title: Biomarkers of oxidant load and type-specific clearance of prevalent oncogenic human papillomavirus infection: markers of immune response?
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.
authors.affiliation: Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL 33612, USA. Erin.Siegel@moffitt.org
authors.forename: Erin M
authors.initials: EM
authors.lastname: Siegel
authors.forename: Nitin
authors.initials: N
authors.lastname: Patel
authors.forename: Beibei
authors.initials: B
authors.lastname: Lu
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Alan G
authors.initials: AG
authors.lastname: Nyitray
authors.forename: Neal E
authors.initials: NE
authors.lastname: Craft
authors.forename: Krystyna
authors.initials: K
authors.lastname: Frenkel
authors.forename: Luisa L
authors.initials: LL
authors.lastname: Villa
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Franco
authors.forename: Anna R
authors.initials: AR
authors.lastname: Giuliano
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D016877:Oxidants / Q000097:blood*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D016016:Proportional Hazards Models; D017382:Reactive Oxygen Species / Q000097:blood*; D013936:Thymidine / Q000031:analogs & derivatives / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000821:virology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D004279:DNA, Viral; D016877:Oxidants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; C018080:5-hydroxymethyl-2'-deoxyuridine; D013936:Thymidine