External Genital Warts: An Update

Continuing Medical Education 

NEW! CME articles now posted on 

the Web at www.femalepatient.com 

External Genital Warts: 

An Update 

E.J. Mayeaux, Jr, MD 

GOAL 

To review the prevalence and treatment of external warts due to 

human papillomavirus (HPV) in women, with an emphasis on choosing 

the best therapeutic option for each case. 

OBJECTIVES 

1. To explore the high incidence of genital HPV infection and its risk 

factors in women. 

2. To differentiate between low-risk HPV types leading to external genital 

warts and high-risk types associated with cervical cancer. 

3. To review patient-applied and provider-applied treatment options. 

ACCREDITATION 

CONTINUING MEDICAL EDUCATION 

This activity has been planned and implemented in accordance with the 

Essential Areas and Policies of the Accreditation Council for Continuing 

Medical Education (ACCME) through the joint sponsorship of Albert Einstein 

College of Medicine and Quadrant HealthCom Inc. Albert Einstein 

College of Medicine is accredited by the ACCME to provide continuing 

medical education for physicians. 

This activity has been peer reviewed and approved by Brian Cohen, MD, 

professor of clinical OB/GYN, Albert Einstein College of Medicine. Review 

date: October 2007. It is designed for OB/GYNs, primary care physicians, 

and nurse practitioners. 

Albert Einstein College of Medicine designates this educational activity 

for a maximum of 1 AMA PRA Category 1 Credit. Physicians should 

only claim credit commensurate with the extent of their participation in 

the activity. 

Participants who answer 70% or more of the questions correctly will 

obtain credit. To earn credit, see the instructions on page 45 and mail your 

answers according to the instructions on page 46. 

CONFLICT OF INTEREST STATEMENT 

The “Conflict of Interest Disclosure Policy” of Albert Einstein College of 

Medicine requires that authors participating in any CME activity disclose 

to the audience any relationship(s) with a pharmaceutical or equipment 

company. Any author whose disclosed relationships prove to create a 

conflict of interest, with regard to their contribution to the activity, will 

not be permitted to present. 

The Albert Einstein College of Medicine also requires that faculty participating 

in any CME activity disclose to the audience when discussing any 

unlabeled or investigational use of any commercial product, or device, 

not yet approved for use in the United States. 

Dr Mayeaux reports that he is a consultant to Kenwood Therapeutics. 

The disclosure reported by the author presents no conflict of interest to 

the article. The author reports no discussion of off-label use. Dr. Cohen 

reports no conflict of interest. 

The bad news is that there is no 

one treatment that can reliably 

cure external genital warts in all 

women—but the good news 

is that with a wide range of 

topical and surgical options, most 

patients can find a therapy that is 

both tolerable and effective. 

Human papillomavirus (HPV) epithelial 

infections cause a spectrum 

of disease that includes 

nonmalignant condylomata, epithelial 

dysplasias, and cancers. 

As HPV is not reportable, comprehensive 

prevalence data are not available. However, it 

is thought to be one of the most common sexually 

transmitted infections (STIs) in women 

of reproductive age. 

EPIDEMIOLOGY 

The Centers for Disease Control and Prevention 

(CDC) estimates that 5.5 million 

Americans on average acquire genital HPV 

annually. 1 It is thought that 6.2 million new 

HPV infections occurred in 2000 among 

those aged 15 to 44 years, of which 4.6 million 

(74%) occurred among those aged 15 to 

24 years. 2 

E.J. Mayeaux, Jr, MD, is Professor, Department of Family 

Medicine, and Professor, Department of Obstetrics 

and Gynecology, Louisiana State University Health Sciences 

Center, Shreveport, LA. 

38 The Female Patient VOL. 32 DECEMBER 2007

Mayeaux 

Key Points 

• Human papillomavirus (HPV) infection 

can cause a spectrum of diseases ranging 

from nonmalignant skin growths 

to epithelial dysplasias and cancers. 

• HPV infects the nuclei basal layer of 

epithelial cells, where it usually exists 

for about 3 months in a latent state. 

• The majority of anogenital HPV infections 

are subclinical. 

• There are no readily available clinical 

diagnostic methods to identify subclinical 

infections. 

• Imiquimod, podophyllin, and podofilox 

are contraindicated in pregnancy. 

• Interferon therapy is not recommended 

as a primary modality 

because it is inconvenient, ineffective, 

and associated with a high frequency 

of systemic adverse effects. 

• Cesarean delivery should not be performed 

solely to prevent HPV transmission 

to the newborn. 

• The use of a cryoprobe in the vagina 

is not recommended because of the 

risk of vaginal perforation and fistula 

formation. 

• Patients with warts on the anal 

mucosa should undergo digital rectal 

examination or anoscopy to detect 

rectal warts. 

