Viral Warts (Verrucae)

Meet the patient

A nine-year-old girl is brought in by her mother with three rough, painless bumps on her knee that have been there for six months. The mother wants them "frozen off today". Each papule is a firm, hyperkeratotic, dome-shaped wart with a corrugated surface, scattered where the child has been scratching. She is otherwise well.[1][4]

Three questions now frame the whole topic: is this actually a wart? (the rough papillomatous surface says yes), does it need treatment at all? (she is nine and it has been six months — most such warts clear within two years), and is there a hidden host factor? (she is otherwise well). Reassure the mother, offer salicylic acid if the cosmetic bother is real, and do not reach for the liquid nitrogen on a child.[1][3]

The wart and the black dots — what you are looking at

A viral wart is a benign proliferation of basal keratinocytes driven by HPV, and its morphology is the virus's signature in skin. HPV enters through a micro-abrasion, reaches the basal keratinocyte, and drives acanthosis, papillomatosis and hyperkeratosis — the rough, dome-shaped papule you see.[1][4]

The black dots within a plantar or common wart are thrombosed capillary loops in the elongated dermal papillae — pathognomonic, and the single best discriminator from a corn or callus. On histology the matching cell is the koilocyte: a keratinocyte with perinuclear vacuolation and a pyknotic, wrinkled "raisin-like" nucleus, actively churning out HPV virions.[1][4]

Warts are ubiquitous — 7 to 12 percent of the population and 20 to 30 percent of school-aged children carry them at any time. The strongest single risk factor is a broken skin barrier: HPV cannot cross an intact stratum corneum, so nail-biting, shaving, swimming pools, atopic eczema and immunosuppression all open the door.[1][9]

Etymology for viva gold: verruca is Latin for "a wart"; vulgaris simply means "common". The names are unromantic because the lesion is ordinary — but the virus that makes it is the same one that causes cervical cancer, which is why a trivial wart and a lethal malignancy share a single pathogen.[1]

The subtypes and their HPV types — the mapping you must own

The HPV-type-to-subtype mapping is the single most reproduced list in a wart viva, and it splits cleanly into the benign cutaneous, the low-risk mucosal, and the high-risk oncogenic groups. Memorise the cluster and the rest follows.[1][9]

[1] [9]

The named number rules every candidate must reproduce: common warts 1, 2, 4, 27; plantar myrmecia HPV 1; flat 3, 10, 28, 49; benign genital 6 and 11 (cause 90 percent of genital warts); oncogenic 16 and 18 (cause 70 percent of cervical cancer); epidermodysplasia verruciformis 5 and 8.[9]

E6 and E7 — why a wart becomes a cancer

The molecular heart of the disease is the oncoprotein pair E6 and E7, and examiners test it relentlessly. These two early proteins are why a wart proliferates and, in high-risk types, why it turns malignant.[1][9]

E6 binds and degrades the tumour suppressor p53 via the E6AP ubiquitin ligase, disabling apoptosis and cell-cycle arrest. E7 binds and inactivates the retinoblastoma protein (pRb), freeing E2F and driving the cell into unscheduled S-phase proliferation. The mantra: E6 eats p53, E7 evicts Rb.[1][9]

In low-risk HPV (6, 11), E6 and E7 are weakly expressed and bind their targets loosely, so proliferation stays benign. In high-risk HPV (16, 18), the oncoproteins are potently expressed, the viral genome integrates into host DNA (disrupting the E2 brake on E6/E7), genomic instability follows, and the result is cancer — the molecular basis of cervical, anal and oropharyngeal malignancy. This is why the HPV vaccine is a cancer vaccine, not just a wart vaccine.[9]

The differentiation-dependent life cycle explains why HPV hides from immunity: the virus replicates only in the upper, differentiating epidermal layers and sheds in desquamating corneocytes without ever causing a viraemia. That is why warts can persist for years and then vanish suddenly when cell-mediated (Th1) immunity finally "switches on" — and why immunosuppressed patients (HIV, transplant) get chronic, refractory, widespread warts.[1][9]

The bedside test — pare it and pinch it

The diagnosis of a wart is clinical, and two bedside manoeuvres resolve the commonest dilemma in plantar dermatology. Both take thirty seconds and need no laboratory.[1]

The paring test. Gently pare the surface with a scalpel. A wart reveals disrupted skin lines and tiny black dots or pinpoint bleeding (thrombosed capillary loops). A corn reveals a central, hard, translucent, conical core with the surrounding skin lines preserved and arching over it. A callus is a diffuse yellow plaque with preserved lines and no black dots.[1]

The pressure test. A plantar wart is tender on lateral (side-to-side) pinching, whereas a corn is tender on direct downward (perpendicular) pressure. That single difference — pinch versus press — separates the two most-confused lesions on the sole.[1]

Investigations are reserved for atypical, refractory, immunosuppression-associated or genital lesions: a skin biopsy (hyperkeratosis, acanthosis, papillomatosis, koilocytes; excludes SCC, verrucous carcinoma, Bowenoid papulosis and melanoma), HPV DNA PCR for typing, and cervical cytology with HPV co-testing for every woman with genital warts. Screen for HIV in extensive or refractory disease.[1][4]

The differential — wart, corn, cancer

The cardinal pitfall is treating a skin cancer as a "wart", so biopsy any atypical, rapidly growing, ulcerated, fixed or bleeding lesion before you destroy it. Most mimics, though, yield to morphology and the paring test.[1]

[1]

Add seborrhoeic keratosis (stuck-on, greasy, horn cysts, older adults), pearly penile papules (normal variant, rows around the coronal margin), skin tags (soft pedunculated), and Bowenoid papulosis (pigmented anogenital papules, HPV 16 or 18, histologically SCC in situ). Each is distinguished from a wart on morphology — and KOH-negative where relevant.[1][4]

The treatment ladder — cutaneous warts

[1]

The first decision is whether to treat at all: watchful waiting is a legitimate first option for asymptomatic childhood warts, because most clear within two years. Treat when the wart is painful, cosmetically distressing, persistent, periungual, facial, genital, or driven by immunosuppression.[1][3]

First-line — topical salicylic acid (the keratolytic with the best evidence).[3]

• Salicylic acid 12 to 40 percent as a paint, gel or plaster — soak and file the wart, apply to the wart only (protect surrounding skin with petrolatum), once or twice daily for up to 12 weeks. The 40 percent plaster under occlusion suits plantar warts.
• The Cochrane review found salicylic acid has the strongest evidence base of any topical, with cure rates around 50 to 70 percent at 12 weeks. Avoid on the face, mucosa, and in infants or on large areas in small children (salicylate toxicity).

[1] [3]

First-line alternative — cryotherapy with liquid nitrogen.[3]

• Apply at minus 196 degrees Celsius until an ice ball forms 1 to 2 mm beyond the wart edge, then thaw; a second freeze-thaw cycle helps thick warts. Repeat every 1 to 3 weeks for 4 to 6 sessions.
• Effective for hand warts, but the Cochrane review found cryotherapy not clearly superior to salicylic acid for common warts — and aggressive freezing is no better than gentle for plantar warts while causing more pigmentation and scarring.

[1] [3]

Second-line and refractory:[2]

• Cantharidin 0.7 percent — painless blistering agent, ideal in children; washed off in 4 to 8 hours.
• 5-Fluorouracil 5 percent, topical retinoids (adapalene 0.1 percent for flat warts), formalin 3 percent soaks for multiple plantar warts, and duct tape occlusion (harmless, acceptable for children).
• Intralesional bleomycin (0.25 to 1 unit per mL, 0.1 to 0.5 mL per wart) — highly effective for recalcitrant plantar and periungual warts; never in pregnancy or in digits (vascular compromise, digital necrosis).
• Intralesional immunotherapy — Candida antigen, MMR or BCG — induces a delayed hypersensitivity response that clears distant warts too.
• Oral cimetidine (30 to 40 mg/kg/day) and oral zinc sulphate (10 mg/kg/day) are off-label systemic options with mixed evidence.

[2] [8]

Genital warts — a different ladder, a cancer risk, and a pregnancy trap

Genital warts never get salicylic acid or any cutaneous wart preparation — they follow their own ladder of patient-applied and provider-applied options, plus STI screening, partner notification and HPV vaccination. The HIPvac RCT confirmed podophyllotoxin and imiquimod are both effective first-line patient-applied choices.[5][7]

Patient-applied (first-line for external genital warts):[7]

• Podophyllotoxin 0.5 percent solution or gel — self-applied twice daily for 3 days, then 4 days off, repeated for up to 4 cycles. Antimitotic; ideal for soft non-keratotic warts. Contraindicated in pregnancy.
• Imiquimod 5 percent cream — self-applied three times weekly, left on 6 to 10 hours then washed off, for up to 16 weeks. A Toll-like receptor 7 agonist that induces local interferon-alpha and cell-mediated immunity. Avoid in pregnancy.

[5] [7]

Provider-applied:[6]

• Cryotherapy with liquid nitrogen every 1 to 2 weeks — effective and safe in pregnancy.
• Trichloroacetic acid 80 to 90 percent — provider-applied weekly; chemically cauterises; safe in pregnancy; useful for vaginal and anal warts.
• Surgical excision or electrocautery for large, pedunculated or biopsy-requiring warts; CO2 laser for refractory or Buschke-Lowenstein-type lesions (plume extraction mandatory).

[1] [6]

The HPV vaccine — a cancer vaccine given for a wart virus

The 9-valent HPV vaccine covers types 6 and 11 (genital warts, recurrent respiratory papillomatosis) and 16, 18, 31, 33, 45, 52 and 58 (cancer). It is prophylactic — assembled from L1 virus-like particles, it prevents infection but does not treat existing disease — and it works best given before sexual debut.[7][9]

The schedule is two doses for those aged 9 to 14 years (0 and 6 to 12 months) and three doses for those aged 15 to 26 years and the immunocompromised. It is recommended for both sexes, and high-coverage countries such as Australia have seen dramatic falls in genital warts and cervical pre-cancer. Offer it to every patient with genital warts — it prevents re-infection with vaccine types and protects against the cancer types.[7][9]

The named lesions that change management

Three named entities turn a "wart" question into a cancer question, and examiners love all three. Each is biopsy-mandatory.[4]

• Bowenoid papulosis — multiple pigmented reddish-brown anogenital papules from HPV 16 or 18; histologically SCC in situ; premalignant. Biopsy pigmented genital papules rather than assume condyloma.
• Buschke-Lowenstein tumour (giant condyloma) — a large, locally destructive cauliflower-like anogenital mass from HPV 6 or 11; histologically a well-differentiated verrucous carcinoma that invades locally. Treat by wide surgical excision.
• Epidermodysplasia verruciformis — autosomal recessive (EVER1/TMC6, EVER2/TMC8) defective immunity to HPV 5 and 8; lifelong pityriasis-versicolor-like macules on sun-exposed skin; 30 to 50 percent develop SCC. Rigorous sun protection and biopsy of any changing lesion.[4][9]

Traps, confessions and preventable harm

Everyone freezes first and asks questions later. That is how a squamous cell carcinoma gets destroyed without a histology specimen. The cardinal, potentially fatal error in wart management is treating a skin cancer — SCC, verrucous carcinoma, amelanotic melanoma — as a wart. Any atypical, rapidly growing, ulcerated, fixed or bleeding lesion gets a biopsy first, not a freeze.[1]

Everyone over-treats childhood warts. Most clear within two years; painful cryotherapy on a child who would have resolved anyway is scarring and unwarranted. Watchful waiting, salicylic acid, or painless cantharidin are the kinder first moves.[1][3]

Consultant confession: the highest-yield question in a wart clinic is not "what does it look like?" but "is the host immunosuppressed?". Extensive, refractory or atypical warts in any adult demand an HIV test — because in HIV and transplant recipients the warts are the visible tip of a cancer-prone, oncogenic-HPV-loaded iceberg.[9]

The preventable-harm list:[1]

• Treating a squamous cell carcinoma or amelanotic melanoma as a wart — biopsy atypical lesions first.
• Using salicylic acid on the genital mucosa — chemical injury; genital warts have their own ladder.
• Giving podophyllotoxin, podophyllin or imiquimod in pregnancy — teratogenic; use cryotherapy, TCA or surgery.
• Using intralesional bleomycin in digits or pregnancy — vascular compromise and digital necrosis.
• Damaging the nail matrix with aggressive periungual cryotherapy or excision — permanent dystrophy.
• Failing to screen and vaccinate in genital warts — missed prevention of cervical cancer and re-infection.

