TY - JOUR
T1 - High-risk HPV, biomarkers, and outcome in matched cohorts of head and neck cancer patients positive and negative for HIV
AU - HNC SPORE HIV supplement consortium
AU - Walline, Heather M.
AU - Carey, Thomas E.
AU - Goudsmit, Christine M.
AU - Bellile, Emily L.
AU - D'Souza, Gypsyamber
AU - Peterson, Lisa A.
AU - McHugh, Jonathan B.
AU - Pai, Sara I.
AU - Lee, J. Jack
AU - Shin, Dong M.
AU - Ferris, Robert L.
N1 - Funding Information:
R.L. Ferris reports receiving commercial research grants from Astra-Zeneca MedImmune, Bristol Myers Squibb, Merck, VentiRX Pharmaceuticals, and is a consultant/advisory board member for Astra-Zeneca/MedImmune, Bristol Myers Squib, Lilly, Merck, and Pfizer. No potential conflicts of interest were disclosed by the other authors. The SPORE HNC network contributed collectively to this study. Biospecimens were provided by the sites and processed by the centralized testing laboratory. In addition to the leading contributions of the authors listed above, other important contributions were made by the following: Pathology contributors: Jonathan B. McHugh, Martin Graham (University of Michigan, Ann Arbor, MI); Raja Seethala, Simion Chiosea (University of Pittsburgh, Pittsburgh, PA); Marina Mosunjac (Emory University, Atlanta, GA); Adel K. El-Naggar (MD Anderson Cancer Center, Houston, TX); William H. Westra (Johns Hopkins University, Baltimore, MD). Data coordination: Jeff Lewis (M.D. Anderson Cancer Center, Houston, TX); Nicole Kluz, Alicia Wentz (Johns Hopkins School of Public Health, Johns Hopkins University, Baltimore, MD); Rachel Moreno (Emory University, Atlanta, GA); James Riddell IV, MD (Medicine-Infectious Disease, University of Michigan, Ann Arbor, MI). The SPORE Directors are listed as follows: Dong Moon Shin, Director, Emory University Head and Neck Cancer SPORE. David Sidransky, Director, Johns Hopkins Head and Neck Cancer SPORE. Jeffrey Myers, Director, MD Anderson Head and Neck Cancer SPORE. Gregory T. Wolf, Director, University of Michigan Head and Neck Cancer SPORE. Jennifer G. Grandis, Director, University of Pittsburgh Head and Neck Cancer SPORE. This work was supported by the NCI HIV Supplement to the Head and Neck SPORE Consortium. This study was also supported by grants to the following institutions: ARRA: University of Michigan: P50 CA097248 R01 CA194536 (to T. Carey); University of Michigan Cancer Center Core Grant P30 CA46592; MD Anderson: 5P50 CA097007; University of Pittsburgh:P50 CA097190; Johns Hopkins University, P50 DE019032 and 3P50 DE019032-14S2; Emory University: P50 CA128613, R01 DE021395 (to G. D'Souza), P50 CA128613, and P50 CA128613-02S1. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Publisher Copyright:
©2016 AACR.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - In this study, high-risk HPV (hrHPV) incidence, prognostic biomarkers, and outcome were assessed in HIV-positive (case) and HIV-negative (control) patients with head and neck squamous cell cancer (HNSCC). HIV-positive cases were matched to controls by tumor site, sex, and age at cancer diagnosis. A tissue microarray (TMA) was constructed and DNA isolated from tumor tissue. MultiPlex-PCR MassArray, L1-PCR, and in situ hybridization were used to assess hrHPV. TMA sections were stained for p16ink4a, TP53, RB, CCND1, EGFR, and scored for intensity and proportion of positive tumor cells. The HNSCC cohort included 41 HIV-positive cases and 41 HIV-negative controls. Tumors from 11 of 40 (28%) cases, and 10 of 41 (24%) controls contained hrHPV. p16 expression, indicative of E7 oncogene activity, was present in 10 of 11 HPV-positive cases and 7 of 10 HPV-positive controls. Low p16 and high TP53 expression in some HPV-positive tumors suggested HPV-independent tumorigenesis. Survival did not differ in cases and controls. RB expression was significantly associated with poor survival (P = 0.01). High TP53 expression exhibited a trend for poorer survival (P = 0.12), but among cases, association with poor survival reached statistical significance (P = 0.04). The proportion of HPV-positive tumors was similar, but the heterogeneity of HPV types was higher in the HIV-positive cases than in HIV-negative controls. High RB expression predicted poor survival, and high TP53 expression was associated with poorer survival in the HIV-positive cases but not HIV-negative controls.
AB - In this study, high-risk HPV (hrHPV) incidence, prognostic biomarkers, and outcome were assessed in HIV-positive (case) and HIV-negative (control) patients with head and neck squamous cell cancer (HNSCC). HIV-positive cases were matched to controls by tumor site, sex, and age at cancer diagnosis. A tissue microarray (TMA) was constructed and DNA isolated from tumor tissue. MultiPlex-PCR MassArray, L1-PCR, and in situ hybridization were used to assess hrHPV. TMA sections were stained for p16ink4a, TP53, RB, CCND1, EGFR, and scored for intensity and proportion of positive tumor cells. The HNSCC cohort included 41 HIV-positive cases and 41 HIV-negative controls. Tumors from 11 of 40 (28%) cases, and 10 of 41 (24%) controls contained hrHPV. p16 expression, indicative of E7 oncogene activity, was present in 10 of 11 HPV-positive cases and 7 of 10 HPV-positive controls. Low p16 and high TP53 expression in some HPV-positive tumors suggested HPV-independent tumorigenesis. Survival did not differ in cases and controls. RB expression was significantly associated with poor survival (P = 0.01). High TP53 expression exhibited a trend for poorer survival (P = 0.12), but among cases, association with poor survival reached statistical significance (P = 0.04). The proportion of HPV-positive tumors was similar, but the heterogeneity of HPV types was higher in the HIV-positive cases than in HIV-negative controls. High RB expression predicted poor survival, and high TP53 expression was associated with poorer survival in the HIV-positive cases but not HIV-negative controls.
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U2 - 10.1158/1541-7786.MCR-16-0255
DO - 10.1158/1541-7786.MCR-16-0255
M3 - Article
C2 - 27899422
AN - SCOPUS:85011982304
VL - 15
SP - 179
EP - 188
JO - Cell Growth and Differentiation
JF - Cell Growth and Differentiation
SN - 1541-7786
IS - 2
ER -