Seroepidemiology of sexually transmitted infections of prostate cancer

Abstract: Background: There has been substantial progress in epidemiological research on prostate cancer over the last decade. An area of increasing interest is the possible role of sexual activity and history of sexually transmitted infections as a risk factor for prostate cancer. Specific sexually transmitted infections have only inconsistently been associated with prostate cancer, with positive associations being reported with syphilis, gonorrhea and Human Papillomavirus (HPV) infection. Some studies have also reported detection of viral DNA in prostate cancer cells, although other studies have not reproduced these findings. Seroepidemiological studies offer an attractive alternative for investigation associations of infections with prostate cancer, as they allow i) a readily standardized measure of long-term viral exposure on a biological sample ii) are objective (i.e. independent of subjective reporting) and iii) allow study designs that are epidemiologically valid in terms of sufficient study size and adequate controls. Aims: A large-scale epidemiological evaluation of possible associations between prostate cancer and infection with HPV-6, HPV-11, HPV-16, HPV-18 and HPV-52, Herpes simplex virus 2 (HSV-2) and Human Herpesvirus 8 (HHV-8) as well as two common human polyomaviruses (BK and JC). Results: Paper I is based on a follow-up of up to 24 years of the serum biobank of the Finnish Social Insurance agency, that identified 165 cases of prospectively occurring prostate cancer cases and matched controls that did not develop cancer during a similar length of follow-up. The seroprevalence of STIs was low in this cohort (2,4% for HHV-8 and 6,9% for HSV-2) and were not associated with prostate cancer risk (OR for prostate cancer if HHV-8-positive 0.74 (95% CI, 0.19–2.88), if HSV-2-positive 0.93 (95% CI, 0.44–1.96). In paper II, we used the biobanks that collaborate in the Nordic Biological Specimen Biobank Working Group on Cancer, Causes and Control that have jointly enrolled more than 200,000 men. Registry linkages identified 799 prospectively occurring cases of cancer and a selection of 2596 matched controls that did not develop prostate cancer. Seroprevalences for HPV-16, -18 or -33 were not significantly associated with prostate cancer risk, neither in the joint cohort nor in any one of the collaborating biobanks in the network. In paper III, we developed a multiplexed serology system for simultaneous one-tube detection of antibodies to several STIs (sexually transmitted infections) and applied it to a population-based case-control study of 245 men with prostate cancer and 204 matched controls. Seropositivities against HPV-6, -16, -18 and -52, HSV-2 or HHV-8 were not associated with prostate cancer. On the contrary, presence of multiple STIs was actually less common among prostate cancer patients (OR 0.18: 95% CI 0.04-0.83). In paper IV, we applied our multiplexed serology system to an even larger population-based case-control study of 2953 men with prostate cancer and 1819 population-based controls. The only infection that was significantly associated with prostate cancer was HHV-8, an inverse association (OR: 0,67; 95% Confidence Interval (CI): 0,51- 0,87). Conclusion: Technical development in high-throughput serology (“serolomics”) enabled sufficiently large-scale epidemiological studies to evaluate the STI hypothesis in prostate carcinogenesis. However, our studies which where of large size and had fairly strong statistical power, showed that it is unlikely, that there would exist any positive associations of STIs and prostate cancer.