Expert: Gary Keel, PA-C - 4/26/2005

Question
Hi Gary, i have a question about genital warts. I recently have been intimate with a guy who has genital warts. i have been getting info about them but i am a little confused about a few things and would like it if you could help me clear it up. first, what are the ways someone can GIVE them to their partner and more specifically, do they have to have a wart on them at the time to infect their partner? can it be transmitted through semen/vaginal fluid?
secondly,  condoms and abstinence are best way i read not to get them from your partner, but what other more specific precautions can i take?
thirdly and maybe the most confusing, i have been getting mixed results on whether or not they are curable or just treatable when the person has outbreaks like with herpes? once you get rid of the warts either by treatment or if they just go away, are they gone for good? or do you have it for life like herpes? i hope i was specific in my questions i really care about my partner and want to be intimate but i DEFINATLY don't want to get genital warts, ESP if they aren't curable. thanks!
LOUISE

Answer
You are right, Louise, they are treatable, not curable. Here is more inf. No, vag. fluids and semen don't carry the viruses.  Human papillomavirus (HPV) causes genital warts, a disease that affects approximately 1% of the sexually active
population of the United States. External genital warts are easily recognizable by their characteristically raised, dry,
cauliflowerlike appearance. Visual inspection is usually sufficient for diagnosis, unless the lesion looks unusual or does not
respond to treatment. Warts can be treated by either the patient or physician. Options available to patients are podofilox
and imiquimod. Physician-applied treatments include podophyllin, trichloroacetic acid, bichloroacetic acid, and cryotherapy.
Warts tend to recur, and no one treatment has proved better than another at preventing the reappearance of lesions. HPV
also causes cervical infection and is responsible for cytologic abnormalities on Pap smears. New information suggests that
HPV testing is sensitive in detecting precancerous lesions in women with ambiguous cytologic abnormalities on Pap testing,
but that it is not useful for women with a Pap test that shows low-grade lesions.
Managing Genital Warts
and Cervical HPV Infection
KEVIN A. AULT, MD
University of Iowa Hospitals
and Clinics, Iowa City
Dr Ault is associate professor in the department of obstetrics and gynecology at the University of Iowa Hospitals and Clinics, Iowa City.
MARCH 2005 (SUPPLEMENT) S26
The well-documented association between certain
genotypes of human papillomavirus (HPV)
and invasive cervical cancer, anogenital cancer,
and genital warts has caused the medical community
to sit up and take notice: the
more the virus is studied, the more
alarming the statistics become. Approximately
20 million Americans are currently
infected, and about 5 million new
cases of HPV infection are acquired
each year.1
HPV transmission is difficult to prevent,
which contributes to its prevalence.
The primary route of HPV transmission
is sexual intercourse, and most
women become infected within a few
years of becoming sexually active. Short
of abstinence, an absolutely monogamous
relationship with an uninfected
partner, or approval of an HPV vaccine,
there is no certain way to prevent becoming
infected. Condoms have not
been documented to be reliable in preventing
HPV infection.1
Because HPV infection is usually
asymptomatic and, with the exception of genital
warts, externally invisible, persons can easily
and unwittingly transmit the virus to their partners.
Not only that, but data from the National
Managing Genital Warts and Cervical HPV Infection
Figure – Genital warts characteristically appear as raised, dry, cauliflowerlike lesions
occurring in the anogenital area. Visual inspection is usually sufficient for diagnosis; biopsy
is generally unnecessary unless the lesion persists despite treatment or has an
unusual appearance. (Photo courtesy of healthac.org.)
MARCH 2005 (SUPPLEMENT) S27
Cancer Institute, collected from a cohort in
Portland, Ore, indicate that 86% of women who
are HPV-infected never have an abnormal Pap
smear.2 Thus, a tremendous amount of disease
is evading our clinical radar.
Traditional thinking is that it takes years for
HPV to transform into invasive cervical cancer.
Emerging data are challenging this concept,
however. It appears that some women progress
relatively quickly from having a normal cervix,
with normal cytology, to severe dysplasia (unpublished
data).
Some 75 to 80 years ago, cervical cancer was
a leading killer in the United States. Much
progress has been made since then, and today,
the Pap smear remains a useful cancer-screening
tool. The challenge is now finding and treating
precancerous dysplastic lesions as quickly
as possible—or, even better, to prevent dysplasia
and cervical cancer completely by eliminating
genital HPV.
In this article, I discuss the clinical evaluation
and management of genital warts. I also review
some basic information about cervical
HPV infection, including
new recommendations
about how best to manage
women with low-grade abnormalities
on their Pap
smears.
GENITAL WARTS
Genital warts are present
in approximately 1% of the
US population, or 1.4 million
persons.3 Although genital
warts are not precancerous
Managing Genital Warts and Cervical HPV Infection
Table 1 – Diagnosis of genital warts
•Visual inspection almost always sufficient for diagnosis
•Differential diagnosis: molluscum contagiosum, condyloma latum
•Biopsy rarely necessary; consider whether: the diagnosis is in doubt,
the patient is immunocompromised, the lesion is worsening with treatment,
or the lesion is pigmented or fixed
•Application of acetic acid can reveal dysplasia
From Workowski KA, Levine WC. MMWR. 2002.4
lesions and are not known to increase a person's
risk of cervical or penile cancer, they nonetheless
are a considerable source of distress to
most patients.
DIAGNOSIS
Most people first notice genital warts as
small bumps, which may be itchy. Genital warts
are easily diagnosed by visual inspection, with
or without magnification. They typically appear
as raised, dry, cauliflowerlike structures (Figure).
Genital warts must be differentiated from
molluscum contagiosum and condylomata lata,
since the appearance of all 3 conditions is similar
(Table 1). Condyloma latum is a lesion of secondary
syphilis and occurs in areas where
syphilis is prevalent. Molluscum can be recognized
by its umbilicated appearance.
Biopsy is usually unnecessary for a definitive
diagnosis of genital warts, unless the lesion
has an unusual appearance or worsens despite
treatment. Biopsy is, however, a diagnostic consideration
in HIV-infected persons, because
such persons are at increased risk for vulvar,
cervical, and other anogenital cancer. Anal cancer
is especially common in men who have sex
with men. Lesions that are atypical or fixed to
the underlying tissue, or that have strange pigmentation,
are also candidates for biopsy.
Warts may be located on the vaginal walls or
cervix. Application of acetic acid solution can
help reveal vulvar, vaginal, or cervical dysplasia.
MANAGEMENT
The approach to management depends on
the presence of symptoms. Internal warts—
vaginal or cervical lesions—cause no symptoms
and can be left alone if there is no suspicion of
cancer.
Warts that cause symptoms will require
treatment. Table 2 lists the current guidelines
for treating genital warts, as recommended by
the CDC.4 Podofilox and imiquimod are recommended
patient-applied treatments. Podophyllin,
cryotherapy, and trichloroacetic acid
are recommended physician-applied treatments.
Since warts often recur, it is prudent to
be familiar with a few different therapeutic approaches—
both physician- and patient-applied.
Managing Genital Warts and Cervical HPV Infection
MARCH 2005 (SUPPLEMENT) S28
One caveat: imiquimod, podofilox,
and podophyllin should be
avoided in pregnant women.
After the CDC guidelines
were published, Wiley and colleagues5
compared the success
rates of the various recommended
treatment options, as reported
in clinical trials (Table 3).
Podophyllin, imiquimod, and
cryotherapy all average a similar
efficacy, ranging from 27% to 89%.
Success rates with trichloroacetic
acid range from 63% to 70%. Laser
therapy has the worst outcome of
all treatments—only 23% to 52%
successful—which is why it is not
included in the CDC guidelines; it
is also expensive.
Keep in mind that treatment
may reduce, but does not necessarily
eradicate, infectivity. Also,
the effect of treatment on future
infectivity is unknown. One would
hope that decreasing the size of
MARCH 2005 (SUPPLEMENT) S29
Managing Genital Warts and Cervical HPV Infection
Table 2 – Treatment for genital warts (2002 CDC guidelines)*
Treatment Comments
Patient-applied
Podofilox,† 0.5% solution or gel Patients should apply podofilox solution with a cotton swab, or podofilox gel with
a finger, to visible genital warts twice a day for 3 days, followed by 4 days of no
therapy. This cycle may be repeated, as necessary, for up to 4 cycles.
The total wart area treated should not exceed 10 cm2, and the total volume of
podofilox should be limited to 0.5 mL per day. If possible, the health care provider
should apply the initial treatment to demonstrate the proper technique and to identify
which warts should be treated.
Imiquimod,† 5% cream Patients should apply once daily at bedtime, 3 times a week, for up to 16 weeks.
The treatment area should be washed with soap and water 6 to 10 hours after the
application.
Provider-administered
Podophyllin resin,† 10% - 25%, A small amount should be applied to each wart and allowed to dry. The
in a compound tincture of benzoin treatment can be repeated weekly, if necessary. To avoid the possibility of complications
associated with systemic absorption and toxicity, some specialists
recommend that application be limited to ≤ 0.5 mL of podophyllin or a wart area
of < 10 cm2 per session, and that the preparation should be thoroughly washed
off 1 to 4 hours after application to reduce local irritation.
Trichloroacetic acid or A small amount should be applied only to warts and allowed to dry, at which
bichloroacetic acid, 80% - 90% time a white “frosting” will develop. If an excess amount of acid is applied, the
treated area should be powdered with talc, sodium bicarbonate (ie, baking soda),
or liquid soap preparations to remove unreacted acid. This treatment can be repeated
weekly, if necessary.
Cryotherapy Repeat applications every 1 to 2 weeks.
(liquid nitrogen or cryoprobe)
Surgical removal This can be done by tangential scissor excision, tangential shave excision,
curettage, or electrosurgery.
*Intralesional interferon and laser surgery are alternatives.
†Podofilox, imiquimod, and podophyllin should be avoided during pregnancy, since their safety in this circumstance has not been established. Because
genital warts can proliferate and become friable during pregnancy, many specialists advocate their removal at this time. Human papillomavirus (HPV) types
6 and 11 can cause respiratory papillomatosis in infants and children. The route of transmission (ie, transplacental, perinatal, or postnatal) is not completely
understood. The preventive value of cesarean section is unknown; thus, cesarean delivery should not be performed solely to prevent transmission of HPV
infection to the newborn. Cesarean delivery may be indicated for women with genital warts if the pelvic outlet is obstructed or if vaginal delivery would result
in excessive bleeding.
From Workowski KA, Levine WC. MMWR. 2002.4
the warts and making them disappear would reduce
the potential for HPV transmission, but
good data are missing.
Warts—especially small ones—often regress
spontaneously. In comparison studies of
various treatments, the placebo group usually
has a 30% to 40% regression rate. Patients, however,
might be reluctant to consider the option
of simple observation with no intervention because
of the stigma associated with genital
warts.
Information about treatment is valuable to
share with patients, because it helps them formulate
realistic expectations. Many patients referred
to me have been concerned because they
were not told about the high failure rates with
the current treatments available for genital
warts.
CERVICAL HPV INFECTION
INTERPRETING PAP SMEAR RESULTS
The ALTS trial, which stands for
ASCUS/LSIL (atypical squamous cells of undetermined
significance/low-grade squamous
MARCH 2005 (SUPPLEMENT) S30
Managing Genital Warts and Cervical HPV Infection
Table 3 – Clinical trials for
genital wart treatments
Therapy Success
Podophyllin 45% - 89%
Imiquimod 27% - 54%
Cryotherapy 27% - 88%
Trichloroacetic acid 63% - 70%
Laser therapy 23% - 52%
From Wiley DJ et al. Clin Infect Dis. 2002.5
intraepithelial lesion) Triage Study, was a large
investigation conducted by the National Cancer
Institute to examine an alternative triage
strategy for women with mild abnormalities on
their Pap smears (see “Highlights from the
ALTS trial,” page S21).6 The Bethesda System,
the standard system of terminology used to
classify Pap smear results, has been revised
several times since it was introduced 15 years
ago.
According to both the ALTS trial and the
most recent Bethesda System revisions, abnormal
cytology and cervical dysplasia are almost always
caused by high-risk HPV infection (Table
4).6 (HPV-negative cervical dysplasia and cancer
are rare.) Women with Pap smears containing either
LSIL or atypical squamous cells with HPV
DNA are histologically classified as having cervical
intraepithelial neoplasia grade 2/3. These
women have a 10% risk of developing a precancerous
cervical lesion.
MANAGEMENT
Treatment options
for cervical infection
with HPV are limited
to methods that destroy
cervical dysplasia
(Table 5).7,8 In lieu
of topical or oral medications,
physicians
can use laser treatment
or freezing,
cryotherapy, or removal,
which is called
MARCH 2005 (SUPPLEMENT) S31
Managing Genital Warts and Cervical HPV Infection
Table 4 – New guidelines concerning cervical dysplasia
•Abnormal cytology and cervical dysplasia are almost always caused by
high-risk HPV infection
•Women with LSIL and ASCUS HPV DNA–positive Pap smears have about
a 10% risk of developing precancerous cervical lesions (CIN 2/3)
•Office procedures offer high cure rates for cervical dysplasia
HPV, human papillomavirus; LSIL, low-grade squamous intraepithelial lesion; ASCUS, atypical squamous
cells of undetermined significance; CIN, cervical intraepithelial neoplasia.
From US National Institutes of Health. 2005.6
loop electrosurgical excision procedure. These
interventions effectively cure established cervical
dysplasia.
Other potential treatments, such as
retinoids, have been tried, but with disappointing
results.7 Some small trials have examined
the efficacy of imiquimod applied to the cervix,
but this use is not FDA-approved. Furthermore,
none of the studies have been placebo-controlled
or randomized.8
5-Fluorouracil is a possible treatment option
to prevent recurrence of cervical dysplasia in
women who are HIV-positive.9 However, 5-fluorouracil
is very harsh; some physicians argue
that the treatment is worse than the disease.
Therefore, I do not recommend its use other
than for cervical dysplasia in HIV-positive
women.
DISCUSSION
GENITAL WARTS
Dr Rakel: How soon after sexual contact with an
infected person do genital warts generally appear?
MARCH 2005 (SUPPLEMENT) S32
Managing Genital Warts and Cervical HPV Infection
Table 5 – Medical therapy
for cervical infection
with HPV
•Current therapies emphasize
destruction of lesions
•Potential therapies include
retinoids and imiquimod-type
immune modifiers
•5-Fluorouracil may be useful in
HIV-positive women
HPV, human papillomavirus.
From Alvarez RD et al. Cancer Epidemiol
Biomarkers Prev. 20037; Campagne G et al.
Eur J Obstet Gynecol Reprod Biol. 2003.8
Dr Ault: Investigators at the University of
Washington recently looked at this issue.
They studied the occurrence of genital warts
in association with HPV types 6 and 11.10 Approximately
25% of the women studied developed
a visible lesion within a year or two
of becoming infected with HPV. Now, keep in
mind that women in a study are probably hypersensitive;
they are examining themselves
and are being examined in a study protocol.
So the true incidence figure might be a little
less than 25%, because some of the lesions
detected are probably subclinical.
Dr Rakel: Do internal genital warts cause any
symptoms?
Dr Ault: Intravaginal warts are less common
than external warts, but generally cause no
symptoms. Usually, these internal warts are
diagnosed when the patient has external lesions,
vaginal warts, or an abnormal Pap
smear. Men can certainly have intraurethral
HPV lesions, but I'm less familiar with those
data.
MARCH 2005 (SUPPLEMENT) S33
Highlights from the ALTS trial6 Of the roughly 50 million Pap tests performed each year in
the United States, 3 to 4 million reveal low-grade squamous
intraepithelial lesions (LSIL) or ambiguous cytologic abnormalities,
also known as atypical squamous cells of undetermined
significance (ASCUS). Most of these low-grade
changes regress spontaneously; very few become cancerous. However,
since there is no way to determine which of these lesions are progressive,
women with low- and high-grade lesions are often managed the same way,
with directed colposcopy and biopsy. The ASUCS/LSIL Triage Study
(ALTS) was undertaken to determine whether an effective management
strategy could be developed that would expose women with low-grade lesions
to fewer unnecessary medical tests, reduce their anxiety, and save
money.
ALTS consisted of 3 management strategies:
•Immediate colposcopy of all women.
•Repeated cytology with colposcopy only if a Pap smear showed a highgrade
lesion.
•Human papillomavirus (HPV) testing and repeated cytology plus colposcopy
if the HPV test was positive or colposcopy showed a high-grade lesion.
These are the study findings, to date:
•HPV testing is sensitive in detecting underlying precancerous lesions
among women with a Pap test that shows ASCUS.
