Role of Viral Infections in Testicular Cancer Etiology: Evidence From a Systematic Review and Meta-Analysis

Abstract

The most represented histotype of testicular cancer is the testicular germ-cell tumor (TGCT), both seminoma and non-seminoma. The pathogenesis of this cancer is poorly known. A possible causal relationship between viral infections and TGCTs was firstly evoked almost 40 years ago and is still a subject of debate. In the recent past, different authors have argued about a possible role of specific viruses in the development of TGCTs including human papillomavirus (HPV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), Parvovirus B-19, and human immunodeficiency virus (HIV). The aim of this present review was to summarize, for each virus considered, the available evidence on the impact of viral infections on the risk of developing TGCTs. The review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all observational studies reported in English evaluating the correlations between viral infections (HPV, CMV, EBV, Parvovirus B19, and HIV) and TGCTs. The methodological quality of studies included in the meta-analysis was evaluated using a modified version of the “Newcastle–Ottawa Scale.” Meta-analyses were conducted using the “Generic inverse variance” method, where a pooled odds ratio (OR) was determined from the natural logarithm (LN) of the studies' individual OR [LN (OR)] and the 95% CI. A total of 20 studies (on 265,057 patients) were included in the review. Meta-analysis showed an association with TGCTs only for some of the explored viruses. In particular, no association was found for HPV, CMV, and Parvovirus B-19 infection ( p = ns). Conversely, EBV and HIV infections were significantly associated with higher risk of developing TGCTs (OR 7.38, 95% CI 1.89–28.75, p = 0.004; OR 1.71, 95% CI 1.51–1.93, p < 0.00001). In conclusion, we found adequate evidence supporting an oncogenic effect of HIV and EBV on the human testis. Conversely, available data on HPV and TGCTs risk are conflicting and further studies are needed to draw firm conclusions. Finally, current evidence does not support an effect of CMV and Parvovirus B-19 on testicular carcinogenesis.

Parental occupation and childhood germ cell tumors: a case–control study in Denmark, 1968–2016

“…One prior study including 451 GCT cases < 6 years identified an imprecise association with maternal Group B streptococcus infection during pregnancy (OR 1.22, 95% CI 0.56-2.65) [3], while another study of 105 malignant GCT cases < 15 years found a strong association with maternal urinary infection during pregnancy (OR 3.1, 95% CI 1.5-6.6), but not with any viral infection (OR 0.4, 95% CI 0.1-1.3) [6]; neither study showed results by histologic subtype. To our knowledge, no other epidemiologic studies have reported on infection and childhood GCTs; however, certain viral infections are thought to be implicated in the pathogenesis of testicular GCTs, which are more common among late adolescent and young adult males [28,29]. In this study, paternal occupational exposure to high/very high occupational social contact was also associated with yolk sac tumors (but not all GCTs nor teratomas), bolstering the findings we observed with maternal exposure.…”

Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

“…Earlier studies in SARS-CoV, which also targeted the same receptor, have revealed that numerous patients had evidence of testicular inflammation (orchitis) [ 230 ]. Indeed, a range of other viral infections such as HIV, mumps, hepatitis B, and human papillomavirus has been shown to cause male sterility, altered expression of hormones, and may even be linked to increased risk of testicular cancer [ 231 , 232 , 233 , 234 , 235 ]. One study demonstrated that the ratio of testosterone and follicle-stimulating hormone to serum luteinizing hormone was significantly decreased in young adult male COVID-19 patients ( n = 81) compared to controls ( n = 100) [ 229 ].…”

Epstein-Barr Virus and Human Adenovirus Viremia in Renal Tumors Is Associated with Histological Features of Malignancy

“…The strong association was proven only for human papilloma virus (HPV) and penile cancer risk [ 10 ]. However, more and more research shows a possible link between viral infections and urothelial cancer [ 11 , 12 , 13 , 14 , 15 ], prostate cancer [ 15 , 16 , 17 ] or testicular cancer [ 18 , 19 ]. Furthermore, the evidence behind the role of latent viral infections in carcinogenesis of RCC is growing.…”