Karen S Anderson1, Jennifer E Gerber2, Gypsyamber D'Souza3, Sara I Pai4, Julia N Cheng5, Rizwan Alam5, Sailaja Kesiraju5, Diego Chowell6, Neil D Gross7, Robert Haddad8, Maura L Gillison9, Marshall Posner10. 1. Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, United States. Electronic address: Dr.Karen@asu.edu. 2. Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States. 3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States. 4. Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, United States. 5. Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, United States. 6. Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, United States; Simon A. Levin Mathematical, Computational and Modeling Sciences Center, Arizona State University, Tempe, AZ 85287, United States. 7. Department of Otolaryngology-Head and Neck Surgery, MD Anderson Cancer Center, Houston, TX, United States. 8. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States. 9. Ohio State University, Comprehensive Cancer Center, Columbus, OH, United States. 10. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, United States.
Abstract
OBJECTIVES: We hypothesized that viral and host factors impact the serologic responses to HPV early antigens in HPV-positive oropharyngeal cancer (HPVOPC). MATERIALS AND METHODS: We conducted a multicenter study to measure HPV16-specific IgG among patients with HPVOPC, their long-term sexual partners, and healthy volunteers. Risk factor surveys and rinse and gargle specimens were collected. Peripheral blood samples at diagnosis were evaluated for IgG Abs to HPV16 antigens using a programmable ELISA assay. Predictors for HPV16 serologic responses were evaluated using univariate and multivariable linear regression. RESULTS: 116 patients with HPVOPC, 43 partners, and 81 healthy volunteers were enrolled and had baseline sera for analysis. Cases were primarily male (90%), with a median age of 56 years. Abs to E1, E2, E6 or E7 antigens were detected more often in HPVOPC compared with volunteers or partner sera (p<0.0001). HPV16 Abs to at least one early protein (E1, E2, E4, E5, E6, or E7) were detected in the sera of 90.6% of cases, 0% of partners and 7.4% of healthy volunteers. Gender, race, sexual behavior, and viral integration were not associated with antibody response. Younger age and higher oral HPV16 copy number were associated with higher HPV16 E6 and NE2 antibody levels. CONCLUSIONS: HPV16 seroreactivity is commonly detected among patients with HPVOPC at diagnosis, but not among partners or healthy volunteers. Seroreactivity among cases are correlated with viral load and stage and not with other demographic or behavioral factors. Positive HPV16 serology was strongly associated with HPV 16 oropharyngeal cancer.
OBJECTIVES: We hypothesized that viral and host factors impact the serologic responses to HPV early antigens in HPV-positive oropharyngeal cancer (HPVOPC). MATERIALS AND METHODS: We conducted a multicenter study to measure HPV16-specific IgG among patients with HPVOPC, their long-term sexual partners, and healthy volunteers. Risk factor surveys and rinse and gargle specimens were collected. Peripheral blood samples at diagnosis were evaluated for IgG Abs to HPV16 antigens using a programmable ELISA assay. Predictors for HPV16 serologic responses were evaluated using univariate and multivariable linear regression. RESULTS: 116 patients with HPVOPC, 43 partners, and 81 healthy volunteers were enrolled and had baseline sera for analysis. Cases were primarily male (90%), with a median age of 56 years. Abs to E1, E2, E6 or E7 antigens were detected more often in HPVOPC compared with volunteers or partner sera (p<0.0001). HPV16 Abs to at least one early protein (E1, E2, E4, E5, E6, or E7) were detected in the sera of 90.6% of cases, 0% of partners and 7.4% of healthy volunteers. Gender, race, sexual behavior, and viral integration were not associated with antibody response. Younger age and higher oral HPV16 copy number were associated with higher HPV16 E6 and NE2 antibody levels. CONCLUSIONS:HPV16 seroreactivity is commonly detected among patients with HPVOPC at diagnosis, but not among partners or healthy volunteers. Seroreactivity among cases are correlated with viral load and stage and not with other demographic or behavioral factors. Positive HPV16 serology was strongly associated with HPV 16oropharyngeal cancer.
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