Infectious Disease and Microbiology - Warts

Basics

Description

Warts, or verrucae, are benign proliferative lesions of the skin or mucous membranes caused by human papillomavirus (HPV) infection.

Transmission occurs through:

• Direct skin-to-skin contact
• Sexual contact
• Contact with contaminated surfaces or objects
• Autoinoculation from one body site to another

Warts may be broadly divided into:

• Cutaneous warts
• Anogenital warts
• Respiratory papillomatosis

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Epidemiology

Warts are common and affect roughly 7–10% of the population.

Cutaneous warts are seen most often in:

• Children
• Adolescents
• Young adults

They are especially common among people who regularly handle:

• Meat
• Poultry
• Fish

because repeated minor trauma facilitates viral inoculation.

Anogenital HPV infection is among the most common sexually transmitted infections worldwide.

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Risk Factors

Important risk factors include:

• Repeated skin trauma
• Meat, poultry, or fish handling
• Atopic dermatitis
• Immunosuppression
• Defects in cell-mediated immunity
• Unprotected sexual contact
• Multiple sexual partners
• Men who have sex with men
• Contact with a partner who has anogenital HPV infection

Immunocompromised patients may develop:

• Numerous lesions
• Larger lesions
• Refractory lesions
• More frequent recurrence

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Etiology

Warts are caused by human papillomaviruses, a large group of double-stranded DNA viruses with tropism for squamous epithelium.

There are more than 200 recognized HPV types.

Important associations include:

HPV 6 and 11

→ Cause most genital warts

HPV 16 and 18

→ High-risk oncogenic types strongly associated with:

• Cervical cancer
• Anal cancer
• Penile cancer
• Vulvar cancer
• Vaginal cancer
• Oropharyngeal cancer

Genital warts themselves are usually caused by low-risk HPV types, particularly 6 and 11.

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Pathophysiology

HPV gains entry through microscopic breaks in the skin or mucosa.

It infects basal keratinocytes and induces epithelial proliferation.

As infected cells migrate toward the surface, viral replication increases and produces the characteristic wart architecture.

Warts may persist for months or years, but immune recognition can eventually cause spontaneous regression.

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General Prevention

Prevention includes:

• Avoiding direct contact with visible warts
• Avoiding picking, scratching, or shaving over warts
• Wearing footwear in communal showers and pool areas
• Avoiding sharing razors or personal items
• Practicing safer sex
• Using condoms, while recognizing that condoms do not completely prevent HPV transmission because uncovered skin may remain infectious
• HPV vaccination

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HPV Vaccination

Modern HPV vaccination is one of the most important preventive measures.

The currently used vaccine in many countries is the 9-valent HPV vaccine, which protects against HPV types:

• 6
• 11
• 16
• 18
• 31
• 33
• 45
• 52
• 58

It protects against both:

• Genital warts
• HPV-associated cancers

Vaccination is most effective when given before exposure to HPV.

Routine vaccination is generally recommended beginning in early adolescence, with catch-up vaccination also recommended for older adolescents and young adults according to national guidelines.

Vaccination prevents new infection but does not treat existing warts or established HPV infection.

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Pregnancy Considerations for Vaccination

HPV vaccine is not a live vaccine.

However, routine administration during pregnancy is generally deferred.

If a dose is given inadvertently during pregnancy, this is not considered an indication for pregnancy termination.

Remaining doses can usually be completed after pregnancy.

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Clinical Types

Common Warts

Common warts, or verruca vulgaris, typically appear as:

• Firm papules
• Hyperkeratotic surface
• Rough or cauliflower-like texture

Common locations include:

• Hands
• Fingers
• Elbows
• Knees
• Periungual areas

They may occur anywhere.

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Plantar Warts

Plantar warts occur on the soles of the feet.

Typical features include:

• Pain with pressure
• Thickened keratotic surface
• Disruption of normal skin lines
• Small thrombosed capillaries appearing as black dots
• Pinpoint bleeding when pared

They may be confused with calluses.

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Flat Warts

Flat or juvenile warts are typically:

• Small
• Smooth
• Flat-topped
• Multiple

They are commonly seen on:

• Face
• Hands
• Shins

They are especially common in children and adolescents.

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Filiform Warts

Filiform warts are:

• Thin
• Finger-like
• Pedunculated

They often occur on:

• Face
• Eyelids
• Lips
• Neck

Because cosmetic outcome matters, treatment should minimize scarring.

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Anogenital Warts

Anogenital warts are also called:

Condylomata acuminata

They may appear as:

• Small papules
• Papillary lesions
• Pedunculated growths
• Large cauliflower-like masses

Possible sites include:

• Vulva
• Vagina
• Cervix
• Penis
• Scrotum
• Perineum
• Perianal region
• Anal canal
• Urethral meatus

Most are caused by HPV 6 and 11.

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Cervical HPV Infection

Cervical HPV infection may produce:

• No visible lesion
• Low-grade squamous intraepithelial lesion
• High-grade squamous intraepithelial lesion
• Cervical intraepithelial neoplasia

Persistent infection with high-risk HPV types is the major cause of cervical cancer.

The presence of external genital warts does not by itself imply cervical cancer.

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Respiratory Papillomatosis

Recurrent respiratory papillomatosis is usually associated with HPV 6 and 11.

It is most often seen in children but can also occur in adults.

Possible manifestations include:

• Hoarseness
• Chronic voice change
• Stridor
• Respiratory distress
• Upper-airway obstruction

Lesions most commonly involve the larynx and may recur repeatedly.

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Diagnosis

Most warts are diagnosed clinically from their characteristic appearance.

Routine laboratory testing is usually unnecessary.

Important questions include:

• Duration
• Number of lesions
• Prior treatment
• Immunosuppression
• Sexual history for anogenital lesions
• Rapid growth
• Bleeding
• Ulceration
• Pain
• Failure to respond to treatment

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Biopsy

Biopsy should be considered when a lesion is:

• Atypical
• Pigmented
• Ulcerated
• Indurated
• Rapidly growing
• Bleeding spontaneously
• Large
• Refractory to therapy

It is also particularly useful in:

• Immunocompromised patients
• Patients in whom malignancy cannot be excluded

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HPV Testing

HPV typing is not routinely used to diagnose ordinary cutaneous or genital warts.

Molecular tests are primarily used in cervical cancer screening and selected anogenital disease evaluation.

Methods may include:

• PCR
• Nucleic acid hybridization
• Other molecular assays

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Acetic Acid Testing

Dilute acetic acid may cause HPV-infected epithelium to become white.

This is known as:

Acetowhitening

However, the finding is nonspecific and should not be used alone to diagnose HPV infection.

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Histopathology

Typical histologic findings include:

• Papillomatosis
• Acanthosis
• Hyperkeratosis
• Parakeratosis

Koilocytes may be present, particularly in genital lesions.

A koilocyte is a squamous epithelial cell with:

• Perinuclear clearing
• Nuclear enlargement
• Nuclear irregularity

It reflects HPV-related cytopathic change.

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Differential Diagnosis

Cutaneous warts may resemble:

• Callus
• Corn
• Seborrheic keratosis
• Actinic keratosis
• Molluscum contagiosum
• Squamous cell carcinoma
• Other keratinizing skin tumors

Anogenital lesions may resemble:

• Molluscum contagiosum
• Condylomata lata of secondary syphilis
• Skin tags
• Pearly penile papules
• Vestibular papillomatosis
• Squamous neoplasia

Atypical anogenital lesions should be assessed carefully before destructive treatment.

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Natural History

Many warts resolve spontaneously.

In immunocompetent children, a substantial proportion disappear within:

• 1 year
• 2 years

Spontaneous regression reflects development of effective cell-mediated immunity.

Anogenital warts can also regress without treatment.

However, treatment may be desired because of:

• Pain
• Bleeding
• Irritation
• Cosmetic concerns
• Sexual transmission concerns
• Functional interference
• Psychological distress

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Treatment Principles

No treatment guarantees eradication of latent HPV infection.

Most therapies remove visible lesions rather than eliminate all infected cells.

Therefore:

Recurrence is common

Treatment is individualized according to:

• Wart type
• Location
• Number
• Size
• Patient age
• Pregnancy
• Immune status
• Cosmetic considerations
• Patient preference

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Cutaneous Warts

Salicylic Acid

Salicylic acid is one of the most commonly used first-line treatments for cutaneous warts.

It works by:

• Keratolysis
• Gradual removal of infected epithelium

Treatment usually requires repeated application for several weeks.

Before application:

• Soak the wart
• Pare excess keratin if appropriate
• Apply the preparation carefully to the lesion

This is particularly useful for:

• Common warts
• Plantar warts
• Palmar warts

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Cryotherapy

Cryotherapy with liquid nitrogen is another standard treatment.

It causes tissue destruction through freezing.

It is commonly used for:

• Common warts
• Plantar warts
• Genital warts

Treatment may be repeated every few weeks.

Adverse effects include:

• Pain
• Blistering
• Erosion
• Temporary pigment changes
• Hypopigmentation
• Hyperpigmentation
• Rare scarring

Pigment alteration is particularly relevant in darker skin.

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Pediatric Considerations

For younger children, salicylic acid is often favored because cryotherapy can be painful.

Treatment is generally unnecessary if:

• Lesions are asymptomatic
• They are not spreading rapidly
• Cosmetic concerns are minimal

Spontaneous resolution is common.

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Flat Warts

Possible treatments include:

• Topical retinoids
• Selected keratolytic therapy
• Cryotherapy in carefully selected lesions

Treatment on the face should be conservative because of the risk of:

• Scarring
• Pigment alteration

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Recalcitrant Cutaneous Warts

For persistent lesions, options may include:

• Intralesional immunotherapy
• Curettage
• Electrosurgery
• Laser therapy
• Selected topical immune-modifying therapies

Management is often best individualized by dermatology.

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Treatment of External Anogenital Warts

Treatment may be:

Patient-applied

or

Clinician-administered

Choice depends on the lesion and patient preference.

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Imiquimod

Imiquimod is a topical immune-response modifier.

It can be used for external anogenital warts.

It promotes local cytokine production and antiviral immune activity.

Potential adverse effects include:

• Erythema
• Burning
• Erosion
• Local irritation

Treatment may require several weeks.

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Podofilox

Podofilox, also called podophyllotoxin, is a patient-applied antimitotic treatment for external genital warts.

It causes local tissue necrosis.

It should not be used:

• Internally
• During pregnancy

Patients should receive careful instructions to avoid application to normal surrounding skin.

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Trichloroacetic Acid

Trichloroacetic acid, or TCA, is a clinician-applied chemical destructive therapy.

It may be used for:

• External genital warts
• Vaginal lesions
• Selected anal lesions

The solution is applied directly to the wart until a white frost develops.

Possible adverse effects include:

• Burning
• Pain
• Ulceration if excessive amounts are applied

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Cryotherapy for Anogenital Warts

Liquid nitrogen cryotherapy is effective for external genital warts.

Advantages include:

• Rapid lesion destruction
• No systemic drug exposure
• Use during pregnancy when needed

Repeated treatments may be required.

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Surgical Treatment

Surgical approaches are useful for:

• Large lesions
• Extensive lesions
• Refractory disease
• Lesions requiring immediate removal

Methods include:

• Scissor excision
• Curettage
• Electrosurgery
• Laser ablation

Potential disadvantages include:

• Pain
• Scarring
• Need for anesthesia
• Recurrence

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Anal Warts

External perianal warts can be managed similarly to other external genital warts.

Patients with lesions involving the anal canal should generally undergo expert evaluation because internal disease may require:

• Anoscopy
• Biopsy
• Specialist treatment

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Cervical Warts

Visible cervical lesions require specialist evaluation.

Before destructive treatment, it is important to exclude:

• High-grade squamous intraepithelial lesions
• Cervical malignancy

Management should follow cervical screening and colposcopy guidelines.

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Vaginal Warts

Potential treatments include:

• Cryotherapy
• TCA
• Surgical approaches when needed

Treatment should be performed carefully to avoid injury to surrounding mucosa.

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Urethral Meatus Warts

Small external lesions may be treated with:

• Cryotherapy
• Other specialist-directed destructive techniques

Warts extending into the urethra may require urologic evaluation.

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Oral Warts

Oral HPV lesions do not always require treatment.

Treatment may be considered when lesions are:

• Painful
• Traumatized
• Growing
• Functionally problematic
• Cosmetically concerning

Options include:

• Excision
• Cryotherapy
• Electrosurgery
• Laser therapy

Persistent oral lesions should be examined carefully to exclude neoplasia.