•HPV testing is not useful for women with a Pap smear that shows LSIL.
In the study, 82.9% of women with LSIL tested positive for HPV. This high
prevalence of HPV limits the value of HPV testing when it is used to decide
how to manage LSIL.
•Experts' interpretations of Pap tests vary significantly. This needs to be
taken into account when using these interpretations to decide on treatment
and when developing standards of practice.
Managing Genital Warts and Cervical HPV Infection
Dr Rakel: The CDC mentions that genital warts
can occur in the mouth. I doubt that many physicians
think to look for, or would necessarily recognize,
genital warts in this area. Do you think
that's a significant problem?
Dr Ault: This is a topic of great interest, especially
among those who care for HIV-positive patients,
because these patients are more likely to
have oral lesions. There's also some evidence
linking HPV to cancers of the head and neck region.
11 Concerning management of these lesions,
I'd have to defer to more knowledgeable
colleagues. But stay tuned to your favorite medical
journals, because this is going to be an area
of considerable interest.
GENITAL WART
MANAGEMENT
Dr Rakel: Dr Ault, you mentioned that there is no
good evidence to suggest that any one treatment
for genital warts is superior to any other,
with the exception of laser being worse than the
others. Is that correct?
Dr Ault: That's correct. There are very few direct
comparisons of treatment A versus treatment B.
This is totally unlike the situation that exists for
genital herpes.
Dr Rakel: What about viral transmission? Are
there any treatments that are known to be superior
in preventing transmission of HPV?
Dr Ault: There are no data to answer that question,
as far as transmission to uninfected partners
is concerned. However, there is one relatively
recent prospective randomized study
from the Netherlands involving women being
treated for cervical dyspla-sia who encouraged
their husbands to use condoms before the first
follow-up visit.12 The condoms protected these
women from reinfection with HPV and further
cervical dysplasia. But there are very few other
studies, if any, documenting condoms as an effective
method for decreasing transmission.
Dr Rakel: You mentioned recurrence as an issue
in genital wart management. Is recurrence
more common with any particular treatment?
MARCH 2005 (SUPPLEMENT) S34
Managing Genital Warts and Cervical HPV Infection
Dr Ault: I know of no evidence supporting one
treatment over another for preventing wart recurrence.
Imiquimod works by inducing immunity
to genital warts. It would be nice to think
that some sort of long-term immunologic memory
could develop in persons taking imiquimod
that would protect them from acquiring future
lesions. There are limited studies on this topic.
So I think the short answer to this question is
no.
Dr Rakel: Which treatments do you find to be
most cost-effective?
Dr Ault: Patient-applied treatments are the most
cost-effective because the patient can do these at
home. I generally ask my patients to come in for
a brief office visit so that I can teach them how to
use the patient-based treatments correctly. My
patients return in 2 to 4 weeks for a follow-up
visit. This not only ensures that patients are using
the medications correctly but also saves money
by keeping the patient out of the office for most
of the treatments.
Dr Rakel: How do the medications compare in
terms of cost—say, for example, podofilox and
imiquimod?
Dr Ault: A cost-benefit analysis of these 2 medications
has been done.13 I believe that imiquimod
is going to be a smidgen more expensive.
But generally speaking, the cost of these
drugs is similar.
Dr Rakel: I searched the Internet for information
on treating genital warts. All sorts of treatments
came up, many of which I'd never heard of.
They all claim to work not only on genital warts
but also on plantar warts, anal warts, etc. What
do you know about these over-the-counter treatments
for genital warts?
Dr Ault: Many of these treatments fall into the
realm of complementary and alternative medicine.
Most are nutritionally oriented, and they
may not be entirely off base. Evidence from
large population-based studies, for instance, indicates
that a diet deficient in folate or betacarotene
puts women at risk for cervical dys-
MARCH 2005 (SUPPLEMENT) S35
Managing Genital Warts and Cervical HPV Infection
plasia.14 But this does not necessarily make dietary
adjustment a treatment for all these problems.
I don't know of any prospective randomized
trials of these alternative therapies for
warts.
HPV RISK FACTORS
Dr Rakel: Are HPV risk factors the same for men
and women, and if not, how do they differ?
