[1240] ProEx C Is Comparable to p16 and HPV ISH for the Detection of High-Risk HPV in Head and Neck Squamous Cell Carcinomas

AM Mills, AH Beck, CS Kong. Stanford University School of Medicine, Stanford, CA

Background: ProEx C is a surrogate marker for HPV that targets cell cycle proteins, MCM2 and TOP2A, and has been shown to perform similarly to p16 as an aid in the diagnosis of cervical dysplasia. However, ProEx C expression has not been well-characterized in head and neck squamous cell carcinomas (HNSCC). The purpose of this study is to determine if ProEx C performs similarly to p16 in HNSCC and to evaluate the Ventana HPV16 in situ hybridization (ISH) in comparison with HPV PCR.
Design: The study set consisted of 84 cases of HNSCC with HPV PCR results and survival data. Two cores from each case were included in a tissue microarray (TMA) which was stained with ProEx C (BD, Franklin Lakes, NJ), p16 (mtm, Westborough, MA), and HPV16 ISH (Ventana, Tucson, AZ). ProEx C was also performed on whole sections of each case. ProExC nuclear staining was scored as negative, 1+ weak (<1/3), 2+ moderate (1/3-2/3) or 3+ strong (>66%). p16 staining was scored as negative, 2+ focal strong (5-80%) or 3+ diffuse strong (>80%). HPV ISH was scored as positive (punctate or diffuse nuclear reactivity) or negative.
Results:

ProEx C (3+) WholeProEx C (2-3+) WholeProEx C (3+) TMAProEx C (2-3+) TMAp16 (3+) TMAp16 (2-3+) TMAHPV ISH TMA
Sensitivity85.7% (30/35)94.4% (34/36)52.8% (19/36)77.8% (28/36)66.7% (24/36)83.3% (30/36)61.1% (22/36)
Specificity72.3% (35/48)18.8% (9/48)77.1% (37/48)20.8% (10/48)95.8% (46/48)83.3% (40/48)93.8% (45/48)


Cases that were positive for ProEx C, p16, and/or HPV ISH showed a positive correlation with improved overall survival and increased time to nodal and distant metastasis using Kaplan Meier and Mantel-Cox log rank tests.
Conclusions: ProEx C has high sensitivity and specificity for the presence of HPV when greater than 2/3 of the tumor exhibits nuclear staining. If a lower cut-off of 1/3 is used, sensitivity is improved but with a marked decrease in specificity. Overall, ProEx C is comparable in sensitivity to p16 and HPV ISH but is less specific. In addition, ProEx C performs better on whole tissue sections than on TMA cores, suggesting that staining results on small biopsy specimens may be less reliable than on resection specimens. As with p16, ProEx C and HPV ISH have prognostic value with positive correlation with increased time to failure and improved patient survival.
Category: Head & Neck

Tuesday, March 23, 2010 8:15 AM

Platform Session: Section G, Tuesday Morning

 

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