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Multiple pathogens and prostate cancer

Infectious Agents and Cancer volume 17, Article number: 23 (2022) Cite this article

Abstract

Background

The aim of this review is to consider whether multiple pathogens have roles in prostate cancer.

Methods

We have reviewed case control studies in which infectious pathogens in prostate cancer were compared to normal and benign prostate tissues. We also reviewed additional evidence from relevant published articles.

Results

We confirmed that high risk human papilloma viruses are a probable cause of prostate cancer. We judged Escherichia coli, Cutibacterium acnes, Neisseria gonorrhoea, Herpes simplex, Epstein Barr virus and Mycoplasmas as each having possible but unproven roles in chronic prostatic inflammation and prostate cancer. We judged Cytomegalovirus, Chlamydia trachomatis, Trichomonas vaginalis and the Polyoma viruses as possible but unlikely to have a role in prostate cancer.

Conclusions and actions

The most influential cause of prostate cancer appears to be infection induced chronic inflammation. Given the high prevalence of prostate cancer it is important for action to can be taken without waiting for additional conclusive evidence. These include:

  1. 1.

    Encouragement of all boys (as well as girls) to have HPV vaccines

  2. 2.

    The vigorous use of antibiotics to treat all bacterial pathogens identified in the urogenital tract

  3. 3.

    The use of antiviral medications to control herpes infections

  4. 4.

    Education about safe sexual practices

Introduction

The aim of this review is to consider whether multiple pathogens have roles in prostate cancer. Multiple pathogens have long been hypothesised as an underlying cause of prostate cancer. However, apart from high-risk for cancer human papilloma viruses (HPVs), no specific pathogens have confirmed causal roles.

We have previously shown that high risk for cancer human papilloma viruses have a probable, but not conclusive, causal role in prostate cancer [1]. This is important because of the availability of safe and effective vaccines against HPV infections. In this review we have updated the evidence which may implicate other infectious pathogens.

We consider it is unlikely that any acute infectious pathogens cause prostate cancer. On the other hand, infectious pathogens that cause long term chronic inflammation are likely to have roles in prostate cancer.

Epidemiology

Prostate cancer develops in 1 in 8 Western men [2]. About 60% of cases occurs in men aged 65 years or older. It is rare in men under the age of 40 years. About 30% of men have undiagnosed prostate cancer at the time of their death, hence the saying “many men die with, rather than from, prostate cancer”. Prostate cancer occurs more frequently in Western than Asian men [2]. When Asian men migrate from low to high risk countries the risk of developing prostate cancer increases [3]. The reason is not known. However, the number of immigrants developing prostate cancer is still lower than that of men in Western countries [4]. This phenomena is also present in breast cancer for Asian women who migrate from low to high risk countries, the risk of breast cancer rapidly increases within two generations to almost equal that of the host country [5].

Methods

We have conducted a review of selected English language publications listed in PubMed from 1960 to 2021 relevant to infectious pathogens and prostate cancer. Only studies which included controls were reviewed. Any form of selection introduces bias. For this reason the two authors independently selected the studies that were considered. Any differences in the selection were discussed and joint decisions were made. Additional problems in the assessment of the role of specific pathogens in prostate cancer include (1) the variations in outcomes of studies using similar methods in the same populations, (2) contamination of the prostate specimens and (4) the absence of benign or normal prostate controls.

The selection of pathogens for this review was based on the many previous studies of infections and prostate cancer. These pathogens included Human papilloma viruses, Cetabacterium acnes, Herpes viruses including Epstein Barr virus, Neisseria gonorrhoea, Herpes simplex, Epstein Barr virus, Cytomegalovirus, Chlamydia bacteria, Trichomonas bacteria, Mycoplasmas and Polyoma viruses. Case control studies were available for each of these pathogens. Other pathogens, for which no case controls have been conducted, may also have roles in prostate cancer, for example Escherichia coli, fungal prostatitis, mouse mammary tumour virus and human immunodeficiency virus [6, 7].

The use of case control studies for the study of infections and prostate cancer can be misleading. This is because in most studies the non-cancer controls were benign prostate tissues. Chronic infections are common in the prostate and this can negate the comparisons between cancer and controls.

The Bradford Hill criteria have been frequently used for assessing causal roles of pathogens and other agents [8]. These criteria have been immensely influential. They have largely replaced the famous Koch postulates. Over the last 50 years, it has been estimated that over 100,000 published articles have used the Hill criteria [9]. Hill developed nine criteria in the context of his research into the links between tobacco smoking and lung cancer [10]. At that time the role of viruses in various human cancers was not known. In addition, since 1965 there have been major developments in knowledge and technology. It has also been realised that the relevance of the individual criteria vary according to the nature of the pathogen or harmful agent. Accordingly, there has been a need to add and modify the classic Hill criteria. The list of the Hill and extended criteria in some order of importance include:

(1) Identification and history of the candidate pathogen. (2) Epidemiology. (3) Strength of the association between the pathogen and prostate cancer. (4). Temporality (timing) of the association which includes evidence of infection by a pathogen in normal tissues before the development of the cancer. (5). Does exposure to the pathogen lead to infection, oncogenesis and cancer? (6) Experimental evidence, for example, capacity of the pathogen to cause cancer in experimental animals, capacity to infect human cells, ability to transform normal human cells into malignant cells, evidence that a vaccine or therapy can inhibit the pathogen from infecting or transforming cells. (7) Coherence, analogy, biological plausibility. (8) Transmission including identification of the source and means of transmission of the pathogen. (9) Oncogenic mechanisms. (10) Multiple viral and causal factors. (11) Specificity- this criteria was in Hill’s original list but is rarely helpful as many viruses and other pathogens can lead to cancer in different organs.

Hill [8] strongly cautioned against dogmatism.” None of my nine viewpoints can bring indisputable evidence for or against the cause-and-effect hypothesis and none can be required as a sine qua non (meaning an essential requirement).

In this current review these criteria could only be fully used with respect to human papilloma viruses because of the limited evidence available for the other pathogens listed above.

Human papilloma viruses (HPV)

We have recently reviewed the evidence and concluded that it is highly likely that high risk for cancer HPVs have a causal role in prostate cancer [1]. The most important evidence is the demonstration that the prevalence of high-risk HPVs is consistently higher in prostate cancer than in benign prostate controls. This is shown in Table 1 [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36]. In brief the evidence is as follows:

  1. 1.

    High risk for cancer HPVs have been identified in many countries by a range of methods in normal, benign and malignant prostate tissues [37].

  2. 2.

    In 10 of 27 case control studies conducted with PCR techniques, the prevalence of high-risk HPV DNA was significantly higher in prostate cancers as compared to normal and benign prostate controls (studies in which HPVs were not identified have not been included in Table 1). In these 27 studies there were 399 HPV positive of 1678 prostate cancers (24%) and129 HPV positive of 1331 benign prostate controls (10%) (p = 0.001).

  3. 3.

    High risk HPV types 16 and 18 have the capacity to immortalise and transform normal prostate cells into malignant cells [38, 39].

  4. 4.

    HPVs are mainly transmitted by sexual activity [40]. HPVs can be transmitted throughout the body via circulating extra-cellular vesicles and blood [41].

  5. 5.

    High risk HPVs are associated with inflammatory prostatitis which can lead to benign prostate hyperplasia and later prostate cancer [42, 43].

  6. 6.

    High risk HPVs of the same type have been identified in benign prostate tissues 1–11 years before the development of HPV positive prostate cancer in the same patients [44].

Table 1 Identification of high risk human papilloma viruses in prostate cancer
Full size table

While the highest prevalence of HPV genital infections occurs in younger people there is an increased prevalence in older age groups (over 55 years) [45, 46]. This increase in older people is unlikely to be due to increased sexual activity. Prostate cancer is much more prevalent in older men. Accordingly there may be an association between older age HPV reactivation and prostate cancer.

