title: Human Papillomavirus 16 Infection and TP53 Mutation: Two Distinct Pathogeneses for Oropharyngeal Squamous Cell Carcinoma in an Eastern Chinese Population.
abstract: OBJECTIVE
  To investigate the clinicopathological characteristics, human papillomavirus (HPV) infection, p53 expression, and TP53 mutations in oropharyngeal squamous cell carcinoma (OPSCC) and determine their utility as prognostic predictors in a primarily eastern Chinese population.
  
  
  METHODS
  The HPV infection status was tested via p16INK4A immunohistochemistry and validated using PCR, reverse blot hybridization and in situ hybridization (ISH) in 188 OPSCC samples. p53 expression levels and TP53 gene mutations were assessed through immunohistochemistry and sequencing, respectively. Clinicopathological characteristics and follow-up information were collected. Overall survival was estimated using the Log-rank test.
  
  
  RESULTS
  Overall, 22 of the 188 OPSCC samples were associated with HPV infection. HPV16 was identified in all 22 samples, whereas no samples were positive for HPV18. All 22 HPV-associated OPSCC samples were p53 negative and lacked TP53 mutations. HPV16 positivity, female patients, non-smokers, and patients with histological grade I and stage N0 diseases showed better overall survival (p = 0.009, 0.003, 0.048, 0.009, and 0.004, respectively). No significant differences in overall survival between smoking and non-smoking patients were observed in the HPV-associated OPSCC group. Patients without mutations in TP53 exons 5-8 had better prognoses (p = 0.031) among the 43 sequenced specimens. Multivariate analysis indicated that HPV16 infection status (p = 0.011), histological grade (p = 0.017), and N stage (p = 0.019) were independent prognostic factors for patients with OPSCC.
  
  
  CONCLUSIONS
  Distinct from the situation in Europe and America, for the patients with OPSCC in this study, HPV16 infection was relatively low, although it was still the most important independent prognostic predictor for the disease. In addition to the high smoking and drinking rate in this population, HPV16 infection and TP53 dysfunction appear to be two distinct pathogens for OPSCC patients in the eastern Chinese population.
authors.affiliation: Department of Oral Pathology, ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Oral Pathology, ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China.
authors.forename: Rong-Hui
authors.initials: RH
authors.lastname: Xia
authors.affiliation: Department of Oral Maxillofacial Surgery, ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China.
authors.forename: Dong-Xia
authors.initials: DX
authors.lastname: Ye
authors.affiliation: Department of Oral Pathology, ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000821:virology; D002681:China; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D060787:Neoplasm Grading; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D011379:Prognosis; D017422:Sequence Analysis, DNA; D012907:Smoking; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53