title: p16 expression independent of human papillomavirus is associated with lower stage and longer disease-free survival in oral cavity squamous cell carcinoma.
abstract: There is limited information regarding the incidence of p16 expression, its association with human papillomavirus (HPV) and prognosis in oral cavity squamous cell carcinoma (OSCC). The role of p16 in OSCC is evaluated in 215 cases using tissue microarrays (TMAs). p16 immunohistochemistry and HPV in situ hybridisation were performed on TMAs following histopathology review of 215 patients with OSCC in the Sydney Head and Neck Cancer Institute database. Thirty-seven (17.2%) cases showed p16 expression without association with HPV. p16 expression significantly decreased with increasing pT category (p=0.002). p16 expression was associated with longer disease-specific survival on univariable analysis (p=0.044) but not on multivariable analysis adjusting for depth of invasion. Amongst patients receiving adjuvant radiotherapy, patients with p16 expression had significantly longer disease-free and overall survival. p16 expression was seen in early stage OSCCs and was associated with better survival following surgery and radiotherapy. While not an independent predictor of survival, p16 may mediate its effects by contributing to reduced proliferative capacity, leading to smaller tumour size and lower invasive potential.
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Laveniya
authors.initials: L
authors.lastname: Satgunaseelan
authors.affiliation: Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
authors.forename: Sohaib A
authors.initials: SA
authors.lastname: Virk
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Trina
authors.initials: T
authors.lastname: Lum
authors.affiliation: Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
authors.forename: Kan
authors.initials: K
authors.lastname: Gao
authors.affiliation: Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Camperdown, NSW, Australia; University of Sydney, Camperdown, NSW, Australia; Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Clark
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; University of Sydney, Camperdown, NSW, Australia; Chris O'Brien Lifehouse, Camperdown, NSW, Australia. Electronic address: Ruta.Gupta@sswahs.nsw.gov.au.
authors.forename: Ruta
authors.initials: R
authors.lastname: Gupta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology* / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology* / Q000821:virology; D052162:Human papillomavirus 16; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology* / Q000821:virology; D016016:Proportional Hazards Models; D000077195:Squamous Cell Carcinoma of Head and Neck; D046888:Tissue Array Analysis
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: Oral cavity SCC; depth of invasion; p16 immunohistochemistry; post-operative radiotherapy; prognosis