Are testicular mixed germ cell tumours associated with hepatitis C (HCV) in HIV-positive men who have sex with men?

Dear Editor,

The UK national prevalence of hepatitis C (HCV) in HIV-positive men who have sex with men (MSM) is estimated to be 7.2%. ¹ HCV infection and testicular germ cell tumours are indicator diseases for HIV testing according to British Association for Sexual Health and HIV (BASHH) guidelines but there is little data on the association of HCV with testicular tumours in HIV-positive MSM. ² We report two HIV-positive MSM who were co-infected with HCV and treated with pegylated-interferon and ribavirin before subsequently presenting with testicular mixed germ cell tumours.

Patient-1, a 51-year-old MSM, was diagnosed with HIV in 2004 and has been on Atripla (Efavirenz, Tenofovir, Emtricibine) since 2010. In May 2012, a routine ALT (alanine transaminase) was 186, and HCV-RNA (genotype 1) was found to be positive. This was treated with pegylated-interferon (180 microgrammes weekly subcutaneously for 24 weeks) and ribavirin. He had a sustained viral response (SVR). Two years later, he presented to the genitourinary medicine (GUM) clinic with a four-month history of testicular swelling. Ultrasound showed this to be likely malignant infiltration and bloods showed AFP = 2484, LDH = 426 HCG = 5.9. This was treated with urgent orchidectomy, and histology demonstrated a mixed germ cell tumour (predominantly embryonal carcinoma with yolk sac tumour minor seminoma component). He is in clinical/radiological remission.

Patient-2, a 41-year-old MSM was diagnosed with HIV in 2004. In 2007, he received interleukin-2 (IL-2) as part of a clinical trial. In both 2008 and 2012, routine ALT was 918 and 505, respectively, and HCV-RNA was positive on both occasions (genotype 2/3 and genotype 1, respectively). HCV was treated with pegylated-interferon (180 microgrammes weekly subcutaneously for 24 weeks) and ribavirin on both occasions with SVR. He was started on Atripla in 2010. In 2012, he presented to the GUM clinic with an E. coli urinary tract infection and testicular swelling. Tumour markers were AFP = 16.5, LDH = 376 and HCG = 16.5. Ultrasound followed by orchidectomy found a mixed germ cell testicular tumour (predominantly embryonal carcinoma with a component of seminoma). He was subsequently treated with bleomycin/etoposide/cisplatin and is also in radiological/clinical remission.

We describe a temporal association of HCV infection and treatment two years prior to testicular tumour diagnosis in both cases. Progression of HCV liver related disease is faster in HIV co-infected individuals than those with HCV alone, ³ therefore HIV/HCV coinfection may lead to other accelerated disease/carcinogenesis in these individuals. In addition, the treatments used for HCV are immunomodulatory, and given that both patients developed tumours subsequent to starting HCV treatment, we should also consider whether pegylated-interferon and ribavirin could have played any role in carcinogenesis.

There are no other reported case series demonstrating a relationship between HIV/HCV coinfection, interferon/ribavirin treatment and testicular neoplasia. We recommend vigilant monitoring in specialist centres of HIV/HCV-coinfected individuals who have started HCV treatment, in view of drug tolerability, interactions and possible long-term complications. Furthermore, national surveillance mechanisms for HCV could have a role to play by incorporating additional clinical information. We recommend physicians have a low threshold for investigating potential tumours in this cohort as well as empowering patients to take responsibility for their own health by informing them of the benefits of regular testicular screening.