Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection

Abstract

Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n 5 55) and controls as men without an IM diagnosis (n 5 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n 5 90) and controls (n 5 220). We found that IM cases were more likely to have a large PSA rise than controls (20 ng/mL: 19.7% versus 8.8%, p 5 0.027; 40% rise: 25.7% versus 9.4%, p 5 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p 5 0.020; 27.7% versus 18.0%, p 5 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men.

Sustained influence of infections on prostate‐specific antigen concentration: An analysis of changes over 10 years of follow‐up

“…Together with findings for genitourinary tract infections, these results suggest that many types of infections may influence the prostate, either directly through prostate infection or indirectly through possible mechanisms such as local genitourinary‐ or systemic inflammation‐mediated cell damage, leading to chronic prostate inflammation. These findings also suggest that the influence of infections may be sustained over a period of at least a few months to 1 year …”

“…In contrast to the above‐described direct prostate‐specific mechanism for PSA elevation, mechanisms for non‐genitourinary, systemic infections, such as varicella, are likely less direct. We previously proposed that these infections may contribute to elevated PSA by several possible mechanisms, including systemic inflammation‐mediated prostate cell damage and increased vascular permeability, or increased vascular permeability in the context of preexisting prostate epithelial cell damage/disruption from other sources . In addition, once infection has resolved, PSA could possibly remain elevated for months to years later for a number of reasons, including chronic inflammation against residual infectious antigens, continued healing, delayed or impaired ability to counteract future prostate insults, or broken tolerance to self‐prostatic antigens, all of which could possibly amplify with repeated infections over time.…”

“…Although our study was originally designed to examine the short‐ and longer‐term influence of exudative STIs and adult‐onset IM on PSA change, we expanded our analysis to include additional infections based on our short‐term findings for IM . These post hoc analyses were limited to men in the original control group to avoid the influence of exudative STIs and IM on our findings.…”

Spurious elevation of Prostate‐specific antigen associated with shingles in a prostate cancer patient undergoing active surveillance

“…A small number of studies demonstrate a correlation between other infectious causes and an increase in PSA. For instance, Epstein‐Barr virus (EBV), a herpes family virus and the causative agent of infectious mononucleosis (IM), has been associated with a PSA rise as well . One case‐control study of a population of US military recruits with or without IM found a statistically significant increase in the probability of large PSA increase (defined as an increase by 20 ng/mL or 40% or greater rise) in those diagnosed with IM compared to controls.…”

“…every 3 months ( Figure 1) and was seen clinically every 6 months. His PSA values were as follows: 3.38 (May 2013), 3.15 (July 2013), 1.71 (October 2013), 3.15 (January 2014), 2.72 (Apr 2014), 2.05 (June 2014), 2.40 (October 2014), 2.43 (December 2014); his PSA velocity had been flat ( Figure 1). In April 2015, his PSA value was markedly elevated at 7.61. Review of systems revealed that the patient was recently diagnosed with shingles.…”