title: Risk stratification of early stage oral tongue cancers based on HPV status and p16 immunoexpression.
abstract: BACKGROUND
  Recent epidemiological data have implicated human papilloma virus (HPV) infection in the pathogenesis of head and neck cancers, especially oropharyngeal cancers. Although, HPV has been detected in varied amounts in persons with oral dysplasia, leukoplakias and malignancies, its involvement in oral tongue carcinogenesis remains ambiguous.
  
  
  METHODS
  HPV DNA prevalence was assessed by PCR with formalin fixed paraffin embedded sections (n=167) of oral tongue squamous cell carcinoma patients and the physical status of the HPV16 DNA was assessed by qPCR. Immunohistochemistry was conducted for p16 evaluation.
  
  
  RESULTS
  We found the HPV prevalence in tongue cancers to be 51.2%, HPV 16 being present in 85.2% of the positive cases. A notable finding was a very poor concordance between HPV 16 DNA and p16 IHC findings (kappa<0.2). Further molecular classification of patients based on HPV16 DNA prevalence and p16 overexpression showed that patients with tumours showing p16 overexpression had increased hazard of death (HR=2.395; p=0.005) and disease recurrence (HR=2.581; p=0.002) irrespective of their HPV 16 DNA status.
  
  
  CONCLUSIONS
  Our study has brought out several key facets which can potentially redefine our understanding of tongue cancer tumorigenesis. It has emphatically shown p16 overexpression to be a single important prognostic variable in defining a high risk group and depicting a poorer prognosis, thus highlighting the need for its routine assessment in tongue cancers. Another significant finding was a very poor concordance between p16 expression and HPV infection suggesting that p16 expression should possibly not be used as a surrogate marker for HPV infection in tongue cancers. Interestingly, the prognostic significance of p16 overexpression is different from that reported in oropharyngeal cancers. The mechanism of HPV independent p16 over expression in oral tongue cancers is possibly a distinct entity and needs to be further studied.
authors.affiliation: Department of Preventive Oncology, Cancer Institute (WIA), Adyar, India E-mail : drarvindkrishnamurthy@gmail.com.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Ramshankar
authors.forename: Viveka T
authors.initials: VT
authors.lastname: Soundara
authors.forename: Vidyarani
authors.initials: V
authors.lastname: Shyamsundar
authors.forename: Prathiba
authors.initials: P
authors.lastname: Ramani
authors.forename: Arvind
authors.initials: A
authors.lastname: Krishnamurthy
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000821:virology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000821:virology; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral