Verrucae Warts

Slide 1 · Verrucae (Warts)

Human papillomavirus–associated epithelial proliferations

Etiology • Clinicopathologic variants • Histomorphology • Oncogenic context

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Classify verrucae by their appearance and anatomic location.

Connect HPV effects on keratinocytes with verrucous architecture and koilocytosis.

Recognize common wart morphology and distinguish low- from high-risk HPV disease.

Interpret selected clinicopathologic vignettes without equating every wart with dysplasia.

Slide 3 · Verrucae are HPV-driven epithelial proliferations

Warts are proliferative lesions caused by human papillomaviruses (HPVs).

The epithelial growth pattern, rather than invasive destruction, characterizes ordinary verrucae.

Clinical naming reflects morphology and distribution.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 4 · Warts are frequent in the young but not age-restricted

Children and adolescents as commonly affected groups.

Verrucae may occur at any age.

Age and site help the differential diagnosis but do not establish HPV type.

Children / adolescents; Any age

Children

Adolescents

Adults

Slide 5 · Transmission: Contact and autoinoculation

Transmission usually involves direct person-to-person contact.

Autoinoculation transfers infection to another location on the same individual.

Multiple lesions do not automatically imply multiple HPV genotypes.

Infected skin

Direct contact or autoinoculation

New wart site

Slide 6 · Natural history: Spontaneous regression

Verrucae are generally self-limited.

Spontaneous regression within approximately 6 months to 2 years.

Persistence at an individual site does not by itself prove malignant change.

HPV-driven lesion

Self-limited course

Spontaneous regression

Slide 7 · HPV comprises multiple biologically distinct types

More than 150 HPV types are described in this dermatopathology section.

Many of these types can produce human warts.

Certain wart variants show associations with particular HPV types.

Genotype diversity

Clinical phenotype

Oncogenic context

Slide 8 · Benign cutaneous wart–associated HPV types

The neoplasia chapter gives HPV 1, 2, 4, and 7 as examples associated with benign squamous papillomas.

This is an illustrative group, not an exhaustive taxonomy of cutaneous HPV.

The clinical label “wart” does not specify a single viral genotype.

Cutaneous HPV types

Examples: 1, 2, 4, 7

Benign squamous papilloma

Slide 9 · Anogenital condylomata: Predominantly HPV 6 and 11

Condyloma acuminatum is a common anogenital wart phenotype.

HPV types 6 and 11 are the predominant associated types.

The neoplasia chapter identifies these as low-malignant-potential HPV types.

HPV 6 → Low-risk

HPV 11 → Low-risk

Slide 10 · HPV 16 is associated with genital precursor lesions

HPV 16 with genital squamous carcinoma in situ.

It also associates HPV 16 with bowenoid papulosis.

Bowenoid papulosis has an in situ carcinoma–like histology yet often regresses.

HPV 16

Genital in situ lesion / bowenoid papulosis

Slide 11 · HPV 5 and 8: The epidermodysplasia context

HPV 5 and 8 are discussed in relation to epidermodysplasia verruciformis.

In affected individuals, some HPV-containing flat warts progress to cutaneous carcinoma.

This is a syndrome-specific association, not the expected outcome of ordinary warts.

Susceptible host

HPV-containing flat warts

Subset progress to SCC

Slide 12 · Three HPV-associated phenotypes require separation

Clinical category

HPV context

Pathologic emphasis

Cutaneous verrucae

Benign cutaneous HPV types

Papillomatosis + koilocytosis

Condyloma acuminatum

Predominantly HPV 6 / 11

Soft papillary proliferation

Genital in situ lesions

HPV 16 association

High-grade atypia may be present

Slide 13 · HPV infection requires access to susceptible epithelium

Genital HPV persistence requires entry into immature basal epithelial cells.

Microtrauma and epithelial repair can provide access to susceptible basal cells.

This mechanism provides context; Anatomy and exposures differ between sites.

Microtrauma / repair

Access to basal cells

Productive infection

Slide 14 · Replication is linked to keratinocyte maturation

HPV infects immature squamous cells, but viral replication takes place in maturing squamous cells.

Infected differentiating cells retain cell-cycle activity.

This coupling explains why superficial epithelial cells may show viral changes.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 15 · Productive infection modifies epithelial maturation

Infected epithelium may develop conspicuous superficial cytopathic change.

The epidermis simultaneously shows hyperplastic architecture.

Low-power architecture and high-power cytopathy therefore answer different diagnostic questions.

HPV infection

Epidermal hyperplasia

Koilocytosis

Slide 16 · Low-risk E6 affects Notch-mediated differentiation

The skin chapter describes interference with Notch signaling by low-risk HPV E6.

Notch signaling contributes to normal keratinocyte maturation.

Altered maturation is proposed to contribute to wart-associated epidermal hyperplasia.

Low-risk HPV E6

Interference with Notch

Altered keratinocyte maturation

Slide 17 · Low-risk versus high-risk HPV is a mechanistic distinction

Feature

Low-risk HPV context

High-risk HPV context

Illustrative types

6, 11

16, 18

Prominent disease

Condyloma / benign papilloma

Intraepithelial neoplasia / carcinoma

E6 behavior

Notch interference

p53 degradation

E7 behavior

Lower-affinity RB interaction

Strong RB disruption

Slide 18 · High-risk E6 antagonizes p53

High-risk HPV E6 promotes p53 degradation.

Reduced p53 function weakens the DNA damage and apoptosis response.

The oncogenic mechanism belongs to the high-risk HPV context—not to all cutaneous warts.

High-risk HPV E6

P53 degradation

Reduced growth safeguards

Slide 19 · High-risk E7 disrupts RB–E2F control

High-risk HPV E7 binds RB and releases E2F transcription factors.

It also inhibits p21 and p27, favoring G1/S progression.

E7 effects complement E6-mediated loss of p53 signaling.

High-risk HPV E7

RB / E2F disruption

Increased G1/S progression

Slide 20 · Viral genome status differs between benign and malignant settings

Feature

Benign wart

HPV-associated cancer

Common viral DNA state

Episomal

Often integrated

E6 / E7 oncogenic drive

Less pronounced

Frequently increased

Clinical inference

Viral presence ≠ malignancy

Other changes contribute to cancer

Slide 21 · Epidermodysplasia verruciformis: A host susceptibility state

This as a rare autosomal recessive disorder.

Patients develop multiple flat warts containing HPV genomes.

Some lesions progress to carcinoma, establishing a special host–virus interaction.

Susceptible host

HPV-containing flat warts

Subset progress to SCC

Slide 22 · HPV 5/8 and cutaneous SCC require context

The chapter links HPV 5/8 to SCC especially in epidermodysplasia verruciformis.

Its discussion does not justify diagnosing SCC in an ordinary wart.

Host background, lesion architecture, and cytologic atypia remain distinct questions.

Susceptible host

HPV-containing flat warts

Subset progress to SCC

Slide 23 · Classification is clinical: Shape plus location

Variant

Typical location

Clinical surface

V. vulgaris

Dorsal / periungual hands

Rough, pebblelike

V. plana

Face, dorsal hands

Smooth, flat

V. palmaris / plantaris

Palm / sole

Rough, scaly

Condyloma acuminatum

Anogenital sites

Soft, cauliflower-like

Slide 24 · Verruca vulgaris favors dorsal and periungual hands

Verruca vulgaris is the commonest wart variant.

Lesions can occur anywhere but are especially frequent on hands.

Dorsal surfaces and periungual regions are emphasized.

Dorsal hand | periungual sites

Location

Dorsal hand | periungual sites

Morphology

Variant defined by clinical pattern

Correlation

Match location with architecture

Slide 25 · Verruca vulgaris: Gross appearance

Typically flat-to-convex papules with a rough, pebblelike surface.

On lighter skin, typical described color is gray-white to tan.

