Human papillomavirus and genital warts

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Human papillomavirus infects basal epithelial cells through small mucocutaneous breaks. Low-risk types, particularly HPV 6 and 11, cause most visible anogenital warts, whereas persistent infection with oncogenic types drives cervical, anal, vulval, vaginal and penile neoplasia. A visible wart is therefore a benign clinical phenotype, not proof that a high-risk lesion is absent elsewhere or that the wart itself will become cancer.

Transmission occurs through close skin and mucosal contact and can occur without penetration or visible lesions. The interval between acquisition and a recognised wart is variable, so diagnosis cannot date transmission or identify one partner. Condoms reduce but do not eliminate exposure because uncovered skin may shed virus. Counselling should explain natural history without blame and should separate wart recurrence from infidelity.

Many warts regress through cell-mediated immunity, while destructive and immune-modulating treatments shorten visible disease for some people but do not eradicate latent virus. No single option is best for every site. Keratinised external lesions, moist mucosal lesions, pregnancy, immune status, pain tolerance and ability to apply treatment accurately shape the decision.

Key points

Typical external anogenital warts are soft papillomatous, filiform or flat-topped papules and are usually diagnosed by inspection.
Routine HPV typing does not confirm that a visible lesion is a wart, choose treatment or reliably predict its future behaviour.
Biopsy atypical, pigmented, indurated, ulcerated, bleeding or treatment-resistant lesions, especially with immunosuppression.
Observation is reasonable because many warts regress; treatment choice depends on site, burden, preference, pregnancy, cost and clinician experience.
Patient-applied podophyllotoxin or imiquimod and clinician-applied cryotherapy are options for suitable external lesions, each with different contraindications and irritation profiles.
Treat visible warts rather than attempting to eradicate latent HPV; recurrence can occur after apparently complete clearance.
Offer routine STI assessment and smoking support, and use the national HPV vaccination schedule according to age and eligibility.
Cervical screening, anal disease assessment and vaccination each have separate indications; external warts alone do not justify inventing a screening interval.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Low-risk HPV infection

HPV 6 and 11 infect anogenital squamous epithelium and account for most visible benign warts. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

Close skin contact

Virus transfers through genital or perianal skin contact, including contact without penetration or visible lesions. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

Autoinoculation

Manipulating or shaving across lesions can transfer virus to adjacent microtraumatised skin and broaden distribution. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

Impaired cellular immunity

HIV, transplantation or immunosuppressive treatment reduces viral control and permits extensive or persistent disease. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Basal-cell entry
HPV reaches basal keratinocytes through microscopic epithelial disruption and establishes episomal infection. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.
2
Epithelial proliferation
Low-risk viral proteins promote cell cycling and thickening, creating papillary or flat wart morphology. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.
3
Immune regression
Cell-mediated immunity recognises infected keratinocytes and permits spontaneous regression in many immunocompetent people. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.
4
Oncogenic persistence
Persistent high-risk HPV expression disrupts tumour-suppressor pathways and can drive intraepithelial neoplasia at susceptible sites. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Exophytic external wart

Soft flesh-coloured or pink papillomatous papules may coalesce into plaques on genital or perianal skin.

Flat lesion

Subtle smooth or slightly raised lesions require good lighting and can resemble normal variants or intraepithelial neoplasia.

Keratinised wart

Firm dry lesions on hair-bearing skin may resemble seborrhoeic keratoses, skin tags or common cutaneous warts.

Atypical lesionRed flag

Pigmentation, ulceration, induration, fixation or bleeding is not a routine wart phenotype and prompts biopsy.

Internal diseaseRed flag

Symptoms such as bleeding, discharge, altered urine stream or anal discomfort can indicate lesions beyond external inspection.

Immune-associated burden

Large, numerous or refractory lesions occur more often with impaired cellular immunity and warrant HIV assessment.

Red flags requiring action

A pigmented, indurated, fixed, ulcerated or spontaneously bleeding lesion may represent intraepithelial neoplasia or invasive cancer rather than a simple wart.
Failure after an adequate, correctly used treatment course requires diagnostic review; repeating destructive therapy indefinitely can delay biopsy.
Extensive, unusually large or rapidly recurrent lesions in an immunosuppressed person need HIV assessment and specialist management.
Urethral, vaginal, cervical or intra-anal lesions may not be fully visible and can require anoscopy, colposcopy, urology or gynaecology expertise.
Anogenital lesions in a child require a careful paediatric and safeguarding assessment that does not infer sexual transmission from appearance alone.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Careful anogenital examinationFirst step
Why
Define morphology, distribution and whether lesions extend into an internal site.
Interpretation and limitations
Typical external warts are diagnosed clinically; examination must also look for ulceration, induration, pigment and fixation.
02
Histological biopsy
Why
Distinguish wart from intraepithelial neoplasia, carcinoma or an inflammatory mimic.
Interpretation and limitations
Use when diagnosis is uncertain or a lesion is atypical, bleeding, indurated, ulcerated or refractory to appropriate therapy.
03
Site-directed internal examination
Why
Assess urethral, vaginal, cervical or intra-anal extension when symptoms or location indicate.
Interpretation and limitations
Choose anoscopy, speculum examination, colposcopy or urological assessment for the actual anatomical site rather than routinely for everyone.
04
HIV test and immune review
Why
Identify immune impairment when disease is extensive, giant, rapidly recurrent or unusually resistant.
Interpretation and limitations
A negative test within its window does not close a recent exposure; repeat with the correct assay interval.
05
Routine STI screen
Why
Identify infections sharing the sexual exposure and address vaccination and prevention needs.
Interpretation and limitations
Select chlamydia and gonorrhoea sites from exposure and add syphilis, HIV and hepatitis tests according to risk.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Molluscum contagiosum

Discrete pearly umbilicated papules differ from the irregular papillomatous surface of many warts. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

Secondary syphilis

Condylomata lata are broad moist lesions accompanied by systemic or serological evidence of syphilis. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

Normal anatomical variant

Vestibular papillae, pearly penile papules and skin tags are symmetrical stable structures needing no treatment. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

Intraepithelial neoplasia

Pigment, induration, ulceration, bleeding or a persistent plaque requires histology rather than clinical reassurance. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

Seborrhoeic keratosis

A waxy stuck-on keratotic lesion can resemble a wart, particularly on hair-bearing groin skin. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Worked caseClassify before treatingFirst stepAn adult presents with new external anogenital papules and requests immediate removal.

1Inspect all reported sites with consent and identify whether morphology is typical or contains biopsy features.
2Explain that diagnosis is usually clinical, HPV typing is not useful for wart treatment, and latency prevents reliable dating of acquisition.
3Offer observation or a site-appropriate patient-applied or clinician-applied option after checking pregnancy and contraindications.
4Arrange a defined review to assess technique, adverse effects, response and whether failure changes the diagnosis.

02AtypicalExclude neoplasia promptlyA lesion is pigmented, indurated, ulcerated, bleeding, fixed or repeatedly treatment resistant.

1Stop empiric cycles of destruction and document size, site, morphology, nodes and immune context.
2Arrange biopsy or urgent specialist review using the service appropriate to vulval, penile, anal, cervical or urethral location.
3Treat pain, bleeding, infection or obstruction while preserving tissue needed for diagnosis.

03TreatmentMatch method to siteThe person chooses active treatment for clinically typical external warts.

1Use patient-applied treatment only where the person can see and reach each suitable external lesion.
2Choose clinician-applied cryotherapy or another specialist method for internal, bulky or difficult lesions.
3Warn that inflammation is expected with some treatments, prevent exposure to unaffected skin and pause for severe reactions.
4Reassess diagnosis and adherence if there is no meaningful response after an adequate course.

04PreventionReduce future HPV harmA wart diagnosis creates an opportunity for prevention and wider care.

1Offer HPV vaccination according to the current UK programme and explain that it does not treat existing visible lesions.
2Support smoking cessation and immune health because persistent HPV disease is more likely with impaired cellular immunity.
3Continue cervical screening according to the national programme and use separate specialist criteria for anal or other site surveillance.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Patient-applied antimitotic treatment causes necrosis of selected keratinised external warts.

Podophyllotoxin for suitable external warts

Apply the licensed preparation to visible suitable external lesions exactly according to its product cycle and maximum treated area.

Avoid in pregnancy, internal sites and uncertain lesions; protect normal skin and stop for severe ulceration or systemic symptoms.

Patient-applied immune response modification can clear selected external anogenital warts.

Imiquimod for suitable external warts

Apply the licensed cream on its formulation-specific schedule, wash off after the specified contact period, and continue only to its maximum course.

No self-applied topical agent is licensed during pregnancy or breastfeeding. Do not routinely use imiquimod when safe ablative options are available; BASHH lists cryotherapy, laser, electrosurgery, excision and TCAA as options that may be used safely in pregnant or breastfeeding adults.

Controlled freezing destroys wart tissue and suits many external or anatomically difficult lesions.

Cryotherapy

Apply liquid nitrogen to each visible lesion in clinician-delivered sessions at intervals determined by response and tissue recovery.

Pain, blistering and pigment change can occur; avoid over-treatment near sensitive structures and biopsy an atypical lesion first.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Psychosexual distress

Stigma, relationship concern and prolonged treatment can affect sexual confidence despite the benign nature of most lesions.

Local obstruction

Bulky urethral, vaginal or anal disease can impair flow, intercourse or defaecation and needs specialist removal.

Treatment injury

Excess chemical or cryotherapy exposure causes ulceration, pain, scarring or pigment change in normal surrounding skin.

Recurrent disease

Latent infection and incomplete immune control permit new visible lesions after successful initial clearance. This distinction guides focused diagnosis and prevents unsupported assumptions about treatment or transmission.

Associated neoplasia

High-risk HPV disease may coexist at another site, particularly with immunosuppression, but is not inferred from a typical wart alone.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record lesion number, size, distribution, chosen option and photographs only with explicit consent and secure handling.
Review patient-applied technique and expected local reaction before declaring a treatment failure.
Re-examine refractory lesions and obtain histology when the diagnosis has become uncertain.
Assess urinary, vaginal or bowel symptoms that suggest internal extension or obstruction.
Offer HIV and site-specific STI testing at assay-appropriate intervals and complete eligible vaccination.
Continue national cervical screening by its own eligibility and interval, independent of whether external warts clear.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Warts do not date infection

Latency can last months or longer, so a new wart cannot establish when or from whom HPV was acquired.

Typing does not guide treatment

Visible-wart care depends on morphology and site; routine viral typing does not select the method.

Clearance is not eradication

Successful removal eliminates visible tissue while latent infection may persist and later recur.

Site changes the pathway

External, cervical, urethral and intra-anal lesions require different examinations and specialist skills.

Vaccination prevents future disease

HPV vaccine protects against included types but does not act as treatment for established warts.

Immunosuppression changes vigilance

Extensive or resistant disease warrants HIV assessment and a lower threshold for biopsy.

11Common pitfallsFrequent interpretation and management errors.

01
Do not call every papule a wart; normal variants, molluscum, syphilis and neoplasia can mimic it.
02
Do not use routine HPV typing to diagnose a visible lesion or choose treatment.
03
Do not repeatedly destroy an indurated, pigmented, ulcerated or bleeding lesion without histology.
04
Do not use podophyllotoxin during pregnancy or on internal sites.
05
Do not promise that treatment eradicates HPV or prevents all recurrence.
06
Do not change cervical screening intervals solely because external warts are present.

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