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High-risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma.
Am J Surg Pathol. 2011 Sep; 35(9):1343-50.AJ

Abstract

Human papillomavirus (HPV) is established as causative in oropharyngeal squamous cell carcinomas (OSCCs), being detected in 50% to 80% of tumors by DNA in situ hybridization (ISH) and/or polymerase chain reaction. However, these tests do not assess viral transcription. Many consider E6/E7 messenger ribonucleic acid (mRNA) the best indicator of HPV status, but it has not been detected in situ in OSCC. We constructed tissue microarrays (TMAs) from a cohort of OSCC for which p16 immunohistochemistry and HPV DNA ISH were previously performed on whole sections. We utilized a novel, chromogenic RNA ISH assay called RNAscope to detect E6/E7 mRNA of HPV-16 and other high-risk types on these TMAs. RNA ISH results were obtained for 196 of 211 TMA cases, of which 153 (78.1%) were positive. p16 immunohistochemistry and HPV DNA ISH were positive in 79.0% and 62.4% of cases, respectively. Concordance between RNA and p16, DNA and p16, and RNA and DNA were 96.4%, 78.7%, and 83.5%, respectively. Only 7 cases (3.6%) were discrepant between RNA ISH and p16. In univariate analysis, all 3 tests correlated with better overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) (all P<0.001). In multivariate analysis, OS correlated significantly with RNA (hazard ratio=0.39, P=0.001), DNA (0.53, P=0.03), and p16 (0.30, P<0.001), but DSS and DFS correlated significantly only with p16 (DSS: 0.36, P=0.006; DFS: 0.42, P=0.016). RNA ISH is more sensitive than DNA ISH in detecting HPV in OSCC, and it correlates strongly with p16. Although both tests were comparable, p16 more strongly stratified patient outcomes.

Authors+Show Affiliations

Department of Pathology and Immunology, Washington University, 660 S. Euclid Ave., St. Louis, MO 63110, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21836494

Citation

Ukpo, Odey C., et al. "High-risk Human Papillomavirus E6/E7 mRNA Detection By a Novel in Situ Hybridization Assay Strongly Correlates With P16 Expression and Patient Outcomes in Oropharyngeal Squamous Cell Carcinoma." The American Journal of Surgical Pathology, vol. 35, no. 9, 2011, pp. 1343-50.
Ukpo OC, Flanagan JJ, Ma XJ, et al. High-risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma. Am J Surg Pathol. 2011;35(9):1343-50.
Ukpo, O. C., Flanagan, J. J., Ma, X. J., Luo, Y., Thorstad, W. L., & Lewis, J. S. (2011). High-risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma. The American Journal of Surgical Pathology, 35(9), 1343-50. https://doi.org/10.1097/PAS.0b013e318220e59d
Ukpo OC, et al. High-risk Human Papillomavirus E6/E7 mRNA Detection By a Novel in Situ Hybridization Assay Strongly Correlates With P16 Expression and Patient Outcomes in Oropharyngeal Squamous Cell Carcinoma. Am J Surg Pathol. 2011;35(9):1343-50. PubMed PMID: 21836494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma. AU - Ukpo,Odey C, AU - Flanagan,John J, AU - Ma,Xiao-Jun, AU - Luo,Yuling, AU - Thorstad,Wade L, AU - Lewis,James S,Jr PY - 2011/8/13/entrez PY - 2011/8/13/pubmed PY - 2011/10/8/medline SP - 1343 EP - 50 JF - The American journal of surgical pathology JO - Am. J. Surg. Pathol. VL - 35 IS - 9 N2 - Human papillomavirus (HPV) is established as causative in oropharyngeal squamous cell carcinomas (OSCCs), being detected in 50% to 80% of tumors by DNA in situ hybridization (ISH) and/or polymerase chain reaction. However, these tests do not assess viral transcription. Many consider E6/E7 messenger ribonucleic acid (mRNA) the best indicator of HPV status, but it has not been detected in situ in OSCC. We constructed tissue microarrays (TMAs) from a cohort of OSCC for which p16 immunohistochemistry and HPV DNA ISH were previously performed on whole sections. We utilized a novel, chromogenic RNA ISH assay called RNAscope to detect E6/E7 mRNA of HPV-16 and other high-risk types on these TMAs. RNA ISH results were obtained for 196 of 211 TMA cases, of which 153 (78.1%) were positive. p16 immunohistochemistry and HPV DNA ISH were positive in 79.0% and 62.4% of cases, respectively. Concordance between RNA and p16, DNA and p16, and RNA and DNA were 96.4%, 78.7%, and 83.5%, respectively. Only 7 cases (3.6%) were discrepant between RNA ISH and p16. In univariate analysis, all 3 tests correlated with better overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) (all P<0.001). In multivariate analysis, OS correlated significantly with RNA (hazard ratio=0.39, P=0.001), DNA (0.53, P=0.03), and p16 (0.30, P<0.001), but DSS and DFS correlated significantly only with p16 (DSS: 0.36, P=0.006; DFS: 0.42, P=0.016). RNA ISH is more sensitive than DNA ISH in detecting HPV in OSCC, and it correlates strongly with p16. Although both tests were comparable, p16 more strongly stratified patient outcomes. SN - 1532-0979 UR - https://www.unboundmedicine.com/medline/citation/21836494/High_risk_human_papillomavirus_E6/E7_mRNA_detection_by_a_novel_in_situ_hybridization_assay_strongly_correlates_with_p16_expression_and_patient_outcomes_in_oropharyngeal_squamous_cell_carcinoma_ L2 - http://dx.doi.org/10.1097/PAS.0b013e318220e59d DB - PRIME DP - Unbound Medicine ER -