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 papovaviruses characterised, with most now fully DNA-sequenced.

• HPV is transmitted sexually in most cases but can also be transmitted prenatally, by autoinoculation or heteroinoculation 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 and 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.

Epidemiology

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

Presentation

Symptoms

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

A relevant sexual history should be obtained to assess the risk of other STIs and sexual health needs:

• Other symptoms, e.g. urethral/vaginal discharge, pelvic or scrotal pain, intermenstrual or postcoital bleeding, dyspareunia
• Sexual activity in the last 3 months
• Contraceptive and condom use
• Possibility of pregnancy
• HIV risk activities

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 the 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

Investigation

Diagnosis by biopsy and viral typing is not routinely required and tends to be reserved for where diagnosis is uncertain or for recalcitrant warts, warts with atypical features or where there is high risk of human papillomavirus (HPV) related malignancy.

Differential diagnosis¹⁰

• Benign or malignant neoplasm (e.g. squamous cell carcinoma in situ, Bowen's disease)
• Molluscum contagiosum
• Epidermoid cysts
• Hair follicles
• Sebaceous glands
• Pearly penile papules (normal variant: 1-3 rows of smooth, discrete, non-coalescing, 1-2 mm papules appearing on the margin of the glans)¹¹
• Hymen remnants
• Vulval papillomatosis (normal variant: regularly shaped, non-coalescing, largely symmetrical papillae on the inside of the labia minora and vestibule)¹¹
• Condyloma lata (secondary syphilis)

Associated diseases¹²

The majority of external genital warts are caused by human papillomavirus (HPV) types 6 and 11 which are not associated with significantly increased risk of neoplastic transformation. However, 10% of genital warts are caused by HPV types 16 and 18 and these types are associated with an increased risk of:

• Cervical carcinoma
• Vaginal, vulval and penile carcinoma
• Anal cancers
• Oral and oropharyngeal cancers

Management^9,13

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. Explain the long latent period associated with HPV, and that recurrence of warts in one partner does not imply infidelity.
• Data are conflicting regarding condom use. Current British guidelines suggest that condom use may be beneficial and advise their use, particularly in new relationships. Ideally, sexual contact with new partners should be avoided until the current warts have cleared. Individuals should be aware that the HPV persists after clinical clearance of warts for very variable lengths of time.
• Psychological distress is common - referral for counselling may be appropriate.
• 20-30% of patients with genital warts have concurrent STIs so appropriate screening should be discussed and offered (including chlamydia, gonorrhoea, HIV, syphilis, and hepatitis B and C).
• Partner notification is not recommended.

Treatment of warts and screening for other STIs may occur within general practice or via the genitourinary medicine (GUM) clinic. Referral should occur where:

• The diagnosis is unclear.
• There is suspicion of intraepithelial neoplasia or malignancy (urgent referral).
• There are internal warts in difficult-to-reach sites (intravaginal, cervical, urethral meatus or intra-anal).
• The patient is a child, pregnant or immunosuppressed.
• There is treatment failure or where treatment cannot be tolerated due to side-effects.
• There are problematic recurrences.
• There are positive results from the screen for other STIs.

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 speed the clearance of symptomatic warts. About 75% are clear of warts within a month of starting treatment; however, warn that about 20% have a recurrence within 3 months. Giving no treatment is also an option since warts regress spontaneously. 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.

Topical treatments^10,14

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). However, where the number of warts is low, irrespective of type, ablative therapy from the outset is recommended.

• Podophyllotoxin is suitable for soft, non-keratinised external genital warts. 0.15% cream should be used twice-daily for 3 days, followed by a 4-day break, resuming only if the warts persist. Use for a maximum of 5 weeks.
• Where there is no response to this regime, podophyllotoxin 0.5% cream should be used (according to the same regime) or imiquimod, applying a half or whole sachet on alternate nights, washing off after 6-10 hours for a maximum of 16 weeks with review every 4-6 weeks.
• All topical treatments can cause local skin reactions and, where severe, patients must stop treatment and seek advice. Normal surrounding skin may be protected from podophyllotoxin by the use of petroleum jelly. Avoid contact with broken skin and open wounds. Unprotected sexual contact soon after application should be avoided (as it may have an irritant effect on the partner). Condoms may be weakened if in contact with imiquimod.
• Accessible keratinised warts can be treated with podophyllotoxin 0.5% liquid or imiquimod cream.
• Perianal warts are usually treated with imiquimod or cryotherapy. If persistent, they should be referred to the surgeons.
• Cervical warts should be treated via colposcopy.
• Warts in the urethral meatus are difficult to treat, refer to GUM or urology.