Genital warts in women may develop 

anywhere in the squamous epithelium of the 

lower genital tract, and multiple sites are 

found in about 50% of patients. 3 Although 

such warts are often asymptomatic, some 

patients may experience anogenital pruritus, 

burning, vaginal discharge, and/or bleeding. 

Rarely, dyspareunia or obstruction of the 

urethra, vagina, or rectum may occur. 

Human papillomavirus primarily infects 

the basal layer of epithelial cells. It usually 

exists in a latent state for about 3 months. 

The virus replicates in dividing epithelial 

cells, eventually producing genital warts. 

The majority of anogenital HPV infections 

are subclinical, and are identified only by 

whitening on application of 5% acetic acid 

(acetowhite effect), or a finding of HPV 

DNA without associated epithelial abnormalities. 

There are no readily available, 

specific clinical diagnostic methods for 

identifying subclinical infections. 

TRANSMISSION 

Prior or coexisting HPV 

infection does not affect 

the risk of acquiring new 

HPV infections. Risk is most 

strongly associated with sex 

with a new partner—ie, 

exposure to new strains. 4 

Although vaginal intercourse 

is the predominant mode of 

transmission, HPV may also 

be transmitted through nonpenetrative 

sexual contact (eg, 

in virgins). 4 

Contrary to traditional 

thinking, male condom use 

can reduce the risk of maleto-female 

transmission 

by 70%. 5 Other risk factors 

include current smoking 

and oral contraceptive 

(OC) use, which may be 

surrogate markers for other 

sexual behaviors. 4 Use of the quadrivalent 

HPV vaccine may decrease the risk of external 

HPV lesions when administered prior 

to exposure. 

VIRAL TYPES 

The majority 

of anogenital 

HPV infections 

are subclinical, 

and are identified 

only by whitening 

on application 

of 5% acetic 

acid (acetowhite 

effect), or a 

finding of HPV 

DNA without 

associated 

epithelial 

abnormalities. 

More than 30 HPV types can infect the 

human genital area. 6 Anogenital HPV types 

are subdivided based on oncogenic risk. 

High-risk types (eg, 16, 18, 31, 33, 35) 

are strongly associated with cervical neoplasia. 

They usually cause flat lesions that are 

only identified on Papanicolaou smear or 

The Female Patient VOL. 32 DECEMBER 2007 39

CME 

External Genital Warts 

application of acetic acid. Persistent infection 

with high-risk HPV types is the most 

important risk factor for cervical neoplasia. 

More than 90% of anogenital warts result 

from low-risk HPV types 6 or 11. Some 

66% of affected individuals have a transient 

infection that is subsequently cleared without 

treatment. 7 Among adolescent women, 

the average HPV infection lasts a median of 

5.6 months, although high-risk HPV types 

tend to be more persistent. 8 

Clinical warts may present as cauliflower-like, 

flesh- to pink-colored lesions 

(condylomata acuminate); dome-shaped, 

flesh-colored, smooth papules; flat papules; 

or keratotic warts that may be confused 

with cancer. 9,10 Typical exophytic condylomata 

are more likely to occur on keratinized 

skin. Multiple lesions may coalesce, producing 

large condylomata. 

Genital HPV infections can be associated 

with warts in the urethra, meatus, cervix, 

vagina, anus, and/or oral cavity. Cervical 

warts are especially worrisome, as they may 

lead to high-grade dysplasia or cancers. 9 

Anal infection is also troubling, as intromissive 

anal intercourse confers an increased 

risk of anal dysplasias and cancer. 

Coding for Benign 


Philip N. Eskew, Jr, MD 

When patients present with external genital warts 

as a chief complaint, the physician should apply the 

following codes from the International Classification of 

Diseases, 9th ed (ICD-9). 

• 078—Other diseases due to viruses and chlamydia 

078.0—Molluscum contagiosum 

078.1— Viral warts; viral warts due to human papillomavirus 

(HPV) 

078.10— Viral warts, unspecified; condyloma not 

otherwise specified (NOS); verruca NOS; 

verruca vulgaris; warts (infectious) 

078.11—Condyloma acuminatum 

078.19— Other specified genital viral warts; genital 

warts NOS; verruca; verruca plana; 

verruca plantaris 

Therapy is covered by Current Procedural Terminology 

(CPT) codes, as opposed to evaluation-andmanagement 

codes: 

• 56501— Destruction of lesion(s), vulva; simple 

(eg, laser surgery, electrosurgery, cryosurgery, 

chemosurgery) 

• 56515—extensive (same modalities) 

• 56820—Vulvar colposcopy 

• 56821—Colposcopy with biopsy 

• 57061— Destruction of vaginal lesion(s); 

simple (eg, laser surgery, electrosurgery, 

cryosurgery, chemosurgery) 

• 57065—extensive (same modalities) 

Preventive vaccination involves age-appropriate 

physical evaluation, which need not include a pelvic 

examination. Applicable CPT codes are: 

