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© 2018 EDIZIONI MINERVA MEDICA Giornale Italiano di Dermatologia e Venereologia 2020 June;155(3):261-8
Online version at http://www.minervamedica.it DOI: 10.23736/S0392-0488.18.06125-4

REVIEW

Anogenital warts treatment options: a practical approach

Sergio DELMONTE 1 *, Susanna BENARDON 2, 3, Caterina CARITI 1,
Simone RIBERO 1, Stefano RAMONI 3, Marco CUSINI 3

1Clinicof Dermatology, Department of Medical Science, University of Turin, Turin, Italy; 2Department of Internal Medicine and
Medical Specialties, State University of Milan, Milan, Italy; 3Unit of Dermatology, Maggiore Polyclinic Hospital, Ca’ Granda IRCCS
and Foundation, Milan, Italy
*Corresponding author: Sergio Delmonte, Clinic of Dermatology, Department of Medical Science, University of Turin, Città della Salute e della Scienza,
Corso Bramante 88/90, 10126 Turin, Italy. E-mail: sergio.delmonte.69@gmail.com

A B S TRA C T
Anogenital warts (AGWs) are an important issue for public health centers dealing with Sexually Transmitted Infections. They are epidemio-
logically relevant, with significant morbidity and an established effective treatment is lacking. In this article, we examine the epidemiological,
diagnostic, and therapeutic aspect of the problem in order to give an up to date picture of the situation and a practical clue for the management
of AGWs.
(Cite this article as: Delmonte S, Benardon S, Cariti C, Ribero S, Ramoni S, Cusini M. Anogenital warts treatment options: a practical approach. G
Ital Dermatol Venereol 2020;155:261-8. DOI: 10.23736/S0392-0488.18.06125-4)
Key words: Condylomata acuminata; Viral sexually transmitted diseases; Papillomaviridae.

H PV infection is the most common sexually transmitted

viral infection and it is equally common in men and
women. About 30 out of 150 known HPV genotypes have
been associated with anogenital lesions in both sexes.1
HPVs are divided into low-risk (LR) and high-risk (HR)
types according to the association of each HPV genotype
with benign warts, cancer and precursor lesions.
Anogenital warts (AGW) are benign lesions and
about 90% are caused by HPV types 6 or 11 (LR types)
while 10% are associated with a coinfection due to HR
types.
In a minority of individuals malignant squamous-cell
tumors may develop: HPV-16 and -18 alone account for
70% of the oncogenic mucosal HPV types.
Epidemiology
The epidemiology of HPV genital infection is still not well
defined. In the literature it is reported that anogenital HPV
infection affects about 40% of the general population.
The annual incidence of genital warts in developed world
populations is estimated to be about 0.15% of the adult
population per year.2
The highest rate of warts is observed in females aged
16-24 years and in males aged 20-24.3
The estimated number of cases of genital warts has been
reported in constant increase in recent years throughout
western countries, probably due to early age at first in-
tercourse, increasing lifetime number of sexual partners
and lack of condom use;4 this has led to increased public
awareness of HPV infection.
The impact of HPV vaccine on the epidemiology seems
to start modifying the epidemiological picture and de-
creases of incidence have been described, mostly in young
people.
In Italy we do not currently have data on the general
population, but only from selected groups of patients. In
2005, in a retrospective survey on a selected sample of
gynecology patients, the calculated incidence was 0.43%,
and the prevalence was 0.6%.5 In the same study the esti-
mated incidence in the male population of the same age
was 0.47% and the prevalence was 0.76%. These rates,

Vol. 155 - No. 3 Giornale Italiano di Dermatologia e Venereologia 261

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DELMONTE ANOGENITAL WARTS TREATMENT
slightly higher than those reported in other international
studies, are probably due to a bias in the study, which un-
derestimated the denominator.
More recent data refer to the sentinel STI surveillance
system started in Italy in 1991.6 Anogenital warts, with
37,491 new cases, were the most common diagnosis:
38.7% of all STIs (40.7% in males and 34.2% in females).
The annual number of AGW cases remained stable up to
2004, then it gradually increased to a peak in 2012 (twice
the number of cases in 2004): this rise occurred equally in
females, heterosexual males and men who have sex with
men (MSM). It is important to highlight the epidemiologi-
cal correlation between AGW and HIV. Among the 26,051
cases of AGW diagnosed in the period 1991-2012, the
prevalence of HIV was 7.7%.6
In 2008, in the UK, a total of 148,790 episodes of care
for genital warts were reported: 80,531 new cases and
68,259 recurrent episodes. The average cost of care per
episode was £ 113, and the estimated annual cost of care
in England was £ 16.8 million. In the USA, about 1 mil-
lion new cases are diagnosed every year, with an estimated
prevalence of 15%.7
According to data from Kjaer et al. 10% of women aged
between 16 and 49 years had suffered from at least one
episode of anogenital warts.8
In contrast, in a study by Dinh et al.,9 about 4% of 18- to
59-year-old men had at least one episode of genital warts.
Transmission
The HPV virus cannot be grown in culture, so information
on its behavior and transmission derives from clinical ob-
servation and experiments in animals.
Anogenital HPVs are predominantly transmitted by
sexual intercourse but HPV can also be transmitted peri-
natally.10
Genital lesions resulting from transfer of infection from
hand warts (HPV type 2) have been reported in children but
not in adults. There is no solid evidence of transmission from
fomites. Autoinoculation from a genital site to an extrageni-
tal site and vice versa is documented, but it is very rare.11
Clinical presentation
AGW can be single or multiple, although solitary lesions
are rare. Size can vary from a few millimeters to several
centimeters.
There are different kinds of anogenital warts: condylo-
mata acuminata, flat warts, papular warts, hyperkeratotic
262 Giornale Italiano di Dermatologia e Venereologia June 2020
warts.12, 13 The most common aspect of anogenital warts
are papular lesions <5 mm in diameter. They can grow on
the mucosal surface or on the skin of the anogenital area;
skin anogenital warts may be pigmented.
The lesions can be distributed all over the anogenital
area; anal lesions are common in both sexes and are en-
hanced by, but not always related to, anal sex.14 Extrageni-
tal lesions due to the same HPVs can be occasionally found
in the oral cavity, larynx, conjunctiva and nasal cavity.
AGW are almost always asymptomatic; if present,
symptoms are usually due to irritation, bleeding or sec-
ondary infection and consist of an itching or burning sen-
sation.
The incubation period for anogenital HPV infection
varies from about 3 weeks to 8 months and it is usually
longer in males.15
It is important to remind that AGW can coexist with
other HPV-related lesions such as intraepithelial neoplasia
of the vagina (VAIN), vulva (VIN), penis (PIN), perianal
skin (PAIN) and anus (AIN).16 There is no actual increase
of the risk of developing a cancer for the patients affected
by AGW. If giant condylomata, particularly Buschke-
Löwenstein tumor, are present, invasive carcinoma must
be ruled out by skin biopsy.7
Diagnosis
The first step is a careful clinical examination of the entire
anogenital area with a bright light and a magnifying lens
to distinguish AGW from other genital lumps (e.g. benign
lesions such as pearly penile papules, or infections such as
molluscum contagiosum).
In the presence of perianal warts and/or symptoms like
irritation, bleeding or discharge, examination of the anal
canal is recommended to identify possible internal warts,
via digital rectal exploration (DRE) and/or anoscopy.17
Sometimes, biopsy may be required to confirm the di-
agnosis, particularly in: immunocompromised patients, in
case of lesions of uncertain diagnosis, lesions which not
respond to standard therapy, lesions which worsening dur-
ing therapy. The presence of pigmentation, underlying im-
mune deficiency and/or prior history of intraepithelial neo-
plasia on the same or different anogenital site may raise
suspicion of anogenital neoplasia.
Treatment
The ultimate goals of treatment are removal of visible clin-
ical lesions, relief of symptoms and prevention of relapses.
 ©
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ANOGENITAL WARTS TREATMENT DELMONTE

Whether the reduction in HPV viral load resulting from Number of lesions
treatment reduces future transmission remains unknown
and it is likely HPV infectivity decreases over time. <5 >5
Treatment decisions should be made after discussion
with the patient, because all treatments may involve dis- Small lesions Large lesions Large lesions Small lesions
comfort and local skin reactions and have significant <3 mm >3 mm >3 mm <3 mm
failure and relapse rates. Patient counseling is highly
warranted because the diagnosis can be distressing for pa- DTC
tients. Indeed, for some patients, the psychological impact
of warts is the worst aspect of the disease.18 Since about Podophyllotoxin If recurrence
Cryotherapy Imiquimod 5%
30% of patients will experience spontaneous clearance of Nitrizinc If failure Sinecatechin 10%
warts within 1 year, no treatment may be an option too.19-21 complex
However, most patients seek treatment for the discomfort, Figure 1.—Low risk of recurrence.
anxiety, distress or the social unacceptability that warts
cause.22
Trend of lesions
The efficacy of treatments, which is difficult to stan-
dardize due to the heterogeneity of the studies reported in Stable or in regression Increasing
the literature, is measured on two parameters: regression
of lesions and frequency of recurrences.
Therapies can be divided into ablative treatments <5 lesions >5 lesions
(chemicals or physical techniques) that are mostly physi-
cian applied and immunomodulatory treatments that are Podophyllotoxin If recurrence
mostly patient-applied (Table I).23 Cryotherapy
If failure
Imiquimod 5%
Nitrizinc complex Sinecatechin 10%
Treatment choice depends on the clinical picture. Non- DTC
surgical treatments have been recently recommended as
Figure 2.—High risk of recurrence.
first line by different international guidelines.12
Two main scenarios may be proposed considering the
number and the size of AGW, the main predictors of recur- consider therapeutic abstinence. A pause can be a choice
rences:24, 25 when treatments prove to be an additional source of pain
•  low risk of recurrence: in patients with few lesions, and stress.
never treated before, the goal is to remove the lesions,
choosing the best treatment based on number and size Physician-applied treatments
(Figure 1);
•  high risk of recurrence: in patients with many untreat- These are often ablative treatments and are the first option
ed or relapsing lesions the goal is prevention of relapse for few keratinized lesions.
after removing the lesions based on evolution and size
(Figure 2). Cryotherapy
In the absence of response after at least 2 months or in The liquid nitrogen spray causes cytolysis at the dermal/
case of recurrence without reduction of the number of le- epidermal junction resulting in necrosis. It is a routine
sions, it is advisable to change the therapeutic option or to treatment because it is easy, rapid, and ready to use at the
time of diagnosis — in a specialist clinic setting only. An-
Table I.—Different treatment methods. esthesia is usually not required.26
Patient-applied therapy Physician-applied therapy It is suitable for small-medium size lesions and it has a
Podophyllotoxin cream/solution Scissor snip excision quick healing time (days); for large lesions, multiple treat-
Imiquimod 5% cream Curettage ments are usually needed (once a week) It is the gold stan-
Sinecatechin 10% cream (Europe) Electrocauterization (DTC) dard for AGW of the urethral meatus.27, 28
CO2 laser
Cryotherapy It does not leave permanent scars but can cause hy-
Nitri-zinc complex popigmentation when performed on the skin of dark pho-
Trichloroacetic acid (<85%)
totypes.29

Vol. 155 - No. 3 Giornale Italiano di Dermatologia e Venereologia 263

 ©
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to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
DELMONTE ANOGENITAL WARTS TREATMENT
Diathermocoagulation
Diathermocoagulation or electrocautery has the advantage
of eliminating the lesions by destroying them in a single
session. It usually requires anesthesia (topical or injective)
and has a long healing time (weeks). Patients may complain
about pain at the treatment site in the following days.30
Whenever possible, it is important to leave skin bridges
between treatment sites to aid healing and minimize scar-
ring.
It is the treatment of choice in medium-large skin le-
sions.
Possible long-term sequelae include dyschromia or
scars/keloids when treating skin lesions in predisposed
patients.23
Laser treatment
Carbon dioxide laser is commonly used for both external
and internal lesions. It is best to use local anesthesia (topi-
cal or by infiltration); the healing time is short (days) and
wounds are usually not painful.
Indications: laser treatment is especially suitable for
medium volume muco-cutaneous warts and can be used
at difficult anatomical sites, such as the urethral meatus,
vagina, or anal canal. It is the best choice for high numbers
of very small size lesions due to its minimal inflammatory
effect on the surrounding healthy skin.31
It is a more expensive and time-consuming treatment
modality compared to other ablative methods.32
Ablative therapies such as CO2 laser that generate
smoke require a vacuum device and special filters. Special
masks and protective lenses are mandatory for patients and
all medical personnel.33
Surgical excision
It can be carried out with scalpel excision, scissor snip ex-
cision or sharp curettage with or without a local anesthetic
injection. Hemostasis, if needed, can be established using
electrosurgery or the application of a hemostatic solution
or paste.
Excision may be considered for pedunculated or large
warts or for small numbers of keratinized lesions.
This should be considered the preferred treatment op-
tion when a biopsy is needed.34
Nitrizinc complex™
It acts by “mummifying” the lesions though protein de-
naturation. Due to its cytolytic properties, it causes only
a weak local inflammatory reaction.35 It is a solution suit-
264 Giornale Italiano di Dermatologia e Venereologia June 2020
able for weekly application on mucosae and application
every two weeks on skin lesions, for up to four cycles.
This can be considered for treatment of small-medium
size mucosal and skin lesions. If applied with caution it
may be used for urethral meatus warts.
Trichloroacetic acid (TCA)
It acts as a caustic agent resulting in cellular necrosis and
can cause significant inflammation of the treated area since
it is extremely corrosive.
TCA 80-90% solution is suitable for weekly application
only in a specialist clinic setting.
This is the preferred treatment for small-medium size
mucosal warts and intracavitary warts (vagina, rectum). It
is an effective and safe treatment in the first half of preg-
nancy.36
Patient-applied treatments
They can act through a chemical destruction of the lesions
or an immunomodulatory action and are all suitable for use
by the patients themselves. Immunomodulatory treatments
need more time to be effective, can cause irritation and are
not as effective as ablative therapy in destroying AGW, but
have a lower recurrence rate than ablative therapy.
Podophyllotoxin 0.5%
Podophyllotoxin acts as an antimitotic agent causing ne-
crosis of the AGW.
Treatment cycles consist of twice-daily application for
three days, followed by four days’ rest, for 4-5 cycles.37
Treatment should be discontinued if significant side ef-
fects arise (e.g. soreness, ulceration). To avoid collateral
effects, it is recommended to treat a small area each time.
This is the treatment of choice for relapses, in particular
when there are few, small both mucosal and skin lesions.
It appears to be less effective in women and circumcised
men.38, 39
It should be avoided in pregnancy and in children <12
years old.40
Imiquimod 5% cream
It is an immune-response modifier. It acts as a toll-like re-
ceptor-7 (TLR7) agonist that leads to the stimulation of
local tissue macrophages to release interferon-alpha and
other cytokines. It influences the local cell-mediated re-
sponse inducing not only the regression of the lesions but
also preventing local relapses.41, 42
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
COPYRIGHT 2020 EDIZIONI MINERVA MEDICA
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to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
ANOGENITAL WARTS TREATMENT DELMONTE
The cream is applied once a day, three times weekly and
washed off 6-10 hours later, for up to 8-16 weeks.
It is commonly associated with a local inflammatory re-
action; less often, flu-like symptoms can appear.43
Long-term effects consist of hypopigmentation of the
skin surface or the worsening of other cutaneous diseases
(psoriasis, vitiligo, lichen planus).44-46
When applied to an uncircumcised penis it may worsen
phimosis, if present.
Imiquimod is indicated for multiple small-medium size
lesions on wide areas and for recurrent lesions and is suit-
able treatment for both keratinized and non-keratinized
warts. It appears to be more effective in women.43
Immune deficiency is not a contraindication for the use
of Imiquimod and it has been used in HIV-positive sub-
jects, although it appears to be less effective.47, 48
Not approved for use in pregnancy.23
Sinecatechin 10% cream
It is an extract of the leaf of the green tea plant Camellia
sinensis and it acts as an immunomodulator although the
exact mechanism of action is uncertain.49, 50
It is applied three times per day, for up to 16 weeks.51
During use, local reactions are common but milder than
imiquimod.
Sinecatechin 10% cream is indicated for multiple small-
medium size lesions on wide areas and for recurrent lesions in
immunocompetent individuals. It is not suitable in pregnancy,
immunocompromised patients or people with genital herpes.
Therapies with interferon α, 5-fluorouracil and podo-
phyllin are no longer recommended and will not be de-
scribed with here.41
Recurrence
Almost 50% of patients experience relapse, usually within
3 months.
We define “relapse” as the development of new lesions
after a total clearance obtained with a previous treatment
in the same or different area.
The rate of relapse depends on the immune status and
number of lesions treated.
To prevent recurrences, it is recommended to avoid
smoking,52 alcohol, genital hair removal, topical steroids
in the treated area, and excessive cleansing.
Although not officially recommended in the literature,
a lower recurrence rate is reported in patients treated with
an ablative method followed by the application of immu-
nomodulatory treatments on healthy skin.26
Vol. 155 - No. 3 Giornale Italiano di Dermatologia e Venereologia 265
Special conditions
Pregnancy
Pregnancy may be considered as a temporary immuno-
suppressive condition, so reactivation of HPV is possible.
Treatment is not always warranted but can be offered be-
fore delivery (8th-9th month) to minimize the number of
lesions present at delivery. Surgical/physical methods are
safer options in pregnancy and therefore preferred.53
Caesarean section is not indicated for prevention of ver-
tical transmission of HPV infection. Rarely, caesarean sec-
tion is indicated because of obstruction of the vaginal outlet
with warts, or massive bleeding from AGW. The only seri-
ous complication is recurrent respiratory papillomatosis in
the infant but it is very rare (4/100,000 births). Sometimes
spontaneous regression of AGW after delivery is possible.
Children
The immaturity of the immune system makes children
more vulnerable to infection and for this reason non-sexu-
al transmission is more common than in adults.
The origin of anogenital warts in children may be cuta-
neous warts on the fingers transmitted by autoinoculation
or by heteroinoculation from caregivers or from vertical
transmission of HPV infection (within 2 years of age), or
from sexual abuse (after 2 years of age).54-56
Treatment options: cryotherapy at any age, imiquimod
after 2 years of age, Nitrizinc complex™ after 6 years of
age, podophyllotoxin after 12 years of age.
Immunocompromised patients
Patients usually experience a reduced response and in-
creased relapse rates following treatment.30
Since they have an increased risk of HPV-related neo-
plasia, mostly in the anal canal, anoscopy is recommend-
ed, even if perianal GW are not present. In HIV patients,
if CD4 >500 cells/mm3, no other treatment modification
is required, but if CD4 <200 cells/mm3, surgical/physical
methods are preferred.
Anal canal
Clinicians may find warts in the anal canal in association
with external AGW, and they may be unrelated to receptive
anal sex. Diagnosis is made by digital rectal examination
(DRE), followed by anoscopy. Treatment options: cryo-
therapy, DTC, laser ablation and trichloroacetic acid.57
No therapy and 6-month follow-up is an option. Topical
imiquimod 5% for recurrent internal warts is possible, but
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
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This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
DELMONTE ANOGENITAL WARTS TREATMENT
it is an unlicensed indication. In HIV-positive patients, bi-
opsy for histological evaluation is recommended.58, 59 Pos-
sible complications: perianal fistula, ano-rectal stenosis.
Intravaginal/cervical involvement
Rare and usually associated with external AGW.60
Treatment options: cryotherapy, DTC, laser ablation,
and trichloroacetic acid. If they are asymptomatic, no ther-
apy and 6-month follow-up is an option. Colposcopy and
PAP test are recommended to rule out associated neoplas-
tic lesions (CIN, VAIN).
Oral cavity
Rare, and if present, often a warning sign of immune im-
pairment.61 Treatment options: cryotherapy, DTC, laser ab-
lation, and trichloroacetic acid. HPV detection and typing
are not recommended, but HIV testing is recommended.
Urethral meatus
Warts in the urethral meatus can be asymptomatic or as-
sociated with strangury or terminal hematuria.62 If the base
of the lesion is visible, treatment options are cryotherapy,
DTC, or laser ablation.27 Lesions deeper in the urethra are
very rare, but if obstructive symptoms are present, patients
should be referred to a urologist who can surgically ablate
AGW under direct vision with the use of a meatoscope.
Possible complications: bacterial cystitis, urethral stenosis.
Follow-up
Patients must be reviewed at the end of the prescribed
treatment. Complications are rare but possible, especially
if there is a strong inflammatory reaction during treatment.
Stenosis is a possible complication in treatment of cir-
cumferential AGW on the prepuce: in this situation better
treatment options are laser ablation, Nitrizinc complex™
or sinecatechins.
Prevention
Condom use reduces the risk of acquisition of HPV infec-
tion and genital warts by 30-60%, but only when lesions
are in areas covered with latex. This barrier seems to be
more effective in preventing male-female transmission.
HPV vaccines are licensed for the protection of indi-
viduals against genital infection and associated diseas-
es.7, 63, 64 None of the existing vaccines has been shown to
reduce the risk of acquisition of HPV infection and genital
266 Giornale Italiano di Dermatologia e Venereologia June 2020
warts if the subject has already had contact with an in-
fected partner.
For this reason, vaccination of the partner of infected
patients is not recommended.
Partners
Partners should be always informed about transmission,
individual variability of immune response, and the possi-
bility of developing AGW in future.
There is a clear need for counseling to prevent a nega-
tive effect on the relationship.40 HPV testing in asymp-
tomatic partners is to be avoided because of the lack of
effective preventive and therapeutic treatments in asymp-
tomatic infection.12, 15
Previous partner notification is not recommended be-
cause the time of infection is usually unknown.23 It is a
good rule to recommend the use of condoms with a new
partner if AGW are still present, and until 3 months after
complete regression.
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2011;87:464–8.
3.  Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent
J, Bruni L, et al. Global burden of human papillomavirus and related dis-
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Conflicts of interest.—The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
Authors’ contributions.—All authors have participated in the acquisition, analysis, or interpretation of data, in manuscript drafting, and in the critical revision
of the manuscript for important intellectual content. Sergio Delmonte and Marco Cusini supervised the work.
Acknowledgements.—This article is an English-language, abridged version of the book “Verruche ano-genitali e cutanee Linee Guida e Raccomandazioni
SIDeMaST 2016-2017” by Pacini Editore, Pisa, Italy. The authors wish to thank Pacini Editore for granting permission to translate and transform this work.
History.—Article first published online: September 24, 2018. - Manuscript accepted: September 13, 2018. - Manuscript received: July 3, 2018.

268 Giornale Italiano di Dermatologia e Venereologia June 2020