BACKGROUND: Infection 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. METHODS: A 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. RESULTS: PCa 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). CONCLUSIONS: Antibody 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.

Charles University Prague 3rd Faculty of Medicine Department of Urology Prague Czech Republic

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Marberger M. Prostate cancer 2008: Challenges in diagnosis and management. Eur Urol Suppl. 2009;3:89–96. doi: 10.1016/j.eursup.2008.10.003. DOI

Jemal A, Siegel R, Xu J, Ward E. Cancer Statistics, 2010. CA Cancer J Clin. 2010;60:277–300. doi: 10.3322/caac.20073. PubMed DOI

Herbert JT, Birkhoff JD, Feorino PM, Caldwell GG. Herpes simplex virus type 2 and cancer of the prostate. J Urol. 1976;116:611–612. PubMed

Baker LH, Mebust WK, Chin TDY, Chapman AL, Hinthorn D, Towle D. The relationship of herpesvirus to carcinoma of the prostate. J Urol. 1981;125:370–374. PubMed

Strickler HD, Burk R, Shah K, Viscidi R, Jackson A, Pizza G, Bertoni F, Schiller JT, Manns A, Metcalf R, Qu W, Goedert JJ. A multifaceted study of human papillomavirus and prostate carcinoma. Cancer. 1998;82(6):1118–1125. doi: 10.1002/(SICI)1097-0142(19980315)82:6<1118::AID-CNCR16>3.0.CO;2-9. PubMed DOI

Hisada M, Rabkin CS, Strickler HD, Wright WE, Christianson RE, van den Berg BJ. Human papillovirus antibody and risk of prostate cancer. JAMA. 2000;3:340–341. doi: 10.1001/jama.283.3.340-a. PubMed DOI

Antilla T, Tenkanen L, Lumme S, Leinonen M, Gislefoss RE, Hallmans G, Thoresen S, Hakulinen T, Luostarinen T, Stattin P, Saikku P, Dillner J, Lehtinen M, Hakama M. Chlamydial antibodies and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 2005;14(2):385–389. doi: 10.1158/1055-9965.EPI-03-0325. PubMed DOI

Korodi Z, Dillner J, Jellum E, Lumme S, Hallmans G, Thoresen S, Hakulinen T, Stattin P, Luostarinen T, Lehtinen M, Hakama M. Human papillomavirus 16, 18, and 33 infections and risk of prostate cancer: a Nordic nested case-control study. Cancer Epidemiol Biomarkers Prev. 2005;14(12):2952–2955. doi: 10.1158/1055-9965.EPI-05-0602. PubMed DOI

Sitas F, Urban M, Stein L, Beral V, Ruff P, Hale M, Patel M, O'Connell D, Yu XQ, Verzijden A, Marais D, Williamson AL. The relationship between anti-HPV-16 IgG seropositivity and cancer of the cervix, anogenital organs, oral cavity and pharynx, oesophagus and prostate in a black South African population. Infectious Agents and Cancer. 2007;2:6. doi: 10.1186/1750-9378-2-6. PubMed DOI PMC

Reiner WG, Walsh PC. An anatomical approach to the surgical management of the dorsal vein and Santorini's plexus during radical retropubic surgery. J Urol. 1979;121:198–200. PubMed

Walsh PC. Anatomic radical prostatectomy. Evolution of the surgical technique. J Urol. 1998;160:2418–2424. doi: 10.1016/S0022-5347(01)62202-X. PubMed DOI

Fuller E. Six successful and successive cases of prostatectomy. J Cutan Genitourin Dis. 1895;13:229–239.

Culp DA. Benign prostatic hyperplasia: early recognition and management. Urol Clin North Am. 1975;2:29–48. PubMed

Montironi R, van der Kwast T, Boccon-Gibod L, Bono AV, Boccon-Gibod L. Handling and patology reporting of radical prostatectomy specimens. Eur Urol. 2003;44:626–636. doi: 10.1016/S0302-2838(03)00381-6. PubMed DOI

Rosai J. Rosai and Ackerman's Surgical Pathology. Edinburgh: Mosby; 2004.

Eble JN, Kauter G, Epstein JI, Sesterhenn I. Pathology and genetics of tumours of the urinary system and male genital organs (IARC/World Health Organization Classification of Tumours) Lyon, France: IARC Press; 2003.

Epstein JI, Allsbrook WC, Amin MB, Egevad LL. ISUP Grading Committee: The 2005 International Society of Urological Pathology (ISUP) Consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol. 2005;29(9):1228–1242. doi: 10.1097/01.pas.0000173646.99337.b1. PubMed DOI

Sobin LH, Wittekind CH. TNM Classification of Malignant Tumours. 6. Wiley; 2002.

Srigley JR, Amin MB, Epstein JI, Grignon DJ, Humphrey PH, Renshaw AA, Wheeler TM. Updated protocol for the examination of specimens from patients with carcinomas of the prostate gland. Arch Pathol Lab Med. 2006;130(7):936–946. PubMed

Hamsikova E, Smahel M, Sapp M, Munoz N, Bosch FX, Shah KV, Vonka V. Correlation between the presence of anti HPV33 VLP antibodies and HPV DNA in cervical neoplasia patients. Arch Virol. 1997;142(2):413–416. doi: 10.1007/s007050050087. PubMed DOI

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epi. 2008;61:344–349. doi: 10.1016/j.jclinepi.2007.11.008. PubMed DOI

Kirby RS, Patel MI. Fast facts: Prostate cancer. Oxford: Health Press Limited; 2009.

Amo FH, Cordero JMD, Tartajo FV, Hernandez FL, Carrillo AB, Burgos JG, Rios DS. Cáncer incidental de próstata. Actas Urol Esp. 1999;23(10):848–852. PubMed

Dillner J, Knekt P, Boman J, Lehtinen M, Geijersstam VA, Sapp M, Schiller J, Maatela J, Aromaa A. Sero-epidemiological association between human-papillomavirus infection and risk of prostate cancer. Int J Cancer. 1998;75:564–567. doi: 10.1002/(SICI)1097-0215(19980209)75:4<564::AID-IJC12>3.0.CO;2-9. PubMed DOI

Korodi Z, Wang X, Tedeschi R, Knekt P, Dillner J. No serological evidence of association between prostate cancer and infection with herpes simplex virus type 2 or human herpesvirus type 8: a nested case-control study. J Inf Dis. 2005;191:2008–2011. doi: 10.1086/430354. PubMed DOI

Huang WY, Hayes R, Pfeiffer R, Viscidi RP, Lee FK, Wang YF, Reding D, Whitby D, Papp JR, Rabkin CS. Sexually Transmissible Infections and Prostate Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2008;17(9):2374–2381. doi: 10.1158/1055-9965.EPI-08-0173. PubMed DOI PMC

Dennis KL, Coughlin JA, McKinnon BC, Wells TS, Gaydos CA, Hamsikova E, Gray GC. Sexually transmitted infections and prostate cancer among men in the U.S. Military. Cancer Epidemio Biomarkers Prev. 2009;18(10):2665–2671. doi: 10.1158/1055-9965.EPI-08-1167. PubMed DOI

Sutcliffe S, Giovannucci E, Gaydos CA, Viscidi RP, Jenkins FJ, Zenilman JN, Jacobson LP, De Marzo AM, Willett WC, Platz EA. Serum antibodies against Chlamydia trachomatis, human papillomavirus, and human herpesvirus type 8 in relation to prostate cancer: a prospective study. Cancer Epidemiol Biomarkers Prev. 2007;16(8):1573–1580. doi: 10.1158/1055-9965.EPI-07-0134. PubMed DOI PMC

Adami HO, Kuper H, Andersson SO, Bergström R, Dillner J. Prostate Cancer Risk and Serologic Evidence of Human Papilloma Virus Infection: A Population-based Case-Control Study. Cancer Epidemiol Biomarkers Prev. 2003;12:872–875. PubMed

Sutcliffe S, Viscidi RP, Till C, Goodman PJ, Hoque AM, Hsing AW, Thompson IM, Zenilman JM, De Marzo AM, Platz EA. Human papillomavirus types 16, 18 and 31 serostatus and prostate cancer risk in the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev. 2010;19(2):614–618. doi: 10.1158/1055-9965.EPI-09-1080. PubMed DOI PMC

Hayes RB, Pottern LM, Strickler H, Rabkin C, Pope V, Swanson GM, Greenberg RS, Schönberg JB, Liff J, Schwartz AG, Hoover RN, Fraumeni JF Jr. Sexual behaviour, STDs and risks for prostate cancer. Br J Cancer. 2000;82(3):718–725. doi: 10.1054/bjoc.1999.0986. PubMed DOI PMC

Rosenblatt KA, Carter JJ, Iwasaki LM, Galloway DA, Stanford JL. Serologic evidence of human papillomavirus 16 and 18 infections and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003;12:763–768. PubMed

Ravich A, Ravich RA. Prophylaxis of cancer of the prostate, penis, and cervix by circumcision. NY State J Med. 1950;50:1519–1520. PubMed

Taylor ML, Mainous AG, Wells BJ. Prostate cancer and sexually transmitted diseases: a meta-analysis. Fam Med. 2005;37(7):506–512. PubMed

Stone KM, Karem KL, Sternberg MR, Mc Quillan GM, Poon AD, Unger ER, Reeves WC. Seroprevalence of Human Papillomavirus Type 16 Infection in the United States. J Infect Dis. 2002;186:1396–1402. doi: 10.1086/344354. PubMed DOI

