title: E6 and E7 Antibody Levels Are Potential Biomarkers of Recurrence in Patients with Advanced-Stage Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma.
abstract: Purpose:There is a paucity of biomarkers to predict failure in human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) following curative therapy. E6/E7 viral oncoproteins are constitutively expressed in HPV+tumors and highly immunogenic, resulting in readily detected serum antibodies. The purpose of this study is to determine whether serum E6 and E7 antibody levels can potentially serve as a biomarker of recurrence in patients with HPV+OPSCC.Experimental Design:We evaluated E6/E7 antibody levels in patients with previously untreated, advanced stage (III, IVa-b), HPV+OPSCC receiving definitive chemoradiation under a uniform protocol from 2003 to 2010. Baseline and longitudinal serum samples were obtained from our archived repository. E6/E7 serum levels were measured using a glutathione-S-transferase capture ELISA and quantified by approximating the area under the dilution curve, and were analyzed using ANOVA and linear mixed model for longitudinal analysis.Results:We compared 22 HPV+OPSCC patients who developed recurrence with 30 patients who remained disease-free. There were no differences in T classification, N classification, disease subsite, or smoking status between the groups. In a longitudinal analysis, recurrent patients had significantly higher E6 and E7 serum antibody levels than the nonrecurrent patients over the follow-up period (P= 0.02 andP= 0.002, respectively). Patients who recurred had a lower clearance of E7 antibody than patients who remained disease-free (P= 0.0016).Conclusions:Patients with HPV+OPSCC whose disease recurs have a lower clearance of E6 and E7 antibodies than patients who do not have recurrence. The ratio of E7 antibody at disease recurrence compared with baseline is potentially a clinically significant measurement of disease status in HPV+OPSCC.Clin Cancer Res; 23(11); 2723-9. ©2016 AACR.
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan. mspector@med.umich.edu.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Spector
authors.affiliation: Moores Cancer Center, University of California at San Diego, La Jolla, California.
authors.forename: Assuntina G
authors.initials: AG
authors.lastname: Sacco
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Emily
authors.initials: E
authors.lastname: Bellile
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Jeremy M G
authors.initials: JMG
authors.lastname: Taylor
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Tamara
authors.initials: T
authors.lastname: Jones
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Kan
authors.initials: K
authors.lastname: Sun
authors.affiliation: University of Michigan High-throughput Protein Laboratory, Center for Structural Biology, Life Sciences Institute, Ann Arbor, Michigan.
authors.forename: William C
authors.initials: WC
authors.lastname: Brown
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Birkeland
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Prince
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Moyer
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Kelly
authors.initials: K
authors.lastname: Malloy
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Paul
authors.initials: P
authors.lastname: Swiecicki
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.|University of Toronto, Toronto, Ontario, Canada.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Laura
authors.initials: L
authors.lastname: Rozek
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Francis P
authors.initials: FP
authors.lastname: Worden
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000097:blood* / Q000276:immunology; D009959:Oropharyngeal Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000097:blood* / Q000276:immunology; D030361:Papillomavirus Infections / Q000097:blood / Q000276:immunology; D012097:Repressor Proteins / Q000097:blood* / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D014408:Biomarkers, Tumor; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins