title: The biomarkers of human papillomavirus infection in tonsillar squamous cell carcinoma-molecular basis and predicting favorable outcome.
abstract: Presence of human papillomavirus (HPV) in variable proportions in tonsillar squamous cell carcinoma tissues has been demonstrated by several worldwide studies. Some reports emphasized the significance of HPV in predicting a better prognosis, as well as ethnic differences between Chinese and Caucasians. In order to understand the biological role of HPV and find out clinically accessible methods to determine its prognostic significance in primary tonsillar squamous cell carcinoma, we collected 92 patients with primary tonsillar squamous cell carcinoma diagnosed or treated in National Taiwan University Hospital, for whom archival tumor tissue were available. Immunohistochemical stains of p16(INK4A), high-risk HPV in situ hybridization, and nested polymerase chain reaction (PCR)-based genechips were performed to detect HPV infection and determine its genotype. Clinical data were compared with HPV infection detected by the different methods mentioned above. Real-time PCR was also performed on the HPV16-positive [HPV16(+)] lesions to understand viral integration status. The positive rates of nested PCR-based genechips, overexpression of p16(INK4A), and high-risk HPV in situ hybridization were 75% (69/92), 53% (49/92), and 44% (40/92), respectively. Both overexpression of P16(INK4A) and high-risk HPV in situ hybridization positivity were associated with favorable prognoses (P=0.004 and 0.001, respectively) and also independent prognostic factors in multivariate analyses (P=0.01 and 0.01, respectively). The positivity of nested PCR-based genechips was not statistically significant. From our data, primary tonsillar squamous cell carcinoma with positive immunohistochemical stains of p16(INK4A) and/or high-risk HPV in situ hybridization is associated with a better outcome, and both methods may serve as clinically accessible markers.
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Medical College, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Kuo
authors.forename: Chen-Hsiang
authors.initials: CH
authors.lastname: Hsiao
authors.forename: Ching-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Lu-Ting
authors.initials: LT
authors.lastname: Kuo
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Huang
authors.forename: Ming-Chieh
authors.initials: MC
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005814:Genes, Viral; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics; D016366:Open Reading Frames; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000235:genetics; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014067:Tonsillar Neoplasms / Q000401:mortality / Q000473:pathology / Q000821:virology*; D014412:Tumor Virus Infections / Q000453:epidemiology* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D009856:Oncogene Proteins, Viral; C076036:oncogene protein E2, Human papillomavirus type 1