Prevalence of Human Papillomavirus in Squamous Cell Carcinoma of the Oral Cavity with Correlation of p16 Immunohistochemistry and Human Papillomavirus Polymerase Chain Reaction
Lisa D Duncan, Marcus Winkler, Solomon Lee. University of Tennessee Graduate School of Medicine, Knoxville, TN
Background: Human Papillomavirus (HPV) has been identified in cases of head and neck squamous cell carcinoma, suggesting an etiologic role. HPV type 16 is the most common serotype, and oropharyngeal tumors are more frequently HPV positive. The oncogenic properties of HPV 16 are the result of HPV host cell genome integration, resulting in increased production of E6 and E7 oncoproteins, inactivation of retinoblastoma protein and p16 over expression. In our study, we examine the clinical utility of p16 immunohistochemistry (IHC) in detecting HPV in oral cavity squamous cell carcinoma (OCSCC). Through comparison with results of HPV polymerase chain reaction (PCR), the use of p16 IHC as a surrogate marker for HPV is investigated.
Design: 83 cases of OCSCC from the tongue, floor of mouth, buccal mucosa, hard palate, and gingiva were included in the study. Oropharyngeal tumors were excluded. Non-decalcified paraffin embedded tumor from each case was subjected to p16 IHC and HPV PCR. Results of IHC and HPV PCR were compared. The intensity of p16 staining was graded 0 to 3+, and the location of staining in tumor sections and individual tumor cells was recorded. The histologic appearance of HPV positive tumors was documented to elucidate potential patterns associated with HPV positivity.
Results: 8 of 83 cases (9.6%) were PCR positive, all HPV serotype 16. All of these cases had 3+ nuclear and cytoplasmic p16 staining. 42 tumors (50.6%) were completely p16 negative. 25 cases (30.1%) had 1+ p16 staining, including 8 cases with faint staining in benign epithelium adjacent to tumor. 8 cases (9.6%) had 2+ p16 staining. All of the HPV PCR positive cases had histologic evidence of keratinization.
Conclusions: In our study, strong cytoplasmic and nuclear staining for p16 (3+) correlates with HPV PCR positivity. This pattern of p16 staining can be used as a surrogate marker for high risk HPV in lieu of HPV PCR. The presence of 1 to 2+ p16 staining in tumor and adjacent benign and dysplastic tissue is due to HPV independent mechanisms of p16 over expression since all of these cases were HPV PCR negative. HPV PCR positive study cases displayed varying amounts of keratinization typical of oral cavity location and not the basaloid growth pattern described in HPV positive tumors in prior studies, most of which were in an oropharyngeal location. This observation confirms that a basaloid tumor growth pattern does not exclusively correlate with HPV positivity.
Category: Head & Neck
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 165, Wednesday Morning