Review

Cutaneous manifestations of human papillomaviruses

Cutaneous manifestations
of human papillomaviruses:
A review
J. C. Cardoso, E. Calonje

K E Y
WORDS
human
papillomavirus,
common warts,
plantar warts,
plane warts,
condyloma
acuminatum,
Bowenoid
papulosis,
epidermodysplasia verruciformis

B S T R A C T

Human papillomaviruses (HPVs) are small DNA viruses of the papovavirus family, with more than 100
types already described. Their importance in human disease cannot be overemphasized because
these agents are among the most common pathogens in cutaneous infectious diseases and are
very important in a subset of predominantly, but not exclusively, genital squamous-cell carcinomas.
HPVs can be associated with a variety of cutaneous as well as mucosal manifestations. Some types
of HPVs are associated with increased risk of epithelial malignancies; these have been divided into
low-risk and high-risk types based on their oncogenic potential. Clinical and histological features of
HPV infection vary according to individual susceptibility (e.g., immunosuppressed patients), site of
involvement, and type of HPV implicated. The histological features of HPV infection are very easy to
identify on sections stained with hematoxylin and eosin. However, many findings usually associated
with HPV infection are entirely non-specific. Additional current diagnostic methods for identification
of HPV in tissues include techniques based on the detection of viral DNA; namely, in-situ hybridization and polymerase chain reaction (PCR). This article reviews the main clinical and histopathological
cutaneous manifestations of HPV infection, including common warts, plantar warts, plane warts, condyloma acuminatum, Bowenoid papulosis, and epidermodysplasia verruciformis. Emphasis is placed
on the clinical and histological features of these various manifestations, including a brief discussion
about the routinely used laboratory methods for detecting HPV in tissues.

Introduction
Human papillomaviruses (HPVs) are small DNA
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cycle and apoptosis mechanisms, potentially leading
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146

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several years), probably because immune mechanisms
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Acta Dermatoven APA Vol 20, 2011, No 3

Review

Cutaneous manifestations of human papillomaviruses

cocktails do not contain less common genotypes (in

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HPVs are associated with a variety of cutaneous
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Common warts

Figure 1. Common wart. Prominent acanthosis,

papillomatosis, and hyperkeratosis. Note inward
projection of the elongated rete ridges.
Acta Dermatoven APA Vol 20, 2011, No 3

Figure 2. Common wart. Coarse and clumped

keratohyalin granules.

147

Cutaneous manifestations of human papillomaviruses

Review

Figure 3. In-situ hybridization for low-risk HPV

in a common wart showing prominent nuclear
positivity.

Figure 4. Plantar wart. Similar histological features to those of a common wart but with endophytic growth and prominent clumps of eosinophilic material are seen in the stratum corneum
and within the cytoplasm of keratinocytes

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demonstrate the presence of HPV DNA in a group of
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acanthosis and papillomatosis, and typically have an
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the vacuolation common to other viral warts, also
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philic cytoplasmic inclusions, which represent altered
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Plantar warts
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epidermoid cysts occurring on the sole of the foot in
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that present as a keratotic plug surrounded by a hyper
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black dots scattered over the surface, which represent
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148

Acta Dermatoven APA Vol 20, 2011, No 3

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Plane warts

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Condyloma acuminatum

Plane warts are very common, especially in chil

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Clinically, lesions most commonly involve the face,
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acanthosis and typically prominent koilocytic change

Condyloma acuminatum usually manifests as mul

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may have more prominent lesions (24), which are fre
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Figure 6. Plane wart. Acanthosis is milder than

in other types of viral warts and papillomatosis
is absent or minimal.

Figure 7. Plane wart. Keratinocytes in the upper

layers of the epidermis appear vacuolated but
koilocytes are not usually seen.

Acta Dermatoven APA Vol 20, 2011, No 3

149

Cutaneous manifestations of human papillomaviruses

Figure 8. Condyloma acuminatum. Prominent

acanthosis, hypergranulosis, hyperkeratosis,
and elongated bulbous rete ridges.

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150

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Figure 9. Condyloma acuminatum. Koilocytes

(keratinocytes with picnotic and hyperchromatic
nuclei) are frequent and there is also clumping
of keratohyalin granules.

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undifferentiated intraepithelial
neoplasia
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the presence of usually multiple papules, which may
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have been described occasionally in other locations
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anymore, it is still used by many clinicians because
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should only be regarded as a form of intraepithelial
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associated with HPV infection, but with other condi
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Acta Dermatoven APA Vol 20, 2011, No 3

Review

Cutaneous manifestations of human papillomaviruses

Figure 10. Undifferentiated intraepithelial neoplasia. Full thickness epidermal dysplasia with
basaloid atypical cells and frequent mitotic
figures.

Figure 11. Undifferentiated intraepithelial neoplasia. In-situ hybridization for high-risk HPV
shows prominent nuclear positivity in most cells.

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ment of malignant transformation is usually associat
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genetic defects in genes predisposing to EV that are
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Epidermodysplasia verruciformis
In its classic form, epidermodysplasia verrucifor
mis (EV) is a rare genodermatosis with an autosomal
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Acta Dermatoven APA Vol 20, 2011, No 3

151

Cutaneous manifestations of human papillomaviruses

Figure 12. Epidermodysplasia verruciformis.

Affected patients often present with numerous
scaly hypopigmented lesions (courtesy of F.
Ajose, Lagos, Nigeria).

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and characteristic feature is the presence of enlarged
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lesions may progress with gradually more pronounced
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152

Review

Figure 13. Epidermodysplasia verruciformis.

Enlarged keratinocytes with typical granular
blue-gray cytoplasm in the upper layers of the
epidermis.

Conclusions
HPVs are among the most common infectious
agents in humans, and can be associated with a variety
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tean spectrum of clinical manifestations, of the possi
ble complications associated with them (especially the
risk of malignant transformation in some settings),
and basic knowledge about the currently available di
agnostic methods provide the essential means for ap
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A U T H O R S Jose Carlos Cardoso, MD, St Johns Institute of Dermatology, St Thomas

A D D R E S S E S Hospital, Westminster Bridge Road, London SE1 7EH, UK
Eduardo Calonje, MD, DipRCPath, same address

154

Acta Dermatoven APA Vol 20, 2011, No 3