[1] [8]

The mantra: reassure the child, treat the symptomatic, biopsy the atypical, screen the genital, and vaccinate everyone.[1]

Prognosis and disposition

The natural history is favourable in the immunocompetent and guarded in the immunosuppressed. About 50 percent of childhood warts clear within a year and two-thirds within two years; recurrence after treatment runs 30 to 50 percent because HPV lingers in clinically normal surrounding skin — which is why combination therapy and patience matter.[1][3]

Primary care manages most cutaneous warts. Refer to dermatology or a sexual health clinic when the wart is recalcitrant to 3 months of first-line therapy, periungual or subungual, facial near the eye, in pregnancy, immunosuppression-associated, large or extensive genital, or suspected to be malignant.[1][2]

The ward-round test

Click to reveal the stems — answer before you open each one

Stem 1. A nine-year-old has three asymptomatic common warts on his knee of six months' duration. What is the best first management, and why?[1]

Answer: Watchful waiting with reassurance — most childhood warts clear within two years. If the family wants treatment, topical salicylic acid 12 to 40 percent for up to 12 weeks is first-line; avoid painful cryotherapy in a child who would resolve spontaneously.[1][3]

Stem 2. A man has a tender lesion on his sole. Name the bedside test that distinguishes a plantar wart from a corn, and the two findings that separate them.[1]

Answer: Paring and pressure. A wart shows disrupted skin lines with black dots (thrombosed capillaries) and is tender on lateral pinch; a corn shows a hard translucent conical core with preserved skin lines and is tender on direct downward pressure.[1]

Stem 3. A 25-year-old pregnant woman has proliferating external genital warts. Which two first-line genital wart drugs are contraindicated, and what do you use instead?[5][7]

Answer: Podophyllotoxin and imiquimod are contraindicated in pregnancy (teratogenic). Use cryotherapy, trichloroacetic acid 80 to 90 percent, or surgical excision; reserve caesarean section for birth-canal obstruction.[5][7]

Stem 4. An atypical, rapidly growing, bleeding "wart" on a sun-exposed forearm in a 70-year-old. What is the first action, and why?[1]

Answer: Biopsy before any destructive treatment — this is squamous cell carcinoma or amelanotic melanoma until proven otherwise. Destroying a cancer without histology is the cardinal, potentially fatal error.[1]

[1]

References

1. [1]McLaughlin JS, Shafritz AB. Cutaneous warts J Hand Surg Am, 2011.PMID 21276900
2. [2]Leerunyakul K, Thammarucha S, Suchonwanit P, Rutnin S. A comprehensive review of treatment options for recalcitrant nongenital cutaneous warts J Dermatolog Treat, 2022.PMID 32116076
3. [3]Kwok CS, Gibbs S, Bennett C, et al. Topical treatments for cutaneous warts Cochrane Database Syst Rev, 2012.PMID 22972052
4. [4]Cardoso JC, Calonje E. Cutaneous manifestations of human papillomaviruses: a review Acta Dermatovenerol Alp Pannonica Adriat, 2011.PMID 22131115
5. [5]Lynde C, Vender R, Bourcier M, Bhatia N. Clinical features of external genital warts J Cutan Med Surg, 2013.PMID 24388559
6. [6]Bertolotti A, Dupin N, Bouscarat F, et al. Cryotherapy to treat anogenital warts in nonimmunocompromised adults: Systematic review and meta-analysis J Am Acad Dermatol, 2017.PMID 28651824
7. [7]Gilson R, Nugent D, Bennett K, et al. Imiquimod versus podophyllotoxin, with and without human papillomavirus vaccine, for anogenital warts: the HIPvac factorial RCT Health Technol Assess, 2020.PMID 32975189
8. [8]Prathibha JP, Varghese N, Aithal VV. Intralesional Vitamin D3 Versus Bleomycin for Difficult-to-Heal Palmoplantar Warts: A Comparative Study J Cutan Aesthet Surg, 2023.PMID 37554676
9. [9]Magalhães GM, Vieira ÉC, Garcia LC, et al. Update on human papilloma virus - part I: epidemiology, pathogenesis, and clinical spectrum An Bras Dermatol, 2021.PMID 33341319