Detection and Significance of Human Papillomavirus, p16 and p21 Overexpression in Squamous Cell Carcinoma of the Larynx.
Rebecca D Chernock, James S Lewis, Qin Zhang, Wade L Thorstad, Samir K El-Mofty. Washington University, St. Louis, MO
Background: Numerous studies have shown a strong etiologic relationship between human papillomavirus (HPV) and the majority of oropharyngeal squamous cell carcinomas (SCCs). HPV-positive SCC of the oropharynx has become increasingly recognized as a distinct variant of head and neck SCC characterized by better patient outcome, nonkeratinizing histology and overexpression of p16. More recently, overexpression of p21, a member of p53 cascade, has also been described as a feature of these tumors. The role of HPV in tumorigenesis of laryngeal SCC and its clinical implications has not been adequately investigated. The aim of this study is first, to identify the presence of HPV and the associated changes in expression of p16 and p21 in laryngeal SCC, and second to determine the effects of these alterations on patient outcome.
Design: Cases of laryngeal SCC from 1997 to 2007 with primary surgical pathology material for review were retrieved from a radiation oncology database. All patients received either upfront surgery with postoperative radiation or definitive radiation based therapy. Immunohistochemistry for p16 and p21 as well as HPV in situ hybridization (ISH) were performed. PCR for HPV was performed on p16 positive tumors.
Results: Of 76 laryngeal SCCs, none showed nonkeratinizing histology. p16 was positive in 21 (27.6%) and p21 was positive in 34 (44.7%) of the tumors. p16 and p21 status strongly correlated with each other (p = 0.0038). Only two tumors were HPV positive by ISH (both p16 and p21 positive cases). Material was available for HPV PCR in 20 of the 21 p16 positive cases. Of these, 13 (65%) were HPV positive by PCR, all of which were high risk genotypes. Patients with p21 positive tumors had better overall survival (69% at 3 years) than those with p21 negative tumors (51.0% at 3 years) [p = 0.045]. There was also a strong trend towards better overall survival in the p16 positive group (p=0.058).
Conclusions: A subset of laryngeal SCCs display a molecular profile typical of HPV-positive SCC of the oropharynx (p16 and p21 overexpression). These tumors lacked the nonkeratinizing histologic features characteristic of HPV-positive oropharyngeal SCC but were frequently HPV-positive by PCR. They also appear to be associated with better overall patient survival.
Category: Head & Neck
Tuesday, March 1, 2011 8:30 AM
Platform Session: Section G, Tuesday Morning