Does p16 Positive Squamous Cell Carcinomas of the Larynx Correlate with HPV? An Analysis of 101 Cases Using E6/E7 mRNA HPV H7 RNA Scope, HPV-16 and High Risk HPV Chromogenic In Situ Hybridization
Sean M Kirby, Theodoros Teknos, Amit Agrawal, Matthew Old, Enver Ozer, Hans Iwenofu. OSUMC, Columbus
Background: The significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (SqCC) is well established. However, HPV oncogenesis in the larynx is less clear. p16 expression is strongly associated with HPV in oropharyngeal SqCC and its utility as a surrogate marker has been validated. Implications of laryngeal SqCC p16 expression are less well described. Recently, a specific HPV test has been developed; chromogenic in situ hybridization (ISH) to detect mRNA of the E6/E7 oncogenes, which are directly involved in dysregulating the cell cycle in HPV oncogenesis. Herein, we examined laryngeal SqCC using p16 immunohistochemistry (IHC), chromogenic ISH for HPV-16, high risk (HR) HPV DNA and E6/E7 mRNA HPV H7 RNA scope.
Design: A computerized search yielded 101 SqCC of the larynx at OSUMC, which were classified as supraglottic, glottic, or subglottic. Tumor sections were used to construct tissue microarrays (TMA). The TMAs were stained for p16 using routine IHC methods and evaluated for intensity (0-3+) and percent of tumor cells stained. Staining of <5% was considered negative. The TMAs were also stained using ISH for HPV-16 and HR-HPV DNA as well as E6/ E7 mRNA H7 (16,18,31,33,35,52,58), which were interpreted as positive or negative.
Results: p16 expression was present in 20/101 (18%) laryngeal SqCC. Supraglottic SqCC showed rate of 30% (14/46) including 8 with strong and diffuse staining (3+, >75%). Glottic SqCCs had a positive rate of 8% (4/52) with weaker staining. 1/9 (11%) subglottic SqCC was positive with only focal staining. The difference in p16 expression for supraglottic, glottic and subglottic groups were statistically significant (p<0.05). All tumors were negative for HPV-16 and HR-HPV ISH. HPV E6/E7 mRNA H7 was detected in 5% (1/20) of p16 positive tumors. This tumor was supraglottic with strong and diffuse p16 expression.
Conclusions: Our study indicates a low overall frequency rate of 18% p16 positivity in SqCC of the larynx with predilection for supraglottic sites. Only 5% of p16 positive cases harbour HPV using a highly sensitive assay. Our data seems to suggest that p16 expression does not correlate with HPV infection in the larynx and might be unrelated to HPV oncogenesis.
Category: Head & Neck
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 171, Wednesday Morning