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

    24 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.
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    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.",
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    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.

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

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