title: Human papillomavirus-related small cell carcinoma of the oropharynx.
abstract: 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.
authors: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors: Justin A
authors: JA
authors: Bishop
authors: William H
authors: WH
authors: Westra
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015142:Baltimore; D014408:Biomarkers, Tumor / Q000032:analysis; D018288:Carcinoma, Small Cell / Q000737:chemistry / Q000401:mortality / Q000556:secondary / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053555:Keratin-5 / Q000032:analysis; D053553:Keratin-6 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology*; D010641:Phenotype; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis; D016708:Synaptophysin / Q000032:analysis; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; C503940:KRT5 protein, human; D053555:Keratin-5; D053553:Keratin-6; D012367:RNA, Viral; D016708:Synaptophysin