title: Prevalence and prognostic value of human papillomavirus genotypes in tonsillar squamous cell carcinoma: a Korean multicenter study.
abstract: BACKGROUND
  This study was aimed at investigating the change in the prevalence of human papillomavirus (HPV) genotypes in tonsillar squamous cell carcinoma (TSCC) and the association of the HPV genotype with the prognosis.
  
  
  METHODS
  This multicenter study included 175 patients with TSCC from 3 general hospitals between 1991 and 2009. HPV DNA was detected in paraffin-embedded tissues with genotyping chips. A survival analysis that considered clinicopathological factors, the HPV genotype, and the expression of p53, retinoblastoma protein, p16, and epidermal growth factor receptor (assessed with immunohistochemistry) was performed with Cox regression analysis.
  
  
  RESULTS
  High-risk HPV types were found in 23.4% of the cases. The prevalence of HPV-18 (10.3%) was as high as that of HPV-16 (10.3%). The proportion of high-risk HPV-positive tumors increased from 5.9% in 1991 to 31.6% in 2009. HPV-16 positivity was associated with an advanced stage and lymph node metastasis, whereas HPV-18 positivity was associated with old age and an advanced T stage. The survival analysis showed that old age and T classification were poor prognostic factors, whereas the expressions of various biomarkers were not associated with prognosis. HPV-18-positive cases had a poorer prognosis than HPV-16-positive cases and non-HPV-related TSCC cases. A multivariate analysis revealed that HPV-18 positivity, old age, and an advanced T stage were independent prognostic factors for predicting poor outcomes for patients with TSCC.
  
  
  CONCLUSIONS
  The proportion of HPV-positive tonsillar cancer cases has increased during the last 20 years in the Republic of Korea. The presence of HPV-18 may serve as a biomarker for a poor prognosis.
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: No
authors.forename: Myung-Whun
authors.initials: MW
authors.lastname: Sung
authors.forename: J Hun
authors.initials: JH
authors.lastname: Hah
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Myung-Chul
authors.initials: MC
authors.lastname: Lee
authors.forename: Hee Seung
authors.initials: HS
authors.lastname: Kim
authors.forename: Yong-Sang
authors.initials: YS
authors.lastname: Song
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology*; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D056910:Republic of Korea / Q000453:epidemiology; D016160:Retinoblastoma Protein / Q000032:analysis; D012189:Retrospective Studies; D014067:Tonsillar Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: biomarker; genotype; human papillomavirus; prognosis; tonsillar cancer