title: Is p16 an adequate surrogate for human papillomavirus status determination?
abstract: OBJECTIVE
  In head and neck cancer management, immunoexpression of protein p16 is widely used as a surrogate marker for human papillomavirus (HPV) positivity due to challenges of direct HPV testing. Previously p16 has been reported to have good sensitivity but only moderate specificity in HPV-status determination. The aim of this review is to evaluate the existing information on sensitivity and specificity of p16 immunohistochemistry (IHC) in HPV-status determination among the recent studies.
  
  
  RESULTS
  We searched the time period from October 2014 to April 2016 and included 28 studies (a total of 31 analyses), which reported both p16 and HPV status in their series. The sensitivity of p16 in HPV determination ranged between 28.2 and 100.0%. The mean and median sensitivities were 90.5 and 95.4%, respectively. The specificity ranged between 31.1 and 100.0%. The mean and median specificities were 83.3 and 87.3%, respectively.
  
  
  CONCLUSIONS
  Our review presents current information on the feasibility of p16 IHC in HPV status determination, which is in line with previous studies. Patients with HPV-positive tumors can be identified with p16 IHC, but a risk for misclassification of HPV-negative tumors as HPV positive exists. This fact has to be taken into consideration if HPV status will influence treatment planning.
authors.affiliation: aDepartment of Otorhinolaryngology - Head and Neck Surgery bDepartment of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland cDivision of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lauri
authors.initials: L
authors.lastname: Jouhi
authors.forename: Jaana
authors.initials: J
authors.lastname: Hagström
authors.forename: Timo
authors.initials: T
authors.lastname: Atula
authors.forename: Antti
authors.initials: A
authors.lastname: Mäkitie
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral; D006258:Head and Neck Neoplasms / Q000821:virology*; D052162:Human papillomavirus 16 / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000821:virology*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral