title: High-Risk HPV, Biomarkers, and Outcome in Matched Cohorts of Head and Neck Cancer Patients Positive and Negative for HIV.
abstract: 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.
  
  
  
  HIV infection did not increase risk of death from HNSCC, and HPV-positive tumors continued to be associated with a significantly improved survival, independent of HIV status. Mol Cancer Res; 15(2); 179-88. ©2016 AACR.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.|Cancer Biology Training Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Walline
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan. Careyte@umich.edu.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Goudsmit
authors.affiliation: Biostatistics Core, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Bellile
authors.affiliation: Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
authors.affiliation: Head and Neck SPORE, University of Michigan Cancer Center, Ann Arbor, Michigan.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Peterson
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Sara I
authors.initials: SI
authors.lastname: Pai
authors.affiliation: Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas.
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Medicine, Medical Oncology Winship Cancer Center, Emory University, Atlanta, Georgia.
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm