Correlation of p16 expression and HPV type with survival in oropharyngeal squamous cell cancer
ORAL ONCOLOGY
Authors: Liu, Sandy Z.; Zandberg, Dan P.; Schumaker, Lisa M.; Papadimitriou, John C.; Cullen, Kevin J.
Abstract
Objectives: Examine the effect of concordance between p16 overexpression and HR (high risk) HPV DNA status on overall survival in a large series of oropharyngeal squamous cell carcinoma (OPSCC) cases. Materials and methods: A total of 185 patients with primary OPSCC had genomic DNA tested by PCR for the HPV16 E6 and E7 oncogenes. 184 of 185 patients had p16 IHC performed. Linear array HPV genotyping was performed in all 21 HPV16/p16 discordant cases (HPV16+/p16- or HPV1-/p16+) as well as in 43 control cases. Results: 73 of 185 patients were positive for HR HPV (39%). Six of 73 HPV infections were due to HR HPV types other than HPV16: types 31 (1), 33 (2), 51 (1), 58 (1), and 59 (1); all 6 cases were p16 positive. p16 IHC was concordant with HR HPV testing in 169 of 184 cases (92%), and had a sensitivity and specificity of 92% and 92%. HR HPV+/p16+ and discordant HR HPV/p16 patients had significantly improved overall survival compared to HR HPV /p16 patients. Conclusion: p16 IHC is a reliable surrogate marker for HR HPV testing in OPSCC. Prognostically favorable HR HPV genotypes other than HPV16 are reflected in p16 positivity. (C) 2015 Elsevier Ltd. All rights reserved.
Expression of membrane type 1 matrix metalloproteinase in papillomavirus-positive cells: role of the human papillomavirus (HPV) 16 and HPV8 E7 gene products
JOURNAL OF GENERAL VIROLOGY
Authors: Smola-Hess, S; Pahne, J; Mauch, C; Zigrino, P; Smola, H; Pfister, HJ
Abstract
Matrix metalloproteinases (MMPs) degrade extracellular matrix. They are involved in cellular proliferation, migration, angiogenesis, invasion and metastasis. MT-1 MMP, a membrane-bound MMP, is expressed in carcinomas of the uterine cervix in vivo. This type of cancer is associated with human papillomavirus (HPV) infection. Here it was shown that keratinocytes transformed with HPV16 or HPV18 in vitro, and HPV-positive cervical carcinoma cell lines, constitutively expressed MT-1 MMP. Expression of the E7 protein from the mucosal and cutaneous high-risk types HPV16 and HPV8, but not from the cutaneous low-risk type HPV1, was sufficient to induce MT-1 MMP expression in primary human keratinocytes and HaCaT cells. As a consequence, MMP-2 was activated. MT-1 MMP expression might play a role in the HPV life cycle by promoting proliferation of host cells and might contribute to their invasive phenotype during malignant progression.