Care should also be taken in the treatment of pregnant patients. Avoid podophyllin, podophyllotoxin, 5-fluorouracil and imiquimod in pregnancy. Cryotherapy is often used to try to minimise lesions present at delivery but risks (perinatal transmission of genital warts, laryngeal papillomatosis, obstructed labour) to the baby are usually considered small and not an indication for Caesarean section.

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 children

The discovery of external genital warts in children often raises concern about sexual abuse.
National Institute for Health and Clinical Excellence (NICE) guidance¹⁵ recommends considering sexual abuse in a child younger than 13 years with anogenital warts unless there is clear evidence of:

• Mother-to-child transmission during birth (it is not currently known at what age this can be confidently excluded)
• Nonsexual transmission from a household member

Studies suggest sexual transmission as the cause of infection in between 31-58% of children with anogenital warts. However, it is often very difficult to determine the mode of transmission in children, even with viral typing of the index case and contacts, and the presence of warts without supporting social and clinical evidence cannot be taken as diagnostic of sexual abuse.¹ Advice should be sought from experienced child protection colleagues.¹⁵

Prognosis

Explain to patients that untreated external genital warts may:

• Resolve spontaneously - up to one third spontaneously regress within three months
• Remain the same
• Increase in size

Lifelong 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.

Prevention

Condoms

Contrary to popular belief, condoms provide very little protection against skin-to-skin contact transmissible diseases such as human papillomavirus (HPV).^4,16 Their routine use, however, may reduce an individual's long-term risk of developing genital wart lesions.¹⁷

Vaccination¹⁸

A quadrivalent vaccine against HPV-6/11/16/18 (Gardasil®) has been developed to give protection against cancer of the cervix, precancerous 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 many countries.²⁰ In Australia, where the quadrivalent vaccine has been part of their national immunisation strategy since 2007, a rapid and drastic reduction in the incidence of genital warts in young women has been reported (25% reduction per quarter in 2008), with a smaller reduction in the incidence in young heterosexual men (5% reduction per quarter in 2008).²¹

The UK Department of Health's decision to back the bivalent vaccine against HPV-16 and 18 (Cervarix®) for the national HPV prevention programme has been controversial since the health benefits and potential savings associated with reduction in genital wart disease of the quadrivalent vaccine will not be realised with this approach.²² Outside the national programme, many doctors will recommend Gardasil® because of its extra protection and because it can be prescribed privately or according to local directives.

Another area of controversy is whether or not HPV vaccination should be extended to young men, as well as women.^23,24 Gardasil® is approved in the USA for use in boys and young men, but remains off license in the UK. Efficacy data relating to this group should be available soon.

The current role of vaccination is solely prophylactic. The age at immunisation is critical since, by their early to mid twenties, many will have serological evidence of exposure to HPV. There is no evidence at the current time of a therapeutic role for the vaccine, e.g. to boost immunity against recalcitrant warts, to prevent relapse once clinically clear of warts or to treat precancerous change in cervical intraepithelial neoplasia (CIN).

