Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations.
BACKGROUND
The role of human papilloma virus (HPV) in the pathogenesis and biological behavior of tonsillar squamous cell carcinoma (TSCC) are areas of intense investigation.


METHODS
This study used PCR analysis to identify HPV in paraffin-embedded tonsillar and nodal tissue from 52 patients with TSCC and 48 age (+/-5 year)/gender-matched controls with benign tonsillar hyperplasia. Results were correlated with HLA-DRB1 haplotype and clinical outcome.


RESULTS
HPV was identified in 46% of patients with TSCC and 6% of controls. DNA sequencing showed the presence of HPV type 16 in 21 patients (40%) with TSCC. There was no statistically significant association between HLA-DRB1 expression and TSCC or HPV infection. Fifteen of 16 patients with HPV-positive TSCC with regional metastases had evidence of HPV in pathologically involved lymph nodes. In eight HPV 16-positive TSCC patients with lymph node metastasis, PCR testing identified HPV 16 in 17 of 23 histologically negative lymph nodes. Patients with HPV-positive TSCC without metastatic disease had no evidence of HPV in their lymphatic tissue. Clinically, HPV-associated carcinoma was present in younger patients in comparison with HPV-negative TSCC patients (mean age, 56.6 versus 66 years; P = 0.001). The odds for patients with HPV infection to develop TSCC were 18.2 times greater than for patients without HPV infection (95% confidence interval 4.6, 73.1). There was no statistically significant association between presence of HPV and cause-specific survival (hazard ratio = 2.5 for HPV negative versus positive; P = 0.26), after adjusting for age in a Cox proportional hazards regression analysis.


CONCLUSIONS
HPV is an independent risk factor for TSCC. Identification of HPV in the histologically positive and negative lymph nodes of patients with HPV-positive TSCC/metastatic disease supports the role of HPV in the oncogenesis of TSCC.
Strome
Scott E
SE
Department of Otorhinolaryngology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Savva
Athanasia
A
Brissett
Anthony E
AE
Gostout
Bobbie S
BS
Lewis
Jean
J
Clayton
Amy C
AC
McGovern
Renee
R
Weaver
Amy L
AL
Persing
David
D
Kasperbauer
Jan L
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000821:virology; D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D012307:Risk Factors; D012907:Smoking; D016019:Survival Analysis; D014067:Tonsillar Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology
D004279:DNA, Viral; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains