Human Papillomavirus 16 Infection and TP53 Mutation: Two Distinct Pathogeneses for Oropharyngeal Squamous Cell Carcinoma in an Eastern Chinese Population

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Wang, Zhen ; Xia, Rong-Hui ; Ye, Dong-Xia ; Li, Jiang (2016)
  • Publisher: Public Library of Science
  • Journal: PLoS ONE, volume 11, issue 10 (issn: 1932-6203, eissn: 1932-6203)
  • Related identifiers: doi: 10.1371/journal.pone.0164491, pmc: PMC5066983
  • Subject: Molecular Biology | Microbial Pathogens | Genitourinary Infections | Habits | Research Article | Anatomy | Infectious Diseases | Pathology and Laboratory Medicine | Geographical Locations | Papillomaviruses | Alcohol Consumption | Artificial Gene Amplification and Extension | Genetics | Pathogens | Histology | People and Places | Molecular Biology Techniques | Diet | Behavior | Polymerase Chain Reaction | Smoking Habits | Viruses | Biology and Life Sciences | DNA viruses | Research and Analysis Methods | Asia | Microbiology | Medicine | Viral Diseases | Human Papillomavirus Infection | Q | Medical Microbiology | Viral Pathogens | Sexually Transmitted Diseases | Mutation | R | Nutrition | China | Science | Urology | Organisms | Medicine and Health Sciences | HPV-16

Objectives 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.
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