title: Histopathologic findings of HPV and p16 positive HNSCC.
abstract: OBJECTIVE
  Human papilloma virus (HPV) and p16INKa (p16) positivity in head and neck squamous cell carcinomas (HNSCCs) is currently thought to be an encouraging prognostic indicator. However, the histopathologic changes responsible for this behavior are poorly understood. It is our objective to elucidate these histopathologic characteristics to help define the clinical utility of these markers.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  71 HNSCC tumors between July 1, 2008 and August 30, 2009 were examined for HPV, p16, and epidermal growth factor receptor (EGFR). Specified pathologic features were examined: perivascular invasion (PVI), perineural invasion (PNI), grade of squamous differentiation, basaloid classification.
  
  
  RESULTS
  HPV and p16 had no direct impact on perineural or perivascular invasion. However, HPV and p16 were strongly predictive of poorly differentiated tumors, as well as basaloid squamous cell carcinoma (SCCA) (P < .001). Additionally, upon multivariate analysis, HPV(+) and p16(+) tumors had an increased risk of nodal metastasis (HPV: odds ratio [OR] = 23.9 (2.2, 265.1) p = .01; p16: OR = 6.5 (1.4, 31.2) p = .02; PVI: OR = 6.0 (1.6, 22.8) p < .01). The area under the curve (AUC) of receiver operating characteristic (ROC) curves demonstrated improved predictive value for lymph node metastasis above standard H&E histopathologic features (76.7%) for both HPV (83.2%) and p16 (81.3%) individually.
  
  
  CONCLUSIONS
  HPV(+) and p16(+) are highly predictive for poorly differentiated tumors and basaloid SCCA. Additionally, HPV and p16 positivity demonstrate superior predictive value for lymph node metastasis above standard H&E histopathologic features. Although exact recommendations should be tempered by considerations of primary tumor subsite, T-stage, and depth of invasion, head and neck multidisciplinary teams should strongly consider aggressive lymph node treatment for any HPV(+) or p16(+) tumor.
authors.affiliation: Division of Head and Neck Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
authors.forename: Abie H
authors.initials: AH
authors.lastname: Mendelsohn
authors.forename: Chi K
authors.initials: CK
authors.lastname: Lai
authors.forename: I Peter
authors.initials: IP
authors.lastname: Shintaku
authors.forename: David A
authors.initials: DA
authors.lastname: Elashoff
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dubinett
authors.forename: Elliot
authors.initials: E
authors.lastname: Abemayor
authors.forename: Maie A
authors.initials: MA
authors.lastname: St John
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D010039:Otorhinolaryngologic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D030361:Papillomavirus Infections / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D011379:Prognosis; D012307:Risk Factors
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins