INTRODUCTION

Background
Until the 19th century, genital warts (GWs) were believed to be a form of syphilis or gonorrhea. The viral
etiology of warts was established in 1907 by inoculation of wart filtrates into skin, inducing papillomas at the
injection site. Today, condyloma acuminatum, or genital warts, generally is recognized as benign
proliferations of the anogenital skin and mucosa that result from infection with human papillomavirus (HPV).
The HPV family has at least 84 well-documented genotypes. Some believe that the number of HPV types
has already approached 130 or more. Despite the generally benign nature of the proliferations, certain
types of HPV can place patients at a high risk for anogenital cancer.

The link between cervical cancer and genital warts was first reported in a Rochester, Minnesota population-
based cohort study in 1981. In 1983, HPV type 16 was implicated in the cause of cervical cancer.

Genital warts are small, benign (harmless) growths caused by a viral infection. A female with genital warts
however is at an increased risk for developing cervical cancer. Genital warts often occur in clusters and can
be very tiny or can spread into large masses on genital tissues. If left untreated, genital warts often
disappear.

Genital warts, alternative Names: Condyloma Acuminatum, Fig Wart, Moist

Wart, Pointed Wart, Venereal Wart, Verruca Acuminata, develop in the
genital and anal area.

Genital Warts are highly contagious sexually transmitted disease and are
90% responsible for all cases of cervical cancers and other health
problems. HPV also decreases sperm count, which is one of the causes of
infertility.

According to the American Academy of Dermatology, the number of cases

of genital warts is growing at a phenomenal rate because genital warts are
extremely contagious. It's also possible for an infected woman to pass on the virus to her child during
pregnancy or birth.

Frequency

United States
Epidemiological studies show genital warts to be the most common sexually transmitted diseases (STDs).
The population-based incidence of genital warts was estimated at 106 cases per 100,000 population in
Rochester, Minnesota (from 175-1978) and 160 cases per 100,000 population in Manitoba, Canada (in
1992), with the highest incidence rate in residents aged 20-24 years.

Figures from 5 Blue Cross/Blue Shield Health Plans projected an incidence of 105 cases per 100,000
population (in 2004). They estimated 340,000 cases nationwide in 2004, with an economic burden of more
than $220 million (USD). These incidence figures were different from data collected from STD clinics and
private practitioners’ offices. Using data from these sources, the US Centers for Disease Control and
Prevention (CDC) suggested a much higher estimate of more than 6 million new patients a year in the
United States (in 2008) and a prevalence of more than 20 million. For comparison, the CDC estimated 1.6
million people have genital herpes and 1.2 million people have chlamydia/gonorrhea.

According to the "National Disease and Therapeutic Index: United States, 1966–2007, the Initial visits to
physicians' offices for STD," the increasing trend of HPV infection, after peaking at 351,000 visits in 1987,
went down in the following 10 years. Unfortunately, the increasing trend resumed again and reached the
highest level ever in 2006 (422,000 visits) before dropping down to 315,000 in 2007.
International
Genital warts have affected as many as 30 million individuals worldwide.

Mortality/Morbidity
Although anogenital warts generally are benign, their significance is drawn from the increased risk of
malignancy secondary to HPV infection. Specifically, HPV types 16, 18, 45, 31, 33, 58, and 52 are
associated with the greatest prevalence of anogenital malignancy. Infectivity of anogenital warts may be up
to two thirds of sexual contacts. High concordance for the same HPV type has been found among sexual
partners.

As many as 20% of patients with genital warts have other sexually transmitted diseases concurrently. In an
Australian sexual health clinic, 5% of genital wart patients were found to also have chlamydia and/or
gonorrhea.

Race
In the United States, African Americans have a rate of HPV infection that is 1.5 times higher than their
white counterparts.

Sex
In a well-defined population study, the female-to-male ratio has been reported to be 1.4:1. The CDC reports
have demonstrated that this disease affects females more frequently than males.

Age
The highest incidence of genital warts consistently is found in young adults aged 15-25 years. This
observation tends to hold true even after adjustment for lifetime number of sexual partners, which itself is a
significant risk factor for HPV infection. In a population study, 80% of the individuals who were affected
were aged 17-33 years.

PATHOPHYSIOLOGY

Papilloma viruses are highly species specific and do not infect other species, even under laboratory
conditions. Humans are the only known reservoir for HPV. Papilloma viruses are non-enveloped viruses of
icosahedral symmetry with 72 capsomeres that surround a genome containing double-stranded circular
DNA with approximately 8000 base pairs.

Papilloma viruses are thought to have 2 modes of replication. One is stable replication of the episomal
genome in basal cells; the other is runaway, or vegetative, replication in more differentiated cells to
generate progeny virus. Although all cells of a lesion contain the viral genome, the expression of viral
genes is tightly linked to the state of cellular differentiation.

Most viral genes are not activated until the infected keratinocyte leaves the basal layer. Production of virus
particles can occur only in highly differentiated keratinocytes; therefore, virus production occurs only at the
epithelial surface where the cells are ultimately sloughed into the environment.

HPV lesions are thought to arise from the proliferation of infected basal keratinocytes. Infection typically
occurs when basal cells in the host are exposed to infectious virus through a disturbed epithelial barrier as
would occur during sexual intercourse or after minor skin abrasions.

HPV infections have not been shown to be cytolytic; rather, viral particles are released as a result of
degeneration of desquamating cells. The HPV virus can survive for many months and at low temperatures
without a host.
Virus multiplication is confined to the nucleus. Consequently, infected cells exhibit a high degree of nuclear
atypia. Koilocytosis (from the Greek koilos, meaning empty) describes a combination of perinuclear clearing
(halo) with a pyknotic or shrunken nucleus and is a characteristic feature of productive papilloma virus
infection.

The HPV genome exists as a circular episomal DNA separate from the host cell nucleus in benign or low-
risk HPV lesions, such as those typically associated with HPV types 6 and 11. The genomes of high-risk
HPV types 16 and 18 are typically integrated into the host cell DNA in malignant lesions.

Integration of the viral genome into the host cell genome is considered a hallmark of malignant
transformation. HPV proteins E6 and E7 of high-risk serotypes have been shown to inactivate the host's
tumor suppressor proteins p53 and Rb, thereby resulting in unregulated host cell proliferation and
malignant transformation.

Genital warts are a result of HPV infection, which is believed to be acquired by inoculation of the virus into
the epidermis via defects in the epithelium (eg, maceration of the skin). Autoinoculation of virus into
opposed lesions is common. Spread of HPV infection is usually through skin-associated virus and not from
blood-borne infection. Probably, cell-mediated immunity (CMI) plays a significant role in wart regression;
patients with CMI deficiency are particularly susceptible to HPV infection and are notoriously difficult to
treat.

CLINICAL SIGNS AND SYMPTOMS

History
Genital warts generally do not become clinically apparent until several months after inoculation with human
papillomavirus (HPV). Genital warts follow a slow and indolent course and may develop by inoculation from
opposing surfaces.

Physical
Anogenital warts consist of pink-to-brown papillomatous papules or nodules of the genitalia, perineum,
crural folds, and anus.

Condyloma acuminatum.
Warts vary in size and can form large, exophytic, cauliflowerlike masses. Discrete papules, 1-3 mm in size
can present on the shaft of the penis. The growth can extend into the vagina, urethra, cervix, perirectal
epithelium, anus, and rectum.

"Cauliflower" condyloma of the penis. Small papilloma of the vulva.

Small papilloma on the shaft of penis. Small papilloma of the anus.

Severe case of genital warts on a female Severe case of genital warts on a male

Symptoms of Genital Warts

 Red, pink or gray-colored cauliflower-shaped lesions in your genital and anal area that looks raised
or flat. These bumps may grow in large clusters and expand into huge masses very rapidly.
 You may have the difficulty in passing urine.
 An increase in moisture and dampness in the infected area.
 The feeling of itching or burning around the sex organs, may be seen.
 An abnormal vaginal bleeding may occur in genital wart patient after sexual intercourse.
 Small fluid-filled blisters may occur, which can be very painful. With the first infection they can even
take around 2 to 4 weeks to heal properly. This is usually more painful for women since their
genital warts can manifest inside their cervix and vagina.
 Genital wart increases vaginal discharge.
 A flu-like illness, backache, headache, swollen glands or fever are the common symptoms during
genital wart.
 The small white/yellow/gray bumpy spots/ tiny papules may occur on the sex organs and anus.

Causes of Genital Warts

The definitive cause of anogenital warts is human papillomavirus (HPV)

infection. HPV is part of the papovavirus class, which includes SV 40, BK,
and JC virus. The HPV capsid lacks an envelope, which makes it very
stable and resistant to various treatments. No serologic typing of HPV is
available because of the lack of consistent in vitro culture methods. Typing
of HPV is according to genotype, which usually is determined by
molecular hybridization techniques using molecularly cloned HPV DNA of
known type as the standard. Two HPV are said to be of different types
when their DNA hybridize (bind) less than 50% as efficiently to each other
as to themselves.

