Prospective study of human herpesvirus type 8 serostatus and prostate cancer risk in the placebo arm of the Prostate Cancer Prevention Trial

Abstract

Background Human herpesvirus type 8 (HHV-8), a gamma herpesvirus associated with Kaposi’s sarcoma, has been proposed as a candidate risk factor for prostate cancer (PCa) because of its detection in benign and malignant prostate specimens, and its relation with histologic prostatic inflammation. We investigated the possible relation between pre-diagnostic HHV-8 infection and PCa risk in a case-control study sampled from the placebo arm of the Prostate Cancer Prevention Trial (PCPT). Methods We defined cases as men with a confirmed diagnosis of PCa after visit 2 (n=315) and controls as men not diagnosed with PCa during the trial who also had a negative end-of-study prostate biopsy (n=315). We tested sera from visit 2 for IgG antibodies against HHV-8 using a monoclonal antibody-enhanced immunofluorescence assay against multiple lytic HHV-8 antigens. Results The adjusted seroprevalence of HHV-8 infection was 11.6% for cases and 11.0% for controls (p=0.81). No association was observed between HHV-8 seropositivity and PCa risk (OR=1.06, 95% CI: 0.65-1.76). Conclusion Our findings of a null association between HHV-8 seropositivity and PCa risk do not support an association between HHV-8 infection and PCa development, consistent with the general tendency of the epidemiologic literature to date.

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

“…Specifically, although our findings differ from previous observations of a large rise in PSA during GC, but not NCNGU, in the same U.S. military population as our present analysis, they are similar to our previous observation of a large PSA rise during CT in the U.S. military, as well as to observations of large PSA rises/high PSA concentrations during exudative STIs, febrile UTIs, and Chikungunya virus infection (one case report). Our findings are also in agreement with several studies that observed sustained PSA concentrations over a period of 3 months to 1 year following infection in young and older men (eg, exudative STIs, febrile UTIs, young‐onset IM, and systemic, non‐genitourinary infections), and with several, but not all, cross‐sectional analyses that observed higher PSA concentrations in men seropositive for curable (CT) and lifelong STIs (human herpesvirus infection type 8). Finally, although we saw less compelling evidence for large PSA rises in the present analysis than in previous studies of acute and recently‐resolved infections, we still observed that PSA remained elevated in the long‐term, demonstrating that PSA levels may not return completely to baseline values even many years after infection.…”

“…Interestingly, in the first of these studies, men's convalescent PSA concentrations remained elevated for at least several months after diagnosis and effective antibiotic therapy, raising the possibility of a longer‐term influence of STIs on the prostate . These findings are consistent with those from cross‐sectional studies of Chlamydia trachomatis (CT) and human herpesvirus type 8 serology that observed positive results with PSA, as well as those from longitudinal studies of men treated for febrile urinary tract infections (UTIs) that observed large PSA rises sustained over several months …”

Trichomonas vaginalis infection and prostate‐specific antigen concentration: Insights into prostate involvement and prostate disease risk

“…This latter finding is more in line with our findings and suggests that smaller long‐term changes may require longitudinal measurements rather than one cross‐sectional measurement to detect as statistically significant. Finally, although our findings differ from previous positive cross‐sectional findings for human herpesvirus type 8 serostatus with PSA in older men, human herpesvirus type 8 is a chronic, lifelong infection that reactivates periodically across the life course, as opposed to an infection, such as T. vaginalis infection, that can be cleared or cured, which may explain its stronger influence on PSA.…”

Trichomonas vaginalis infection and risk of prostate cancer: associations by disease aggressiveness and race/ethnicity in the PLCO Trial

“…We estimated a prevalence of 9.5% in Caucasian controls (similar to the HPFS study: 9.4% [8]), whereas the PCPT, PHS, and King County studies estimated prevalences of 15.0–23.2% in their controls [10, 11]. However, these types of differences are not unusual for serologic testing [23, 24] and should not have affected our relative comparisons between cases and controls. We were also able to detect an expected association between T. vaginalis seropositivity and African-American race/ethnicity in our study, supporting the criterion validity of our serologic results.…”