Human Papillomavirus Is Uniformly Retained in the Distant Metastases of Primary Oropharyngeal Squamous Cell Carcinomas
Mitra Mehrad, Ge Gao, Hongwei Zhao, Xiaowei Wang, James S Lewis, Jr.. Washington University in St Louis, School of Medicine, St. Louis, MO
Background: High-risk human papillomavirus (HPV) is both causative and prognostic in the majority of oropharyngeal squamous cell carcinomas (OpSCCs). Distant metastases in such tumors are relatively uncommon (<10% of patients). No studies have thoroughly evaluated distant metastases to see if the HPV is consistently retained. The aim of this study was to evaluate for transcriptionally-active HPV in matched primary OpSCCs and their distant metastases.
Design: Surgical pathology files were searched and 20 matched pairs of primary OpSCCs and their metastases, for which tissue specimens were available, were retrieved. Two study pathologists reviewed all cases to confirm the diagnoses and to evaluate histologic features. Real-time PCR (RT-PCR) for detection of E6/E7 mRNA for all high-risk HPV types and p16 immunohistochemistry (IHC) were performed.
Results: Cases were from 1996 to 2012. Distant metastases were found in lung (65%), bone (20%), non-regional lymph nodes (10%) and pericardium (5%). Histologically, 15 primary tumors were nonkeratinizing (NK), 3 NK with maturation, one basaloid, and one keratinizing (K) SCC. Seventeen (85%) of the metastases had the same histologic type as the primary tumor (p=1.0). p16 was extensively positive in 19 of the primary tumors, and p16 results were identical for all matched pairs. The single pair that was negative for p16 was a K SCC. All 20 matched pairs were concordant for HPV status by RT-PCR with 19 of 20 positive for high risk HPV. Three different types of HPV were identified: HPV-16 in 17 pairs and HPV-18 and HPV-35 in a single pair each. All 19 HPV positive tumors were p16 positive. HPV transcriptional activity was assessed relative to control genes and there was no significant difference between primary tumors (mean 5.8 units) and their distant metastases (mean 5.7 units).
Conclusions: The distant metastases from HPV-related primary OpSCCs uniformly retain HPV and p16 status, and HPV transcriptional activity. They also retain similar morphology. This argues that p16 IHC can be utilized to differentiate metastatic OpSCCs from separate, new, primary SCCs in other organs. These findings also have major treatment implications for any future agents that would specifically target HPV proteins or associated molecules in such patients.
Category: Head & Neck
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 192, Monday Morning