Human papillomavirus and p53 mutational status as prognostic factors in head and neck carcinoma.
BACKGROUND
Mutations of the p53 tumor-suppressor gene are common in squamous cell carcinoma of the head and neck (SCCHN) and may portend a worse prognosis. Human papillomavirus (HPV) represents another potential prognostic factor for SCCHN. The oncogenic potential of HPV may be due to the ability of its E6 oncoprotein to promote degradation of wild-type p53 protein. We wish to determine whether there is a lower incidence of p53 mutations in HPV-positive versus HPV-negative tumors, and if HPV and/or p53 status has an impact on survival.


METHODS
Thirty-two SCCHN specimens were analyzed for mutations of the p53 gene using single-strand conformational polymorphism (SSCP) analysis followed by DNA sequencing. The HPV status of all specimens was evaluated by use of polymerase chain reaction with HPV consensus primers and Southern blot hybridization. Pertinent clinical information was obtained from chart review.


RESULTS
Nonsilent p53 mutations were present in 2 of 15 (13%) of HPV-positive tumors compared with 6 of 17 (35%) of HPV-negative tumors (p =.229; Fisher's exact test, odds ratio.28). A survival advantage was found between HPV-positive compared with HPV-negative specimens (p =.0264) and between p53 wild type compared with p53 mutant specimens (p =.01) by univariate log rank analysis. When stratified according to both HPV and p53 status, a statistically significant survival difference was observed largely because of a 100% survival for the HPV-positive/p53 wild-type group (p =.003).


CONCLUSIONS
This preliminary study supports the notion that the presence of HPV confers a survival advantage among HNSCC patients, particularly when p53 is wild type.
Sisk
Elizabeth A
EA
Department of Otolaryngology/Head and Neck Surgery, University of Michigan, 1904 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109, USA.
Soltys
Scott G
SG
Zhu
Shaobo
S
Fisher
Susan G
SG
Carey
Thomas E
TE
Bradford
Carol R
CR
D014408:Biomarkers, Tumor / Q000032:analysis; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D016158:Genes, p53 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000821:virology*; D006801:Humans; D009154:Mutation; D027383:Papillomaviridae / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011336:Probability; D013223:Statistics as Topic / Q000379:methods; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D004279:DNA, Viral