The reason for the reactivation of HPVs is not known. An explanation may be the concept of “trained immunity” [47]. This concept involves the long-term reprogramming of innate immune cells, which can be reactivated by stimuli such as infections or chemicals. While this response can be protective against a harmful stimulus, over- reactions such as inflammation can develop. In turn, chronic inflammation can be oncogenic. While there is no direct evidence available with respect to prostate cancer, HPVs can remain dormant in the host cell genome, thus evading the host immune response until they are reactivated [48].

The oncogenic mechanisms for HPV oncogenesis in prostate cancer are not clear and may differ from HPV oncogenesis in cervical cancer. There is evidence that HPV E7 oncogenic proteins may be directly involved early in prostate oncogenesis [17]. HPV infections may have an indirect role by inhibiting the protective function of APOBEC3B enzymes against other virus infections [49, 50].

Effective and safe vaccines are available for the prevention of a wide range of different types of HPV infections [51].

With respect to Silvestre et al. [22], Tachezy et al. [26] and Mokhtari et al. [28] the numbers of positive cases are too few to justify statistical analysis.

Cutibacterium (Propionbacterium) acnes

Cutibacterium acnes (C. acnes) are part of the commensal flora of the skin where they colonize hair follicles and sebaceous glands [52]. Different types of C. acnes can also cause serious post-operative infections. Cutibacterium acnes may also be present in the urogenital tract including the prostate. Cutibacterium acnes can damage blood cells, cause host tissue degradation and disrupt cell surface components.

Cutibacterium acnes has been identified in prostate cancer tissues. In 2 of 6 case control studies C. acnes was significantly more prevalent in prostate cancer than in control benign prostate tissues (Table 2) [53,54,55,56,57,58]. Most C. acnes from prostate cancer tissues differ genetically from common skin C. acnes [59]. Alexeyev et al. [53] have identified C. acnes in benign prostate tissues taken up to 6 years apart from individual subjects. This indicates that C. acnes infection can be chronic and a cause of chronic inflammation. Cutibacterium acnes infections induce upregulation of inflammatory genes and cytokine secretion in prostate epithelial cells [60].

Table 2 Cutabacterium acnes infections and prostate cancer
Full size table

Accordingly C. acnes is a candidate pathogen in prostatitis and prostate cancer.

The evidence that antibiotics can control C. acnes infections is based on skin infections [61]. Resistance to antibiotics is an increasing problem.

Escherichia coli

Escherichia coli have been consistently identified by PCR and Next Generation Sequencing in prostate cancer and benign prostate tissues [54, 62]. Unfortunately, good controls have not been used in these studies and no case control studies have been identified. A problem in studying E. coli and prostate cancer is that biopsies are usually conducted by gaining access to the prostate via the rectum. This can cause contamination of the prostate tissues by rectal located E. coli.

Escherichia coli is usually a harmless commensal bacteria that colonizes the human gut. However, many different types and strains exist, some of them have virulence properties that can result in inflammation and damage of the prostate. Jain et al. [63] have isolated E. coli from benign prostate tissues and demonstrated that this pathogen activated NF-kB and induced damage to normal cultured prostate epithelial cells. NF-kB proteins are activated by carcinogens and are known to be involved in oncogenesis [64]. Hemolysin and necrotizing factor type 1 occur significantly more frequently among C. coli isolates causing prostatitis than among those causing cystitis or pyelonephritis [65].

It is considered likely that some types of E. coli have causal roles in colon cancer [66]. Accordingly it is possible that E. coli can also cause prostate cancer.

Neisseria gonorrhoea (N. gonorrhoea)

Neisseria gonorrhoeae is the well known cause of the sexually transmitted disease gonorrhea [67]. The organism can manipulate the immune response which leads to a lack of protective immunity. Therefore individuals can become repeatedly infected. Gonorrhoea is generally a mucosal infection of the urethra with a pustular discharge. More severe sequalae include salpingitis and pelvic inflammatory disease which may lead to sterility and/or ectopic pregnancy. Neisseria gonorrhoeae can cause chronic inflammation of the prostate which in turn can be oncogenic [68]. Gonorrhoea is susceptible to an array of antibiotics. Antibiotic resistance is becoming a major problem.

There have been 22 case control studies in which the prevalence of N. gonorrhoea in prostate cancer has been compared to controls (Table 3) [69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90]. In six of these studies it was shown that N. gonorrhoea was significantly more prevalent in the prostate cancer cases. In 16 of these studies there was no significant difference been the cases and controls.

Table 3 Neisseria gonorrhoea infections and prostate cancer
Full size table

There is a possible explanation for these conflicting data, namely that sexually transmitted diseases are frequently due to multiple pathogens. In the meta-analysis by Taylor et al. [91] there were significant correlations between both N. gonorrhoea and HPVs and increased prevalence of prostate cancer (odds ratios gonorrhoea 1.35, HPV 1.39). It is possible that high risk HPVs were the cause of prostate cancer in these studies and that N. gonorrhoea was also present but not oncogenic.

Herpes viruses

Herpes simplex

Herpes simplex virus 1 (HSV-1) commonly causes infections of the mouth (cold sores).

HSV-2 is associated with anogenital infections and is a sexually transmitted infection.

Both virus types can cause both kinds of infection. Infections due to herpes simplex do not usually confer immunity. No vaccines are currently available.

In four of 12 studies Herpes simplex 1 or 2 were significantly more prevalent in the prostate cancer cases (Table 4) [70, 87, 88, 92,93,94,95,96,97,98]. Dennis et al. demonstrated that herpes simplex 2 could be identified in prostate cancer tissues over a period of 8 years [98]. These findings suggest that if herpes simplex has an oncogenic capacity there may be a long latency period for prostate cancer development after HSV-2 infection.

Table 4 Herpes simplex virus infections and prostate cancer
Full size table

Acyclovir has been successfully used to treat genital herpes simplex infections [99].

Epstein Barr virus (EBV) (Herpes virus 4)

Cancers including breast and prostate cancer [1, 100].

There have been four case control studies of EBV and prostate cancer. In one study by Sfanos et al. [54], EBV was significantly more prevalent in prostate cancer compared to controls (Table 5) [54, 97, 100, 101].

Table 5 Epstein Barr virus (herpes virus 4) infections and prostate cancer
Full size table

The effectiveness of antiviral agents (acyclovir, valomaciclovir and valacyclovir) in acute infectious mononucleosis is uncertain [99, 102].

Cytomegalovirus (CMV) (herpes virus 5)

Human CMV is present in over 80% of most populations. Transmission can occur during foetal life, via breast milk, saliva and during sexual activities. Human CMV infections in healthy people are mostly mild or without symptoms. In contrast, CMV can cause serious defects during foetal life and life threatening illness among immunocompromised patients such as transplant recipients and patients with AIDS [103].

As shown in Table 6 [23, 87, 93, 104, 105] in four of five case control studies there were no significant differences between the prevalence of CMV in prostate cancers and controls. In one study CMV was identified in the controls but not in prostate cancers [23].

Table 6 Cytomegalovirus infections and prostate cancer
Full size table

Chlamydia trachomatis (C. trachomatis)

Chlamydia trachomatis is a common, sexually transmitted bacteria. Chlamydia trachomatis initiates and can maintain inflammation and persistent infection including prostatitis [105]. Human prostate cancer epithelial cells are susceptible to C. trachomatis infection and initiate inflammation [106, 107]. As inflammation is associated with prostate cancer it has been hypothesized that C. trachomatis could have a causal role.

However, as shown in Table 7 [81, 87, 88, 98, 106, 108,109,110] in eight case control studies there were no positive associations between C. trachomatis infections and prostate cancer. On the other hand, all these studies are based on serology, and it is possible that these case control studies are misleading as C. trachomatis may be causing chronic infection in the prostate leading to prostate cancer. This would lead to positive antibodies in both benign prostate controls and prostate cancer.

Table 7 Chlamydia trachomatis infections and prostate cancer
Full size table

Azithromycin and Doxycycline antibiotics appear to be effective in the treatment of sexually transmitted C. trachomatis [111].

Trichomonas vaginalis (T.vaginalis)

Trichomonas vaginalis is a common protozoan infection frequently transmitted during sexual activities [112]. Trichomonas vaginalis in men is usually asymptomatic but may cause urethritis, prostatitis, epididymitis and infertility [113].

As shown in Table 8 [86, 114,115,116,117,118,119,120,121] in eight of nine case control studies there is no increase in risk of prostate cancer in association with T. vaginalis infections. In two studies positive antibodies were higher in the controls than the cancer. These nine studies were all based on serology and involved a high number of subjects.

Table 8 Trichomonas vaginalis infections and prostate cancer
Full size table

In a large serology based study by Tsang et al. [122] there was no increase in prostate cancer deaths associated with T. vaginalis. This finding makes it unlikely that T. vaginalis is associated with prostate cancer.

The 5-nitroimidazoles (metronidazole, tinidazole, secnidazole) are the only class of antimicrobials effective against T. vaginalis [113]. Unfortunately, there is growing concern over drug resistance with metronidazole.

Mycoplasma

Mycoplasma bacteria frequently infect prostate tissues and prostate cancer. The most common are M. hominus, M. ureaplasma and M. hyorhinus [123]. A recent meta-analysis showed that Mycoplasma bacterial infections were 2.24 times more frequent in patients with prostate cancer as compared to benign prostate hyperplasia [124]. These data are shown in Table 9 [88, 123, 125,126,127,128,129].

Table 9 Mycoplasma infections and prostate cancer
Full size table

Of particular interest are the studies based on PCR analyses of tissues as compared to studies based on serology. Three of the PCR studies with positive results were significant, and two showed a trend that Mycoplasma infections were more frequent in prostate cancers than benign prostate controls. Accordingly, it is possible that Mycoplasma bacteria may have a role in prostate cancer. However additional evidence is required.

Antibiotics can be effective in treating Mycoplasma bacterial infections. Unfortunately, resistance to antibiotic treatment is emerging [130].

Polyoma viruses (hPy)

The two human polyomaviruses (hPy), BK virus (BKV), and JC virus (JCV), are commonly present in human populations. Infections usually occurs in childhood but rarely cause clinical symptoms. In immunocompromised patients JCV can cause serious neurodegenerative conditions. There is no direct evidence that hPy viruses are oncogenic [131].

We have identified 11 case control studies of BKV and JCV and their associations with prostate cancer in which polyoma viruses were identified (Table 10) [97, 132,133,134,135,136,137,138,139]. In two small studies based on PCR there was a significant association with prostate cancer. There were no significant associations in 9 studies.

Table 10 Polyoma BKV, JCV prostate cancer
Full size table

Accordingly it is unlikely that these polyomaviruses have causal roles in prostate cancer.

Fungal prostatitis

Infections of the prostate by several fungi are the unusual cause of prostatitis. These fungi include Blastomycosis, Candida albicans and Cryptococcus [140]. There is no evidence that these fungi are associated with prostate cancer. However, there must be suspicions about any pathogen which leads to chronic inflammation.

Mouse mammary tumour virus (MMTV)

MMTV is the proven cause of breast cancer in mice. There is compelling evidence that MMTV—like viruses are also causal in human breast cancer [7]. MMTV has been identified in prostate glands of mice [141]. MMTV—like viruses have been identified in human prostate cancers [6]. However, no studies have been conducted to determine if MMTV is causal in human prostate cancer.

Human immunodeficiency virus (HIV)

Compared to the general population, people living with HIV have a lower prevalence of prostate cancer [142, 143]. This is probably due to the suppression of immune related B and T cells associated with both HIV and MMTV infections.

The gut microbiome and prostate cancer

The gut microbiome may also play an indirect role in various cancers [144]. In a study which compared the gut microbiota in men with prostate cancer and benign controls there was a significant difference in gut microbiol composition [145]. The meaning of these observations is not known.

Discussion

High risk human papilloma viruses are the only pathogens for which there is sufficient evidence to indicate a probable causal role in prostate cancer. Fortunately, there are safe and effective vaccines available to prevent HPV infections [146].

Other pathogens may have roles in prostate cancer but the evidence is limited. These include Cutibacterium acnes, Neisseria gonorrhoea, Herpes simplex, Epstein Barr virus, and Mycoplasmas. In our view it is unlikely that Cytomegalovirus, Trichomonis vaginalis, Chlamydia trachomonis, Polyoma viruses, Human immunodeficiency virus and fungi have causal roles in prostate cancer.

HPVs are the only pathogen considered in this review which have a proven oncogenic capacity. However, in its acute stage it is unlikely that an HPV infection leads to prostate cancer as HPV infections are common in young men and prostate cancer occurs mainly in older men. On the other hand, as considered above, the influence of HPV may be reactivated and lead to prostate oncogenesis via long-term reprogramming of innate immune cells.

While the oncogenic mechanisms probably differ between these pathogens, of particular relevance is the potential role of inflammation in prostate cancer. Different pathogens may each cause chronic inflammation. Multiple pathogens are frequently present in prostate tissues and chronic exposure can lead to chronic inflammation and ultimately to prostate cancer. The relevant evidence has been reviewed in detail by De Bono et al. [147] and Gobel et al. [148].

A precise mechanism linking inflammation to cancer is the nuclear transcription factor “kappa-light-chain-enhancer” of B-cells known as NF-kB. This is a protein activated by many carcinogens. It controls genes commonly associated with oncogenesis [64]. Almost all infectious agents linked with cancer activate NF-nB. This has been confirmed experimentally in mice by the inactivation of NF-kB which reduced inflammation initiated cancer formation [149]. Infectious pathogens can activate inflammatory pathways which lead to genomic instability in tissue cells which in turn lead to malignant transformation. HPV, human herpes virus, and EBV, have been specifically shown to activate NF-kB. Confirmation of this evidence has been provided by the reduction in risk of cancer by anti-inflammatory agents such as aspirin [150].

Conclusions and actions

The most influential cause of prostate cancer appears to be infection induced chronic inflammation.

Given the high prevalence of prostate cancer it is important for action to can be taken without waiting for additional conclusive evidence. These include:

  1. 1.

    Encouragement of all boys (as well as girls) to have HPV vaccines

  2. 2.

    The vigorous use of antibiotics to treat all bacterial pathogens identified in the urogenital tract

  3. 3.

    The use of antiviral medications to control herpes infections

  4. 4.

    Education about safe sexual practices

Availability of data and materials

Not applicable.

Abbreviations

HPV:

Human papilloma viruses

C. acnes :

Cutibacterium acnes

N. gonorrhoea :

Neisseria gonorrhoea

HSV:

Herpes simplex virus

EBV:

Epstein Barr virus

CMV:

Cytomegalovirus

C. trachomatis :

Chlamydia trachomatis

T. vaginalis :

Trichomonas vaginalis

hPy:

Polyoma virus

MMTV:

Mouse mammary tumour virus

HIV:

Human immunodeficiency virus

References

  1. Lawson JS, Glenn WK. Evidence for a causal role by human papillomaviruses in prostate cancer: a systematic review. Infect Agent Cancer. 2020;15:41.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. Cancer statistics for the year 2020: an overview. Int J Cancer. 2021. https://doi.org/10.1002/ijc.33588.

    Article  PubMed  Google Scholar 

  3. Muir CS, Nectoux J, Staszewski J. The epidemiology of prostatic cancer. Geographical distribution and time-trends. Acta Oncol. 1991;30:133–40.

    Article  CAS  PubMed  Google Scholar 

  4. Kumar S, Singh R, Malik S, Manne U, Mishra M. Prostate cancer health disparities: an immuno-biological perspective. Cancer Lett. 2018;414:153–65.

    Article  CAS  PubMed  Google Scholar 

  5. Stanford JL, Herrington LJ, Schwartz SM, Weiss NS. Breast cancer incidence in Asian migrants to the US and their descendants. Epidemiology. 1995;6:181–3.

    Article  CAS  PubMed  Google Scholar 

  6. Johal H, Faedo M, Faltas J, Lau A, Mousina R, Cozzi P, Defazio A, Rawlinson WD. DNA of mouse mammary tumor virus-like virus is present in human tumors influenced by hormones. J Med Virol. 2010;82:1044–50.

    Article  CAS  PubMed  Google Scholar 

  7. Lawson JS, Glenn WK. Evidence for a causal role by mouse mammary tumour-like virus in human breast cancer. NPJ Breast Cancer. 2019;5:40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295–330.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Kleinberg S. On the use and abuse of Hill’s viewpoints on causality. Obs Stud. 2020;6:17–9.

    Google Scholar 

  10. Doll R, Hill AB. Smoking and carcinoma of the lung; preliminary report. Br Med J. 1950;2(4682):739–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. McNicol PJ, Dodd JG. High prevalence of human papillomavirus in prostate tissues. Urol J. 1991;145:850–3.

    Article  CAS  Google Scholar 

  12. Anwar K, Nakakuki K, Shiraishi T, Naiki H, Yatani R, Inuzuka M. Presence of ras oncogene mutations and human papillomavirus DNA in human prostate carcinomas. Cancer Res. 1992;52:5991–6.

    CAS  PubMed  Google Scholar 

  13. Ibrahim GK, Gravitt PE, Dittrich KL, Ibrahim SN, Melhus O, Anderson SM, et al. Detection of human papillomavirus in the prostate by polymerase chain reaction and in situ hybridization. J Urol. 1992;148:1822–6.

    Article  CAS  PubMed  Google Scholar 

  14. Rotola A, Monini P, Di Luca D, Savioli A, Simone R, Secchiero P, et al. Presence and physical state of HPV DNA in prostate and urinary-tract tissues. Int J Cancer. 1992;52:359–65.

    Article  CAS  PubMed  Google Scholar 

  15. Dodd JG, Paraskevas M, McNicol PJ. Detection of human papillomavirus 16 transcription in human prostate tissue. J Urol. 1993;149:400–2.

    Article  CAS  PubMed  Google Scholar 

  16. Moyret-Lalle C, Marçais C, Jacquemier J, Moles JP, Daver A, Soret JY, et al. Ras, p53 and HPV status in benign and malignant prostate tumors. Int J Cancer. 1995;64:124–9.

    Article  CAS  PubMed  Google Scholar 

  17. Wideroff L, Schottenfeld D, Carey TE, Beals T, Fu G, Sakr W, et al. Human papillomavirus DNA in malignant and hyperplastic prostate tissue of black and white males. Prostate. 1996;28:117–23.

    Article  CAS  PubMed  Google Scholar 

  18. Terris MK, Peehl DM. Human papillomavirus detection by polymerase chain reaction in benign and malignant prostate tissue is dependent on the primer set utilized. Urology. 1997;50:150–6.

    Article  CAS  PubMed  Google Scholar 

  19. Serth J, Panitz F, Paeslack U, Kuczyk MA, Jonas U. Increased levels of human papillomavirus type 16 DNA in a subset of prostate cancers. Cancer Res. 1999;59:823–5.

    CAS  PubMed  Google Scholar 

  20. Carozzi F, Lombardi FC, Zendron P, Confortini M, Sani C, Bisanzi S, et al. Association of human papillomavirus with prostate cancer: analysis of a consecutive series of prostate biopsies. Int J Biol Markers. 2004;19:257–61.

    Article  CAS  PubMed  Google Scholar 

  21. Leiros GJ, Galliano SR, Sember ME, Kahn T, Schwarz E, Eiguchi K. Detection of human papillomavirus DNA and p53 codon 72 polymorphism in prostate carcinomas of patients from Argentina. BMC Epidemiol Health. 2015;37:e2015005.

    Google Scholar 

  22. Silvestre RV, Leal MF, Demachki S, Nahum MC, Bernardes JG, Rabenhorst SH, et al. Low frequency of human papillomavirus detection in prostate tissue from individuals from northern Brazil. Mem Inst Oswaldo Cruz. 2009;104:665–7.

    Article  PubMed  Google Scholar 

  23. Martinez-Fierro ML, Leach RJ, Gomez-Guerra LS, Garza-Guajardo R, Johnson-Pais T, Beuten J, et al. Identification of viral infections in the prostate and evaluation of their association with cancer. BMC Cancer. 2010;10:326.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Aghakhani A, Hamkar R, Parvin M, Ghavami N, Nadri M, Pakfetrat A, et al. The role of human papillomavirus infection in prostate carcinoma. Scand J Infect Dis. 2011;43:64–9.

    Article  PubMed  Google Scholar 

  25. Chen AC, Waterboer T, Keleher A, Morrison B, Jindal S, McMillan D, et al. Human papillomavirus in benign prostatic hyperplasia and prostatic adenocarcinoma patients. Pathol Oncol Res. 2011;17:613–7.

    Article  CAS  PubMed  Google Scholar 

  26. Tachezy R, Hrbacek J, Heracek J, Salakova M, Smahelova J, Ludvikova V, et al. HPV persistence and its oncogenic role in prostate tumors. J Med Virol. 2012;84:1636–45.

    Article  CAS  PubMed  Google Scholar 

  27. Ghasemian E, Monavari SH, Irajian GR, Jalali Nodoshan MR, Roudsari RV, Yahyapour Y. Evaluation of human papillomavirus infections in prostatic disease: a cross-sectional study in Iran. Asian Pac J Cancer Prev. 2013;14:3305–8.

    Article  PubMed  Google Scholar 

  28. Mokhtari M, Taghizadeh F, Hani M. Is prostatic adenocarcinoma in a relationship with human papilloma virus in Isfahan -Iran. J Res Med Sci. 2013;18:707–10.

    PubMed  PubMed Central  Google Scholar 

  29. Michopoulou V, Derdas SP, Symvoulakis E, Mourmouras N, Nomikos A, Delakas D, et al. Detection of human papillomavirus (HPV) DNA prevalence and p53 codon 72 (Arg72Pro) polymorphism in prostate cancer in a Greek group of patients. Tumour Biol. 2014;35:12765–73.

    Article  CAS  PubMed  Google Scholar 

  30. Singh N, Hussain S, Kakkar N, Singh SK, Sobti RC, Bharadwaj M. Implication of high risk Human papillomavirus HR-HPV infection in prostate cancer in Indian population: a pioneering case-control analysis. Sci Rep. 2015;5:7822.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Huang L, Wu MG, He J, Wei ZS, Lü WX, Song XJ, et al. Correlation of highrisk HPV 16/18 infections with prostate cancer. Zhonghua Nan Ke Xue. 2016;22:501–5.

    CAS  PubMed  Google Scholar 

  32. Dávila-Rodríguez MI, Ignacio Morales CV, Aragón Tovar AR, Olache Jimenez D, Castelán Maldonado E, Lara Miranda S, et al. Human papilloma virus detection by INNOLiPA HPV in prostate tissue from men of Northeast Mexico. Asian Pac J Cancer Prev. 2016;17:4863–5.

    PubMed  Google Scholar 

  33. Atashafrooz F, Rokhbakhsh-Zamin F. Frequency and type distribution of human papilloma virus in patients with prostate Cancer, Kerman, southeast of Iran. Asian Pac J Cancer Prev. 2016;17:3953–8.

    PubMed  Google Scholar 

  34. Medel-Flores O, Valenzuela-Rodríguez VA, Ocadiz-Delgado R, Castro-Muñoz LJ, Hernández-Leyva S, Lara-Hernández G, et al. Association between HPV infection and prostate cancer in a Mexican population. Genet Mol Biol. 2018;41:781–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nahand JS, Esghaei M, Hamidreza Monavari S, Moghoofei M, Jalal Kiani S, Mostafaei S, Mirzaei H, Bokharaei-Salim F. The assessment of a possible link between HPV-mediated inflammation, apoptosis, and angiogenesis in Prostate cancer. Int Immunopharmacol. 2020;88:106913.

    Article  CAS  Google Scholar 

  36. Fatemipour M, Nahand JS, Fard Azar ME, Baghi HB, Taghizadieh M, Sorayyayi S, Hussen BM, Mirzaei H, Moghoofei M, Bokharaei-Salim F. Human papillomavirus and prostate cancer: the role of viral expressed proteins in the inhibition of anoikis and induction of metastasis. Microb Pathog. 2021;152:104576.

    Article  CAS  PubMed  Google Scholar 

  37. Whitaker NJ, Glenn WK, Sahrudin A, Orde MM, Delprado W, Lawson JS. Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer. Prostate. 2013;73:236–41.

    Article  CAS  PubMed  Google Scholar 

  38. Rhim JS, Webber MM, Bello D, Lee MS, Arnstein P, Chen LS, et al. Stepwise immortalization and transformation of adult human prostate epithelial cells by a combination of HPV-18 and v-Ki-ras. Proc Natl Acad Sci U S A. 1994;91:11874–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schütze DM, Snijders PJ, Bosch L, Kramer D, Meijer CJ, Steenbergen RD. Differential in vitro immortalization capacity of eleven (probable) high-risk human papillomavirus types. J Virol. 2014;88:1714–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Crocetto F, Arcaniolo D, Napolitano L, Barone B, La Rocca R, Capece M, Caputo VF, Imbimbo C, De Sio M, Calace FP, Manfredi C. Impact of sexual activity on the risk of male genital tumors: a systematic review of the literature. Int J Environ Res Public Health. 2021;18:8500.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Guenat D, Hermetet F, Prétet J-L, Mougin C. Exosomes and other extracellular vesicles in HPV transmission and carcinogenesis. Viruses. 2017;9:211.

    Article  PubMed Central  CAS  Google Scholar 

  42. La Vignera S, Condorelli RA, Cannarella R, Giacone F, Mongioi L, Scalia G, et al. High rate of detection of ultrasound signs of prostatitis in patients with HPV-DNA persistence on semen: role of ultrasound in HPV-related male accessory gland infection. J Endocrinol Invest. 2019;42:1459–65.

    Article  PubMed  CAS  Google Scholar 

  43. Zhang L, Wang Y, Qin Z, Gao X, Xing Q, Li R, et al. Correlation between prostatitis, benign prostatic hyperplasia and prostate cancer: a systematic review and meta-analysis. J Cancer. 2020;11:177–89.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Glenn WK, Ngan CC, Amos TG, Edwards RJ, Swift J, Lutze-Mann L, et al. High risk human papillomaviruses (HPVs) are present in benign prostate tissues before development of HPV associated prostate cancer. Infect Agent Cancer. 2017;12:46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Sudenga SL, Torres BN, Silva R, Villa LL, Lazcano-Ponce E, Abrahamsen M, Baggio ML, Salmeron J, Quiterio M, Giuliano AR. Comparison of the natural history of genital HPV infection among men by country: Brazil, Mexico, and the United States. Cancer Epidemiol Biomark Prev. 2017;26:1043–52.

    Article  Google Scholar 

  46. Wei F, Gaisa MM, D’Souza G, Xia N, Giuliano AR, Hawes SE, Gao L, Cheng SH, Donà MG, Goldstone SE, et al. Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies. Lancet HIV. 2021;8:e531–43.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM, Riksen NP, Schlitzer A, Schultze JL, Stabell Benn C, Sun JC, Xavier RJ, Latz E. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020;20:375–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Korostil IA, Regan DG. The potential impact of HPV-16 reactivation on prevalence in older Australians. BMC Infect Dis. 2014;14:312.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ohba K, Ichiyama K, Yajima M, Gemma N, Nikaido M, Wu Q, et al. in vivo and in vitro studies suggest a possible involvement of HPV infection in the early stage of breast carcinogenesis via APOBEC3B induction. PLoS ONE. 2014;9:e97787.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Vieira VC, Leonard B, White EA, Starrett GJ, Temiz NA, Lorenz LD, et al. Human papillomavirus E6 triggers upregulation of the antiviral and cancer genomic DNA deaminase APOBEC3B. MBio. 2014;5:e02234-e2314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Markowitz LE, Schiller JT. Human papillomavirus vaccines. J Infect Dis. 2021;224(Supplement_4):S367–78.

    Article  CAS  PubMed  Google Scholar 

  52. Dekio I, Asahina A, Shah HN. Unravelling the eco-specificity and pathophysiological properties of Cutibacterium species in the light of recent taxonomic changes. Anaerobe. 2021;71:102411.

    Article  CAS  PubMed  Google Scholar 

  53. Alexeyev O, Bergh J, Marklund I, Thellenberg-Karlsson C, Wiklund F, Grönberg H, Bergh A, Elgh F. Association between the presence of bacterial 16S RNA in prostate specimens taken during transurethral resection of prostate and subsequent risk of prostate cancer (Sweden). Cancer Causes Control. 2006;17:1127–33.

    Article  CAS  PubMed  Google Scholar 

  54. Sfanos KS, Sauvageot J, Fedor HL, Dick JD, De Marzo AM, Isaacs WB. A molecular analysis of prokaryotic and viral DNA sequences in prostate tissue from patients with prostate cancer indicates the presence of multiple and diverse microorganisms. Prostate. 2008;68:306–20.

    Article  CAS  PubMed  Google Scholar 

  55. Severi G, Shannon BA, Hoang HN, Baglietto L, English DR, Hopper JL, Pedersen J, Southey MC, Sinclair R, Cohen RJ, Giles GG. Plasma concentration of Propionibacterium acnes antibodies and prostate cancer risk: results from an Australian population-based case–control study. Br J Cancer. 2010;103:411–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bae Y, Ito T, Iida T, Uchida K, Sekine M, Nakajima Y, Kumagai J, Yokoyama T, Kawachi H, Akashi T, Eishi Y. Intracellular Propionibacterium acnes infection in glandular epithelium and stromal macrophages of the prostate with or without cancer. PLoS ONE. 2014;9:e90324.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Davidsson S, Molling P, Rider JR, Unemo M, Karlsson MG, Carlsson J, Andersson SO, Elgh F, Soderquis B, Andren O. Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer. Infect Agent Cancer. 2016;11:26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Kakegawa T, Bae Y, Ito T, Uchida K, Sekine M, Nakajima Y, Furukawa A, Suzuki Y, Kumagai J, Akashi T, Eishi Y. Frequency of propionibacterium acnes infection in prostate glands with negative biopsy results is an independent risk factor for prostate cancer in patients with increased serum PSA Titers. PLoS ONE. 2017;12:e0169984.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Cohen RJ, Shannon BA, McNeal JE, Shannon T, Garrett KL. Propionibacterium acnes associated with inflammation in radical prostatectomy specimens: a possible link to cancer evolution? J Urol. 2005;173:1969–74.

    Article  PubMed  Google Scholar 

  60. Drott JB, Alexeyev O, Bergström P, Elgh F, Olsson J. Propionibacterium acnes infection induces upregulation of inflammatory genes and cytokine secretion in prostate epithelial cells. BMC Microbiol. 2010;10:126.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Dessinioti C, Dreno B. Acne treatments: future trajectories. Clin Exp Dermatol. 2020;45:955–61.

    Article  CAS  PubMed  Google Scholar 

  62. Brüggemann H, Al-Zeer MA. Bacterial signatures and their inflammatory potentials associated with prostate cancer. APMIS. 2020;128:80–91.

    Article  PubMed  Google Scholar 

  63. Jain S, Samal AG, Das B, Pradhan B, Sahu N, Mohapatra D, Behera PK, Satpathi PS, Mohanty AK, Satpathi S, Senapati S. Escherichia coli, a common constituent of benign prostate hyperplasia-associated microbiota induces inflammation and DNA damage in prostate epithelial cells. Prostate. 2020;80:1341–52.

    Article  CAS  PubMed  Google Scholar 

  64. Aggarwal BB, Vijayalekshmi RV, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res. 2009;15:425–30.

    Article  CAS  PubMed  Google Scholar 

  65. Ruiz J, Simon K, Horcajada JP, Velasco M, Barranco M, Roig G, Moreno-Martínez A, Martínez JA, Jiménez de Anta T, Mensa J, Vila J. Differences in virulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men. J Clin Microbiol. 2002;40:4445–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Alhinai EA, Walton GE, Commane DM. The role of the gut microbiota in colorectal cancer causation. Int J Mol Sci. 2019;20:5295.

    Article  CAS  PubMed Central  Google Scholar 

  67. Hill SA, Masters TL, Wachter J. Gonorrhea: an evolving disease of the new millennium. Microb Cell. 2016;3:371–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Sfanos KS, Yegnasu Bramanian S, Nelson WG, De Marzo AM. The inflammatory microenvironment and microbiome in prostate cancer development. Nat Rev Urol. 2018;15:11–24.

    Article  PubMed  Google Scholar 

  69. Heshmat MY, Kovi J, Herson J, Jones GW, Jackson MA. Epidemiologic association between Gonorrhea and prostatic carcinoma. Urology. 1975;6:457–60.

    Article  CAS  PubMed  Google Scholar 

  70. Baker LH, Mebust WK, Chin TD, Chapman AL, Hinthorn D, Towle D. The relationship of herpesvirus to carcinoma of the prostate. J Urol. 1981;125:370–4.

    Article  CAS  PubMed  Google Scholar 

  71. Lees RE, Steele R, Wardle D. Arsenic, syphilis, and cancer of the prostate. J Epidemiol Community Health. 1985;39:227–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mishina T, Watanabe H, Araki H, Nakao M. Epidemiological study of prostatic cancer by matched-pair analysis. Prostate. 1985;6:423–36.

    Article  CAS  PubMed  Google Scholar 

  73. Checkoway H, DiFerdinando G, Hulka BS, Mickey DD. Medical, life-style, and occupational risk factors for prostate cancer. Prostate. 1987;10:79–88.

    Article  CAS  PubMed  Google Scholar 

  74. Honda GD, Bernstein L, Ross RK, Greenland S, Gerkins V, Henderson BE. Vasectomy, cigarette smoking, and age at first sexual intercourse as risk factors for prostate cancer in middle-aged men. Br J Cancer. 1988;57:326–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Oishi K, Okada K, Yoshida O, Yamabe H, Ohno Y, Hayes RB, Schroeder FH. Case-control study of prostatic cancer in Kyoto, Japan: demographic and some lifestyle risk factors. Prostate. 1989;14:117–22.

    Article  CAS  PubMed  Google Scholar 

  76. La Vecchia C, Franceschi S, Talamini R, Negri E, Boyle P, D’Avanzo B. Marital status, indicators of sexual activity and prostatic cancer. J Epidemiol Community Health. 1993;47:450–3.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Hiatt RA, Armstrong MA, Klatsky AL, Sidney S. Alcohol consumption, smoking, and other risk factors and prostate cancer in a large health plan cohort in California (United States). Cancer Causes Control. 1994;5:66–72.

    Article  CAS  PubMed  Google Scholar 

  78. Ilić M, Vlajinac H, Marinković J. Case-control study of risk factors for prostate cancer. Br J Cancer. 1996;74:1682–6.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Hsieh CC, Thanos A, Mitropoulos D, Deliveliotis C, Mantzoros CS, Trichopoulos D. Risk factors for prostate cancer: a case-control study in Greece. Int J Cancer. 1999;80:699–703.

    Article  CAS  PubMed  Google Scholar 

  80. Hayes RB, Pottern LM, Strickler H, Rabkin C, Pope V, Swanson GM, Greenberg RS, Schoenberg JB, Liff J, Schwartz AG, Hoover RN, Fraumeni JF Jr. Sexual behaviour, STDs and risks for prostate cancer. Br J Cancer. 2000;82:718–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Rosenblatt KA, Wicklund KG, Stanford JL. Sexual factors and the risk of prostate cancer. Am J Epidemiol. 2001;153:1152–8.

    Article  CAS  PubMed  Google Scholar 

  82. Sanderson M, Coker AL, Logan P, Zheng W, Fadden MK. Lifestyle and prostate cancer among older African-American and Caucasian men in South Carolina. Cancer Causes Control. 2004;15:647–55.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Patel DA, Bock CH, Schwartz K, Wenzlaff AS, Demers RY, Severson RK. Sexually transmitted diseases and other urogenital conditions as risk factors for prostate cancer: a case-control study in Wayne County, Michigan. Cancer Causes Control. 2005;16:263–73.

    Article  PubMed  Google Scholar 

  84. Pelucchi C, Talamini R, Negri E, Franceschi S, La Vecchia C. Genital and urinary tract diseases and prostate cancer risk. Eur J Cancer Prev. 2006;15:254–7.

    Article  PubMed  Google Scholar 

  85. Sarma AV, McLaughlin JC, Wallner LP, Dunn RL, Cooney KA, Schottenfeld D, Montie JE, Wei JT. Sexual behavior, sexually transmitted diseases and prostatitis: the risk of prostate cancer in black men. J Urol. 2006;176:1108–13.

    Article  PubMed  Google Scholar 

  86. 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 Biomark Prev. 2006;15:2160–6.

    Article  Google Scholar 

  87. 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 Biomark Prev. 2008;17:2374–81.

    Article  CAS  Google Scholar 

  88. Hrbacek J, Urban M, Hamsikova E, Tachezy R, Eis V, Brabec M, Heracek J. Serum antibodies against genitourinary infectious agents in prostate cancer and benign prostate hyperplasia patients: a case-control study. BMC Cancer. 2011;11:53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Vázquez-Salas RA, Torres-Sánchez L, López-Carrillo L, Romero-Martínez M, Manzanilla-García HA, Cruz-Ortíz CH, Mendoza-Peña F, Jiménez-Ríos MÁ, Rodríguez-Covarrubias F, Hernández-Toríz N, Moreno-Alcázar O. History of gonorrhea and prostate cancer in a population-based case-control study in Mexico. Cancer Epidemiol. 2016;40:95–101.

    Article  PubMed  Google Scholar 

  90. Wang YC, Chung CH, Chen JH, Chiang MH, Ti-Yin CH, Tsao CH, Lin FH, Chien WC, Shang ST, Chang FY. Gonorrhea infection increases the risk of prostate cancer in Asian population: a nationwide population-based cohort study. Eur J Clin Microbiol Infect Dis. 2017;36:813–21.

    Article  PubMed  Google Scholar 

  91. Taylor ML, Mainous AG 3rd, Wells BJ. Prostate cancer and sexually transmitted diseases: a meta-analysis. Fam Med. 2005;37:506–12.

    PubMed  Google Scholar 

  92. Lüleci G, Sakizli M, Günalp A, Erkan I, Remzi D. Herpes simplex type 2 neutralization antibodies in patients with cancers of urinary bladder, prostate, and cervix. J Surg Oncol. 1981;16:327–31.

    Article  PubMed  Google Scholar 

  93. Boldogh I, Baskar JF, Mar EC, Huang ES. Human cytomegalovirus and herpes simplex type 2 virus in normal and adenocarcinomatous prostate glands. J Natl Cancer Inst. 1983;70:819–26.

    CAS  PubMed  Google Scholar 

  94. Haid M, Sharon N. Immunofluorescent evidence of prior herpes simplex virus type-2 infection in prostate carcinoma. Urology. 1984;24:623–5.

