Serum antibodies against genitourinary infectious agents in prostate cancer and benign prostate hyperplasia patients: a case-control study

Abstract

BackgroundInfection plays a role in the pathogenesis of many human malignancies. Whether prostate cancer (PCa) - an important health issue in the aging male population in the Western world - belongs to these conditions has been a matter of research since the 1970 s. Persistent serum antibodies are a proof of present or past infection. The aim of this study was to compare serum antibodies against genitourinary infectious agents between PCa patients and controls with benign prostate hyperplasia (BPH). We hypothesized that elevated serum antibody levels or higher seroprevalence in PCa patients would suggest an association of genitourinary infection in patient history and elevated PCa risk.MethodsA total of 434 males who had undergone open prostate surgery in a single institution were included in the study: 329 PCa patients and 105 controls with BPH. The subjects' serum samples were analysed by means of enzyme-linked immunosorbent assay, complement fixation test and indirect immunofluorescence for the presence of antibodies against common genitourinary infectious agents: human papillomavirus (HPV) 6, 11, 16, 18, 31 and 33, herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (CMV), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Neisseria gonorrhoeae and Treponema pallidum. Antibody seroprevalence and mean serum antibody levels were compared between cases and controls. Tumour grade and stage were correlated with serological findings.ResultsPCa patients were more likely to harbour antibodies against Ureaplasma urealyticum (odds ratio (OR) 2.06; 95% confidence interval (CI) 1.08-4.28). Men with BPH were more often seropositive for HPV 18 and Chlamydia trachomatis (OR 0.23; 95% CI 0.09-0.61 and OR 0.45; 95% CI 0.21-0.99, respectively) and had higher mean serum CMV antibody levels than PCa patients (p = 0.0004). Among PCa patients, antibodies against HPV 6 were associated with a higher Gleason score (p = 0.0305).ConclusionsAntibody seropositivity against the analyzed pathogens with the exception of Ureaplasma does not seem to be a risk factor for PCa pathogenesis. The presence or higher levels of serum antibodies against the genitourinary pathogens studied were not consistently associated with PCa. Serostatus was not a predictor of disease stage in the studied population.

Herpes simplex virus type 2 or human herpesvirus 8 infection and prostate cancer risk: A meta-analysis

“…No studies from Africa or Asia were included; therefore, assessment regarding these areas was not possible. Furthermore, in HSV-2-related analyses, there were five studies with 1,213 cases and 1,737 controls in the North and South American group (11,14,25,26) and three studies with 508 cases and 428 controls in the European group (10,15,27). With fewer studies and participants, the results from the European group may not be representative or stable.…”

“…We aimed to conduct a stratified analysis according to age. However, of all the studies included, only a few provided the mean or median age (10,14,26,30). Moreover, a study demonstrated that the association with HSV-2 was strengthened when earlier sera analyses were restricted to specimens collected at least five years prior to diagnosis and suggested a long latency period from HSV-2 infection to prostate cancer development (14).…”

“…We identified a total of 11 articles on infection by HSV-2 or HHV-8 and prostate cancer risk, updated up to May 2012 (8)(9)(10)(11)(14)(15)(16)(17)(25)(26)(27). The process of identifying and selecting articles is shown in Fig.…”

“…Five studies were located in North and South America, with 1,213 cases and 1,737 controls (11,14,25,26) and three were located in Europe, with 508 cases and 428 controls (10,15,27). No statistically significant heterogeneity was detected in pooled analysis (P=0.243, I 2 =23.4%) and the fixed-effects model was adopted.…”

“…Since the 1970s, it has been a matter of debate whether prostate cancer, or at least a subgroup of prostate cancer cases, are associated with infection. With the development of serological assays for the detection of infectious agents, studies were conducted to investigate the relationship between prostate cancer and viral infection (8)(9)(10)(11).…”