p16 INK4A overexpression is frequently detected in tumour-free tonsil tissue without association with HPV.

Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 7704136 Publication Model: Print Cited Medium: Internet ISSN: 1365-2559 (Electronic) Linking ISSN: 03090167 NLM ISO Abbreviation: Histopathology Subsets: MEDLINE

Original Publication: Oxford, Blackwell Scientific Publications.

Carcinoma, Squamous Cell/*metabolism ; Cyclin-Dependent Kinase Inhibitor p16/*metabolism ; Human papillomavirus 16/*metabolism ; Palatine Tonsil/*metabolism ; Papillomavirus Infections/*metabolism ; Tonsillar Neoplasms/*metabolism; Adolescent ; Adult ; Aged ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/virology ; Chi-Square Distribution ; Child ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; DNA, Viral/genetics ; Female ; Human papillomavirus 16/genetics ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Palatine Tonsil/virology ; Papillomavirus Infections/genetics ; Papillomavirus Infections/virology ; Polymerase Chain Reaction ; Tonsillar Neoplasms/genetics ; Tonsillar Neoplasms/virology ; Up-Regulation

Aims: Oncogenic human papillomavirus (HPV) type 16 has been strongly associated with tonsillar squamous cell carcinoma (TSCC) and appears to be of prognostic significance. Because HPV+ TSCC also accumulates p16(INK4A), this cyclin-dependent kinase inhibitor has been proposed as a potential biomarker for HPV in clinical diagnosis. The aim of this study was to determine the prevalence of HPV in tumour-free tonsillar tissue and the value of p16(INK4A) overexpression in predicting its presence.
Methods and Results: p16(INK4A) overexpression was detected by immunohistochemistry in tissue sections of tumour-free tonsils of 262 patients. They were treated for non-oncological reasons (snoring or chronic/recurrent tonsillitis) consisting of tonsillectomy. Genomic DNA isolated from these tissues was subjected to HPV-specific polymerase chain reaction (PCR) analysis. p16(INK4A) immunoreactivity was detected in 28% of samples in both crypt epithelium (49/177) and lymphoid germinal centres (52/187), which correlated with each other (P < 0.0001). No reactivity was observed in superficial squamous cell epithelium. HPV16 and 18 were detected by PCR analysis in 2/195 cases (1%), which, however, were negative on fluorescence in situ hybridization analysis and discrepant on p16(INK4A) immunostaining.
Conclusions: No proof was found for the presence of HPV in tumour-free tonsil tissue, despite increased p16(INK4A) expression in a quarter of tonsil cases. Other mechanisms than HPV infection are therefore implicated in p16(INK4A) up-regulation.

0 (Biomarkers, Tumor)
0 (Cyclin-Dependent Kinase Inhibitor p16)
0 (DNA, Viral)

Date Created: 20100720 Date Completed: 20101025 Latest Revision: 20220408

20250114

10.1111/j.1365-2559.2010.03576.x

20636796