title: Histologic Typing in Oropharyngeal Squamous Cell Carcinoma: A 4-Year Prospective Practice Study With p16 and High-Risk HPV mRNA Testing Correlation.
abstract: Oropharyngeal squamous cell carcinomas (OPSCCs) associated with human papillomavirus (HPV) represent a distinct clinical and pathologic entity. The majority of HPV-related OPSCCs have a characteristic nonkeratinizing morphology. This study sought to determine the strength of the association between nonkeratinizing histology and HPV status compared with other squamous cell carcinoma variants in 4 years of routine clinical practice on a high-volume head and neck service. Primary and/or nodal metastatic tumors in all cases of OPSCC from 2010 to 2013 were typed by 1 of 3 head and neck pathologists as keratinizing, nonkeratinizing, nonkeratinizing with maturation, or another defined variant. All were assessed for p16 by immunohistochemistry with a 70% nuclear and cytoplasmic positivity cutoff as part of routine clinical practice. In addition, 70 consecutive cases from 1 year were "audited" for high-risk HPV mRNA by reverse transcription polymerase chain reaction and in situ hybridization. Of the 435 cases, the majority (90%) consisted of 1 of the 3 main types described and the rest (10%) of uncommon variants. Nonkeratinizing morphology had 99.1% and 100.0% positive predictive value for p16 and high-risk HPV mRNA positivity, respectively. Nonkeratinizing with maturation, keratinizing, and other specific squamous cell carcinoma variants were p16 positive in 91.8%, 22.8%, and 79.5%, respectively. All 47 nonkeratinizing OPSCCs tested for HPV mRNA were positive. In summary, strictly defined nonkeratinizing OPSCC (which constitutes ∼55% of all tumors) essentially implies positivity for both p16 and transcriptionally active high-risk HPV.
authors.affiliation: Departments of *Pathology and Immunology †Radiation Oncology ‡Otolaryngology Head and Neck Surgery, Washington University School of Medicine, St Louis, MO Departments of §Pathology, Microbiology, and Immunology ∥Otolaryngology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Dikson Dibe
authors.initials: DD
authors.lastname: Gondim
authors.forename: Wesley
authors.initials: W
authors.lastname: Haynes
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Chernock
authors.forename: Samir K
authors.initials: SK
authors.lastname: El-Mofty
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000096:biosynthesis*; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000821:virology*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger; D012367:RNA, Viral / Q000032:analysis; D012680:Sensitivity and Specificity; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D012367:RNA, Viral