Some 'asthma' is anxiety breathing
In this series a GP interviews an expert to get first-hand information that goes beyond the textbook on a topic of current clinical interest
GP Dr Patrick Wills speaks to Liz Foley, a consultant in GU medicine, about the latest thinking on HSV and HPV
Liz Foley, a consultant in GU medicine, about the latest thinking on HSV and HPV
Practical points · Patients may present many years after first acquiring HSV as it is often asymptomatic. · Genital HSV disease has been shown to double the risk of transmission and acquisition of HIV disease, so controlling HSV disease may have important public health implications. · A recent study showed a suppressive dose of valaciclovir can prevent sexual transmission of the virus to partners, a major anxiety to those with HSV. · Home treatments for genital warts are now normally given. · Condoms do not give great protection, at least in part because of perineal contact.
· Patients may present many years after first acquiring HSV as it is often asymptomatic.
· Genital HSV disease has been shown to double the risk of transmission and acquisition of HIV disease, so controlling HSV disease may have important public health implications.
· A recent study showed a suppressive dose of valaciclovir can prevent sexual transmission of the virus to partners, a major anxiety to those with HSV.
· Home treatments for genital warts are now normally given.
· Condoms do not give great protection, at least in part because of perineal contact.
How do these viruses manifest themselves?
Are herpes and warts 'for life'?
Once HSV enters the body, the virus establishes latency. This means the virus is there for life. Most patients who carry HSV, however, are unaware of their disease, and do not have symptoms. For those patients with symptoms, although there is no cure, symptomatic recurrences will burn out after some years.
Sub-clinical or asymptomatic shedding is an important aspect of the clinical and epidemiological understanding of genital herpes. Most episodes of sexual and vertical transmission appear to occur during such shedding. Sexual contact with a person who is shedding either HSV 1 or HSV 2 sub-clinically in other words with someone who is asymptomatic is the typical way in which the virus is passed on.
Sub-clinical reactivation is highest in the six months after acquisition of HSV. PCR testing for HSV finds reactivation of the virus on 20 to 35 per cent of days tested, reducing over time to an average of 2 per cent of days.
In contrast, many cases of HPV are transient, and can clear spontaneously after a number of months. In a similar way to HSV, those patients with visible warts will find that recurrences will eventually stop.
What is the incubation period of these viruses?
Some 70 per cent of individuals with HSV will be asymptomatic. Patients may present many years after first acquiring the disease.
The incubation period for those with symptoms tends to be seven to 10 days. Systemic symptoms occur first, typically followed by lesions two days later.
The majority of newly acquired genital HPV infections appear to be sub-clinical and asymptomatic. At least 35 of 130 different HPV types primarily infect genital epithelium. HPV 6 is the most frequent type detected in genital warts.
Only 10 per cent of individuals who carry genital HPV will have visible warts. As the disease is asymptomatic it may be many years before a patient develops symptoms, but 50 per cent of patients who develop visible warts will do so within three months of acquisition of the virus.
What is the relevance of non-sexual transmission of these viruses?
Fomite transmission of HPV is important for skin warts, but it is not known whether this occurs with genital HPV. Digital transmission of warts to genital skin may occur; HPV 16 (a common genital HPV type) has been detected in finger lesions and HPV types 1, 2 and 4 (common in hand warts) have been found in genital tract lesions.
Little is known about the role of cross-protective immunity between HPV types. It is unclear whether having certain HPV types changes the risk of acquisition of other types. However, it appears that neither hand warts nor verrucae protect against genital warts.
Prior oral-labial HSV 1 appears to protect against genital HSV 1 disease. However, previous oro-labial HSV 1 may not protect against HSV 2 disease, but may make acquisition more likely to be asymptomatic or less severe and without constitutional symptoms.
What should the GP do?
Who should GPs refer for screening?
It is beneficial for patients with first episode genital HSV and HPV disease to be screened for other STIs. Most STIs are asymptomatic and many studies have shown the presence of one STI increases the likelihood of a second concurrent STI.
Patients with recurrent disease do not necessarily need to be referred for screening, but patients with difficult to control recurrences or atypical lesions should be referred for specialist help.
Genital HSV disease has been shown to double the risk of transmission and acquisition of HIV disease. Controlling HSV disease may have important public health implications especially for those patients not on antiretroviral treatment who have a detectable HIV viral load.
What can usefully be done at the GP's surgery?
For patients with HSV disease, a viral swab should be taken for typing of disease. The HSV type largely predicts the prognosis for recurrent episodes which is an important part of patient discussion. If viral swabs are not available treatment should not be delayed but urgent referral to a GU department should be made.
What is the value of serology?
HSV serology can be useful in a number of situations such as in patients with recurrent genital lesions but no viral culture, in sexual partnerships and in pregnancy. In a low prevalence population such as the UK, the predictive value of the test decreases considerably and so interpretation of results should be undertaken with care and with expert assistance. With current tests available in the UK there is no role for general population screening.
There is currently no role for HPV serology outside research projects.
What factors predict long-term disease?