Individual papules of approximately 0.1–1 cm.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 26 · Pigmentation modifies visual recognition

On more deeply pigmented skin, verrucae may appear hyperpigmented.

Texture, shape, and distribution remain useful when hue changes.

Avoid treating a single photographic color appearance as universal.

Lighter skin

Often gray-white to tan

Darker skin

May be hyperpigmented

Slide 27 · The rough surface reflects a papillomatous process

A verrucous papule is not simply an elevated patch of normal epidermis.

Its uneven contour corresponds to proliferative epithelial architecture.

Microscopy reveals the epithelial pattern responsible for the gross texture.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 28 · Verruca plana: A low-profile wart

Verruca plana is slightly elevated and typically flat topped.

Its surface is smooth rather than markedly pebblelike.

Lesions are generally smaller than verruca vulgaris.

Common wart

Raised rough surface; Often convex

Flat wart

Smooth, flat-topped, slightly elevated

Slide 29 · Flat warts: Typical distribution

The face is a classic site.

The dorsal hands are another frequent site.

A smooth low papule at these sites can be more compatible with verruca plana than a rough common wart.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 30 · Verruca vulgaris versus verruca plana

Feature

V. vulgaris

V. plana

Profile

Flat to convex

Slightly raised, flat-topped

Surface

Rough / pebbled

Smooth

Distribution

Hands, periungual

Face / dorsal hands

Relative size

Usually 0.1–1 cm

Generally smaller

Slide 31 · Plantar verrucae: Warts of the sole

“Plantaris” identifies the sole as the anatomic location.

Rough, scaly lesions.

Palmoplantar verrucae may reach about 1–2 cm.

Plantar surface

Location

Plantar surface

Morphology

Variant defined by clinical pattern

Correlation

Match location with architecture

Slide 32 · Palmar verrucae: Warts of the palm

“Palmaris” identifies the palm.

Surface roughness and scale overlap with plantar lesions.

Location is therefore essential to the naming convention.

Palmar surface

Location

Palmar surface

Morphology

Variant defined by clinical pattern

Correlation

Match location with architecture

Slide 33 · Palmoplantar wart versus callus

Feature

Palmoplantar verruca

Callus

Appearance

Rough, scaly

Keratinized mimic

Location

Palm / sole

Weight or friction–related sites can overlap

Diagnostic concern

HPV-associated epithelial lesion

Can look similar clinically

Tissue correlation

Papillomatosis + koilocytosis

HPV cytopathic pattern not expected

Slide 34 · Condyloma acuminatum: Anatomic distribution

Lesions occur on the penis and female genitalia.

Additional sites include the urethra, perianal region, and rectum.

The term describes the anogenital distribution and papillomatous appearance.

Penis, vulva, urethra, perianal and rectal sites

External genital

Urethral / anorectal

Perianal / rectal

Slide 35 · Condyloma acuminatum: Exophytic architecture

The clinical surface is soft and cauliflower-like.

Tan masses.

Lesions can occasionally reach several centimeters.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 36 · Genital wart is not synonymous with high-grade dysplasia

Finding

Condyloma acuminatum

High-risk HPV lesion

Typical HPV context

6 and 11

HPV 16 is an important type

Architecture

Papillary hyperplasia

May show intraepithelial atypia

Risk interpretation

Usually low malignant potential

Assess dysplasia / carcinoma risk

Slide 37 · Clinical variants at a glance

Variant

Typical surface / morphology

Characteristic site

Vulgaris

Rough, convex or flat papule

Dorsal hand, periungual

Plana

Small, smooth, flat-topped

Face, dorsal hand

Plantaris / palmaris

Coarse and scaly

Sole / palm

Condyloma

Soft, cauliflower-like

Anogenital

Slide 38 · Microscopy: Orient the epidermal compartments

Stratum corneum caps the lesion.

Superficial viable epidermis is where koilocytic change is described.

Deeper epidermal proliferation produces the papillary contour.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 39 · Verrucous / papillomatous epidermal hyperplasia

The epidermis expands in an undulating or spire-like pattern.

