27th June 2023

Viral STIs

Genital warts – HPV

Presentation

Genital warts (condylomata acuminata) are caused by a very common sexually transmitted infection called human papillomavirus (HPV); typically HPV types 6 and 11 cause genital warts. Genital warts are small, fleshy papules that arise anywhere in the genital or perianal region, including the mucosa. In some cases, the warts can coalesce to form plaques. They are commonly asymptomatic, however, they can be painful, itchy, or may bleed.

Diagnosis is based on clinical presentation, however, biopsy may be performed in some cases, particularly if ulceration is present or lesions refractory to treatment, to rule out dysplasia or carcinoma.

Genital warts follow a benign course and can resolve spontaneously within a few months in a third of those affected, however, treatments exist to remove visible lesions. There is not currently evidence to prove that treatment of genital warts decreases sexual transmission of HPV.

Treatment

The choice of treatment for genital warts is dependent on many factors, including location of lesions, immune status of the patient, pregnancy, and patient choice of application method.

Options include patient-applied topical therapy, such as podophyllotoxin 0.5% or imiquimod 5%, or provider-administered therapy, such as cryotherapy, trichloroacetic acid, or surgical removal. Immunocompromised patients tend to require a longer duration of treatment or a combination of treatments.

Prevention of HPV infection is through abstinence; condom use may reduce transmission but does not entirely prevent it. There are now 3 HPV vaccines available, consisting of bivalent (types 16 and 18 – these are most associated with the risk of development of cervical cancers), quadrivalent (types 6, 11, 16, 18) and 9-valent (types 6, 11, 16, 18, 31, 33, 45, 52, 58). The quadrivalent and 9-valent vaccines are approved for use against genital warts. HPV vaccination is now given to both female and male children from 11 years old as part of the school vaccination programme in the UK.

Herpes

Presentation

Infection with herpes simplex virus (HSV) is common; it classically presents with painful ulcers on the affected part of the body (e.g. orolabial, genital, ocular) however, infection can be asymptomatic, or there may be symptoms of tingling or burning without the presence of lesions. There are two main types of HSV: HSV-1 and HSV-2.

Orolabial herpes is usually caused by HSV-1 and refers to herpes infection affecting the lips and mouth, causing blisters and ulcers commonly known as ‘cold sores’. Initial infection may, in addition, present with fever, sore throat and lymphadenopathy; however, HSV-1 subsequently can remain dormant in the trigeminal nerve ganglion, periodically reactivating and causing episodes of ulcers on the lips or in the mouth. Lesions tend to crust over and heal within ten days.

Genital herpes can be caused by infection with either HSV-1 or HSV-2. Many infected people will be asymptomatic, however, symptoms can include a prodromal tingling sensation followed by the development of genital vesicles, which progress to painful ulcers. Primary infection may involve systemic symptoms such as fever, lymphadenopathy, and neuralgia. Transmission of the virus is via direct contact with lesions or bodily fluids of an infected person, and therefore genital herpes is considered a sexually transmitted infection. It should be noted that shedding of the virus can occur even in the absence of symptoms or lesions.

The median average recurrence rate for genital herpes after a symptomatic primary episode is approximately one recurrence per year for HSV-1 and four recurrences per year for HSV-2. Recurrence rates tend to decline over time, however, this is variable.

Diagnosis of both orolabial herpes and genital herpes can be made clinically, however, confirmation can be obtained by HSV PCR (high sensitivity) or HSV culture.

Treatment

Treatment can be divided into ‘episodic’ and ‘suppressive’ therapy. Episodic treatment with oral antiviral therapy such as aciclovir, valaciclovir or famciclovir is initiated within 2-3 days of symptoms, and can provide symptomatic relief, shorten the duration of symptoms, as well as reducing the severity and risk of neurological complications. Topical treatment of genital herpes is not recommended; oral therapy is also the preferred treatment of orolabial herpes, however topical antiviral therapy can have a small benefit (reducing duration of outbreak by a matter of hours) in those who do wish to take oral treatment. Daily suppressive therapy can be given to those with recurrent outbreaks (typically six or more recurrences per year) to reduce the rate of recurrence, and it can therefore reduce the risk of transmission of genital herpes to sexual partners.

Herpes simplex encephalitis (HSE) is a rare but life-threatening complication, thought to be caused by the spread of the infection from a peripheral site to the brain. In adults, it is more commonly caused by HSV-1 than HSV-2. Diagnosis is through HSV PCR on CSF analysis. Presentation and treatment of HSE is covered in more detail in the ‘Meningitis and Encephalitis’ section. As well as affecting the neurological system, disseminated HSV can also rarely cause a hepatitis or pneumonitis. Treatment is usually with high-dose intravenous aciclovir.

HIV

Human immunodeficiency virus (HIV) is a global pandemic disease which infects and destroys CD4⁺ T cells. Without treatment, this leads to progressive immune depletion and a wide array of opportunistic infections and malignancies, which form the diagnosis of Acquired Immune Deficiency Syndrome (AIDS). The advancement in treatment options for HIV with antiretroviral therapies over the past 30 years has transformed the trajectory of the disease, with significantly improved morbidity and mortality associated with HIV-positive patients on treatment. Many patients on antiretroviral therapy have an undetectable viral load, meaning they are unable to transmit the virus to others.

