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 prior to 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.

Subhaplogroup D4b1 enhances the risk of cervical cancer initiation: A case‐control study in southern China

“…Presumably, there could be no doubt that a variant at mt10398 would be associated with reactive oxygen species (ROS) generation, which plays an essential role in cancer occurrence. An accumulation of ROS was found to be associated with oncogenic HPV infection in cervical cancer occurrence . However, we found no significant difference between patients with cervical cancer and controls with respect to the distribution of mt10398A and mt10398G.…”

“…An accumulation of ROS was found to be associated with oncogenic HPV infection in cervical cancer occurrence. 21 However, we found no significant difference between patients with cervical cancer and controls with respect to the distribution of mt10398A and mt10398G. In addition, we found conflicting reports on whether the mt10398G variant is associated with a risk of cancer.…”

New Insights in the Pathogenesis of HPV Infection and the Associated Carcinogenic Processes: The Role of Chronic Inflammation and Oxidative Stress

“…Anti-5-hydroxymethyl-2′-deoxyuridine autoantibody (anti-HMdU Ab) and MDA levels were measured. They observed elevated levels of the two biomarkers, which have been associated with a faster clearance of oncogenic HPV types [ 97 ]. In addition, in another study, Siegel et al highlighted that HPV-infected women with elevated levels of ferritin were less likely to achieve viral clearance than those with low levels.…”

Trends in beliefs about the harmfulness and use of stop-smoking medications and smokeless tobacco products among cigarettes smokers: Findings from the ITC four-country survey

“…The limited available evidence also shows that use of nicotine replacement products for up to at least 5 years is safe [ 3 ]. Evidence from use of the lowest toxin forms of smokeless tobacco (SLT) suggests that even longer use can be done with much lower risks compared to smoking [ 4 ]. The available evidence shows that nicotine is not a carcinogen [ 5 ], although it may be a co-factor in the cause of cancer [ 6 ].…”

“…Typically, smokeless forms of tobacco are less harmful than smoked forms and there exist low toxin forms that produce few of the adverse effects of other tobacco products [ 7 ]. While many existing smokeless products are very harmful (e.g., South-East Asian and Sudanese forms; [ 8 ]), low nitrosamine versions like Swedish snus have been estimated to be 90 - 95% less harmful than cigarettes when used long-term [ 4 ], and others contend it is even less harmful [ 9 ]. There is no doubt that the toxicity of SLT can be systematically reduced without it unduly reducing user acceptability, something that has not been achieved for smoked tobacco.…”