p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma

Christine H. Chung, Qiang Zhang, Christina S. Kong, Jonathan Harris, Elana Fertig, Paul M. Harari, Dian Wang, Kevin P. Redmond, George Shenouda, Andy Trotti, David Raben, Maura L. Gillison, Richard C. Jordan, Quynh Thu Le

Research output: Contribution to journalArticle

Abstract

Purpose: Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. Patients and Methods: p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics. Results: p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95% CI, 0.42 to 0.95; P = .03) and 0.56 (95% CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes. Conclusion: Similar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.

Original languageEnglish (US)
Pages (from-to)3930-3938
Number of pages9
JournalJournal of Clinical Oncology
Volume32
Issue number35
DOIs
StatePublished - Dec 10 2014

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Squamous Cell Carcinoma
Biomarkers
Papillomavirus Infections
Carcinoma, squamous cell of head and neck
human P16 protein
In Situ Hybridization
Immunohistochemistry
Hypopharynx
Oropharynx
Survival
Mouth Neoplasms
Larynx
Proportional Hazards Models
Mouth
Clinical Trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma. / Chung, Christine H.; Zhang, Qiang; Kong, Christina S.; Harris, Jonathan; Fertig, Elana; Harari, Paul M.; Wang, Dian; Redmond, Kevin P.; Shenouda, George; Trotti, Andy; Raben, David; Gillison, Maura L.; Jordan, Richard C.; Le, Quynh Thu.

In: Journal of Clinical Oncology, Vol. 32, No. 35, 10.12.2014, p. 3930-3938.

Research output: Contribution to journalArticle

Chung, CH, Zhang, Q, Kong, CS, Harris, J, Fertig, E, Harari, PM, Wang, D, Redmond, KP, Shenouda, G, Trotti, A, Raben, D, Gillison, ML, Jordan, RC & Le, QT 2014, 'p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma', Journal of Clinical Oncology, vol. 32, no. 35, pp. 3930-3938. https://doi.org/10.1200/JCO.2013.54.5228
Chung, Christine H. ; Zhang, Qiang ; Kong, Christina S. ; Harris, Jonathan ; Fertig, Elana ; Harari, Paul M. ; Wang, Dian ; Redmond, Kevin P. ; Shenouda, George ; Trotti, Andy ; Raben, David ; Gillison, Maura L. ; Jordan, Richard C. ; Le, Quynh Thu. / p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 35. pp. 3930-3938.
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abstract = "Purpose: Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. Patients and Methods: p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics. Results: p16 expression was positive in 14.1{\%} (12 of 85), 24.2{\%} (23 of 95), and 19.0{\%} (27 of 142) and HPV ISH was positive in 6.5{\%} (six of 93), 14.6{\%} (15 of 103), and 6.9{\%} (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95{\%} CI, 0.42 to 0.95; P = .03) and 0.56 (95{\%} CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes. Conclusion: Similar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.",
author = "Chung, {Christine H.} and Qiang Zhang and Kong, {Christina S.} and Jonathan Harris and Elana Fertig and Harari, {Paul M.} and Dian Wang and Redmond, {Kevin P.} and George Shenouda and Andy Trotti and David Raben and Gillison, {Maura L.} and Jordan, {Richard C.} and Le, {Quynh Thu}",
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T1 - p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma

AU - Chung, Christine H.

AU - Zhang, Qiang

AU - Kong, Christina S.

AU - Harris, Jonathan

AU - Fertig, Elana

AU - Harari, Paul M.

AU - Wang, Dian

AU - Redmond, Kevin P.

AU - Shenouda, George

AU - Trotti, Andy

AU - Raben, David

AU - Gillison, Maura L.

AU - Jordan, Richard C.

AU - Le, Quynh Thu

PY - 2014/12/10

Y1 - 2014/12/10

N2 - Purpose: Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. Patients and Methods: p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics. Results: p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95% CI, 0.42 to 0.95; P = .03) and 0.56 (95% CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes. Conclusion: Similar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.

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