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Detection and significance of human papillomavirus, CDKN2A(p16) and CDKN1A(p21) expression in squamous cell carcinoma of the larynx
by
Thorstad, Wade L
, El-Mofty, Samir K
, Gao, Ge
, Wang, Xiaowei
, Lewis, James S
, Zhang, Qin
, Chernock, Rebecca D
in
631/208/199
/ 631/326/596/2560
/ 692/699/67/1536
/ 692/700/139/422
/ Adult
/ Aged
/ Aged, 80 and over
/ Biomarkers
/ Cancer
/ Carcinoma, Squamous Cell - metabolism
/ Carcinoma, Squamous Cell - pathology
/ Carcinoma, Squamous Cell - virology
/ Cyclin-Dependent Kinase Inhibitor p16 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Female
/ Human papillomavirus
/ Humans
/ Hybridization
/ Immunology
/ Infections
/ Laboratory Medicine
/ Laryngeal Neoplasms - metabolism
/ Laryngeal Neoplasms - pathology
/ Laryngeal Neoplasms - virology
/ Larynx
/ Larynx - metabolism
/ Larynx - pathology
/ Larynx - virology
/ Male
/ Medical prognosis
/ Medicine
/ Medicine & Public Health
/ Middle Aged
/ Morphology
/ Neck
/ original-article
/ Papillomaviridae - genetics
/ Papillomaviridae - isolation & purification
/ Papillomavirus Infections - metabolism
/ Papillomavirus Infections - pathology
/ Papillomavirus Infections - virology
/ Pathology
/ Proteins
/ Radiation
/ Tumors
2013
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Detection and significance of human papillomavirus, CDKN2A(p16) and CDKN1A(p21) expression in squamous cell carcinoma of the larynx
by
Thorstad, Wade L
, El-Mofty, Samir K
, Gao, Ge
, Wang, Xiaowei
, Lewis, James S
, Zhang, Qin
, Chernock, Rebecca D
in
631/208/199
/ 631/326/596/2560
/ 692/699/67/1536
/ 692/700/139/422
/ Adult
/ Aged
/ Aged, 80 and over
/ Biomarkers
/ Cancer
/ Carcinoma, Squamous Cell - metabolism
/ Carcinoma, Squamous Cell - pathology
/ Carcinoma, Squamous Cell - virology
/ Cyclin-Dependent Kinase Inhibitor p16 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Female
/ Human papillomavirus
/ Humans
/ Hybridization
/ Immunology
/ Infections
/ Laboratory Medicine
/ Laryngeal Neoplasms - metabolism
/ Laryngeal Neoplasms - pathology
/ Laryngeal Neoplasms - virology
/ Larynx
/ Larynx - metabolism
/ Larynx - pathology
/ Larynx - virology
/ Male
/ Medical prognosis
/ Medicine
/ Medicine & Public Health
/ Middle Aged
/ Morphology
/ Neck
/ original-article
/ Papillomaviridae - genetics
/ Papillomaviridae - isolation & purification
/ Papillomavirus Infections - metabolism
/ Papillomavirus Infections - pathology
/ Papillomavirus Infections - virology
/ Pathology
/ Proteins
/ Radiation
/ Tumors
2013
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Detection and significance of human papillomavirus, CDKN2A(p16) and CDKN1A(p21) expression in squamous cell carcinoma of the larynx
by
Thorstad, Wade L
, El-Mofty, Samir K
, Gao, Ge
, Wang, Xiaowei
, Lewis, James S
, Zhang, Qin
, Chernock, Rebecca D
in
631/208/199
/ 631/326/596/2560
/ 692/699/67/1536
/ 692/700/139/422
/ Adult
/ Aged
/ Aged, 80 and over
/ Biomarkers
/ Cancer
/ Carcinoma, Squamous Cell - metabolism
/ Carcinoma, Squamous Cell - pathology
/ Carcinoma, Squamous Cell - virology
/ Cyclin-Dependent Kinase Inhibitor p16 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Female
/ Human papillomavirus
/ Humans
/ Hybridization
/ Immunology
/ Infections
/ Laboratory Medicine
/ Laryngeal Neoplasms - metabolism
/ Laryngeal Neoplasms - pathology
/ Laryngeal Neoplasms - virology
/ Larynx
/ Larynx - metabolism
