H. Westra.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Westra, W.H. The Morphologic Profile of HPV-Related Head and Neck Squamous Carcinoma: Implications for Diagnosis, Prognosis, and Clinical Management. Head and Neck Pathol 6 (Suppl 1), 48–54 (2012). https://doi.org/10.1007/s12105-012-0371-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-012-0371-6

Keywords

Search

Navigation