title: Use of cyclin D1 in conjunction with human papillomavirus status to predict outcome in oropharyngeal cancer.
abstract: There is increasing use of multiple molecular markers to predict prognosis in human cancer. Our aim was to examine the prognostic significance of cyclin D1 and retinoblastoma (pRb) expression in association with human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma. Clinical records and specimens of 226 patients with follow-up from 1 to 235 months postdiagnosis were retrieved. Tumor HPV status was determined by HPV E6-targeted multiplex real-time PCR/p16 semiquantitative immunohistochemistry and cyclin D1 and pRb expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modeled using Cox regression with censoring at dates of last follow-up. The HPV-positivity rate was 37% (91% type 16). HPV was a predictor of recurrence, an event (recurrence or death) and death after adjustment for clinicopathological variables. There were inverse relationships between HPV status and cyclin D1 and pRb. On univariate analysis, cyclin D1 predicted locoregional recurrence, event and death and pRb predicted event and death. Within the HPV-positive group, after adjusting for clinicopathological factors, patients with cyclin D1-positive cancers had up to a eightfold increased risk of poor outcome relative to those with cyclin D1-negative tumors. However, within the HPV-negative group, there was only a very small adjusted increased risk. A combination of pRb and HPV did not provide additional prognostic information. Our data provide the first evidence that a combination of HPV and cyclin D1 provides more prognostic information in oropharyngeal cancer than HPV alone. If findings are confirmed, treatment based on HPV and cyclin D1 may improve outcomes.
authors.affiliation: Department of Radiation Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Sydney, Australia. ahon6809@mail.usyd.edu.au
authors.forename: Angela M
authors.initials: AM
authors.lastname: Hong
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Dobbins
authors.forename: Cheok S
authors.initials: CS
authors.lastname: Lee
authors.forename: Deanna
authors.initials: D
authors.lastname: Jones
authors.forename: Jimin
authors.initials: J
authors.lastname: Fei
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Clark
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Armstrong
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Harnett
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Milross
authors.forename: Nham
authors.initials: N
authors.lastname: Tran
authors.forename: Luiza D
authors.initials: LD
authors.lastname: Peculis
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ng
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Milne
authors.forename: Christine
authors.initials: C
authors.lastname: Loo
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Hughes
authors.forename: Dion F
authors.initials: DF
authors.lastname: Forstner
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Brien
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Rose
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000821:virology*; D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000821:virology*; D030361:Papillomavirus Infections / Q000378:metabolism*; D011379:Prognosis; D012008:Recurrence; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D016896:Treatment Outcome
chemical_list: D016160:Retinoblastoma Protein; D019938:Cyclin D1