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Respiratory Papillomatosis Treatment

Recurrent respiratory papillomatosis is usually managed by otolaryngology.

Treatment may include:

• Endoscopic debulking
• Laser therapy
• Microdebrider techniques
• Selected intralesional or systemic adjunctive therapies

Repeated procedures are often necessary because recurrence is common.

Airway obstruction can be life-threatening.

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Partner Management

Sex partners of patients with genital warts do not require treatment unless they have visible lesions.

However, partners may benefit from:

• STI screening
• HPV education
• Vaccination if eligible
• Counseling about transmission

Condoms reduce but do not eliminate HPV transmission.

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Follow-Up

Follow-up depends on:

• Lesion type
• Treatment used
• Immune status
• Recurrence

Patients with genital warts should continue routine cervical cancer screening according to age and national recommendations.

Having external genital warts does not automatically require more frequent cervical screening than otherwise indicated.

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Prognosis

The prognosis is generally excellent.

Many cutaneous warts resolve spontaneously.

Treatment often works but recurrence is common because:

• HPV may persist in surrounding clinically normal tissue
• Latent infection can reactivate

Recurrence does not necessarily represent reinfection.

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Complications

Possible complications include:

• Pain
• Bleeding
• Secondary bacterial infection
• Cosmetic disfigurement
• Recurrence
• Extensive disease in immunosuppressed patients

High-risk HPV infection can lead to:

• Cervical intraepithelial neoplasia
• Cervical cancer
• Anal cancer
• Penile cancer
• Vulvar and vaginal cancer
• Oropharyngeal cancer

Genital warts caused by HPV 6 and 11 themselves are generally not considered precancerous lesions.

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Pregnancy

Genital warts may enlarge during pregnancy because of:

• Hormonal changes
• Increased vascularity
• Altered immunity

They may also become:

• More friable
• More prone to bleeding

Treatment options that can be used during pregnancy include selected clinician-administered therapies such as:

• Cryotherapy
• TCA

Agents such as podofilox should be avoided.

Cesarean delivery is not routinely performed solely to prevent neonatal HPV transmission. It may be considered when massive genital lesions obstruct the birth canal or would cause excessive bleeding during vaginal delivery.

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High-Yield Comparison

Common wart

→ Rough hyperkeratotic papule

→ Usually hands and fingers

Plantar wart

→ Sole of foot

→ Painful

→ Black thrombosed capillary dots

Flat wart

→ Smooth, flat-topped papules

→ Often multiple

Genital wart

→ Condyloma acuminatum

→ Usually HPV 6 or 11

High-risk oncogenic HPV

→ HPV 16 and 18 among the most important types

Respiratory papillomatosis

→ Usually HPV 6 and 11

→ Hoarseness/stridor

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High-Yield Clinical Approach

Child with rough papules on fingers

→ Common warts

Painful lesion on sole + black dots

→ Plantar wart

Multiple smooth facial papules in adolescent

→ Flat warts

Cauliflower-like genital lesions

→ Condylomata acuminata

Genital wart + atypical pigmentation/ulceration

→ Biopsy before routine destructive therapy

Immunocompromised patient + extensive refractory warts

→ Consider specialist evaluation and biopsy of atypical lesions

Hoarseness + recurrent laryngeal papillomas in child

→ Recurrent respiratory papillomatosis

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Exam Essentials

Cause of warts:

→ Human papillomavirus

Virus type:

→ Double-stranded DNA virus

Most common genital-wart types:

→ HPV 6 and 11

Major oncogenic types:

→ HPV 16 and 18

Classic plantar-wart clue:

→ Thrombosed capillaries/black dots

First-line treatment for many cutaneous warts:

→ Salicylic acid or cryotherapy

Common patient-applied genital-wart therapies:

→ Imiquimod or podofilox

Clinician-applied genital-wart therapies:

→ Cryotherapy or TCA

Genital warts are usually caused by:

→ Low-risk HPV

HPV vaccine treats existing warts:

→ No

HPV vaccination prevents:

→ New infection with vaccine-covered HPV types

Best prevention of HPV-associated cancer:

→ Vaccination plus appropriate screening

Recurrence after treatment:

→ Common

External genital warts mean cervical cancer is present:

→ No