HIV is covered in significant detail in the HIV/AIDS section.

Hepatitis B

Presentation

Hepatitis B virus (HBV) is the most common liver infection worldwide and can be transmitted by exposure to infectious blood or bodily fluids, hence can be transmitted by sexual contact as well as by blood product transfusion, use of contaminated needles, or vertical transmission during childbirth.

70% of those infected with HBV are asymptomatic and can have a self-limiting course to the infection; however, some people develop chronic infection, which may present with complications such as liver failure, cirrhosis, or hepatocellular carcinoma, particularly if acquired in early life. Co-infection with HIV increases the risk of developing chronic infection. Acute infection may present with generalised symptoms such as fever, arthralgia, skin rash, or symptoms of right upper quadrant pain, jaundice, and nausea/vomiting.

Serology

Analysis of HBV serological markers to differentiate between acute and chronic HBV infection remains a common question topic in MRCP. The HBV serological profile includes:

• Hepatitis B surface antigen (HBsAg) – the first serological marker to appear following acute infection. A positive result indicates active infection (both acute and chronic).
• Antibody to hepatitis B surface antigen (anti-HBs) – a positive result indicates either recovery and immunity from previous HBV infection, or successful vaccination against HBV.
• Antibody to hepatitis B core antigen (anti-HBc) IgM and IgG – positive IgM anti-HBc indicates recent infection with HBV (<6 months) and acute infection. IgM anti-HBc is gradually replaced with IgG anti-HBc, which persists for life following HBV infection and can therefore represent previous resolved infection or chronic HBV infection.
• Hepatitis B envelope antigen (HBeAg) – this indicates active viral replication and is a marker of infectivity.
• Antibody to HBeAg (anti-HBe) – this marks the transition from active to inactive disease. It remains positive for life and therefore represents acquired immunity from previous infection (not from vaccination).
• HBV DNA – this can be tested in those with serology indicating active infection and quantifies the viral load. Those with high HBV DNA viral load are at increased risk of progression to complications such as cirrhosis or hepatocellular carcinoma.

HBsAg and anti-HBs can be used for screening of high-risk individuals to aid early diagnosis and treatment.

Treatment

Treatment of acute infection is usually through supportive care alone, as 95% of immunocompetent adults with acute HBV will clear the virus without treatment. A small proportion of patients, e.g. those developing acute liver failure, may benefit from antiviral treatment with entecavir, tenofovir disoproxil or tenofovir alafenamide for acute infection; there may also be a requirement for liver transplant in some of these cases.

The treatment of chronic HBV is dependent on several factors, including ALT and HBV DNA levels, the severity of hepatic dysfunction and the presence of cirrhosis. Complete eradication of HBV is rare, and the aim of treatment is to suppress HBV DNA to undetectable levels for a sustained period, thereby reducing the risk of complications such as liver failure, cirrhosis, and hepatocellular carcinoma. Currently, the agents used for the treatment of chronic HBV include the antivirals interferon alfa 2b, peginterferon alfa 2a, nucleoside analogues such as entecavir or lamivudine, and nucleotide analogues such as tenofovir disoproxil or tenofovir alafenamide. Local guidelines for the treatment of chronic HBV should always be consulted as therapy is frequently evolving and novel treatments are being developed.

Since 2017, Hepatitis B vaccination is given as part of the childhood immunisation programme in the UK at 8, 12 and 16 weeks of age. Immunisation is also recommended for those at high risk of exposure or those at risk of complications (e.g. individuals from countries with a high prevalence of hepatitis B, healthcare or custodial institution workers, incarcerated individuals, commercial sex workers, parenteral drug users, men who have sex with men, individuals known to be HIV or Hepatitis C positive, patients with severe liver disease or end-stage renal failure, and patients receiving regular blood transfusions.) Vaccination may be recommended before travelling to some countries with a high prevalence of hepatitis B and can also be used in post-exposure prophylaxis.

Hepatitis C

The most common routes of transmission of hepatitis C virus (HCV) are through shared drug injecting equipment and transfusion of infected blood products (prior to 1991 in the UK). Sexual transmission is less common however the risk is increased if the individual is co-infected with HIV.

Acute infection is asymptomatic in >60%, although acute icteric hepatitis is possible. <1% of acute cases develop fulminant hepatitis. Up to 85% of those infected become chronic carriers, with a third of those progressing to severe liver disease. Approximately 14% of all patients and 33% of those with cirrhosis will develop hepatocellular carcinoma.

Positive HCV RNA indicates current acute or chronic infection (positive six months after initial positive test); a positive HCV antibody test indicates previous infection, however, it can take three months to become positive and therefore may be negative during early initial infection.

Treatment is with direct-acting antiviral (DAA) medication taken over several months, which can clear the virus in the majority of people. There are many different DAA medications, and most are used in combination. Some examples include sofosbuvir, ledipasvir, paritaprevir, ritonavir. dasabuvir, and elbasvir.