[1335] B7-H1 Expression Model for Immune Evasion in Human Papillomavirus Associated Squamous Cell Carcinomas

Odey C Ukpo, Wade L Thorstad, James S Lewis. Washington University, Saint Louis, MO

Background: Human papillomavirus (HPV) has been associated with oropharyngeal squamous cell carcinomas (OSCC). Persistent viral infection is postulated as the mechanism leading to carcinogenesis. It is known that immune evasive cells can provide an ideal niche for a virus. The B7-H1/PD-1 cosignaling pathway plays an important role in viral immune evasion by making CD8+ cytotoxic T-cells anergic. Tumor cell B7-H1 expression has also been associated with poorer survival in numerous carcinomas, but its role in HPV-related OSCCs is unknown. We hypothesized that HPV-related OSCCs express B7-H1 as a potential mechanism for HPV immune evasion.
Design: A tissue microarray of OSCC was utilized, for which HPV E6/E7 mRNA by in situ hybridization was previously performed. Immunohistochemistry was performed to detect B7-H1 on tumor cells, which was scored as positive or negative. Either membranous or cytoplasmic staining was considered positive. Screening was performed by two pathologists (OCU, JSL), both blinded to clinical information.
Results: B7-H1 was expressed in 82 of the 181 (45.8%) cases. Tumors expressing B7-H1 were more likely to be HPV positive.

B7-H1 and HPV E6/E7 mRNA Expression
 B7-H1 PositiveB7-H1 Negative
HPV mRNA Positive6870
HPV mRNA Negative1427
Total8297
p-value= 0.08

B7-H1 showed a significant trend toward correlation with distant metastasis in the entire cohort (OR= 2.85, p=0.12), a strong trend in HPV negative cases (OR=7.01, p=0.10), but no trend in the HPV positive cases (OR= 1.56, p=0.63). B7-H1 expression was not associated with recurrence in the entire cohort (OR= 1.09, p=0.80), HPV positive (OR= 0.80, p=0.69) or HPV negative (OR=2.02, p=0.22) cases. B7-H1 was not associated with overall survival for the entire cohort (RR= 0.91, p=0.73), and HPV positive cases (OR=0.84, p=0.64), but showed a trend toward poorer survival in HPV negative cases (OR= 1.65, p=0.38).
Conclusions: B7-H1 is expressed in a significant subset of tumors with HPV mRNA viral transcript expression. This suggests that B7-H1 positive tumor cells may play a role in harboring persistent HPV infection. However, it does not appear to be associated with tumor recurrence or poorer survival, perhaps due to risk modification by the presence of HPV. Distal metastasis may be associated with B7-H1 expression, but a larger sample size is required.
Category: Head & Neck

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 199, Monday Morning

 

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