/ Larynx - pathology
/ Larynx - virology
/ Male
/ Medical prognosis
/ Medicine
/ Medicine & Public Health
/ Middle Aged
/ Morphology
/ Neck
/ original-article
/ Papillomaviridae - genetics
/ Papillomaviridae - isolation & purification
/ Papillomavirus Infections - metabolism
/ Papillomavirus Infections - pathology
/ Papillomavirus Infections - virology
/ Pathology
/ Proteins
/ Radiation
/ Tumors
2013
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Detection and significance of human papillomavirus, CDKN2A(p16) and CDKN1A(p21) expression in squamous cell carcinoma of the larynx
Journal Article
Detection and significance of human papillomavirus, CDKN2A(p16) and CDKN1A(p21) expression in squamous cell carcinoma of the larynx
2013
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Overview
Although a strong etiologic relationship between human papillomavirus (HPV) and a majority of oropharyngeal squamous cell carcinomas has been established, the role of HPV in non-oropharyngeal head and neck carcinomas is much less clear. Here, we investigated the prevalence and clinicopathologic significance of HPV and its reported biomarkers, CDKN2A(p16) and CDKN1A(p21), in laryngeal squamous cell carcinomas in patients treated either with primary surgery and postoperative radiation or with definitive radiation-based therapy. Nearly all of 76 tumors were keratinizing and none displayed the nonkeratinizing morphology that is typically associated with HPV infection in the oropharynx. However, CDKN2A(p16) immunohistochemistry was positive in 21 cases (28%) and CDKN1A(p21) in 34 (45%). CDKN2A(p16) and CDKN1A(p21) status strongly correlated with each other (
P
=0.0038). Yet, only four cases were HPV positive by DNA
in situ
hybridization or by reverse transcriptase PCR E6/E7 mRNA (all four were CDKN2A(p16) and CDKN1A(p21) positive). Unexpectedly, 9 additional tumors out of 20 CDKN2A(p16) positive cases harbored high-risk HPV DNA by PCR. For further investigation of this unexpected result,
in situ
hybridization for E6/E7 mRNA was performed on these nine cases and all were negative, confirming the absence of transcriptionally active virus. Patients with CDKN1A(p21)-positive tumors did have better overall survival (69% at 3 years) than those with CDKN1A(p21)-negative tumors (51% at 3 years) (
P
=0.045). There was also a strong trend towards better overall survival in the CDKN2A(p16)-positive group (
P
=0.058). Thus, it appears that the role of HPV is more complex in the larynx than in the oropharynx, and that CDKN2A(p16) and CDKN1A(p21) expression may not reflect HPV-driven tumors in most cases. Because of this, CDKN2A(p16) should not be used as a definitive surrogate marker of HPV-driven tumors in the larynx.
Publisher
Nature Publishing Group US,Elsevier Limited
Subject
/ Adult
/ Aged
/ Cancer
/ Carcinoma, Squamous Cell - metabolism
/ Carcinoma, Squamous Cell - pathology
/ Carcinoma, Squamous Cell - virology
/ Cyclin-Dependent Kinase Inhibitor p16 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Female
/ Humans
/ Laryngeal Neoplasms - metabolism
/ Laryngeal Neoplasms - pathology
/ Laryngeal Neoplasms - virology
/ Larynx
/ Male
/ Medicine
/ Neck
/ Papillomaviridae - isolation & purification
/ Papillomavirus Infections - metabolism
/ Papillomavirus Infections - pathology
/ Papillomavirus Infections - virology
/ Proteins
/ Tumors
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