Risk Stratification of Early Stage Oral Tongue Cancers Based on HPV Status and p16 Immunoexpression

Background: Recent epidemiological data have implicated human papilloma virus (HPV) infection in thepathogenesis of head and neck cancers, especially oropharyngeal cancers. Although, HPV has been detected invaried amounts in persons with oral dysplasia, leukoplakias and malignancies, its involvement in oral tonguecarcinogenesis remains ambiguous. Materials and
Methods: HPV DNA prevalence was assessed by PCR withformalin fixed paraffin embedded sections (n=167) of oral tongue squamous cell carcinoma patients and thephysical status of the HPV16 DNA was assessed by qPCR. Immunohistochemistry was conducted for p16evaluation.
Results: We found the HPV prevalence in tongue cancers to be 51.2%, HPV 16 being present in85.2% of the positive cases. A notable finding was a very poor concordance between HPV 16 DNA and p16 IHCfindings (kappa<0.2). Further molecular classification of patients based on HPV16 DNA prevalence and p16overexpression 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 oftongue cancer tumorigenesis. It has emphatically shown p16 overexpression to be a single important prognosticvariable in defining a high risk group and depicting a poorer prognosis, thus highlighting the need for its routineassessment in tongue cancers. Another significant finding was a very poor concordance between p16 expressionand HPV infection suggesting that p16 expression should possibly not be used as a surrogate marker for HPVinfection in tongue cancers. Interestingly, the prognostic significance of p16 overexpression is different from thatreported in oropharyngeal cancers. The mechanism of HPV independent p16 over expression in oral tonguecancers is possibly a distinct entity and needs to be further studied.