Human Papillomavirus Infections

AT-A-GLANCE

 Human papillomavirus (HPV) has a worldwide occurrence, affecting people of all

ages and all races. It is most common in children and young adults.
 There are more than 150 genotypes of HPV, with some regional specificity. Low-risk
types cause warts; high-risk types are associated with intraepithelial neoplasia and
malignancy.
 The lesions are well-defined, raised papules or plaques with a rough or hard surface,
usually without inflammation.
 The lesions are most common on the hands or feet, but any skin site may be
affected, including the lower genital or oral mucosa.
 Treatments include destructive, antiviral, antiproliferative, and immunologic
modalities.

Human papillomavirus (HPV) infections are very common, occurring in a worldwide

distribution, affecting all ages and lasting months or years. The majority of individuals
will have at least one infection with the virus during the course of a lifetime, although
the severity and duration of the disease will depend, to a large extent, on the immune
response raised against the virus-infected cells.

The clinical disease caused by the virus is also dependent on the viral genotype and the
body site. Whereas skin and mucosal warts are benign and induced by one of several
different types according to body site, premalignancies and invasive cancer of the
anogenital area or oropharynx are associated with other, so-called high-risk, HPV types 
VIROLOGY
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The papillomaviruses form a large group of closely related viruses, defined by their host
range. HPVs only infect humans and, in particular, epithelial keratinocytes. In experimental
systems, the virus does not infect keratinocytes in monolayer tissue culture.

Papillomaviruses are DNA viruses with each virus particle or virion consisting of a
nonenveloped icosahedral capsid containing the double-stranded genetic material as a
circular genome (Fig. 167-1). The virus is much smaller, both in particle size and length of
genetic material, than other common viruses that infect skin such as herpes simplex virus
and molluscum contagiosum virus. The genes are all transcribed in one direction from one
DNA strand, leading to the production of 5 to 6 early (E) proteins involved in DNA
replication, cell cycle control and immune evasion; and 2 late (L) proteins, L1 and L2, that
form the outer shell or capsid (Fig. 167-2).

FIGURE 167-1
Papillomavirus virus–like particles. Transmission electron micrograph of human
papillomavirus type 16 virus–like particles composed of the L1 and L2 proteins. These
proteins were synthesized in cell culture and self-assembled into 55-nm particles that are
morphologically similar to natural infectious virus except that they do not contain the viral
DNA. The particles in the electron micrograph were purified from the cells. (Micrograph
used with permission from Heather Greenstone. Courtesy of Prof. Elliot Androphy.)
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FIGURE 167-2
Genetic organization of papillomaviruses. The circular human papillomavirus genome of
approximately 8000 nucleotide base pairs is represented here as a linear strand. (Used with
permission from Prof. Elliot Androphy.)
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The virus is shed from the surface of the skin or mucosa within sloughed, dead
keratinocytes. New infection occurs when the virus particle contacts the basal epidermal
keratinocyte, presumed to be via small microabrasions in the skin or mucosa. Maceration of
skin can increase the chance of infection because of impairment of barrier function. Cell
entry depends on an initial adherence of the virion to the cell via heparin sulphate and α6-
integrins,1,2 although the full process of receptor binding leading to internalization by
endocytosis has not yet been clarified. Within a stem cell or transit amplifying cell of the
basal layer, the virus is maintained in low copy number. It is carried to the surface in
daughter cells, producing, as it goes, the early viral proteins. High-volume viral DNA
amplification and L1 and L2 protein production occurs in the upper layers, with formation of
completely new virus particles in the granular layer. The switch to capsid protein production
depends on a change in splice site usage in the early genes. 3 The E6 and E7 proteins are
pivotal to the process of viral genome amplification, which also depends on the E1 and E2
proteins. The viral E1^E4 protein can interact with keratin filaments, weakening cytoplasmic
structure and potentially facilitating virus particle release at the surface. 4

There are more than 150 HPV types, defined according to the DNA sequence within
the L1gene.5 A virus is defined as a distinct type if there is greater than 10% dissimilarity
from other known HPVs in the DNA of this region. The HPVs have been grouped, according
to phylogeny, into five genera: alpha, beta, gamma, mu, and nu (see Table 167-1). HPVs that
are not found in malignancies or premalignancies are termed low-risk types, and those
found in invasive or preinvasive disease are called high-risk types. The high-risk anogenital
HPVs fall into the large alpha genus. High-risk genital HPV types can integrate within the
host cell genome, and the maintained expression of their E6 and E7 proteins has oncogenic
effects on cell division and cell function. These E6 and E7 proteins affect cell cycle control
and apoptosis via interaction with ubiquitin ligases, telomerase, and several other cellular
pathways.6 In the process of integration, the E2, E4, L2, and to a lesser extent the L1 regions
of the genome are frequently disrupted. In malignant lesions, late proteins and virus
particles are rarely, if ever found, although episomal (nonintegrated) viral DNA may be
maintained in preinvasive disease.

EPIDEMIOLOGY
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Infection with HPV occurs throughout the world and in all ages. Benign cutaneous warts are
most common in childhood and into the 20s, with 30% to 70% of school-age children having
skin warts,7,8 but anogenital warts, which are usually spread via sexual contact, are most
common in early adult life. In children, anogenital warts should raise consideration of sexual
abuse, although HPV types that cause common warts may often be found in warts of
prepubertal children.9 Squamous cell malignancy, associated most strongly with the high-
risk anogenital HPV types, usually only develops after an infection has persisted for several
years.

Spread of infection can be via direct contact, but the virus particles, released from epithelial
surfaces as keratinocytes are shed, can remain present in the environment for an unknown
duration and may later lead to infection in another individual. 10 Even after infection, it can
take months before a visible wart appears.11 After being established, infection can spread on
the surface to adjacent skin.

Protection against a new infection is via neutralizing antibodies. The anti-HPV vaccines,
produced as the L1 capsid protein assembled into virus-like particles, lead to a humoral
response against the virus particle. In natural infection, seroconversion also occurs, but in
this situation, anti-HPV antibodies are not effective in the resolution of established infection.
Clearance of the virus from infected tissue is dependent on a cell-mediated immune
response, and as yet there is no available, effective therapeutic vaccine. Most warts in
children will clear within 2 years,8 but in a minority of otherwise well individuals, warts can
spread and persist longer.12

In individuals with long-term immune compromise, especially those with inherited

immunodeficiency and transplant recipients receiving high-dose immune suppression, warts
and malignancy caused by HPVs can be a major problem. Five years after renal transplant, it
is estimated that approximately 90% of patients have warts13 caused by the HPV types that
cause warts in healthy people.14 Many other HPV types, mainly from the beta papilloma
viruses (PVs), can be detected by polymerase chain reaction (PCR) on the skin (normal or
lesional) of transplant recipients.15-17 Using such sensitive methods, these virus types are also
found on the skin and in the hair follicles of healthy individuals.

SKIN HUMAN PAPILLOMAVIRUS INFECTIONS

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CUTANEOUS WARTS
CLINICAL FEATURES
Viral warts are initially asymptomatic and often unnoticed but grow to form well-defined,
thickened, hyperkeratotic lesions (Fig. 167-3). These are often unsightly and may cause pain
if sited at pressure points or if they crack and bleed. Walking and use of the hands can be
affected according to the site of the warts (Fig. 167-4). Common sites are the hands and
feet, especially at areas of minor trauma, such as knuckles or around nails (Fig. 167-5). On
the dorsal aspects of hands or feet or on the limbs, warts are exophytic or “cauliflower
shaped” (Fig. 167-6), but on soles or palms, they are often relatively flat to the surface with
a more endophytic growth pattern. The term mosaic warts is applied to a group of small
adjacent but relatively flat warts on the sole (Fig. 167-7). Smaller and flatter warts, often on
the backs of the hands or face, may be plane warts (also called verruca plana; see Fig. 167-
8). On the face and limbs, warts can sometimes have a small base and longer, fingerlike
projections, a morphological type called filiform warts (Fig. 167-9).

Warts are most common in children and young adults19 but can occur at any age.

FIGURE 167-3
Well-defined wart on the finger. Small thrombosed capillaries are visible as black dots. (The
nail had been damaged previously from trauma.)

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FIGURE 167-4
Very hyperkeratotic warts over the Achilles tendon.
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FIGURE 167-5
Multiple warts on the hand with periungual warts affecting nail growth.

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FIGURE 167-6
Warts on the knee.

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FIGURE 167-7
Mosaic warts on the sole.
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FIGURE 167-8
Plane warts (verruca plana). A, Multiple pink flat warts on the face of an 11-year-old
girl. B, Many flat-topped papules occur in a linear configuration resulting from self-
inoculation. (Used with permission from Prof. Elliot Androphy.)

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FIGURE 167-9
Common warts. Filiform warts on the chin and lips of a child. (Used with permission from
Prof. Elliot Androphy.)

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ETIOLOGY AND PATHOGENESIS
Common warts are caused most frequently by HPV-2/27/57, HPV-4, and HPV-1 (soles and
palms) and less frequently by HPV-7 (called butcher’s warts). Flat warts are usually caused
by type 3 or 10 or very occasionally type 28.

Butchers’ warts were originally described in meat workers, whose hands were in direct
contact with wet meat. The finding of HPV-7 is not limited to these warts but has been
reported rarely in hand warts, face warts, and HIV infection.

HPV-1 warts are found only on the palms and soles and may be called myrmecia. They
produce higher amounts of new particles compared to other cutaneous types. Some
unusual HPV types, HPV-57 and -60, have been found in epidermoid plantar cysts of
Japanese patients.20

DIAGNOSIS AND HISTOLOGY

Warts can usually be diagnosed clinically without the need for histologic confirmation.
Paring the surface of a wart will reveal capillary loops close to the surface and often causes
bleeding. These capillaries often thrombose and then appear as black dots (see Fig. 167-3).

The histology is of acanthosis, hypergranulosis, and hyperkeratosis of the epidermis. The

keratinocytes of the upper granular layer may show koilocytosis with clear cytoplasm and a
dense twisted nucleus (Fig. 167-10). Detection of HPV DNA by PCR or in situ hybridization
will confirm the diagnosis but is not in use for standard clinical care.

FIGURE 167-10
Verruca vulgaris. The process is one of extensive hyperplasia, and the hyperplastic cells
contain both intranuclear and intracytoplasmic inclusion bodies. (Used with permission from
Prof. Elliot Androphy.)
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The differential diagnoses are listed in Table 167-2.

TABLE 167-2Differential Diagnosis of Warts

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CLINICAL COURSE, PROGNOSIS, AND MANAGEMENT
Untreated, warts in young people usually clear spontaneously within about 2 years, and only
a few remain at 4 years.21 In adults, clearance can often be very slow, with warts persisting
for years. Large and widespread warts (Fig. 167-11) are common in immunosuppressed
individuals such as transplant recipients and in children or adults with genetic
immunodeficiency (Table 167-3). In these cases, large areas of skin may be affected as well
as mucous membranes, and the condition may be called generalized verrucosis.22
FIGURE 167-11
Leg with numerous warts. The large, scaly, and horny warts contain human papillomavirus
(HPV)-2. The smaller, flatter, less scaly papules are warts that contain HPV-3. With extensive
warts such as these, an assessment of immune function is indicated. (Used with permission
from Prof. Elliot Androphy.)

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TABLE 167-3Syndromes of Immune Compromise in Which Warts May Be a Prominent
Clinical Feature
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Treatment can speed clearance in warts but often fails in immunosuppressed individuals.

There is no virus-specific anti-viral therapy for warts, so available treatments aim to (1)
damage the infected epithelium and debulk the lesions, (2) have some effect on the virus
life cycle, or (3) to stimulate an immune response (Table 167-4). It is possible that most
treatments may have more than one effect. Recent reviews of treatments for warts give
more detail of the spectrum and potential efficacy of the range of treatments used today. 38–
40

TABLE 167-4Commonly Used Treatments for Cutaneous and Anogenital Warts

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The most commonly used treatments for warts are destructive and include topical
applications with salicylic acid and physical treatment with cryotherapy. For the greatest
effect, treatment needs to be repeated and of long duration. It is worth informing patients
that regular treatment for at least 3 months or longer is likely to be required. Even with
assiduous treatment, the clearance rate for most common treatments is 60% to 70%
compared with 30% clearing with placebo.41

Salicylic acid (12%–17% in a paint or up to 50% in plasters or an ointment) is applied to the

wart, which can be rubbed down or pared gently beforehand. Occlusion with an adhesive
dressing after application may improve clearance. Daily treatment is recommended, but as
the salicylic acid gradually destroys and so removes the keratin layer, the wart or more likely
surrounding tissue can become sore, and treatment may need to be reduced in frequency.
For this reason, salicylic acid in these strengths is not recommended for facial or anogenital
warts.

Cryotherapy (see Chap. 206) with liquid nitrogen is best used as a double freeze, repeated
every 3 weeks for at least 3 months. This is a painful treatment and often not tolerated to
warts around nails, on the soles, or by children.

Other treatments that damage or destroy the infected epithelium include caustics such
as silver nitrate, phenol, mono- or trichloroacetic acid, and surgical approaches with laser or
excisional surgery.

Plane warts require less keratolysis, and treatment with other topical applications such as
the immune modulator imiquimod can be effective.

Severe proliferative warts may be helped but sometimes only for the duration of the
treatment by treatments that reduce or slow epidermal growth, such as podophyllotoxin or
retinoids.

In immune compromise, clearance of warts, either spontaneously or with treatment, is rare

and treatment is usually aimed at measures to reduce wart bulk, maintain function, and
avoid pain.

EPIDERMODYSPLASIA VERRUCIFORMIS AND EPIDERMODYSPLASIA VERRUCIFORMIS–LIKE

SYNDROMES
CLINICAL FEATURES
Epidermodysplasia verruciformis (EV) is a rare, heritable skin disorder with a mild underlying
primary immunodeficiency. The signs of EV become apparent in late childhood or
adolescence, but in the absence of a family history, diagnosis may be delayed until a decade
or two later. Widespread flaky, scaly, or flat warty lesions are seen on the face, hands, and
forearms and other sun-exposed sites (Fig. 167-12). There is often erythema,
hyperpigmentation, or more rarely hypopigmentation of lesions, and there can be confusion
with pityriasis versicolor and plane warts. In early adult life, actinic keratoses, Bowen
disease, and invasive squamous cell carcinoma (SCC) can develop at affected sites (Fig. 167-
13). Metastatic disease can follow.
FIGURE 167-12
Epidermodysplasia verruciformis. Plane wart–like lesions on the dorsa of the hands and
forearms associated with human papillomavirus-5 and -8. The lesions are numerous, flat,
reddish, and partly confluent. (Used with permission from Prof. Elliot Androphy.)

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FIGURE 167-13
Invasive cancer in an epidermodysplasia verruciformis patient infected with numerous
human papillomavirus (HPV) types, including HPV-5, -8, -9, -14, and others. In the tumor
cells, HPV-5 DNA was detected in a high copy number. This large squamous cell carcinoma
did not metastasize and did not recur after surgery. There are numerous actinic keratoses
on the forehead. (Used with permission from Prof. Elliot Androphy.)
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Patients with EV have a mild cell-mediated immune impairment. 42 This is often not obvious
on clinical grounds because widespread susceptibility to other infections is not a feature but
can reduce susceptibility to contact allergy.

A clinical appearance very similar to EV, called acquired EV, may be seen after long-term
immunocompromise from several causes43,44 (Table 167-5).

TABLE 167-5Conditions That May Lead to Acquired Epidermodysplasia Verruciformis

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ETIOLOGY AND PATHOGENESIS
EV can be inherited, usually with an autosomal recessive pattern. The genes implicated most
commonly are EVER-1 and -2, which produce the transmembrane, zinc-containing proteins
TMC6 and TMC8.45

A large number of HPV types are associated with EV lesions and the clinically unaffected skin
of patients.46 These include HPV-3 and -10, the cause of plane warts, as well as the beta PVs,
some of which are found in SCCs and some of which are only found in benign lesions
(see Table 167-1). Patients may also have warts harboring the usual HPV types found in
common warts.
 DIAGNOSIS AND HISTOLOGY
Diagnosis may be made on a combination of clinical features and family history. Skin biopsy
shows mild acanthosis and hyperkeratosis. In some lesions, there may also be pallor or
clearing of the cytoplasm of the upper spinous layer keratinocytes, called ballooning, with
small dense nuclei (so-called clear cells; see Fig. 167-14). With sensitive HPV detection, the
beta PVs are found most commonly.

FIGURE 167-14
Characteristic cytopathic effect of epidermodysplasia verruciformis–specific human
papillomavirus (HPV) in a patient found to be infected with HPV-5, -8, and -9. Very abundant
clear large cells with small pyknotic nuclei replace almost the entire epidermis. (Used with
permission from Prof. Elliot Androphy.)

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CLINICAL COURSE, PROGNOSIS, AND TREATMENT
Treatments usually make little lasting difference, but short-term, cosmetic improvement can
be obtained by a number of approaches that remove the hyperkeratosis. 42,43Cryotherapy,
topical salicylic acid, 5-fluorourcil, and imiquimod have all been used with varying
results.47,48 Photodynamic therapy (PDT)49 or an oral retinoid, such as acitretin,50can produce
a useful improvement in lesions.

To reduce the risk of skin cancers, sun protection is important. Regular surveillance for SCC
and early treatment of suspicious lesions may avoid metastatic disease.
SQUAMOUS CELL CARCINOMA AND HUMAN PAPILLOMAVIRUS
Common warts in immunocompetent individuals are not forerunners of skin cancer.
However, there are a very few reports, usually in the setting of immunosuppression, of long-
standing periungual warts progressing into Bowen disease (full-thickness dysplasia) or
invasive SCC.51 In such cases, the high-risk anogenital HPV type, HPV-16, is usually present.
Long-standing and slowly enlarging warty areas on the soles, fingers, or anogenital skin can
be a feature of carcinoma cuniculatum or verrucous carcinoma (Buschke-Löwenstein
tumour), in which the HPV types usually associated with anogenital warts, HPV-6 or -11, are
occasionally detected.52,53

Skin SCCs on sun exposed skin are also found to contain a number of EV-related beta HPV
types, with a higher yield in the cancers of immunosuppressed individuals. These HPVs are
often found in normal skin of both immunocompetent and immunocompromised
individuals,16,18 and the exact role they play in the steps of carcinogenesis is still under
debate.54

MUCOSAL AND PERI-MUCOSAL HUMAN PAPILLOMAVIRUS INFECTIONS

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ANOGENITAL WARTS
CLINICAL FEATURES
Warts can affect the vulva, vagina, cervix, penis, scrotum, perianal skin, and anal canal. They
may present singly but are usually found as multiple, well-defined papules or as flat or
filiform lesions and may grow into larger protuberant lesions (Fig. 167-15). The moist fold
beneath an abdominal apron of an obese patient is another site for these warts. 55 On
mucosal surfaces, they are often macerated and appear pale, but on drier skin, they can
become more obviously hyperkeratotic and hard. They may be asymptomatic but can be
itchy and uncomfortable and may be traumatized with movement or sexual activity.

FIGURE 167-15
Mucosal warts. A, Multiple condylomata acuminata on the shaft of the
penis. B, Erythroplasia of the glans with exophytic squamous cell carcinoma extending onto
prepuce. C, Multiple perianal condylomata in a child. Sexual abuse must be
considered. D, Multiple confluent condylomata on the labia minora, majora, and fourchette.
(Images A, C,Used with permission from Prof. Elliot Androphy. Image B, Used with
permission from Reinhard Kirnbauer, MD.)
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DIAGNOSIS
HPV-6 or -11 are the most common causative agents, but other HPV types are found with
PCR analysis. Anogenital warts produce less virus particles than cutaneous warts.

For differential diagnosis, see Table 167-2.

CLINICAL COURSE, PROGNOSIS, AND TREATMENT

Anogenital warts are usually treated with a topical application as first-line
therapy.56Podophyllotoxin or imiquimod are both self-applied treatments with a 50% to 70%
clearance rate.57 Recurrence rates after imiquimod treatment are slightly less than after
podophyllotoxin.58

Other treatments in use include topical trichloroacetic acid, 59 sinecatechins from green
tea,60 and physical therapies with cryotherapy, PDT, laser, electrocautery, or surgery.

Since the introduction of the quadrivalent anti-HPV vaccine in 2007, there has been a
recorded decrease in presentation of genital warts or prevalence of HPV-6 and -11. 61,62
ORAL WARTS
Warts can develop on the lips, in the oral cavity, and in upper respiratory tract and are
usually regarded as a sexually transmitted disease. Because of the moist site, they are
usually macerated and can be flat or cauliflower shaped (Fig. 167-16). The low-risk genital
HPV types are the usual cause. Laryngeal warts (laryngeal papillomatosis) can develop in
childhood, probably caused by infection from the mother at birth, and can affect speech and
breathing.

FIGURE 167-16
Multiple mucosal warts extending to the vermillion border, where they become highly
keratinized. (Used with permission from Prof. Elliot Androphy.)

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Oral warts are common in HIV infection and may worsen, rather than improve, during
antiretroviral therapy.63

ANOGENITAL INTRAEPITHELIAL NEOPLASIA AND CANCER

CLINICAL FEATURES
Anogenital intraepithelial neoplasia (AGIN) includes dysplasia of the vulva (vulvar
intraepithelial neoplasia; see Fig. 167-17), vagina (vaginal intraepithelial neoplasia), cervix
(cervical intraepithelial neoplasia), penis (penile intraepithelial neoplasia), perianal skin, and
anal canal (anal intraepithelial neoplasia). The term Bowenoid papulosis has been used to
describe the disorder, especially when the lesions are pigmented and resemble seborrheic
keratosis. AGIN may also present with velvety plaques, white macerated, warty lesions or
less distinct erythematous areas.64
FIGURE 167-17
Vulval intraepithelial neoplasia, grade III. Small area of raised and minimally pigmented skin
near the posterior fourchette.

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ETIOLOGY
The high risk HPV types, especially HPV-16, are associated with these disorders.

Biopsy is essential for diagnosis with the histology showing full-thickness epidermal
dysplasia, classified as undifferentiated intraepithelial neoplasia. Differentiated
intraepithelial neoplasia occurs in association with chronic inflammatory genital disease,
such as lichen sclerosus, and histologically is a subtler basal dysplasia, often with acanthosis
and hyperkeratosis, and is not associated with HPV infection (see Chap. 64).

CLINICAL COURSE, PROGNOSIS, AND MANAGEMENT

Surgery is the treatment of choice for single lesions if the site is easily operable but may not
be best for multifocal or multicentric disease. Laser or topical immunotherapy with
imiquimod offers an alternative approach.65 Both the patient and physician need to be
aware of the changes that could indicate malignant change, and these include a persistent
area of discomfort, an ulcer, or a frank tumor. It is estimated that an individual with AGIN
has an approximate 5% lifetime risk of developing cancer. Cancer can be the presenting
feature.

ORAL AND OROPHARYNGEAL SQUAMOUS CELL CARCINOMA

Silent infection with high risk HPVs within the mouth or throat can present later in life with
oropharyngeal SCC. The traditional association of this malignancy with smoking and alcohol
is being replaced with a stronger association with HPV infection, especially in younger male
patients. The incidence of this malignancy is rising but should be reduced following the
introduction of the anti-HPV vaccine to male patients.
Definisi

Veruka vulgaris adalah infeksi HPV pada epidermis dengan gambaran klinis berupa papul,
nodul berbentuk kubah sewarna dengan kulit, permukaan kasar dan berbatas tegas, dapat
tunggal maupun berkelompok. Predileksi terutama di daerah tangan, siku, lutut, kaki dan
jari-jari

Etiologi

Veruka vulgaris disebabkan oleh infeksi HPV pada epidermis. Sub tipe HPV yang telah
diketahui menyebabkan veruka vulgaris adalah sub tipe HPV 1, 2, 4, 7, 27, 29, 57 dan 63.

Epidemiologi

Sebagian besar orang pernah terinfeksi dengan HPV dalam hidupnya . terdapat paling
banyak pada usia 5-20 tahun dan hanya 15% yang terdapat pada usia di atas 35 tahun.

Veruka vulgaris dapat mengenai seluruh ras.

Sering terpapar dengan air merupakan faktor resiko untuk terjadinya veruka vulgaris.
Tukang daging dan tukang ikan memiliki insiden yang lebih tinggi terjadinya veruka vulgaris
pada tangan, prevalensinya mencapai hingga 50% bagi yang sering kontak dengan daging
dan ikan. Terjadi juga peningkatan insiden veruka vulgaris pada perenang yang sering
menggunakan kolam renang umum.

Patogenesis

Human papiloma virus ditularkan secara kontak langsung antara orang dengan orang (kulit
dengan kulit) atau secara tidak langsung dari benda-benda yang dapat menjadi sumber
penularan. Virus dapat bertahan pada lingkungan hangat dan lembab, misalnya lantai kamar
ganti kolam renang, lantai pinggir kolam renang, lantai tempat mandi pancuran dan
sebagainya . Autoinokulasi juga merupakan cara penularan yang penting dimana Massing
dan Epstain menemukan peningkatan insiden dan resiko infeksi berulang pada orang yang
telah mendapat veruka vulgaris sebelumnya.

Transmisi virus biasanya terjadi pada tempat trauma atau bagian kulit yang terdapat abrasi,
maserasi atau fisura. Virus akan mengadakan inokulasi pada epidermis melalui defek pada
epitelium.

Agar dapat menyebabkan infeksi, virus tampaknya harus memasuki sel punca atau merubah
sel yang terinfeksi menjadi menyerupai sel punca. Setelah masuk, sebuah salinan atau
beberapa salinan dari genom viral berperan sebagai plasmid ekstrakromosom atau episom
di dalam nukleus sel basal epitel yang terinfeksi. Ketika sel ini membelah viral genom juga
bereplikasi dan mengambil tempat pada sel anakan, yang akan mengantarkan infeksi virus
ke lapisan-lapisan epitelium berikutnya.

Masa inkubasi dari inokulasi hingga menimbulkan veruka bervariasi dari 1-6 bulan atau
lebih.
Gambaran klinis

Gambaran klinis veruka vulgaris berupa papul, nodul berbentuk kubah sewarna dengan kulit
dengan permukaan kasar, berbatas tegas, dapat tunggal ataupun berkelompok. Predileksi
terutama di daerah tangan, siku, lutut, kaki dan jari-jari. Biasanya asimtomatik, tetapi dapat
mengganggu secara kosmetik.

Histopatologi

Veruka vulgaris memberikan gambaran histopatologi berupa epidermal akantosis dengan

papilomatosis, hiperkeratosis dan parakeratosis. Terdapat pemanjangan rete ridge pada
bagian tengah veruka. Pembuluh darah kapiler dermis menonjol dan dapat terjadi
thrombosis.

Diagnosis

Diagnosis veruka vulgaris dapat ditegakkan berdasarkan gambaran klinis dan anamnesis.
Lesi veruka vulgaris yang khas jarang membutuhkan pemeriksaan histopatologi.
Pemeriksaan ini hanya dilakukan pada kasus-kasus yangmemerlukan konfirmasi. Selain
histopatologi,jika diagnosis veruka vulgaris meragukan, dapat dilakukan pemotongan sedikit
permukaan lesi veruka vulgaris dengan mata pisau bedah nomor 15 dan dilihat karakteristik
berupa bintik hitam yang merupakan gambaran dari trombosis kapiler.

Penatalaksanaan

Tujuan dari penatalaksanaan veruka vulgaris adalah untuk mengobati ketidaknyamanan

pasien baik fisik maupun psikologis dan untuk mencegah penyebaran infeksi. Hal ini
dilakukan dengan menghilangkan lesi pada kulit dengan kerusakan seminimal mungkin pada
kulit sehat.
Sesuai namanya, kondiloma akuminata atau kutil kelamin adalah kutil yang terdapat pada
area kelamin. Kutil yang dapat berjumlah satu atau sekumpulan ini ditularkan dari orang
yang sudah terinfeksi virus human papillomavirus (HPV). 
Wanita lebih berisiko mengalami kondiloma akuminata dibanding pria, dengan angka
kejadian tertinggi adalah pada usia 15-30 tahun, terutama 20-24 tahun. Rasa gatal pada
area kelamin dan perdarahan saat berhubungan seksual adalah gejala yang mungkin
dirasakan pasien kondiloma akuminata. Kutil ini umumnya menyerang area vagina, leher
rahim, perineum, vulva, penis, kantong zakar, dan kulit di sekitar anus. Kutil juga bisa
muncul di mulut atau tenggorokan. Kondisi tersebut terjadi karena penularan melalui oral
seks. Bentuk kutil kelamin berupa benjolan daging yang menyerupai bunga kol, namun
umumnya berukuran kecil sehingga sering tidak terlihat.