The term “papillomatosis” describes the surface architecture.

A broad low-power view is especially useful for recognizing this configuration.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 40 · Acanthosis and epidermal thickening

The epithelial proliferation expands the viable epidermal compartment.

The thickening accompanies the clinically elevated lesion.

Describe the location and configuration of thickened epidermis, not only its presence.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 41 · Koilocytosis is a superficial viral cytopathic effect

Koilocytes show cytoplasmic clearing around the nucleus.

The resulting pale perinuclear halo is a characteristic HPV-associated change.

The vacuolated cells in more superficial epidermal layers.

Schematic — HPV cytopathic cell

Perinuclear halo

Slide 42 · Why the perinuclear halo matters

The halo highlights a virus-related epithelial cell change.

It is a cellular finding, distinct from the papillary architecture.

Koilocytosis should be interpreted alongside tissue pattern and site.

Schematic — HPV cytopathic cell

Perinuclear halo

Slide 43 · Additional virally altered keratinocyte features

Prominent, condensed keratohyaline granules may be visible.

Jagged eosinophilic intracytoplasmic keratin aggregates are described.

These changes accompany, rather than replace, the diagnostic emphasis on papillomatosis and koilocytosis.

Schematic — HPV cytopathic cell

Perinuclear halo

Slide 44 · Electron microscopy: Intranuclear HPV virions

Numerous HPV virions within nuclei of affected superficial zones.

This is a biologic observation supporting the viral etiology.

Routine morphologic interpretation does not require demonstrating virions in every lesion.

Infected superficial keratinocyte

HPV virions observed in nuclei

Evidence of viral etiology

Slide 45 · Low-power versus high-power recognition

Low power: Assess epidermal profile, surface undulations, and epithelial proliferation.

High power: Assess superficial cytoplasmic vacuoles and accompanying keratinization changes.

Combining architecture and cytopathy is more informative than a single isolated feature.

Low magnification

Architecture: Papillomatosis

High magnification

Cells: Superficial koilocytosis

Slide 46 · Condyloma: Papillary architecture is especially important

Condylomata are hyperplastic papillary lesions.

Koilocytic changes may be less conspicuous than in common cutaneous warts.

Wedge-shaped zones of koilocytosis within papillae are described.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 47 · Do not overrequire dramatic koilocytosis in condyloma

A weakly expressed cytopathic effect does not negate the papillary pattern.

Site and soft papillary gross morphology remain relevant.

Assessment for dysplasia remains conceptually separate from proving papillomavirus-associated change.

Common wart

Koilocytosis often conspicuous

Condyloma

Papillary architecture helps when koilocytosis is subtle

Slide 48 · Differential: Molluscum contagiosum

Feature

Verruca

Molluscum

Virus

Human papillomavirus

Poxvirus

Architecture

Papillomatous hyperplasia

Verrucous hyperplasia can occur

Signature cytology

Koilocytosis

Large cytoplasmic inclusions

Primary conclusion

HPV-driven wart

Distinct viral infection

Slide 49 · Differential: Reactive callus

Callus is explicitly noted as a potential clinical mimic of palmoplantar warts.

Both may display prominent surface keratinization.

Viral cytopathic change and papillomatous architecture support a verruca when tissue is examined.

Palmoplantar wart

Viral cytopathic changes can support wart

Reactive callus

Keratinized mimic; Viral cytopathy is not implied

Slide 50 · Differential: High-grade HPV-associated lesions

Entity

Typical clue

Diagnostic issue

Ordinary verruca

Papillomatosis with koilocytes

Benign viral proliferation

Bowenoid papulosis

Genital lesion; in situ–like histology

May regress, but atypia is high grade

Squamous carcinoma in situ

Full-thickness atypia

Not classified as a simple wart

Slide 51 · When HPV typing is used, two techniques are described

Viral typing can be accomplished by in situ hybridization.

Polymerase chain reaction is another described option.

These methods identify viral material; Histologic architecture is a separate line of evidence.

