Document Detail

Detection of transcriptionally active high-risk HPV in patients with head and neck squamous cell carcinoma as visualized by a novel E6/E7 mRNA in situ hybridization method.
MedLine Citation:
PMID:  23060353     Owner:  NLM     Status:  MEDLINE    
Evidence for transcriptional activation of the viral oncoproteins E6 and E7 is regarded as the gold standard for the presence of clinically relevant human papillomavirus (HPV), but detection of E6/E7 mRNA requires RNA extraction and polymerase chain reaction amplification-a challenging technique that is restricted to the research laboratory. The development of RNA in situ hybridization (ISH) probes complementary to E6/E7 mRNA permits direct visualization of viral transcripts in routinely processed tissues and has opened the door for accurate HPV detection in the clinical care setting. Tissue microarrays containing 282 head and neck squamous cell carcinomas from various anatomic subsites were tested for the presence of HPV using p16 immunohistochemistry, HPV DNA ISH, and an RNA ISH assay (RNAscope) targeting high-risk HPV E6/E7 mRNA transcripts. The E6/E7 mRNA assay was also used to test an additional 25 oropharyngeal carcinomas in which the HPV status as recorded in the surgical pathology reports was equivocal due to conflicting detection results (ie, p16 positive, DNA ISH negative). By the E6/E7 mRNA method, HPV was detected in 49 of 282 (17%) HNSCCs including 43 of 77 (56%) carcinomas from the oropharynx, 2 of 3 (67%) metastatic HNSCCs of an unknown primary site, 2 of 7 (29%) carcinomas from the sinonasal tract, and 2 of 195 (1%) carcinomas from other head and neck sites. p16 expression was strongly associated with the presence of HPV E6/E7 mRNA: 46 of 49 HPV-positive tumors exhibited p16 expression, whereas only 22 of 233 HPV-negative tumors were p16 positive (94% vs. 9%, P<0.0001). There was also a high rate of concordance (99%) between the E6/E7 mRNA method and HPV DNA ISH. For the selected group of discordant HNSCCs (p16/HPV DNA), the presence of E6/E7 transcripts was detected in 21 of 25 (84%) cases. The E6/E7 mRNA method confirmed the presence of transcriptionally active HPV-related HNSCC that has a strong predilection for the oropharynx and is strongly associated with high levels of p16 expression. Testing for HPV E6/E7 transcripts by RNA ISH is ideal because it confirms the presence of integrated and transcriptionally active virus, permits visualization of viral transcripts in tissues, and is technically feasible for routine testing in the clinical laboratory.
Justin A Bishop; Xiao-Jun Ma; Hongwei Wang; Yuling Luo; Peter B Illei; Shanaz Begum; Janis M Taube; Wayne M Koch; William H Westra
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of surgical pathology     Volume:  36     ISSN:  1532-0979     ISO Abbreviation:  Am. J. Surg. Pathol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-01-21     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  7707904     Medline TA:  Am J Surg Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1874-82     Citation Subset:  IM    
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MeSH Terms
Carcinoma, Squamous Cell / chemistry,  pathology,  virology*
Cyclin-Dependent Kinase Inhibitor p16 / analysis
DNA, Viral / analysis
Feasibility Studies
Gene Expression Regulation, Viral
Head and Neck Neoplasms / chemistry,  pathology,  virology*
Human Papillomavirus DNA Tests
In Situ Hybridization / methods*
Nucleic Acid Probes / drug effects
Oncogene Proteins, Viral / genetics*
Papillomaviridae / genetics*
Papillomavirus Infections / complications,  virology*
Predictive Value of Tests
RNA, Messenger / analysis*
RNA, Viral / analysis*
Risk Factors
Tissue Array Analysis
Transcription, Genetic*
Tumor Markers, Biological / analysis
Grant Support
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p16; 0/DNA, Viral; 0/Nucleic Acid Probes; 0/Oncogene Proteins, Viral; 0/RNA, Messenger; 0/RNA, Viral; 0/Tumor Markers, Biological

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