Abstract

Purpose/Objective(s): Human papilloma virus (HPV) is considered to play a major role in the pathogenesis of oropharyngeal squamous cell carcinoma (OPSCC). The vast majority of patients with HPV-related OPSCC exhibit p16 overexpression; in fact, some investigators have suggested that the p16 immunohistochemistry (IHC) is a better predictor of disease specific and overall survival than the presence of HPV DNA since p16+/HPVcases demonstrate clinical behavior that resembles p16+/ HPV+ cases. Among the several laboratory testing platforms available to determine the presence of HPV in formalin-fixed paraffin-embedded (FFPE) tissue, most clinical laboratories employ HPV in situ hybridization (ISH), p16 IHC, or a combination thereof. Although elucidating viral transcriptional activity by detecting HPV E6/E7 mRNA provides greater insight into molecular events than identifying HPV DNA alone, its clinical utility has not been adequately evaluated using surgical material. Materials/Methods: Retrospective clinical and histopathologic review of 75 cases of OPSCC that underwent surgical resection at Mayo Clinic Rochester in 2009 was performed. Clinicopathologic data including patient age and sex, tumor site and size, treatment (surgery, radiation therapy and/ or chemotherapy), and clinical outcome parameters were abstracted from the medical records. Surgical pathology archival material was re-examined histopathologically using HE sixty-three cases (84%) were positive for HPV E6/E7 mRNA; and fifty-one cases (68%) were positive for HPV DNA. Concordance between HPV RNA and p16, HPV DNA and p16, and HPV RNA and DNAwas 92% (kappaZ 0.74), 89% (kappaZ 0.73), and 81% (kappa Z 0.51), respectively. The sensitivity of HPV E6/E7 mRNA ISH to detect p16-positive cases was 98% (58/59), whereas that of HPV DNA ISH was 86% (51/59). Conclusions: Consideration should be given to detecting HPV E6/E7 mRNA using ISH and p16 overexpression using IHC in the setting of OPSCC to determine appropriate surveillance and treatment algorithms. Importantly, utilization of HPV E6/E7 mRNA ISH provides insight into transcriptional activity and reduces discordance between HPV ISH and p16 IHC results. Author Disclosure: J.J. Garcia: None. M.G. Keeney: None. M.E. Law: None. D.S. Wismayer: None. M. Rivera: None. J.L. Kasperbauer: None. E.J. Moore: None. X. Ma: A. Employee; Advanced Cell Diagnostics. D.J. Ma: None. K.A. Price: None.

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