Biomarkers of oxidant load and type-specific clearance of prevalent oncogenic human papillomavirus infection: Markers of immune response?†‡
Corresponding Author
Erin M. Siegel
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL
Department of Epidemiology & Biostatistics, College of Public Health, University of South Florida, Tampa, FL
Tel: (813) 745-6533, Fax: (813) 745-6507
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, FL 33612, USASearch for more papers by this authorNitin Patel
James A. Haley Veterans' Hospital, HSR&D/RR&D Research Center of Excellence, Tampa, FL
Search for more papers by this authorBeibei Lu
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL
Department of Epidemiology & Biostatistics, College of Public Health, University of South Florida, Tampa, FL
Search for more papers by this authorJi-Hyun Lee
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL
Department of Epidemiology & Biostatistics, College of Public Health, University of South Florida, Tampa, FL
Search for more papers by this authorAlan G. Nyitray
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL
Search for more papers by this authorKrystyna Frenkel
Department of Environmental Medicine, NYU School of Medicine, New York City, NY
Search for more papers by this authorLuisa L. Villa
Ludwig Institute for Cancer Research, São Paulo, Brazil
Search for more papers by this authorEduardo L. Franco
Departments of Oncology and of Epidemiology and Biostatistics, McGill University, Montreal, Canada
Search for more papers by this authorAnna R. Giuliano
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL
Department of Epidemiology & Biostatistics, College of Public Health, University of South Florida, Tampa, FL
Search for more papers by this authorCorresponding Author
Erin M. Siegel
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL
Department of Epidemiology & Biostatistics, College of Public Health, University of South Florida, Tampa, FL
Tel: (813) 745-6533, Fax: (813) 745-6507
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, FL 33612, USASearch for more papers by this authorNitin Patel
James A. Haley Veterans' Hospital, HSR&D/RR&D Research Center of Excellence, Tampa, FL
Search for more papers by this authorBeibei Lu
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL
Department of Epidemiology & Biostatistics, College of Public Health, University of South Florida, Tampa, FL
Search for more papers by this authorJi-Hyun Lee
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL
Department of Epidemiology & Biostatistics, College of Public Health, University of South Florida, Tampa, FL
Search for more papers by this authorAlan G. Nyitray
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL
Search for more papers by this authorKrystyna Frenkel
Department of Environmental Medicine, NYU School of Medicine, New York City, NY
Search for more papers by this authorLuisa L. Villa
Ludwig Institute for Cancer Research, São Paulo, Brazil
Search for more papers by this authorEduardo L. Franco
Departments of Oncology and of Epidemiology and Biostatistics, McGill University, Montreal, Canada
Search for more papers by this authorAnna R. Giuliano
Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL
Department of Epidemiology & Biostatistics, College of Public Health, University of South Florida, Tampa, FL
Search for more papers by this authorPresented at the 26th International Papillomavirus Conference and Workshop, July, 2010, Montreal, Quebec, Canada, Abstract 648.
Conflict of Interest: A.G.N has received research support from Merck and CO, Inc. L.L.V. is a consultant to and on the Speakers Bureau of Merck and CO, Inc. E.L.F. has served as occasional advisory board member or consultant to companies involved with HPV vaccines (GlaxoSmithKline and Merck and CO, Inc.), HPV diagnostics (Gen-Probe, Roche, Qiagen), or cervical cancer cytology screening (Cytyc, Ikonisys). A.R.G is a consultant to and on the Speakers Bureau of Merck and CO, Inc.
Abstract
Human papillomavirus (HPV) infection is the cause of cervical cancer. Increased production of reactive oxygen species (ROS) maybe the common mechanism through which HPV-cofactors (i.e., smoking and inflammation) influence duration of infections. Biomarkers of total oxidant load may serve as cumulative measures of ROS exposure due to these cofactors. Therefore, we conducted a study evaluating the association between biomarkers of oxidant load and duration of HPV infections, early HPV natural history events. Serum samples were obtained from 444 HPV-positive women in the Ludwig-McGill Cohort Study. Anti-5-hydroxymethyl-2′-deoxyuridine autoantibody (anti-HMdU aAb) and malondialdehyde (MDA) were measured at baseline. Cox-proportional hazard models were used to estimate the probability of clearing any HPV, oncogenic HPV, non-oncogenic HPV and HPV-16 infections. Women with elevated MDA were significantly more likely to clear prevalent oncogenic HPV infections compared to those with lower MDA levels (Adjusted Hazard Ratio (AHR) = 2.7; 95%CI = 1.4-5.1). There did not appear to be an association between elevated MDA and clearance of incident oncogenic HPV infections. Similarly, women with elevated anti-HMdU aAb levels had higher rates of prevalent oncogenic HPV infection clearance (Quartile 3:AHR = 2.2; 95%CI = 1.2-4.4; Quartile 4:AHR = 2.4; 95%CI = 1.2-4.9). Higher levels of oxidant load biomarkers were associated with increased clearance of prevalent HPV infections. However, oxidant load biomarkers measured before incident infections were not associated, suggesting that the elevation of MDA and anti-HMdU aAb may reflect an ongoing effective immune response, such as increased innate immunity. More research focused on the immune responses to HPV and elevated markers of oxidant load is needed.
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