Human Papilloma Virus and Genital Warts

Synonyms:HPV, condylomata acuminata, condyloma acuminata, genital warts, penile warts, vulval warts, labial warts, anogenital warts, vaginal warts, cervical warts

Genital warts are a cutaneous manifestation of infection with the epidermotropic, sexually-transmitted human papillomavirus (HPV). There are >100 of these double-stranded-DNA papova viruses characterised, with most now fully DNA sequenced.

• HPV is transmitted sexually in most cases but can also be transmitted prenatally, by auto or heteroinnoculation from non-genital warts and possibly by fomites.¹
• An individual's lifetime risk of HPV infection exceeds 50% but most are asymptomatically infected, with only about 1–2% developing genital warts.
• About 90% of genital warts are caused by infection with HPV types 6 & 11. These types are not associated with a significant risk of neoplastic transformation.
• Types 16 and 18 are associated with a high risk of neoplastic transformation.

Incidence

Genital warts are the most commonly diagnosed sexually transmitted infection (STI) in the UK. In 2003, there were an estimated 76,457 initial and 55,657 recurrent or persistent cases of genital warts dealt with at a cost of £22.4 million.²

Risk factors

• Smoking
• Multiple sexual partners
• Early age of onset of sexual intercourse
• Illicit drug use³
• Anoreceptive intercourse⁴
• Manual sexual practices such as fisting and fingering increase the risk of anal warts⁵
• Immunosuppression (including iatrogenic variety in transplant recipients and HIV)⁶

Symptoms

After an incubation period of several weeks to months (occasionally years), lesions appear which are usually painless and asymptomatic but may itch, burn, bleed or discharge.

Signs^7,8

• Lesions are usually papular and pink, red or brown and may be single but often multiple. A number of lesions may form a confluent mass. Over time the lesion may grow and develop into the classical florid warty appearance. They may become huge in immunocompromised patients.
• Four types are seen:
  • Small papular
  • Cauliflower floret
  • Keratotic
  • Flat-topped papules or plaques (usually seen on cervix)
• In males, genital warts mainly appear on the frenulum, corona, glans, prepuce, shaft and scrotum.
• In females, they tend to be seen on the labia, clitoris, periurethral area and cervix.
• Both sexes may be affected in the perineum, perianal area and anal canal.

The anogenital and surrounding skin should be examined under good illumination. Female patients should undergo a vaginal speculum examination and proctoscopy may be indicated in both sexes if there is a history of anoreceptive sex. Recording lesions on genital maps can be useful to enable a visual record and monitor response to treatment.⁹
Diagnosis by biopsy and viral typing is not routinely required and tends to be reserved for where diagnosis is uncertain, recalcitrant warts, warts with atypical features (eg pigmented, indurated, fixed or ulcerated warts) or where there is high risk of HPV-related malignancy.

• Benign or malignant neoplasm (eg squamous cell carcinoma in situ, Bowen's disease)
• Molluscum contagiosum
• Condyloma lata
• Fibroepitheliomas
• Pearly penile papules

• Cervical carcinoma is associated with infection with HPV types 16 and 18. Recent longitudinal studies suggest that the time between infection and the development of CIN lesions may be relatively short.¹¹
• Other genital cancers, such as cancer of the vulva, vagina and penis, appear to be linked to HPV (usually genotype 16).¹²
• Anal carcinoma may develop, particularly among patients with AIDS.¹³
• Recent studies have indicated that HPV may be an important aetiological factor in some cases of oropharyngeal cancer.¹⁴

General points:

• Patients will require a detailed explanation of the condition with emphasis on long term health implications for themselves and their partners. Reinforce with written information.
• Data is conflicting regarding condom use but condoms have been shown to protect against acquiring HPV infection and genital warts. Current British guidelines suggest that condom use may be beneficial and advise their use, particularly in new relationships.
• Psychological distress is common - referral for counselling may be appropriate.
• Patients may also have concurrent STIs. One study undertaken in a GUM clinic (with a 40% primary care referral rate) found a co-existing STI rate of 14%, with an increased risk in those aged under 25 or with additional genital symptoms.¹⁶
• Current sexual partner(s) may benefit from assessment but previous partner tracing is not recommended.

There are many effective treatments, both topical and ablative, and these tend to be selected largely on the preference of clinician and patient and the severity of disease. The primary goal of treatment is to remove symptomatic warts. Some evidence suggests that treatment may reduce HPV DNA persistence in genital tissues possibly reducing infectivity but there is no evidence that treatment reduces the incidence of cervical or genital cancer.

For mild, early lesions, there is an emphasis on self-administered topical therapies such as podophyllotoxin and imiquimod which are effective and well tolerated and may be used for home treatment by patients (following a demonstration). Podophyllum and podophyllotoxin are suitable for soft, non-keratinised external genital warts whilst imiquimod may be used for both keratinised and non-keratinised warts. Where the number of warts is low, irrespective of type, ablative therapy from the outset is recommended.

Seek specialist help where lesions are resistant to treatment, relapse or lesions are internal (intravaginal, cervical, urethral meatus or intra-anal). Care should also be taken in the treatment of pregnant patients - avoid podophyllin, podophyllotoxin, 5-fluorouracil and imiquimod- but aim to minimise lesions present at delivery to reduce risk of perinatal transmission.
Review should be undertaken at the end of a course of treatment. Change in treatment is indicated where a patient does not tolerate the current regimen or has under 50% response to current treatment by 6 weeks (8-12 weeks in the case of imiquimod).

Genital warts in children¹

The discovery of external genital warts in children often raises concern about sexual abuse. However, mode of transmission in paediatric patients frequently is untraceable and the presence of warts without supporting social and clinical evidence should not be taken as diagnostic of sexual abuse. One study suggested a positive predictive value of external genital warts for sexual abuse of 37% in children aged 2-12 years (increasing with age). Seek advice from child protection colleagues

Explain to patients that untreated external genital warts may resolve spontaneously (up to one third spontaneously regress within three months), remain the same or increase in size. Life-long, subclinical infection may persist. Warts may recur with or without immunosuppression, especially condylomata.
Patients should be reassured that over 90% of genital warts are caused by HPV types which are low risk for neoplastic transformation.

Condoms

Contrary to popular belief, condoms provide very little protection against skin-to-skin contact transmissible diseases such as HPV.^4,17 Their routine use, however, may reduce an individual's long-term risk of developing genital wart lesions.¹⁸

Vaccination

A quadrivalent vaccine against HPV-6/11/16/18 has been recently developed to give protection against cancer of the cervix, pre-cancerous lesions of the vulva and vagina and genital warts. It provides 96-100% efficacy at preventing genital warts when young women receive prophylactic vaccination and efficacy remains high for at least 5 years.¹⁹ It is now licensed in over 80 countries worldwide and part of national immunisation programmes in some countries eg USA²⁰ (currently in the UK, Gardasil® is licensed but not part of the routine immunisation schedule). Whilst the impact of such programmes is still to be realised, it is expected to drastically reduce the incidence of genital warts in these countries.