Dr Bocchini: The risk factor for HPV is having
sex. That's it—end of discussion. Beyond that,
it's difficult to identify a group of sexually active
persons who are at special risk, because the
virus is so common.
Dr Rakel: During my Internet search, I came
across a book entitled Fatal Probe: Doctors Infecting
Women. It's all about doctors transmitting
HPV to women by not using sterile instruments
to perform a Pap smear. Do you know about
that?
Dr Weber: I haven't seen that. Practice guidelines
do state that any instrument that touches mucous
membranes needs to be cleaned and then
high-level disinfected. Cleaning removes 4 logs
of viruses or bacteria, and disinfection removes
several more logs. As long as instruments are
sterilized or high-level disinfected between patients,
it seems tremendously unlikely that HPV
could be transmitted through vaginal examinations.
Plus, we change our gloves between patients.
Now in other parts of the world where instruments
cannot be disinfected properly, I
think it would be possible to transmit infection
between patients. But I don't know what the
exact likelihood is, because there are almost no
data on that. ■
REFERENCES:
1. Gerberding JL. Report to Congress. Prevention of genital human papillomavirus
infection. Atlanta: CDC Department of Health and Human Services;
January 2004. Available at: http://www.nccc-online.org/hpv.htm
Accessed February 1, 2005.
2. Castle PE, Wacholder S, Sherman ME, et al. Absolute risk of a subsequent
abnormal Pap among oncogenic human papillomavirus DNA-positive,
cytologically negative women. Cancer. 2002;95:2145-2151.
3. Koutsky L. Epidemiology of genital human papil-lomavirus infection.
Am J Med. 1997;102:3-8.
4. Workowski KA, Levine WC. Sexually transmitted diseases treatment
guidelines—2002. MMWR. 2002;51:1-80.
5. Wiley DJ, Douglas J, Beutner K, et al. External genital warts: diagno-
MARCH 2005 (SUPPLEMENT) S36
Managing Genital Warts and Cervical HPV Infection
sis, treatment, and prevention. Clin Infect Dis. 2002;35(suppl 2):S210-
S214.
6. The ASCUS/LSIL Triage Study for Cervical Cancer (ALTS). National
Cancer Institute Division of Cancer Prevention. US National Institutes of
Health. Available at: http://www3 cancer.gov/prevention/alts. Accessed
February 3, 2005.
7. Alvarez RD, Conner MG, Weiss H, et al. The efficacy of 9-cis-retinoic
acid (aliretinoin) as a chemopreventive agent for cervical dysplasia: results
of a randomized double-blind clinical trial. Cancer Epidemiol Biomarkers
Prev. 2003;12:114-119.
8. Campagne G, Roca M, Martinez A. Successful treatment of a highgrade
intraepithelial neoplasia with imiquimod, with vulvar pemphigus as
a side effect. Eur J Obstet Gynecol Reprod Biol. 2003;109:224-227.
9. Maiman M, Watts DH, Andersen J, et al. Vaginal 5-fluorouracil for
high-grade cervical dysplasia in human immunodeficiency virus infection:
a randomized trial. Obstet Gynecol. 1999;94:954-961.
10. Mao C, Hughes JP, Kiviat N, et al. Clinical findings among young
women with genital human papillomavirus infection. Am J Obstet
Gynecol. 2003;188:677-684.
11. Braakhuis BJ, Snijders PJ, Keune WJ, et al. Genetic patterns in head
and neck cancers that contain or lack transcriptionally active human
papillomavirus. J Natl Cancer Inst. 2004;96:998-1006.
12. Hogewoning CJ, Bleeker MC, van den Brule AJ, et al. Condom use
promotes regression of cervical intraepithelial neoplasia and clearance of
human papillomavirus: a randomized clinical trial. Int J Cancer. 2003;107:
811-816.
13. Langley PC, Tyring SK, Smith MH. The cost effectiveness of patient-
applied versus provider administered intervention strategies for the
treatment of external genital warts. Am J Manag Care. 1999;5:69-77.
14. Hernandez BY, McDuffie K, Wilkens LR, et al. Diet and premalignant
lesions of the cervix: evidence of a protective role for folate, riboflavin,
thiamin, and vitamin B12. Cancer Causes Control. 2003;14:
859-870.
Hope this helps.. sorry it is so long.