It can be difficult to predict the courses of both diseases. Typing of HSV is helpful. Recurrences occur on average every three to four months with HSV 2 and every 18 months with HSV 1.
Those having a prolonged first episode (more than 35 days) are twice as likely to have recurrences. Remember, though, that those with HSV 1 may have a severe first episode, as there is no protective effect from pre-existing disease (for instance, oro-labial HSV).
Many patients report recurrent episodes of HSV at time of stress and women commonly report recurrent episodes peri-menstrually. Long-term stress may increase the frequency and severity of recurrent episodes but studies have not confirmed any relationship with short-term stress or with the menstrual cycle.
For both HSV and HPV patients with asymptomatic disease, symptoms may develop if the immune system is damaged in any way. Patients undergoing chemotherapy or with HIV disease are good examples.
Smokers are more likely to have persistence of HPV compared with non-smokers.
Are vaccines or alternative treatments likely to have a future role?
Is there any value in complementary therapy?
Studies using echinacea or acupuncture have not shown any benefit in reducing the numbers of recurrence of HSV. The amino acid lysine is recommended; however, no studies have yet been published on the benefit of this although a study is currently under way in the UK.
There are currently no recommended complementary therapies for warts.
Are there likely to be any useful vaccines against these conditions?
So far no therapeutic vaccines have been proven to be of sustained benefit for HSV. Phase 3 trials are taking place in the UK for a prophylactic vaccine.
Vaccine development for HPV presents a problem because of the large number of types that infect genital epithelium. However, there is currently a multivalent prophylactic vaccine against genital warts in phase 3 trials.
To date there has been little success with therapeutic vaccines for HPV.
What is new in the treatment of these conditions?
Aciclovir is still widely used in the UK for treatment of first and recurrent episodes of HSV, and as suppressive therapy. The five-times-a-day dosing is inconvenient for patients so famciclovir three times a day or valaciclovir twice a day may be preferred.
Suppressive treatment is given for at least six months, attempting to discontinue at a year if there have been no recurrences.
Recently a study has shown the benefit of a suppressive dose of valaciclovir in preventing sexual transmission of the virus to partners. This is a major anxiety to those with HSV.
There is no benefit in using topical aciclovir.
Home treatments for genital warts are very useful. They not only help the patient avoid weekly treatment visits, but also free up clinic time to see new patients in GU departments.
Podophyllin is now rarely applied in the GU medicine clinic podophyllotoxin is the preferred choice, and is more convenient as home therapy.
The newer immune modifier treatment imiquimod (Aldara) has been shown to be effective, especially with keratinised multiple warts and perianal warts. This novel product works via interferons, induction of NK cells and IL-2 in improving the local immunity of the affected skin. It has been shown to reduce recurrences of visible warts compared with other available treatments.
The disadvantages are that it can cause inflammation in the treatment area and, because of its different mechanism of action, there can appear to be a delay in treatment response. It is more expensive than other available treatments.
What is the relevance of finding HPV on a cervical smear or in a cervical biopsy?
Many cytology laboratories have stopped reporting HPV on cervical smears as it leads to a lot of unnecessary anxiety. Women without visible genital warts who are found to have HPV on a smear or biopsy do not need to be referred to GU clinics.
What about these conditions in pregnancy?
Patients and health care professionals worry about vertical transmission of HSV. In the UK neonatal herpes is quite rare with a reported incidence of 1.6 cases per 100,000 deliveries. Patients most at risk are those who acquire herpes in the last trimester. Aciclovir is not licensed for use in pregnancy, but it appears to be effective and safe. Delaying its use may lead to miscarriage.
Women with known herpes or who develop herpes in pregnancy should be referred to the GU clinic. Suppressive aciclovir may be given from about 34 weeks to prevent lesions appearing at term. If neonatal transmission of herpes occurs, most babies will present with skin, eye and mucus membrane disease approximately 10 days after delivery. GPs should be aware of this possibility and ensure prompt referral.
Some women who carry asymptomatic HPV may develop visible warts for the first time during pregnancy. However, treatments other than cryotherapy or trichloro acetic acid are not licensed for use in pregnancy and may be teratogenic. Many genital warts disappear spontaneously post-partum. They commonly do not need treatment during pregnancy unless they are particularly distressing to the mother. If warts are untreated in pregnancy the mother should be given a careful explanation of the reasons and be followed up after delivery.
Perinatal exposure may result in the rare conditions of laryngeal or genital papillomatosis in infancy or childhood through symptomatic or asymptomatic disease. The latter is significant as an innocent reason for the development of genital warts in children.
Do condoms prevent spread of these viruses?
Condoms do not give great protection, at least in part because of perineal contact. The more visible warts there are, the more infectious a person is, so theoretically there may be some protection against HPV. Condoms are probably not helpful for pre-existing long-term partners but may show some protection in new partners.There is some protection overall with condoms against herpes, but more protection in male to female transmission because of the location of the lesions.
Liz Foley is consultant in genito-urinary medicine at Southampton General Hospital
Patrick Wills is a GP and hospital practitioner in GU medicine at St Mary's Hospital, Newport, Isle of Wight