Document references

1. Jayasinghe Y, Garland SM; Genital warts in children: what do they mean? Arch Dis Child. 2006 Aug;91(8):696-700. Epub 2006 May 2. [abstract]
2. Brown RE, Breugelmans JG, Theodoratou D, et al; Costs of detection and treatment of cervical cancer, cervical dysplasia and genital warts in the UK. Curr Med Res Opin. 2006 Apr;22(4):663-70. [abstract]
3. Khan A, Hussain R, Schofield M; Correlates of sexually transmitted infections in young Australian women. Int J STD AIDS. 2005 Jul;16(7):482-7. [abstract]
4. Wiley DJ, Harper DM, Elashoff D, et al; How condom use, number of receptive anal intercourse partners and history of external genital warts predict risk for external anal warts. Int J STD AIDS. 2005 Mar;16(3):203-11. [abstract]
5. Jin F, Prestage GP, Kippax SC, et al; Risk factors for genital and anal warts in a prospective cohort of HIV-negative homosexual men: the HIM study. Sex Transm Dis. 2007 Jul;34(7):488-93. [abstract]
6. Ault KA; Epidemiology and natural history of human papillomavirus infections in the female genital tract. Infect Dis Obstet Gynecol. 2006;2006 Suppl:40470. [abstract]
7. Ghadishah D Condyloma Acuminata; eMedicine. Last Updated: Nov 2009
8. Fitzpatrick TB et al, Colour Atlas and Synopsis of Clinical Dermatology. McGraw-Hill 2001
9. Management of Anogenital Warts, British Association for Sexual Health and HIV (2007)
10. Delaney EK, Baguley S; Genital warts. BMJ. 2008 Oct 17;337:a1171. doi: 10.1136/bmj.a1171.
11. von Krogh G, Lacey CJ, Gross G, et al; European course on HPV associated pathology: guidelines for primary care physicians for the diagnosis and management of anogenital warts. Sex Transm Infect. 2000 Jun;76(3):162-8. [abstract]
12. Human papillomavirus (HPV) - cervical cancer and genital warts, Health Protection Agency
13. Kodner CM, Nasraty S; Management of genital warts. Am Fam Physician. 2004 Dec 15;70(12):2335-42. [abstract]
14. Anogenital warts, Clinical Knowledge Summaries (October 2008)
15. When to suspect child maltreatment, NICE Clinical Guideline (July 2009); Guidance on when to suspect child maltreatment
16. Lyttle PH, Thompson SC; Maintaining sexual health in commercial sex workers in Australia: condom effectiveness, screening, and management after acquiring sexually transmissible infections. Aust N Z J Public Health. 2004 Aug;28(4):351-9. [abstract]
17. Manhart LE, Koutsky LA; Do condoms prevent genital HPV infection, external genital warts, or cervical neoplasia? A meta-analysis. Sex Transm Dis. 2002 Nov;29(11):725-35. [abstract]
18. No authors listed; Vaccination against human papillomavirus. Drug Ther Bull. 2008 Dec;46(12):89-93. [abstract]
19. Barr E, Tamms G; Quadrivalent human papillomavirus vaccine. Clin Infect Dis. 2007 Sep 1;45(5):609-7. Epub 2007 Jul 25. [abstract]
20. Zimmerman RK; HPV vaccine and its recommendations, 2007. J Fam Pract. 2007 Feb;56(2 Suppl Vaccines):S1-5, C1. [abstract]
21. Fairley CK, Hocking JS, Gurrin LC, et al; Rapid decline in presentations of genital warts after the implementation of a Sex Transm Infect. 2009 Dec;85(7):499-502. Epub 2009 Oct 16. [abstract]
22. Dasbach EJ, Insinga RP, Elbasha EH; The epidemiological and economic impact of a quadrivalent human papillomavirus BJOG. 2008 Jul;115(8):947-56. Epub 2008 May 22. [abstract]
23. Hibbitts S; Should boys receive the human papillomavirus vaccine? Yes. BMJ. 2009 Dec 7;339:b4928. doi: 10.1136/bmj.b4928.
24. Cuschieri K; Should boys receive the human papillomavirus vaccine? No. BMJ. 2009 Dec 7;339:b4921. doi: 10.1136/bmj.b4921.

Internet and further reading

• Chester Sexual Health; NHS GUM clinic site with photographic illustrations and case study of imiquimod induced erythema
• DermIS; Dermatology Information System - Condyloma Acuminatum; Images of genital warts in male and female patients.
• Brashear R, Chuang T; Brashear R and Chuang T; Genital Warts. eMedicine, October 2009.
• Gearhart P, Randall T; Human Papillomavirus. eMedicine, Feburary 2010.

Acknowledgements