The relationship between human papillomavirus status and other molecular prognostic markers in head and neck squamous cell carcinomas.
OBJECTIVE
To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status.


METHODS
HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16(INK4a) staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO(2) and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining).


RESULTS
Forty-four percent of evaluable tumors had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16(INK4a) staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16(INK4a) staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO(2) or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors.


CONCLUSIONS
HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.
Kong
Christina S
CS
Department of Pathology, Stanford University, Santa Cruz, CA, USA.
Narasimhan
Balasubramanian
B
Cao
Hongbin
H
Kwok
Shirley
S
Erickson
Julianna P
JP
Koong
Albert
A
Pourmand
Nader
N
Le
Quynh-Thu
QT
D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy / Q000821:virology*; D015687:Cell Hypoxia; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy / Q000821:virology*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007111:Immunity, Cellular; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D013601:T-Lymphocytes; D046888:Tissue Array Analysis / Q000379:methods; D016896:Treatment Outcome
D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors