HPV serum antibodies as predictors of survival and disease progression in patients with HPV-positive Squamous cell carcinoma of the Oropharynx

Kristina R. Dahlstrom, Karen Anderson, Julia N. Cheng, Diego Chowell, Guojun Li, Marshall Posner, Erich M. Sturgis

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Purpose: Oropharyngeal carcinoma positive for human papillomavirus type 16 (HPV16) has a significantly better prognosis than oropharyngeal carcinoma unrelated to HPV. Within HPV16-positive oropharyngeal carcinoma, biomarkers of prognosis are urgently needed to individualize care. We hypothesized that serum antibodies specific to HPV16, the major HPV type causing oropharyngeal carcinoma, have biologic relevance and are potential biomarkers for improved prognosis among patients with HPV16-positive oropharyngeal carcinoma. Experimental Design: IgG antibodies to the HPV16 antigens E1, E4-E7, L1, L2, and the N-Terminal and C-Terminal fragments of E2 (NE2, CE2) were quantified using a custom programmable enzyme-linked immunosorbent assay. Sera were obtained at diagnosis from 209 oropharyngeal carcinoma patients (96 HPV16-positive). The ratios of median fluorescent intensity (MFI) for each antigen to MFI for control GST protein were determined. Kaplan-Meier survival curves and Cox proportional hazards regression were used to determine survival differences between groups. ROC curves were used to determine the best combination of E antibodies to predict disease recurrence. Results: E1, NE2, and E6 antibody positivity were all strongly associated with improved overall and progressionfree survival in the entire cohort and in patients with known HPV16-positive tumors (P < 0.05). For both overall and progression-free survival among HPV-positive patients, hazard ratios were 0.2 for NE2, 0.3 for E1, and 0.3 for E6 antibody positivity. Conclusions: We identified three HPV16-specific antibodies that are associated with improved overall and progression-free survival in patients with HPV-related oropharyngeal carcinoma. These results suggest that differential serologic responses in patients may reflect differential biologic processes within the host and tumor and may have prognostic value.

Original languageEnglish (US)
Pages (from-to)2861-2869
Number of pages9
JournalClinical Cancer Research
Volume21
Issue number12
DOIs
StatePublished - Jun 15 2015

Fingerprint

Oropharynx
Human papillomavirus 16
Disease Progression
Squamous Cell Carcinoma
Survival
Carcinoma
Antibodies
Serum
Disease-Free Survival
Biomarkers
Antigens
Kaplan-Meier Estimate
ROC Curve
Neoplasms
Research Design
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

HPV serum antibodies as predictors of survival and disease progression in patients with HPV-positive Squamous cell carcinoma of the Oropharynx. / Dahlstrom, Kristina R.; Anderson, Karen; Cheng, Julia N.; Chowell, Diego; Li, Guojun; Posner, Marshall; Sturgis, Erich M.

In: Clinical Cancer Research, Vol. 21, No. 12, 15.06.2015, p. 2861-2869.

Research output: Contribution to journalArticle

Dahlstrom, Kristina R. ; Anderson, Karen ; Cheng, Julia N. ; Chowell, Diego ; Li, Guojun ; Posner, Marshall ; Sturgis, Erich M. / HPV serum antibodies as predictors of survival and disease progression in patients with HPV-positive Squamous cell carcinoma of the Oropharynx. In: Clinical Cancer Research. 2015 ; Vol. 21, No. 12. pp. 2861-2869.
@article{6ec969a122c040ca950302ce09c09540,
title = "HPV serum antibodies as predictors of survival and disease progression in patients with HPV-positive Squamous cell carcinoma of the Oropharynx",
abstract = "Purpose: Oropharyngeal carcinoma positive for human papillomavirus type 16 (HPV16) has a significantly better prognosis than oropharyngeal carcinoma unrelated to HPV. Within HPV16-positive oropharyngeal carcinoma, biomarkers of prognosis are urgently needed to individualize care. We hypothesized that serum antibodies specific to HPV16, the major HPV type causing oropharyngeal carcinoma, have biologic relevance and are potential biomarkers for improved prognosis among patients with HPV16-positive oropharyngeal carcinoma. Experimental Design: IgG antibodies to the HPV16 antigens E1, E4-E7, L1, L2, and the N-Terminal and C-Terminal fragments of E2 (NE2, CE2) were quantified using a custom programmable enzyme-linked immunosorbent assay. Sera were obtained at diagnosis from 209 oropharyngeal carcinoma patients (96 HPV16-positive). The ratios of median fluorescent intensity (MFI) for each antigen to MFI for control GST protein were determined. Kaplan-Meier survival curves and Cox proportional hazards regression were used to determine survival differences between groups. ROC curves were used to determine the best combination of E antibodies to predict disease recurrence. Results: E1, NE2, and E6 antibody positivity were all strongly associated with improved overall and progressionfree survival in the entire cohort and in patients with known HPV16-positive tumors (P < 0.05). For both overall and progression-free survival among HPV-positive patients, hazard ratios were 0.2 for NE2, 0.3 for E1, and 0.3 for E6 antibody positivity. Conclusions: We identified three HPV16-specific antibodies that are associated with improved overall and progression-free survival in patients with HPV-related oropharyngeal carcinoma. These results suggest that differential serologic responses in patients may reflect differential biologic processes within the host and tumor and may have prognostic value.",
author = "Dahlstrom, {Kristina R.} and Karen Anderson and Cheng, {Julia N.} and Diego Chowell and Guojun Li and Marshall Posner and Sturgis, {Erich M.}",
year = "2015",
month = "6",
day = "15",
doi = "10.1158/1078-0432.CCR-14-3323",
language = "English (US)",
volume = "21",
pages = "2861--2869",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

TY - JOUR

T1 - HPV serum antibodies as predictors of survival and disease progression in patients with HPV-positive Squamous cell carcinoma of the Oropharynx

AU - Dahlstrom, Kristina R.

AU - Anderson, Karen

AU - Cheng, Julia N.

AU - Chowell, Diego

AU - Li, Guojun

AU - Posner, Marshall

AU - Sturgis, Erich M.

PY - 2015/6/15

Y1 - 2015/6/15

N2 - Purpose: Oropharyngeal carcinoma positive for human papillomavirus type 16 (HPV16) has a significantly better prognosis than oropharyngeal carcinoma unrelated to HPV. Within HPV16-positive oropharyngeal carcinoma, biomarkers of prognosis are urgently needed to individualize care. We hypothesized that serum antibodies specific to HPV16, the major HPV type causing oropharyngeal carcinoma, have biologic relevance and are potential biomarkers for improved prognosis among patients with HPV16-positive oropharyngeal carcinoma. Experimental Design: IgG antibodies to the HPV16 antigens E1, E4-E7, L1, L2, and the N-Terminal and C-Terminal fragments of E2 (NE2, CE2) were quantified using a custom programmable enzyme-linked immunosorbent assay. Sera were obtained at diagnosis from 209 oropharyngeal carcinoma patients (96 HPV16-positive). The ratios of median fluorescent intensity (MFI) for each antigen to MFI for control GST protein were determined. Kaplan-Meier survival curves and Cox proportional hazards regression were used to determine survival differences between groups. ROC curves were used to determine the best combination of E antibodies to predict disease recurrence. Results: E1, NE2, and E6 antibody positivity were all strongly associated with improved overall and progressionfree survival in the entire cohort and in patients with known HPV16-positive tumors (P < 0.05). For both overall and progression-free survival among HPV-positive patients, hazard ratios were 0.2 for NE2, 0.3 for E1, and 0.3 for E6 antibody positivity. Conclusions: We identified three HPV16-specific antibodies that are associated with improved overall and progression-free survival in patients with HPV-related oropharyngeal carcinoma. These results suggest that differential serologic responses in patients may reflect differential biologic processes within the host and tumor and may have prognostic value.

AB - Purpose: Oropharyngeal carcinoma positive for human papillomavirus type 16 (HPV16) has a significantly better prognosis than oropharyngeal carcinoma unrelated to HPV. Within HPV16-positive oropharyngeal carcinoma, biomarkers of prognosis are urgently needed to individualize care. We hypothesized that serum antibodies specific to HPV16, the major HPV type causing oropharyngeal carcinoma, have biologic relevance and are potential biomarkers for improved prognosis among patients with HPV16-positive oropharyngeal carcinoma. Experimental Design: IgG antibodies to the HPV16 antigens E1, E4-E7, L1, L2, and the N-Terminal and C-Terminal fragments of E2 (NE2, CE2) were quantified using a custom programmable enzyme-linked immunosorbent assay. Sera were obtained at diagnosis from 209 oropharyngeal carcinoma patients (96 HPV16-positive). The ratios of median fluorescent intensity (MFI) for each antigen to MFI for control GST protein were determined. Kaplan-Meier survival curves and Cox proportional hazards regression were used to determine survival differences between groups. ROC curves were used to determine the best combination of E antibodies to predict disease recurrence. Results: E1, NE2, and E6 antibody positivity were all strongly associated with improved overall and progressionfree survival in the entire cohort and in patients with known HPV16-positive tumors (P < 0.05). For both overall and progression-free survival among HPV-positive patients, hazard ratios were 0.2 for NE2, 0.3 for E1, and 0.3 for E6 antibody positivity. Conclusions: We identified three HPV16-specific antibodies that are associated with improved overall and progression-free survival in patients with HPV-related oropharyngeal carcinoma. These results suggest that differential serologic responses in patients may reflect differential biologic processes within the host and tumor and may have prognostic value.

UR - http://www.scopus.com/inward/record.url?scp=84941961689&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941961689&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-14-3323

DO - 10.1158/1078-0432.CCR-14-3323

M3 - Article

VL - 21

SP - 2861

EP - 2869

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 12

ER -