    Article  CAS  PubMed  Google Scholar 

  95. Leskinen MJ, Vainionp R, Syrjnen S, Leppilahti M, Marttila T, Kylml T, Tammela TL. Herpes simplex virus, cytomegalovirus, and papillomavirus DNA are not found in patients with chronic pelvic pain syndrome undergoing radical prostatectomy for localized prostate cancer. Urology. 2003;61:397–401.

    Article  PubMed  Google Scholar 

  96. 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 Infect Dis. 2005;191:2008–11.

    Article  PubMed  Google Scholar 

  97. Bergh J, Marklund I, Gustavsson C, Wiklund F, Grönberg H, Allard A, Alexeyev O, Elgh F. No link between viral findings in the prostate and subsequent cancer development. Br J Cancer. 2007;96:137–9.

    Article  CAS  PubMed  Google Scholar 

  98. Dennis LK, 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 Epidemiol Biomark Prev. 2009;18:2665–71.

    Article  Google Scholar 

  99. Taylor M, Gerriets V. Acyclovir. 2021 Jun 28. In: StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2021.

  100. Nahand JS, Khanaliha K, Mirzaei H, Moghoofei M, Baghi HB, Esghaei M, Khatami AR, Fatemipour M, Bokharaei-Salim F. Possible role of HPV/EBV coinfection in anoikis resistance and development in prostate cancer. BMC Cancer. 2021;21:926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Grinstein S, Preciado MV, Gattuso P, Chabay PA, Warren WH, De Matteo E, Gould VE. Demonstration of Epstein-Barr virus in carcinomas of various sites. Cancer Res. 2002;62:4876–8.

    CAS  PubMed  Google Scholar 

  102. De Paor M, O'Brien K, Fahey T, Smith SM. Antiviral agents for infectious mononucleosis (glandular fever). Cochrane Database Syst Rev. 2016;12:CD011487.

  103. Griffiths P, Reeves M. Pathogenesis of human cytomegalovirus in the immunocompromised host. Nat Rev Microbiol. 2021;19:759.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Eizuru Y, Hyman RW, Nahhas WA, Rapp F. Herpesvirus RNA in human urogenital tumors. Proc Soc Exp Biol Med. 1983;174:296–301.

    Article  CAS  PubMed  Google Scholar 

  105. 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.

    Article  PubMed  Google Scholar 

  106. Dillner J, Knekt P, Boman J, Lehtinen M, Af Geijersstam V, Sapp M, et al. Sero-epidemiological association between human-papillomavirus infection and risk of prostate cancer. Int J Cancer. 1998;75:564–7.

    Article  CAS  PubMed  Google Scholar 

  107. Sellami H, Said-Sadier N, Znazen A, Gdoura R, Ojcius DM, Hammami A. Chlamydia trachomatis infection increases the expression of inflammatory tumorigenic cytokines and chemokines as well as components of the Toll-like receptor and NF-κB pathways in human prostate epithelial cells. Mol Cell Probes. 2014;28:147–54.

    Article  CAS  PubMed  Google Scholar 

  108. Anttila 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 Biomark Prev. 2005;14:385–9.

    Article  CAS  Google Scholar 

  109. Sutcliffe S, Giovannucci E, Gaydos CA, Viscidi RP, Jenkins FJ, Zenilman JM, et al. Plasma antibodies against chlamydia trachomatis, human papillomavirus, and human herpesvirus type 8 in relation to prostate cancer: a prospective study. Cancer Epidemiol Biomark Prev. 2007;16:1573–80.

    Article  CAS  Google Scholar 

  110. Lumme S, Tenkanen L, Langseth H, Gislefoss R, Hakama M, Stattin P, Hallmans G, Adlercreutz H, Saikku P, Stenman UH, Tuohimaa P, Luostarinen T, Dillner J. Longitudinal biobanks-based study on the joint effects of infections, nutrition and hormones on risk of prostate cancer. Acta Oncol. 2016;55:839–45.

    Article  CAS  PubMed  Google Scholar 

  111. Blanco JL, Fuertes I, Bosch J, De Lazzari E, Gonzalez-Cordón A, Vergara A, Blanco-Arevalo A, Mayans J, Inciarte A, Estrach T, Martinez E, Cranston RD, Gatell JM, Alsina-Gibert M. Effective treatment of lymphogranuloma venereum proctitis with azithromycin. Clin Infect Dis. 2021;73:614–20.

    Article  CAS  PubMed  Google Scholar 

  112. Johnston VJ, Mabey DC. Global epidemiology and control of Trichomonas vaginalis. Curr Opin Infect Dis. 2008;21:56–64.

    Article  PubMed  Google Scholar 

  113. Van Gerwen OT, Camino AF, Sharma J, Kissinger PJ, Muzny CA. Epidemiology, natural history, diagnosis, and treatment of trichomonas vaginalis in men. Clin Infect Dis. 2021;73:1119–24.

    Article  PubMed  Google Scholar 

  114. Sutcliffe S, Alderete JF, Till C, Goodman PJ, Hsing AW, Zenilman JM, De Marzo AM, Platz EA. Trichomonosis and subsequent risk of prostate cancer in the prostate cancer prevention trial. Int J Cancer. 2009;124:2082–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Stark JR, Judson G, Alderete JF, Mundodi V, Kucknoor AS, Giovannucci EL, Platz EA, Sutcliffe S, Fall K, Kurth T, Ma J, Stampfer MJ, Mucci LA. Prospective study of Trichomonas vaginalis infection and prostate cancer incidence and mortality: Physicians’ Health Study. J Natl Cancer Inst. 2009;101:1406–11.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Chen YC, Huang YL, Platz EA, Alderete JF, Zheng L, Rider JR, Kraft P, Giovannucci E, Sutcliffe S. Prospective study of effect modification by Toll-like receptor 4 variation on the association between Trichomonas vaginalis serostatus and prostate cancer. Cancer Causes Control. 2013;24:175–80.

    Article  PubMed  Google Scholar 

  117. Shui IM, Kolb S, Hanson C, Sutcliffe S, Rider JR, Stanford JL. Trichomonas vaginalis infection and risk of advanced prostate cancer. Prostate. 2016;76:620–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Fowke JH, Han X, Alderete JF, Moses KA, Signorello LB, Blot WJ. A prospective study of Trichomonas vaginalis and prostate cancer risk among African American men. BMC Res Notes. 2016;9:224.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Marous M, Huang WY, Rabkin CS, Hayes RB, Alderete JF, Rosner B, Grubb RL 3rd, Winter AC, Sutcliffe S. Trichomonas vaginalis infection and risk of prostate cancer: associations by disease aggressiveness and race/ethnicity in the PLCO Trial. Cancer Causes Control. 2017;28:889–98.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Kim JH, Moon HS, Kim KS, Hwang HS, Ryu JS, Park SY. Comparison of seropositivity to trichomonas vaginalis between men with prostatic tumor and normal men. Korean J Parasitol. 2019;57:21–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Saleh NE, Alhusseiny SM, El-Zayady WM, Aboelnaga EM, El-Beshbishi WN, Saleh YM, Abou-ElWafa HS, El-Beshbishi SN. Trichomonas vaginalis serostatus and prostate cancer risk in Egypt: a case-control study. Parasitol Res. 2021;120:1379–88.

    Article  PubMed  Google Scholar 

  122. Tsang SH, Peisch SF, Rowan B, Markt SC, Gonzalez-Feliciano AG, Sutcliffe S, Platz EA, Mucci LA, Ebot EM. Association between Trichomonas vaginalis and prostate cancer mortality. Int J Cancer. 2019;144:2377–80.

    Article  CAS  PubMed  Google Scholar 

  123. Barykova YA, Logunov DY, Shmarov MM, Vinarov AZ, Fiev DN, Vinarova NA, Rakovskaya IV, Baker PS, Shyshynova I, Stephenson AJ, Klein EA, Naroditsky BS, Gintsburg AL, Gudkov AV. Association of mycoplasma hominis infection with prostate cancer. Oncotarget. 2011;2:289–97.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Tantengco OAG, Aquino IMC, de Castro SM, Rojo RD, Abad CLR. Association of mycoplasma with prostate cancer: a systematic review and meta-analysis. Cancer Epidemiol. 2021;75:102021.

