Human papillomavirus-related small cell carcinoma of the oropharynx

Justin A. Bishop, William H. Westra

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSqCC) represents an important subgroup of head and neck cancer that is characterized by a distinct risk factor profile, a relatively consistent microscopic appearance, and a favorable prognosis. A growing experience with HPV testing of OPSqCCs has uncovered variants that deviate from prototypic HPV-related cancer with respect to morphology but not clinical behavior. In effect, HPV positivity confers a favorable prognosis independent of morphologic subtype. We report 5 cases of HPV-related oropharyngeal carcinomas with well-developed features of small cell carcinoma (SCC) to define the prognostic impact of HPV positivity in a tumor type universally regarded as highly aggressive. Four of the SCCs arose in association with a conventional HPV-related OPSqCC. All 5 SCCs were HPV positive by in situ hybridization. By immunohistochemistry, all 5 cases were p16 positive, synaptophysin positive, and cytokeratin 5/6 negative. Four of the patients were men. The mean age was 61 years (range, 49 to 67 y). The SCCs were associated with metastatic spread to distant sites (60%) and poor survival outcomes: 3 patients (60%) died as a result of their disease (mean survival time, 10 mo; range, 6 to 15 mo). HPV testing has disclosed a previously unrecognized variant of HPV-related oropharyngeal carcinoma that is microscopically characterized by the small cell phenotype. Recognition of this component, even in association with conventional HPV-related OPSqCC, is important as it may indicate an aggressive phenotype that supersedes HPV positivity as a prognostic indicator.

Original languageEnglish (US)
Pages (from-to)1679-1684
Number of pages6
JournalAmerican Journal of Surgical Pathology
Issue number11
StatePublished - Nov 2011


  • HPV
  • HPV-related squamous cell carcinoma
  • high-grade neuroendocrine carcinoma
  • human papillomavirus
  • in situ hybridization
  • p16
  • p63
  • small cell carcinoma

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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