Lesion requiring viral identity

In situ hybridization OR PCR

HPV material / genotype

Slide 52 · Clinicopathologic evaluation: A structured sequence

Start with anatomic site and clinical surface morphology.

Correlate with low-power epithelial architecture.

Assess superficial cytopathic features and any concerning atypia.

Use virologic methods selectively when the diagnostic question requires viral identity.

Clinical site + surface

Architecture + cytopathic findings

Risk / atypia / targeted testing

Slide 53 · Case 1: Rough papules on a dorsal hand

Constructed teaching vignette

Constructed vignette: An adolescent has several gray-tan, rough, elevated papules over the dorsal hand.

Which clinical wart variant is most likely?

Which low- and high-power histologic findings would support the diagnosis?

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 54 · Case 1: Morphology establishes the pattern

Likely clinical phenotype: Verruca vulgaris.

Expected architecture: Verrucous/papillomatous epidermal hyperplasia.

Expected cytopathy: Superficial koilocytosis with perinuclear halos.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 55 · Case 2: Multiple smooth facial papules

Constructed teaching vignette

Constructed vignette: Several small, slightly raised, smooth, flat-topped facial papules.

Which wart class best matches this morphology?

Why would a rough pebblelike surface favor another variant?

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 56 · Case 2: Flat architecture changes the clinical name

Likely clinical phenotype: Verruca plana.

The description emphasizes smooth, low, flat papules.

The face and dorsal hands are characteristic sites.

Common wart

Raised rough surface; Often convex

Flat wart

Smooth, flat-topped, slightly elevated

Slide 57 · Case 3: A scaly lesion on the sole

Constructed teaching vignette

Constructed vignette: A coarse, scaly plantar lesion clinically resembles a callus.

Name the wart variant suggested by the site.

Identify the specific diagnostic ambiguity emphasized.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 58 · Case 3: Site and mimic must both be considered

Feature

Palmoplantar verruca

Callus

Appearance

Rough, scaly

Keratinized mimic

Location

Palm / sole

Weight or friction–related sites can overlap

Diagnostic concern

HPV-associated epithelial lesion

Can look similar clinically

Tissue correlation

Papillomatosis + koilocytosis

HPV cytopathic pattern not expected

Slide 59 · Case 4: A soft anogenital cauliflower-like mass

Constructed teaching vignette

Constructed vignette: A soft papillary anogenital lesion forms an exophytic tan mass.

What is the clinical classification?

Which HPV types are most often associated with this phenotype?

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 60 · Case 4: Distinguish condyloma from oncogenic HPV disease

Clinical pattern: Condyloma acuminatum.

Usual type association: HPV 6 and 11.

Assess cytologic atypia separately; HPV 16-associated precursor lesions have different implications.

Schematic — not a micrograph

Continuous epidermal proliferation over dermis

Slide 61 · Frequent diagnostic reasoning errors

Do not identify HPV genotype solely from the papule surface.

Do not assume absence of conspicuous koilocytosis excludes condyloma.

Do not mistake an ordinary plantar wart for callus without considering HPV.

Do not equate all HPV-related papillary lesions with high-grade neoplasia.

Slide 62 · Morphology integrates virus, epithelium, and location

Virus: HPV subtype influences phenotype and oncogenic context.

Epidermis: Proliferation produces papillomatosis; Cytopathy produces koilocytosis.

Location: Distribution distinguishes common, flat, palmoplantar, and anogenital lesions.

Cancer risk: Genotype and host setting require separate interpretation.

HPV genotype + host

Keratinocyte maturation + growth

Variant-specific morphology

Slide 63 · Core references and scope

Robbins, Cotran & Kumar, Pathologic Basis of Disease, 11th ed. (2026), Chapter 25: The Skin, pp. 1059–1060.

Supporting context: Chapter 7, HPV and oncogenic DNA viruses; Chapter 22, HPV pathogenesis.

All schematics are newly constructed, editable conceptual illustrations—not clinical photographs or histologic specimens.