    Article  PubMed  Google Scholar 

  125. Urbanek C, Goodison S, Chang M, Porvasnik S, Sakamoto N, Li CZ, Boehlein SK, Rosser CJ. Detection of antibodies directed at M. hyorhinis p37 in the serum of men with newly diagnosed prostate cancer. BMC Cancer. 2011;11:233.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Erturhan SM, Bayrak O, Pehlivan S, Ozgul H, Seckiner I, Sever T, Karakök M. Can mycoplasma contribute to formation of prostate cancer? Int Urol Nephrol. 2013;45:33–8.

    Article  PubMed  Google Scholar 

  127. Yow MA, Tabrizi SN, Severi G, Bolton DM, Pedersen J, Longano A, et al. Detection of infectious organisms in archival prostate cancer tissues. BMC Cancer. 2014;14:579.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Miyake M, Ohnishi K, Hori S, Nakano A, Nakano R, Yano H, Ohnishi S, Owari T, Morizawa Y, Itami Y, Nakai Y, Inoue T, Anai S, Torimoto K, Tanaka N, Fujii T, Furuya H, Rosser CJ, Fujimoto K. Mycoplasma genitalium infection and chronic inflammation in human prostate cancer: detection using prostatectomy and needle biopsy specimens. Cells. 2019;8:212.

    Article  CAS  PubMed Central  Google Scholar 

  129. Saadat S, Karami P, Jafari M, Kholoujini M, Rikhtegaran Tehrani Z, Mohammadi Y, Alikhani MY. The silent presence of Mycoplasma hominis in patients with prostate cancer. Pathog Dis. 2020;78:ftaa037.

    Article  CAS  PubMed  Google Scholar 

  130. Seña AC, Bachmann L, Johnston C, Wi T, Workowski K, Hook EW 3rd, Hocking JS, Drusano G, Unemo M. Optimising treatments for sexually transmitted infections: surveillance, pharmacokinetics and pharmacodynamics, therapeutic strategies, and molecular resistance prediction. Lancet Infect Dis. 2020;20:e181–91.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Imperiale MJ. The human polyomaviruses, BKV and JCV: molecular pathogenesis of acute disease and potential role in cancer. Virology. 2000;267:1–7.

    Article  CAS  PubMed  Google Scholar 

  132. Monini P, Rotola A, Di Luca D, De Lellis L, Chiari E, Corallini A, Cassai E. DNA rearrangements impairing BK virus productive infection in urinary tract tumors. Virology. 1995;214:273–9.

    Article  CAS  PubMed  Google Scholar 

  133. Zambrano A, Kalantari M, Simoneau A, Jensen JL, Villarreal LP. Detection of human polyomaviruses and papillomaviruses in prostatic tissue reveals the prostate as a habitat for multiple viral infections. Prostate. 2002;53:263–76.

    Article  CAS  PubMed  Google Scholar 

  134. Lau SK, Lacey SF, Chen YY, Chen WG, Weiss LM. Low frequency of BK virus in prostatic adenocarcinomas. APMIS. 2007;115:743–9.

    Article  PubMed  Google Scholar 

  135. Das D, Wojno K, Imperiale MJ. BK virus as a cofactor in the etiology of prostate cancer in its early stages. J Virol. 2008;82:2705–14.

    Article  CAS  PubMed  Google Scholar 

  136. Russo G, Anzivino E, Fioriti D, Mischitelli M, Bellizzi A, Giordano A, Autran-Gomez A, Di Monaco F, Di Silverio F, Sale P, Di Prospero L, Pietropaolo V. p53 gene mutational rate, Gleason score, and BK virus infection in prostate adenocarcinoma: Is there a correlation? J Med Virol. 2008;80:2100–7.

    Article  CAS  PubMed  Google Scholar 

  137. Delbue S, Matei DV, Carloni C, Pecchenini V, Carluccio S, Villani S, Tringali V, Brescia A, Ferrante P. Evidence supporting the association of polyomavirus BK genome with prostate cancer. Med Microbiol Immunol. 2013;202:425–30.

    Article  CAS  PubMed  Google Scholar 

  138. Taghavi A, Mohammadi-Torbati P, Kashi AH, Rezaee H, Vaezjalali M. Polyomavirus hominis 1(BK virus) Infection in prostatic tissues: cancer versus hyperplasia. Urol J. 2015;12:2240–4.

    PubMed  Google Scholar 

  139. Gorish BMT, Ournasseir MEH, Shammat IM. A correlation study of BK polyoma virus infection and prostate cancer among sudanese patients - immunofluorescence and molecular based case-control study. Infect Agent Cancer. 2019;14:25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Wise GJ, Shteynshlyuger A. How to diagnose and treat fungal infections in chronic prostatitis. Curr Urol Rep. 2006;7:320–8.

    Article  PubMed  Google Scholar 

  141. Wajjwalku W, Takahashi M, Miyaishi O, Lu J, Sakata K, Yokoi T, Saga S, Imai M, Matsuyama M, Hoshino M. Tissue distribution of mouse mammary tumor virus (MMTV) antigens and new endogenous MMTV loci in Japanese laboratory mouse strains. Jpn J Cancer Res. 1991;82:1413–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Grulich AE, Vajdic CM. The epidemiology of cancers in human immunodeficiency virus infection and after organ transplantation. Semin Oncol. 2015;42:247–57.

    Article  PubMed  Google Scholar 

  143. Coghill AE, Engels EA, Schymura MJ, Mahale P, Shiels MS. Risk of breast, prostate, and colorectal cancer diagnoses among HIV-infected individuals in the United States. J Natl Cancer Inst. 2018;110:959–66.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Jiang Z, Li L, Chen J, Wei G, Ji Y, Chen X, Liu J, Huo J. Human gut-microbiome interplay: analysis of clinical studies for the emerging roles of diagnostic microbiology in inflammation, oncogenesis and cancer management. Infect Genet Evol. 2021;93:104946.

    Article  CAS  PubMed  Google Scholar 

  145. Golombos DM, Ayangbesan A, O’Malley P, Lewicki P, Barlow L, Barbieri CE, et al. The role of gut microbiome in the pathogenesis of prostate cancer: a prospective. Pilot Study Urol. 2018;111:122–8.

    PubMed  Google Scholar 

  146. Gallego L, Dominguez A, Parmar M. Human papilloma virus vaccine. In: StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2021.

  147. de Bono JS, Guo C, Gurel B, De Marzo AM, Sfanos KS, Mani RS, Gil J, Drake CG, Alimonti A. Prostate carcinogenesis: inflammatory storms. Nat Rev Cancer. 2020;20:455–69.

    Article  PubMed  CAS  Google Scholar 

  148. Göbel A, Dell’Endice S, Jaschke N, Pählig S, Shahid A, Hofbauer LC, Rachner TD. The role of inflammation in breast and prostate cancer metastasis to bone. Int J Mol Sci. 2021;22:5078.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004;118:285–96.

    Article  CAS  PubMed  Google Scholar 

  150. Qiao Y, Yang T, Gan Y, Li W, Wang C, Gong Y, Lu Z. Associations between aspirin use and the risk of cancers: a meta-analysis of observational studies. BMC Cancer. 2018;18:288.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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  1. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, 2052, Australia

    James S. Lawson & Wendy K. Glenn

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Lawson, J.S., Glenn, W.K. Multiple pathogens and prostate cancer. Infect Agents Cancer 17, 23 (2022). https://doi.org/10.1186/s13027-022-00427-1

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Keywords

  • Prostate cancer
  • Infections
  • Causation
  • Human papilloma virus
  • Pathogens

Infectious Agents and Cancer

ISSN: 1750-9378

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