Siapa yang Lebih Berisiko dan Penanganannya

Sebagian besar orang yang aktif secara seksual memang pernah terpapar setidaknya salah
satu jenis HPV, namun tidak semuanya berkembang menjadi kutil kelamin.  Penularan
kondiloma akuminata adalah melalui kontak fisik langsung. Terdapat beberapa kondisi yang
dapat meningkatkan risiko terjadinya infeksi, yaitu:

 Aktif secara seksual di usia muda.

 Bergonta-ganti pasangan seksual, terutama berhubungan seksual dengan seseorang
yang riwayat kesehatan seksualnya tidak diketahui.
 Pernah menderita penyakit menular seksual.

Sebagian kondiloma akuminata dapat reda dengan sendirinya. Tetapi, kutil kelamin yang

segera ditangani dengan baik dapat mendatangkan efek lebih positif karena beberapa
alasan, seperti:

 Meredakan gatal dan rasa sakit.

 Menurunkan risiko penyebaran virus HPV.
 Meyakinkan pasien bahwa kondisi yang mereka alami bukan kanker.
 Agar kutil yang sulit hilang dengan sendirinya dapat diangkat.

Oleh sebab itu, daripada menangani kondiloma akuminata dengan obat bebas yang tidak
tepat, lebih baik konsultasikan diri lebih dulu ke dokter spesialis kulit dan kelamin untuk
mendapatkan penanganan yang tepat. Kutil kelamin berbeda dengan kutil biasa, karena itu
kondisi ini memerlukan obat yang berbeda pula. Agar dapat tertangani dengan tepat,
dermatologis perlu memeriksa posisi dan jumlah kutil, serta kondisi kesehatan pasien secara
umum.
Di bawah ini adalah beberapa penanganan yang mungkin akan diberikan dokter untuk
meredakan kondiloma akuminata.

 Obat-obatan, seperti:
o Podofilox, dioleskan pada kutil di bagian luar kelamin untuk menghentikan
pertumbuhan sel kutil.
 o Imiquimod untuk meningkatkan sistem kekebalan tubuh dalam memerangi
infeksi
o Salep dari sinecatechins (ekstrak teh hijau) yang dioleskan pada kondiloma
akuminata di sekitar alat kelamin dan anus.
 Tindakan pembedahan untuk membuang kutil.
 Membekukan kondiloma akuminata dengan nitrogen cair. Cara ini
disebut cryosurgery atau teknik bedah beku.
 Terapi sinar laser untuk menghancurkan kondiloma akuminata.
 Electrocautery atau kauterisasi yaitu menghancurkan kutil dengan arus listrik.
 Ada kalanya obat-obatan seperti interferon disuntikkan pada kutil. Namun efektivitas
interferon sebagai penanganan tambahan kondiloma akuminata masih perlu
dievaluasi lebih lanjut.

Untuk mencegah kondiloma akuminata, penting untuk menghindari perilaku seks berisiko,
misalnya dengan menggunakan kondom saat berhubungan seks. Namun metode ini tidak
memberikan perlindungan sepenuhnya. Pencegahan lainnya adalah dengan melakukan
vaksinasi. Vaksinasi kanker serviks selain dapat mencegah kanker serviks juga dapat
mencegah kondiloma akuminata.
Meski umumnya tidak berbahaya, tetapi beberapa jenis HPV dapat menyebabkan kanker
serviks, kanker penis, kanker anus, atau pun kanker tenggorokan dan mulut. Oleh sebab itu,
penting untuk memeriksakan diri ke dokter jika mencurigai terinfeksi kondiloma akuminata,
untuk menandapatkan diagnosis dan penanganan yang tepat.