Nearly 40 types of HPV (of nearly 80 sequenced to date) have been found
in genital warts. They are very host specific. These viruses do not infect laboratory animals and are not
susceptible to acyclovir. As a rule, HPV types causing common warts of the skin do not infect moist
epithelium and vice versa.
Multiple clinical associations with unique genotypes of HPV have been documented. HPV types and their
association with the clinical disease are as follows:

 Plantar warts - Types 1, 2, 4, 60, and 63

 Common warts - Types 1, 2, 4, 26, 27, 29, 57, 65, and 75-78
 Meat/poultry/fish handlers - Types 1-4, 7, 10, and 28
 Flat warts - Types 3, 10, 27, 28, 38, and 49
 Epidermodysplasia verruciformis - Types 2, 3, 5, 8, 9, 10, 12, 14, 15, 17, 19, 20, 21-25, 28, 36-38,
40, 47, and 50
 Squamous cell carcinoma or actinic keratosis - Types 14, 16, 18, 36, and 41
 Squamous cell carcinoma, keratoacanthoma type - Types 7, 9, 16, 29, and 37
 Squamous cell carcinoma, in immunocompromised - Types 48 and 60
 Bowen disease (nongenital) - Types 2, 16, 26-29, 31, 33, 34, 54, 56, 58, 61, 62, and 73
 Melanoma - Types 16, 18, 35, and 38
 Oral focal epithelial hyperplasia - Types 13 and 32
 Oral papilloma - Types 11, 7, 32, 57, 72, and 73
 Laryngeal papilloma (recurrent respiratory papillomatosis) 10 - Types 2, 6, 11, 16, 30, 40, and 57
 Laryngeal carcinoma – Types 6, 11
 Conjunctival papillomas and cancer - Types 6, 11, and 16
 Epidermal cyst - Types 57, 60
 Condyloma acuminatum -1-5, 6, 11, 10, 16, 18, 30, 31, 33, 35, 39-45, 51-59, 70, and 83
 Giant condyloma of Buschke and Löwenstein and other verrucous carcinoma - Types 6, 11, 57, 72,
and 73
 Bowenoid papulosis - Types 16, 34, 39, 40, 42, and 45
 Vulvar intraepithelial neoplasia - Types 56, 59-64, 67, and 71
 Anal squamous cell carcinoma and intraepithelial neoplasia - Types 16, 18, 58, and 83
 Cervical squamous intraepithelial lesions
o Low-grade squamous intraepithelial lesions (LGSIL) - Types 6, 11, 16, 18, 26, 27, 30, 31,
33-35, 40, 42-45, 51-58, 61, 62, 67-69, 71-74, 79, and 81-84
o High-grade squamous intraepithelial lesions (HGSIL) - Types 6, 11, 16, 18, 31, 33, 35, 39,
42, 44, 45, 51, 52, 56, 58, 59, 61, 64, 66, 68, and 82
 Cervical cancer11 - Types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73, and 82
 High-risk HPV types - Southeast Asia, type 18; West Africa, type 45; Central/South America, types
39 and 59

Diagnosis of Genital Warts

 Genital warts are sexually transmitted disease that is caused by the human papillomavirus (HPV).
The symptoms of genital warts may not appear for as short as a few weeks to as long as several
months so it is very hard to determine whether or not you are a carrier of the virus. The best way to
find out is to consult your doctor so that he/she can make the proper diagnosis and recommend the
best treatment plan for your case.
 Before making a diagnosis of genital warts, the medical practitioner will usually ask you several
questions regarding the symptoms you are currently experiencing, your medical and sexual history,
other medical problems that you may have, and what medications you are taking.
 Do a physical test in order to spot the signs and symptoms of genital warts, which can be easily
detected through a direct visual examination. This involves a thorough observation of the pelvic
region, genital areas, and the thighs. The doctor will also examine your mouth and tongue areas for
any appearance of warts. To the naked eye, genital warts may look like flesh-colored flat or raised
lesions on the skin. The warts may be small or large and are found in clumps.
  However, not all genital warts can be easily seen. Thus, doctors may use some solutions in order
to verify their presence. A 3-5% percent acetic acid solution (i.e. white vinegar) is usually applied
on the penis, labia, cervix, and around the anus in order to check for the presence of unnoticeable
genital warts. These warts will then turn white as the ascetic acid solution comes into contact with
them. However the presence of white spots does not always mean that the patient has genital
warts. The test may also turn positive for other medical conditions, such as psoriasis, yeast
infections, and lichen planus.
 Aside from a direct visual examination, your doctor may also recommend a Pap smear if you’re a
woman. During a Pap smear, your doctor will scrape some cells from your uterine cervix. These
cells are then thoroughly examined for any abnormalities. If the doctor detects an abnormality,
he/she will recommend that you undergo further tests to determine its exact root.
  The doctor may also do another test called a colposcopy. During colposcopy, the doctor uses a
special lighted magnifying device in order to have a better look at your vagina, cervix, and vulva
and to check for any signs and symptoms of genital warts. Moreover, some cases may warrant a
biopsy. This involves removing a small tissue sample from the cervix and examining it using a
microscope.
  Before making a final diagnosis, the doctor will also do other tests that will rule out other similar-
looking infections like herpes, skin tag, seborrheic keratoses, and pearly penile papules, among
others.
  The key to fighting genital warts is early detection and immediate treatment. As with other health
conditions, the chances of successfully treating it increase if it is dealt with in its earlier stages.

Laboratory Studies

Diagnosis usually is made clinically; it may be helped by the application of acetic acid and biopsy.

Identification of precise HPV genotypes is available only in research laboratories by using DNA
hybridization techniques. This technique includes Southern blot (highly sensitive and also most time
consuming), dot blot, and in situ hybridization. Others methods include enzyme-linked immunosorbent
assay (ELISA) for immunoglobulin G (IgG) antibody (Ab) against HPV 16 capsid.

Certain screening tests are available with a relatively high sensitivity and specificity; they include ViraPap,
ThinPrep Pap, and Hybrid capture II.

Histologic Findings

Histopathology can elucidate diagnosis in most cases.

 Verrucae consist of acanthotic epidermis with papillomatosis, hyperkeratosis, and parakeratosis.

 Elongated rete ridges may point to the center of the wart and dermal capillary vessels may be
thrombosed.
 Koilocytes are indicative of HPV infection. These are large keratinocytes with an eccentric,
pyknotic, or large steel-gray nucleus surrounded by a perinuclear halo.
 Anogenital warts lack a granular layer and tend to be more papillomatous and vascular than
common warts.
 An electron microscope may show viral particles in nuclei.
 Immunohistochemical staining with the peroxidase-antiperoxidase technique stains cells infected
by viral particles.
MODE OF TRANSMISSION

Genital HPV is highly infectious, particularly when warts are present, and is spread mainly through direct
skin to skin contact with the infected area. Genital HPV is passed on during sexual contact especially
through vaginal and anal sex, but oral sex and even non-penetrative sex play (when hand transmission of
genital warts can take place) are risky too. It is even possible for genital warts transmission to occur
through the use of sex toys which can carry an infection from one person to another and by touching the
genitals of someone who already has a genital wart. Experts estimate that around 66 percent of those who
have sex with an infected partner will contract genital warts either through vaginal, oral, or anal sex

Genital warts can also be transmitted through fomites, which are objects that carry viruses from one person
to another. In rare cases, the genital warts virus may be spread without direct sexual contact. It may be
possible, for example, to pick up the virus if you use a towel to wipe your genitals after is has been used by
someone who has HPV or genital warts. You should always only use your own towel at all times. However
you can rest assured that genital warts cannot be caught from toilet seats or swimming pools and even the
different type of wart which appears on your hand will not be passed on to your genital area.

Genital warts on the penis are common in both heterosexual and gay man while anal warts in males tend to
occur more frequently in gay men, primarily as a result of unprotected anal intercourse and direct penis-to-
rectum contact during sex.

Although lesbian sex is generally considered to be low risk for sexually transmitted infections, it is still
possible for HPV to be spread between women and recent studies have suggested that it is probably more
common that had previously been thought.

Genital warts grow much better inside the anus or the vagina than the penis so even though most people
never see warts on their sexual partner’s penis, they can catch the infection nevertheless.

Another avenue of transmission is through childbirth. When the baby passes through an infected birth
canal, there is a chance that he/she will develop warts in the mouth and throat called laryngeal
papillomatosis. As well, a child can become infected while being bathed or changed. However, if a child has
genital warts, then you seriously need to suspect sexual abuse as a possible cause and investigate fully.

The incidence of genital warts and other complications of HPV can be increased by several risk factors.
These include:

 Becoming sexually active early,

 Having multiple sex partners, or a single sexual partner who in turn has multiple sexual partners.
 having other sexually transmitted diseases in the past, and
 Having sexual relations with a partner whose sexual history you are not aware of.
 The use of birth control pills and other oral contraceptives also increases the chances of getting
genital warts because of increased unprotected sexual intercourse.
 Excessive stress, smoking, and alcohol consumption may also increase the chances of contracting
genital warts.
 Having a poor nutrition and compromised immune system also raises the risk of genital warts.
 Those who have experienced trauma in the form of surgery and serious illnesses such as cervical
cancer will most likely get infected.  
TREATMENTS

Medical Care

Treatment is aimed at destruction of the warty growths rather than elimination of the virus. Subclinical
infection probably is lifelong, and no cure is available. Most partners are likely to be subclinically infected
with human papillomavirus (HPV), even if they do not have exophytic lesions.

Standard therapies for genital warts can remove most warts; however, no ideal treatment is available for all
warts and all patients. Various treatment methods are as follows:

 Caustics/acids - Eighty to ninety percent bichloracetic acid (BCA) or trichloroacetic acid (TCA)
 Podophyllin resin (20-25% solution) - Applied by healthcare providers twice a week for 6 weeks
 Podophyllotoxin 0.5% gel, cream, or solution (Condylox) - Twice a day, 3 days a week for 4 weeks;
lower recurrence rate than podophyllin resin
 Fluorouracil (5%) cream or solution(Efudex) - Approximately 1-3 days a week for 4 weeks
 Imiquimod 5% cream (Aldara) - Three nights per week for up to 4 months (A recent article reported
that the optimal duration of use for women's genital warts may be 1 mo.)
 Sinecatechins (15%) ointment (Veregen) - Three times a day for up to 16 weeks; cheaper than
imiquimod; recurrence rate as low as 5%
 Interferon, intramuscular or intralesional injection - 3 million units, 3 times per week for 3 weeks

The HPV vaccine Gardasil (against HPV types 6, 11, 16, and 18 infection) is recommended for males and
females aged 9-26 years. The vaccine is given at day 1, at month 2, and at month 6. A randomized
controlled study involving 17,622 women aged 15-26 years reported after an average of 3.6 years of follow
up that genital warts were reduced 62% and high-grade cervical neoplasms were reduced 19% in the
vaccinated group versus the placebo group). Another vaccine against HPV types 16 and 18, Cervarix, has
been approved by the US Food and Drug Administration (FDA) for females aged 10-25 years
(administrated in the same manner as Gardasil). Of note, Gardasil also provides cross-protection against
nonvaccine HPV types (ie, HPV types 31, 33, 45, 52, and 58 in 30-40% of recipients. The latter HPVs are
responsible for greater than 20% of cervical cancers.

MEDICATION

Keratolytic agents
Cause cornified epithelium to swell, soften, macerate, and then desquamate.

Podofilox (Condylox)

Topical antimitotic that can be chemically synthesized or purified from plant families Coniferae and
Berberidaceae (eg, species of Juniperus and Podophyllum). Treatment of anogenital warts results in
necrosis of visible wart tissue. Exact mechanism of action is unknown. Genital warts are epidemiologically
associated with cervical carcinoma

Adult: Apply 0.5% solution to external genital warts with drug-dampened applicator bid for 3 d, followed by 4 d without
treatment; repeat cycle for maximum of 4 wk
Pediatric: Not established

Podophyllum resin (Podocon-25)

Topical treatment for benign growths, including external genital and perianal warts, papillomas, and
fibroids. Arrests mitosis in metaphase; active agent is podophyllotoxin; type of podophyllum resin used
determines strength. American podophyllum contains one-fourth the amount of Indian source.

Although procedure is simple, home treatment should be avoided in most cases because patients tend to
overtreat and cause excessive inflammation.

Adult: 20% podophyllin resin in compound tincture of benzoin; apply to lesion and allow to dry, then remove by
washing 1 h later; treat again in 1 wk
Pediatric: Apply as in adults

Trichloroacetic acid (TCA, Tri-Chlor)

Cauterizes skin, keratin, and other tissues. Although caustic, causes less local irritation and systemic
toxicity than other drugs in the same class. However, response is often incomplete, and recurrence occurs
frequently. Most clinicians use 25-50% TCA, although some use as high as 85% and then neutralize with
either water or bicarbonate; tissue sloughs and subsequently heals in 7-10 d. Less destructive than laser
surgery, electrocautery, or cryotherapy.

Adult: Paint onto lesions, avoid uninvolved skin; can be used in anal areas; repeat q1-2wk prn
Pediatric: Not established

Immunomodulators

Stimulate the release of key factors that regulate the immune system.

Imiquimod (Aldara)

Induces secretion of interferon alpha and other cytokines; mechanism of action is unknown. May be more
effective in women than in men.

Adult: Apply 3 times/wk prior hs; leave on skin for 6-10 h

Pediatric: Not established

Interferons
Are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha, beta, and
gamma interferons may be given topically, systemically, and intralesionally.

Interferon alfa-2b (Intron A)

Protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not
clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host
immune response may play important roles. For patients >18 y with genital warts refractory to other forms
of treatment.

Adult: Inject 0.1 mL of 10 million IU Intron A in 1 mL of diluent into each lesion 3 times/wk qod for 3 wk
Pediatric: Not established

Antimetabolites
Inhibit cell growth and proliferation.

5-Fluorouracil or 5-FU (Efudex, Adrucil, Fluoroplex)

For management of superficial basal cell carcinomas. Interferes with DNA synthesis by blocking the
methylation of deoxyuridylic acid and inhibits thymidylate synthetase, which subsequently reduces cell
proliferation. For use on warts resistant to other forms of treatment.
Adult:
Alternative for vaginal warts: Insert a special applicator that is one-third full with 5% 5-FU cream deeply into vagina,
1-2 times/wk for up to 10 consecutive wk
Pediatric:
Administer as in adults

Vaccines

An HPV vaccine is now available for prevention of HPV-associated dysplasias and neoplasia, including
cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions. Immunization
series should be completed in girls and young women aged 11-26 y. Also indicated for boys and men aged
9-26 years for prevention of condyloma acuminata caused by HPV types 6 and 11.

Papillomavirus vaccine (Gardasil)

Quadrivalent HPV recombinant vaccine. First vaccine indicated to prevent cervical cancer, genital warts
(condyloma acuminata), and precancerous genital lesions (eg, cervical adenocarcinoma in situ; cervical
intraepithelial neoplasia grades 1, 2, and 3; vulvar intraepithelial neoplasia grades 2 and 3; vaginal
intraepithelial neoplasia grades 2 and 3) due to HPV types 6, 11, 16, and 18.
Vaccine efficacy mediated by humoral immune responses following immunization series.

FDA-approved for females aged 9-26 years. Currently under FDA priority review to evaluate efficacy in
women aged 27-45 years. Indicated for boys and men aged 9-26 years for prevention of condyloma
acuminata caused by HPV types 6 and 11.

Adult
<26 years: 0.5 mL IM administered as 3 separate doses; administer second and third doses 2 and 6 mo
after first dose, respectively
>26 years: Not established
Pediatric
<9 years: Not established
>9 years: Administer as in adults

Miscellaneous topical ointments

Topical product that has gained FDA approval for genital warts.

Sinecatechins (Veregen)

Botanical drug product for topical use consisting of extract from green tea leaves. Mode of action unknown
but does elicit antioxidant activity in vitro. Indicated for topical treatment of external genital and perianal
warts (condylomata acuminatum) in immunocompetent patients. Ointment containing 15% sinecatechins,
available in 15- and 30-g tubes.

Adult:
Apply tid; use approximately a 0.5-cm strand of ointment topically for each external genital or perianal wart; continue
treatment until complete clearance of all warts, but not to exceed 16 wk
Pediatric:
<18 years: Not recommended
Surgical Care

Physical destruction or excision has been more effective in eradicating genital warts than medical
therapeutic regimens, but it carries a relatively high recurrence rate of 25-55%.

 Cryosurgery is very effective for treating multiple, small, and genital warts. Warts on the shaft of the
penis and vulva respond very well to cryotherapy. Cryotherapy of the rectum is painful and less
successful. Cryotherapy is effective and safe for the mother and fetus when used during the
second and third trimesters of pregnancy. Cryotherapy involves the use of extreme cold in order to
destroy abnormal growths. It is used to treat several skin disorders like moles, warts, solar
keratoses, and skin tags. It is one of the most effective treatment methods for genital warts. Even
though you can obtain the needed chemicals to freeze your genital warts right at your home, it is
firmly recommended that you let a medical practitioner do it. Cryotherapy can be very excruciating
and dangerous if it is performed in the wrong way.
 Electrosurgery is quite effective for a limited number of lesions on the shaft of the penis. Large,
unresponsive lesions around the rectum or vulva can be treated with scissor excision of the bulk of
the mass followed by electrocautery of the remaining tissue down to the skin surface. Loop
electrocautery excisional procedure (LEEP) after colposcopic biopsy has become a standard
procedure for cervical lesions particularly for the ones with neoplastic features. Removal of a very
large mass of warts is a painful procedure, best performed under either general or spinal
anesthesia.
 Carbon dioxide laser is an efficient method of treating primary and recurrent anogenital warts
because of its precision and rapid healing without scarring. Primary cure rates as high as 91%
have been reported. Carbon dioxide laser is the treatment of choice for pregnant women with
extensive lesions or lesions that do not respond to TCA.
 Pulsed-dye laser and other new lasers have been used by some with various successful rates.
Pulsed dye lasers target hemoglobin (the oxygen carrying molecule in the blood) within the blood
vessels of the wart.  The heat spreads out to surrounding tissue which seals the blood vessels and
so starves the wart of nutrients.  The wart dries up, becomes necrotic, and eventually falls off. 
 Surgery is indicated particularly for large genital warts or malignant lesions.
 For recurrent carcinoma, Mohs surgery also known as chemosurgery, is a good choice. It is
microscopically controlled surgery used to treat common types of skin cancer.

FOLLOW-UP

Further Outpatient Care

Patients typically are monitored on a periodic basis to assess for efficacy of treatment, unwanted side
effects, and the development of complications. Outpatient follow-up care also provides an opportunity to
evaluate for other sexually transmitted diseases (STDs) and provides patient education on an ongoing
basis.

After visible genital warts have cleared, a follow-up evaluation might be helpful. Patients should be
cautioned to watch for recurrences, which occur most frequently during the first 3 months. External genital
warts can be difficult to identify, so it might be useful for patients to have a follow-up evaluation 3 months
after treatment. Earlier follow-up visits also might be useful for some patients to document the absence of
warts, to monitor for or treat complications of therapy, and to provide an additional opportunity for patient
education and counseling. Women should be counseled to undergo regular Pap screening as
recommended for women without genital warts.
Prevention

Genital warts may be a sexually transmitted disease, but the virus does not require the exchange of bodily
fluids during intercourse in order to be passed on to another person. Instead, it is spread through direct skin
contact with an infected person. Thus, you may get genital warts not just through vaginal and anal sex, but
also through oral sex, which may result in the formation of warts in the mouth and throat areas.

Furthermore, using forms of barrier protection such as condoms won’t totally wipe out the chances of you
contracting the disease. According to studies, they may only reduce your risk of getting the virus. They
don’t completely cover the genital area so skin-to-skin contact is still a possibility. However, it would not
hurt if you have protected sex. 

Abstinence is the only sure-fire way to save yourself from getting HPV, but you may also avoid getting
genital warts by adapting healthier and safer sex practices. If your partner still has visible warts, it would be
better to refrain from having sexual contact until all of his/her warts have been eliminated. It would also help
that you talk to your partner about your sexual history so that you will know whether or not you both need to
be screened for infection.

If you’re a woman, you can opt to be vaccinated against cervical cancer. This new vaccine called “ Gardasil”
offers protection from four strains of HPV, which cause cancer and genital warts. It was approved for use
by women from ages 13 to 26 by the Food and Drug Administration (FDA). This vaccine is most effective if
administered to girls before becoming sexually active. 

Complications

Disease complications can include progression to malignancy and transmission to other sexual contacts. In
the setting of genital warts active during a pregnancy delivery, there is a small risk of laryngeal
papillomatosis.

Each therapeutic modality carries its own unique set of risks. Risks of individual medical options are
discussed in Treatment. Expected effects of cryosurgery include pain, edema, vesicles, bullae, weeping,
and some necrosis. There is a small risk of infection, bleeding, abnormal scarring, pigment alteration,
paresthesias, and alopecia with cryosurgery. Similarly, laser surgery of genital warts may result in pigment
alteration, abnormal scarring, and infection. Special care must be taken to prevent respiratory infection from
the laser plume generated by vaporization of virally infected tissue.

Special Concerns/Consideration

Increased risk of anogenital malignancy

Patients with genital warts have an increased risk of anogenital malignancy. Infection with HPV is the
primary cause of cervical malignancy, although most patients with HPV-infected cervices have a benign
outcome. This mandates that female patients with genital warts should have an annual screening
examination and Papanicolaou test. Up to 90% of cervical cancers are caused by HPV infection of the
cervix.

Strong epidemiologic evidence suggests that 10% of patients who had a high-grade squamous
intraepithelial lesion (HGSIL, which includes so-called moderate-to-severe dysplasia, carcinoma in situ, and
cervical intraepithelial neoplasia II and III) would have persistence of lesions that eventually would progress
to invasive cancer without treatment. Patients with perianal warts, patients who are HIV positive, and those
with a history of receptive anal intercourse are at increased risk for anal HGSIL. No direct evidence
suggests that this would progress to invasive anal cancer, as lesions of the cervix are capable of doing.
Nonetheless, penile, vulvar, vaginal, ovarian, and anal carcinomas have been linked to HPV infection.

Pregnancy

Imiquimod, podophyllin, and podofilox should not be used during pregnancy. However, because genital
warts can proliferate and become friable during pregnancy, many specialists advocate their removal during
pregnancy. HPV types 6 and 11 can cause respiratory papillomatosis in infants and children. The route of
transmission (i.e., transplacental, perinatal, or postnatal) is not completely understood. Whether cesarean
section prevents respiratory papillomatosis in infants and children is unclear; therefore, cesarean delivery
should not be performed solely to prevent transmission of HPV infection to the newborn. Cesarean delivery
might be indicated for women with genital warts if the pelvic outlet is obstructed or if vaginal delivery would
result in excessive bleeding. Pregnant women with genital warts should be counseled concerning the low
risk for warts on the larynx (recurrent respiratory papillomatosis) in their infants or children. No controlled
studies have suggested that cesarean section prevents this condition.

Anogenital warts in children

Anogenital warts are rare in the general pediatric population. More than one half of children with anogenital
warts have a manifestation either of viral inoculation at birth or of incidental spread of cutaneous warts.
Such cases often are caused by nongenital HPV types.

Diagnosis of genital warts in a child requires that the clinician report suspected abuse to begin an
evaluation process that may or may not confirm sexual abuse.

Laryngeal papillomatosis of neonates and infants

Although childhood laryngeal papillomas frequently are acquired from condyloma of the mother (HPV types
6 and 11 are frequently cited), most infants of mothers with condyloma do not contract laryngeal
papillomas.

Accordingly, cesarean delivery should not be performed solely to prevent transmission of HPV infection to
the newborn. Route of transmission in pregnancy is not known, and infants born by cesarean delivery have
developed laryngeal papillomatosis. However, it is advisable to remove visible lesions during pregnancy.

Patients who are immunosuppressed

Patients who are immunosuppressed such as those with AIDS and those on immunosuppressive therapy
(eg, patients with renal transplants) are more likely to develop persistent HPV infection and subsequent
dysplasia and malignancy. No data suggest that treatment modalities for external genital warts should be
different in the setting of HIV-infection. However, persons who are immunosuppressed because of HIV or
other reasons might have larger or more numerous warts, might not respond as well as immunocompetent
persons to therapy for genital warts, and might have more frequent recurrences after treatment

Verrucous carcinoma of genitalia (giant condyloma of Buschke-Löwenstein)

It is a low-grade, locally invasive, squamous cell carcinoma that is associated with HPV types 6 and 11 and
should be considered in the differential of lesions measuring greater than 1 cm in diameter. Only radical
surgical extirpation is considered appropriate treatment.

Prognosis

Prognosis is good, and most cases of genital warts are amenable to treatment. Patients who are
immunosuppressed with genital warts may represent a special challenge.
Patient Education

Patients with genital warts deserve a focused history and physical examination, with appropriate testing to
assess for other STDs. In a population study, 7% of men and 31% of women who had genital warts had
concurrent STDs. In fact, 28% of these men and 71% of women had other STDs before or after their genital
warts. Additionally, several consort studies documented that 30% of female consorts and 80% of male
consorts had HPV infection. Usually, the same type of HPV involved both parties, and often they were HPV
6, 11, 16, and 18.

The benefit of evaluating sex partners of patients with genital warts has been apparent.

Management of Sex Partners

Examination of sex partners is not necessary for the management of genital warts because no data indicate
that reinfection plays a role in recurrences. In addition, providing treatment for genital warts solely for the
purpose of preventing future transmission cannot be recommended because the value of treatment in
reducing infectivity is unknown. However, sex partners of patients who have genital warts might benefit
from counseling and examination to assess the presence of genital warts and other STDs.

The counseling of sex partners provides an opportunity for these partners to:

1) Learn that HPV infection is common and probably shared between partners and

2) Receive STD evaluation and screening and Pap screening if they are female. Female sex partners of
patients who have genital warts should be reminded that cytologic screening for cervical cancer is
recommended for all sexually active women.

Counseling

Education and counseling are vital aspects of managing patients with genital warts. Patients can be
educated through patient education materials, including pamphlets, hotlines, and websites.

 Genital warts are caused by specific types of HPV infection. The types that cause genital warts are
different from the types that cause cervical and other anogenital cancers.
 Persons can possibly have infection with the types of HPV that cause genital warts but never
develop symptoms. Why some persons with genital HPV infection develop warts and others do not
is unclear. Immunity probably plays a key role.
 The natural history of genital warts is usually benign, but recurrence of genital warts within the first
several months after treatment is common. Treatment for genital warts can reduce HPV infection,
but whether the treatment results in a reduction in risk for transmission of HPV to sex partners is
unclear. The duration of infectivity after wart treatment is unknown.
 Condoms might reduce the risk for HPV-associated diseases (e.g., genital warts and cervical
cancer). Consistent condom use also may reduce the risk for genital HPV
 HPV infection can occur in areas that are not covered or protected by a condom (e.g., scrotum,
vulva, or perianus).
 Maintain good hygiene
 The presence of genital warts is not an indication for HPV testing, a change in the frequency of
Pap tests, or cervical colposcopy.

 Wear only 100% cotton underwear and change them more then once a day. Only use natural
detergent to wash clean your underwear.
 HPV testing is not indicated for partners of persons with genital warts.