Giuliano AR, Tortolero-Luna G, Ferrer E, Burchell AN, de Sanjose S, Kjaer SK, Munoz N, Schiffman M, Bosch FX. Epidemiology of Human Papillomavirus Infection in Men, Cancers otherthan Cervical and Benign Conditions. Vaccine. 2008;26(Suppl 10):K17–K28. doi: 10.1016/j.vaccine.2008.06.021. PubMed DOI PMC

Jeong WJ, Park SW, Shin M, Lee YJ, Jeon YK, Jung YH, Hah JH, Kwon TK, Song YS, Kim KH, Sung MW. Presence of HPV type 6 in dysplasia and carcinoma arising from recurrent respiratory papillomatosis. Head Neck. 2009;31(8):1095–1101. doi: 10.1002/hed.20998. PubMed DOI

González AB, Urban MI, Sitas F, Blackburn N, Hale M, Patel M, Ruff P, Sur R, Newton R, Beral V. Antibodies against six human herpesviruses in relation to seven cancers in black South Africans: A case control study. Infectious Agents and Cancer. 2006;1:2. http://www.infectagentscancer.com/content/1/1/2 PubMed PMC

Xu F, Schillinger JA, Sternberg MR, Johnson RE, Lee FK, Nahmias AJ, Markowitz LE. Seroprevalence and Coinfection with Herpes Simplex Virus Type 1 and Type 2 in the United States, 1988- 1994. J Infect Dis. 2002;185:1019–1024. doi: 10.1086/340041. PubMed DOI

Smith JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J Infect Dis. 2002;186(Suppl 1):S3–28. doi: 10.1086/343739. PubMed DOI

Samanta M, Harkins L, Klemm K, Britt WJ, Cobbs CS. High prevalence of human cytomegalovirus in prostatic intraepithelial neoplasia and prostatic carcinoma. J Urol. 2003;170:998–1002. doi: 10.1097/01.ju.0000080263.46164.97. PubMed DOI

Staras SAS, Dollard SC, Radford KW, Flanders WD, Pass RF, Cannon MJ. Seroprevalence of cytomegalovirus infection in the United States, 1988-1994. Clin Inf Dis. 2006;43:1143–1151. doi: 10.1086/508173. PubMed DOI

Wagenlehner FME, Weidner W, Naber KG. Chlamydial infections in urology. World J Urol. 2006;24:4–12. doi: 10.1007/s00345-005-0047-x. PubMed DOI

Stamm WE. Chlamydia trachomatis Infections: Progress and Problems. J Inf Dis. 1999;179(Suppl 2):S380–383. doi: 10.1086/513844. PubMed DOI

Kramer G, Mitteregger D, Marberger M. Is Benign Prostatic Hyperplasia (BPH) an Immune Inflammatory Disease? Eur Urol. 2007;51:1202–1216. doi: 10.1016/j.eururo.2006.12.011. PubMed DOI

Palapattu GS, Sutcliffe S, Bastian PJ, Platz EA, De Marzo AM, Isaacs WB, Nelson WG. Prostate carcinogenesis and inflammation: Emerging insights. Carcinogenesis. 2004;26:1170–1181. doi: 10.1093/carcin/bgh317. PubMed DOI

Takeyama K, Mitsuzawa H, Shimizu T, Konishi M, Nishitani C, Sano H, Kunishima Y, Matsukawa M, Takahashi S, Shibata K, Tsukamoto T, Kuroki Y. Prostate cell lines secrete IL-8 in response to Mycoplasma hominis through toll-like receptor 2-mediated mechanism. Prostate. 2006;66:386–391. doi: 10.1002/pros.20358. PubMed DOI

Namiki K, Goodison S, Porvasnik S, Allan RW, Iczkowski KA, Urbanek C, Reyes L, Sakamoto N, Rosser CJ. Persistent exposure to Mycoplasma induces malignant transformation of human prostate cells. PLoS ONE. 2009;4(9):e6872. doi: 10.1371/journal.pone.0006872. PubMed DOI PMC

Sutcliffe S, Giovannucci E, De Marzo AM, Leitzmann MF, Willett WC, Platz EA. Gonorrhea, Syphilis, Clinical Prostatitis, and the Risk of Prostate Cancer. Cancer Epidemiol Biomarkers Prev. 2006;15(11):2160–2166. doi: 10.1158/1055-9965.EPI-05-0913. PubMed DOI

Pretransplantation seroreactivity in kidney donors and recipients as a predictive factor for posttransplant BKPyV-DNAemia

Pretransplant BK Virus-Specific T-Cell-Mediated Immunity and Serotype Specific Antibodies May Have Utility in Identifying Patients at Risk of BK Virus-Associated Haemorrhagic Cystitis after Allogeneic HSCT

Cross-sectional study on the prevalence of HPV antibodies in the general population of the Czech Republic