Abstract
HPV-positive oropharyngeal squamous cell carcinomas (OSCC) represent a distinct disease entity from traditional OSCC. We hypothesized that for HPV DNA-positive cases, p16 expression status differentiates the biologically relevant ones.
We determined HPV16DNA viral load in a cohort of 79 oropharyngeal squamous cell cancers by real-time polymerase chain reaction (PCR). We used cervical cancer as a disease model for HPV-initiated epithelial cancer. In cervical cancer, p53 and Rb expression is reduced, while p16 expression is increased. We used TMA technology to facilitate interrogation of this cohort for p53, Rb, and p16 protein expression using a quantitative, in situ method of protein analysis (AQUA analysis). Our results indeed delineate three biologically and clinically distinct types of oropharyngeal squamous cell cancers based on HPV-DNA determination and p16 expression status: one class of HPV-negative/p16-nonexpressing (HPV-negative), one class of HPV-positive/p16-nonexpressing (HPV-inactive), and one class of HPV positive/p16-expressing (HPV-active) oropharyngeal tumors. We demonstrated that only the HPV-active tumors share a similar molecular phenotype to cervical cancers, and are the ones associated with favorable prognosis.
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de Villiers EM, Weidauer H, Otto H, zur Hausen H (1985) Papillomavirus DNA in human tongue carcinomas. Int J Cancer 36:575-578
Franceschi S, Munoz N, Bosch XF, Snijders PJ, Walboomers JM (1996) Human papillomavirus and cancers of the upper aerodigestive tract: a review of epidemiological and experimental evidence. Cancer Epidemiol Biomarkers Prev 5:567-575
Snijders PJ, Scholes AG, Hart CA, Jones AS, Vaughan ED, Woolgar JA et al (1996) Prevalence of mucosotropic human papillomaviruses in squamous-cell carcinoma of the head and neck. Int J Cancer 66:464-469
McKaig RG, Baric RS, Olshan AF (1998) Human papillomavirus and head and neck cancer: epidemiology and molecular biology. Head Neck 20:250-265
Psyrri A, DeFilippis RA, Edwards AP, Yates KE, Manuelidis L, DiMaio D (2004) Role of the retinoblastoma pathway in senescence triggered by repression of the human papillomavirus E7 protein in cervical carcinoma cells. Cancer Res 64:3079-3086
Alani RM, Munger K (1998) Human papillomaviruses and associated malignancies. J Clin Oncol 16:330-337
Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J et al (2006) Molecular classification identifies a subset of human papillomavirus - associated oropharyngeal cancers with favorable prognosis. J Clin Oncol 24:736-747
Fischer C, Zlobec I, Stockli E, Probst S, Storck C, Tornillo L et al (2008) Is immunohistochemical epidermal growth factor receptor expression overestimated as a prognostic factor in head-neck squamous cell carcinoma? A retrospective analysis based on a tissue microarray of 365 carcinomas. Hum Pathol 39:1527-1534
Graham AD, Faratian D, Rae F, Thomas JS (2008) Tissue microarray technology in the routine assessment of HER-2 status in invasive breast cancer: a prospective study of the use of immunohistochemistry and fluorescence in situ hybridization. Histopathology 52:847-855
Goldstine J, Seligson DB, Beizai P, Miyata H, Vinters HV (2002) Tissue microarrays in the study of non-neoplastic disease of the nervous system. J Neuropathol Exp Neurol 61:653-662
Camp RL, Chung GG, Rimm DL (2002) Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med 8:1323-1327
McCabe A, Dolled-Filhart M, Camp RL, Rimm DL (2005) Automated quantitative analysis (AQUA) of in situ protein expression, antibody concentration, and prognosis. J Natl Cancer Inst 97:1808-1815
Coombs NJ, Gough AC, Primrose JN (1999) Optimisation of DNA and RNA extraction from archival formalin-fixed tissue. Nucleic Acids Res 27:15
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Gouveris, P., Weinberger, P.M., Psyrri, A. (2010). Use of Tissue Microarray to Facilitate Oncology Research. In: Chittur, S.V. (eds) Microarray Methods for Drug Discovery. Methods in Molecular Biology, vol 632. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-663-4_15
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DOI: https://doi.org/10.1007/978-1-60761-663-4_15
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