Viral Genitourinary Infections

Viruses involve the genitourinary tract in two ways that must be kept separate. A few viruses have tropism for the genital and urinary organs and cause disease there: genital herpes, anogenital warts and the cancers that follow oncogenic human papillomavirus, and a small set of urinary tract infections. Many other and more dangerous viruses are sexually transmitted or shed in genital secretions but cause no disease in the genital tract itself, HIV foremost among them. Confusing the two leads to error: the commonest “genital” viruses seen in a clinic are organ-tropic and often trivial, while the viruses that spread through sexual contact and matter most for the patient act systemically and are diagnosed and managed elsewhere.

This article covers the organ-tropic infections, which are its main focus, and draws the distinction from the systemic sexually transmitted viruses clearly. The detailed virology of herpes simplex and human papillomavirus, the two organ-tropic agents that dominate the field, lives in their own profiles; here they are treated as clinical syndromes.

The spectrum of genitourinary viral disease

The organ-tropic infections divide into genital and urinary, summarised below.

Site	Disease	Virus
Genital	Genital herpes	Herpes simplex viruses (HSV-2 more than HSV-1)
Genital	Genital warts	Human papillomaviruses 6, 11 and others
Genital	Genital carcinomas	Human papillomaviruses 16, 18 and others
Genital	Cervicitis	Adenovirus 37
Genital	Genital molluscum	Molluscum contagiosum virus
Urinary	Urethritis	Herpes simplex virus, adenovirus 37
Urinary	Acute haemorrhagic cystitis	Adenovirus 11 and 21, BK polyomavirus
Urinary	Glomerulonephritis (immune-complex)	Hepatitis B and C viruses, HIV
Urinary	Nephropathy	BK polyomavirus, cytomegalovirus; Hantaan virus (renal syndrome)

Set against these organ-tropic infections is a longer list of viruses that are transmitted sexually or perinatally, or shed in semen and genital secretions, yet produce their disease in other systems. This group includes HIV-1 and HIV-2, the human T-lymphotropic viruses HTLV-1 and HTLV-2, hepatitis B (with hepatitis D), hepatitis C, cytomegalovirus and Epstein-Barr virus, and the enteric hepatitis A virus, which is transmitted sexually among men who have sex with men. They are the subject of their own topics; they appear here only to be told apart from the genitourinary infections proper.

Genital herpes

Genital herpes is caused mostly by herpes simplex virus type 2 (HSV-2), and increasingly by HSV-1. At least one in four adults is seropositive for HSV-2, yet only a minority give a history of genital ulcers, because most infections are unrecognised or asymptomatic. Primary infection classically causes widespread painful genital vesicles that ulcerate, with tender inguinal nodes and systemic symptoms; recurrent episodes are milder, localised and preceded by a prodrome of tingling as the virus travels down the sensory nerve from its latent site in the sacral ganglia.

The clinical burden lies in frequent, unpredictable recurrences and in asymptomatic shedding, which drives transmission from people unaware they are infected. Diagnosis of a genital ulcer is by PCR of vesicle or ulcer swabs, which has replaced insensitive culture, with type-specific serology used to establish past HSV-1 versus HSV-2 infection. Treatment is with the aciclic nucleoside analogues aciclovir, valaciclovir or famciclovir, given either episodically for recurrences or as daily suppressive therapy to reduce recurrences and shedding; there is no cure and no licensed vaccine. Genital ulceration from HSV also facilitates the transmission and acquisition of HIV, an important interaction where both infections are common.

Anogenital HPV and neoplasia

Anogenital human papillomavirus (HPV) infection is extremely common: about three-quarters of sexually active adults are infected by age 50, though most clear the virus and only a small fraction develop clinically evident lesions. The number of sexual partners is the strongest risk factor.

Genital warts (condyloma acuminata) are caused in over 90% of cases by the low-risk types HPV-6 and HPV-11. They are exophytic, cauliflower-like lesions on the moist anogenital surfaces, benign but often persistent and recurrent, appearing after a mean incubation of about 2 to 3 months (range 3 weeks to 8 months). Uncommon variants include the locally invasive Buschke-Lowenstein giant condyloma and bowenoid papulosis. HPV from genital lesions can also seed the upper airway, causing recurrent respiratory papillomatosis in a child infected at vaginal delivery.

The important disease is malignant. The high-risk types, above all HPV-16 and HPV-18, drive cervical dysplasia that can progress over years to invasive cervical cancer, and the same types cause a substantial share of anal, vaginal, vulvar, penile and oropharyngeal cancers. The mechanism is persistent infection with an oncogenic type leading to progressive dysplasia rather than the productive, self-limited infection of the low-risk types.

Diagnosis reflects this split. Benign warts are usually a clinical diagnosis. Because HPV cannot be cultured and serology is unhelpful, detection rests on HPV DNA or messenger RNA testing, and screening for pre-cancer uses cervical cytology (the Papanicolaou, or Pap, smear) with high-risk HPV DNA testing, and colposcopy where indicated. Warts are treated by ablation (cryotherapy, podophyllotoxin, trichloroacetic acid, excision) or with the immune-modulator imiquimod, a Toll-like receptor 7 agonist that induces interferon and gives a low recurrence rate. Prevention is by HPV vaccination: the vaccines protect against HPV-16 and HPV-18, which cause about 70% of cervical cancer, and the nine-valent vaccine adds five further oncogenic types and the wart-causing HPV-6 and HPV-11.

Viral infections of the urinary tract

Viruses infect the urinary tract far less often than the genital tract. Herpes simplex virus and adenovirus 37 can cause urethritis, and adenovirus 37 also causes cervicitis. Acute haemorrhagic cystitis, an abrupt illness of young boys, is caused by adenovirus types 11 and 21, and also by BK polyomavirus in the immunosuppressed.

The polyomaviruses and cytomegalovirus dominate the transplant setting. BK polyomavirus persists in the urinary tract and reactivates under immunosuppression, causing haemorrhagic cystitis in bone-marrow recipients and a nephropathy in renal-transplant patients that can mimic graft rejection. Cytomegalovirus persists asymptomatically in the renal tubules, is shed in the urine, and can accelerate graft rejection when it reactivates around transplantation. A distinct picture is the profound renal failure of haemorrhagic fever with renal syndrome, caused by Hantaan virus.

Finally, several chronic infections injure the kidney indirectly through immune-complex deposition: glomerulonephritis complicates chronic hepatitis B, hepatitis C and HIV infection. Beyond the urinary tract, mumps virus has a tropism for the reproductive organs, causing orchitis (and, less often, oophoritis), typically in post-pubertal males following parotitis.

Sexually transmitted viruses without genital-tract disease

The viruses that matter most in sexual transmission cause no disease in the genital tract and are therefore easy to overlook in a syndromic account. HIV-1 and HIV-2 are transmitted principally by sexual contact, along with exposure to blood and perinatally, and their disease is systemic immunodeficiency. Hepatitis B (with its satellite hepatitis D) and hepatitis C are transmitted sexually and parenterally and cause liver disease. The human T-lymphotropic viruses HTLV-1 and HTLV-2, cytomegalovirus and Epstein-Barr virus are all shed in genital secretions and transmitted sexually while causing disease elsewhere, and even the enteric hepatitis A virus spreads sexually among men who have sex with men. Molluscum contagiosum, an organ-tropic skin poxvirus, also has a sexually transmitted genital form. Several further viruses are now recognised to spread sexually: Zika virus can be transmitted in semen, Ebola virus persists in semen and can be transmitted sexually during convalescence, Kaposi sarcoma-associated herpesvirus (HHV-8) spreads sexually, particularly among men who have sex with men, and mpox was transmitted substantially through sexual contact in its 2022 global outbreak.

South African context

Genital HPV and its cancers carry a heavy burden in South Africa, amplified by the high prevalence of HIV. Cervical cancer is one of the commonest cancers in South African women, and national policy addresses it on two fronts. A school-based HPV vaccination programme offers the vaccine to young adolescent girls, and the cervical screening programme is moving from cytology towards primary high-risk HPV DNA testing, in line with the national cervical cancer policy and current screening guidelines. Screening starts earlier and is more frequent in women living with HIV, in whom HPV persists more readily and cervical disease progresses faster. Genital herpes and genital warts are managed within the national sexually transmitted infection services.

References and recommended reading

• Nawas ZY, Tyring SK. Viral Diseases of the Skin. In: Richman DD, Whitley RJ, Hayden FG, editors. Clinical Virology, 4th edition, Chapter 8. Washington: ASM Press; 2016. The backbone source for genital herpes and anogenital HPV.
• Burrell CJ, Howard CR, Murphy FA. Fenner and White’s Medical Virology, 5th edition. Academic Press / Elsevier; 2017. The source for the genitourinary-tract table and the distinction between organ-tropic and systemic sexually transmitted viruses.
• National Department of Health. Cervical Cancer Prevention and Control Policy. Pretoria: NDoH; 2017. The South African policy on HPV vaccination and cervical screening.
• Southern African Society of Obstetricians and Gynaecologists. Cervical Cancer Screening Guidelines for South Africa. 2024. The current South African screening reference.
• World Health Organization. Human papillomavirus vaccines: WHO position paper. 2022. The reference for HPV vaccine composition and use.