Conventional (Keratinizing) Squamous Cell Carcinoma of the Oropharynx – Extensive p16 Expression Is Associated with Improved Survival
Chunyu Cai, James Lewis, Jr., Meredith Pittman, Samir El-Mofty, Wade Thorstad, Rebecca Chernock. Washington University School of Medicine, St. Louis, MO
Background: Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal squamous cell carcinomas (SCCs). HPV positive SCC are strongly associated with the nonkeratinizing (NK) phenotype in the oropharynx, which are associated with better survival compared to keratinizing squamous cell carcinomas (K SCCs), despite early nodal metastatic spread. Transcriptionally-active HPV has also been detected in a minority of K SCCs, but it has never been determined if this morphology or the HPV status determines patient outcomes. This study compares clinical outcomes among patients with HPV-positive and negative KSCC.
Design: Materials from patients with oropharyngeal K SCC who were enrolled in an IRB approved radiotherapy database from 1997 to 2011 were retreived from pathology files. All patients received either definitive or postoperative intensity-modulated radiation therapy (IMRT). Cases with any nonkeratinizing features, characterized by nests of oval to spindled cells with hyperchromatic nuclei, scant cytoplasm and indistinct cell borders, were excluded, as were other specific histologic SCC variants. DNA in-situ hybridization (ISH) for high-risk HPV and immunohistochemistry for p16, a surrogate marker for HPV-related carcinomas, were performed. p16 was deemed positive if >75% of cells had nuclear and cytoplasmic staining.
Results: There were 54 cases, 7 (13%) of which were extensively p16 positive. DNA ISH was positive in only 3/6 (50%) of these p16+ patients. Four of the 7 (57%) were treated with definitive IMRT, and 3 with surgery + IMRT. None of these 7 patients developed recurrent disease at 18 to 143 months of follow up. Conversely, 19 of the remaining 47 patients (40%) with negative or partial p16 staining developed recurrent disease. The difference was statistically significant (p = 0.04). Kaplan-Meier survival analysis showed significantly better overall survival in the p16 positive group (mean survival 124 months) compare to p16 negative/partial group (mean survival 40 months) (p=0.024).
Conclusions: Diffuse p16 expression in more than 75% of cells identified a small group of patients (13%) with significantly better prognosis. As such, it appears that HPV status is an important prognostic marker to take into account, even in patients with keratinizing squamous cell carcinoma.
Category: Head & Neck
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 188, Monday Morning