• 99384— Initial comprehensive preventive medicine; 

adolescent (aged 12 through 17 

years) 

• 99385— Initial comprehensive preventive medicine, 

18-39 years 

Codes for vaccination alone are: 

• 90649— HPV vaccine, types 6, 11, 16, 18 (quadrivalent); 

3-dose schedule for intramuscular 

use 

• 90471— Immunization administration (includes 

percutaneous, intradermal, subcutaneous, 

or intramuscular); one vaccine 

(single or combination vaccine/toxoid) 

The ICD-9 codes are: 

• V04— Prophylactic vaccination; inoculation against 

certain diseases 

V04.89—Other viral diseases 

Philip N. Eskew, Jr, MD, is Past Member, Current 

Procedural Terminology (CPT) Editorial Panel; Past 

Member, CPT Advisory Committee; Past chair, 

ACOG Coding and Nomenclature Committee; 

and Instructor, CPT coding and documentation 

courses and seminars. 


Mayeaux 

TABLE. Centers for Disease Control and Prevention Recommended Regimens 

for Condylomata Acuminata 

Location Treatment Comments 

External genital warts Podofilox 0.5% solution Imiquimod, podophyllin, and 

Imiquimod 5% cream 

podofilox are contraindicated in 

Cryotherapy 

pregnancy 

Podophyllin resin 10%-25% 

in tincture of benzoin 

Trichloroacetic acid (TCA) or 

bichloroacetic acid (BCA) 80%-90% 

Surgical removal 

External genital warts, Sinecatechins 15%* Systemic interferon is not effective 

alternative regimens Laser surgery and not recommended as a primary 

Intralesional interferon 

modality 

Extensive genital warts Imiquimod 5% cream* These modalities can be applied to 

Laser surgery* 

large areas to reduce or treat 

Sinecatechins 15%* 

extensive lesions. Imiquimod, 

podophyllin, and podofilox 

are contraindicated in pregnancy 

Warts during pregnancy Cryotherapy with liquid nitrogen 

or cryoprobe 

TCA or BCA 80%-90% 


Cesarean delivery should not be 

performed solely to prevent HPV 

transmission to the newborn 

Vaginal warts Cryotherapy with liquid nitrogen The use of a cryoprobe in the vagina 


is not recommended because of the 

risk for vaginal perforation and 

fistula formation 

Urethral meatus warts Cryotherapy with liquid nitrogen Some specialists recommend 

Podophyllin 10%-25% in 

podofilox and imiquimod in these 

tincture of benzoin 

patients, but the data are limited 

Anal warts Cryotherapy with liquid nitrogen Also inspect for rectal warts using 


digital examination or anoscopy 


*Author’s recommendations. 

DIAGNOSIS 

There are no specific screening tests for external 

HPV lesions, which are usually identified 

visually. Although usually unnecessary, 

detection of flat HPV lesions can be enhanced 

with the use of a colposcope or hand lens and 

5 minutes’ application of 5% acetic acid. A 

biopsy should be obtained from any lesion 

that has an atypical appearance, is pigmented, 

or is resistant to therapy. Histologic examination 

of HPV lesions usually demonstrates 

koilocytic atypia, including enlarged cells with 

perinuclear halos and hyperchromatic nuclei. 

Tests for HPV DNA typing are not indicated 

for external lesions. 11 


CME 


The differential diagnosis for HPV lesions 

includes condyloma latum (syphilis), which 

presents as smooth, broad-based papules. 

Benign skin lesions such as seborrheic keratoses, 

nevi, microglandular hyperplasia, and 

hymenal remnants may occasionally be confused 

with condylomata. Molluscum contagiosum 

and herpetic lesions must be excluded 

as well. 

More serious HPV 

mimics include bowenoid 

A higher index 

of suspicion for 

malignancy should 

be maintained for 

immunocompromised 

patients, 

atypical-appearing 

lesions, lesions 

refractory 

to treatment, and 

pigmented lesions. 

papulosis, malignant 

melanoma, and Buschke- 

Lowenstein tumor. 11 As 

squamous cell carcinomas 

may arise in or resemble 

genital warts, biopsy is 

recommended. It is very 

important to distinguish 

vulvar papillomatosis 

(a normal variant) from 

condylomata acuminata, 

because inappropriate 

treatment may produce 

chronic pelvic pain. Warts, 

dysplasia, and cancer all 

may be similar in appearance. 

A higher index of 

suspicion for malignancy 

should be maintained 

for immunocompromised patients, atypical-appearing 

lesions, lesions refractory to 

treatment, and pigmented lesions. A biopsy 

should be obtained in these cases, but again, 

HPV typing is generally not useful. 12 

THERAPY 

The CDC recommends that treatment be 

guided by patient preference (Table). 6 None 

of the available treatments is superior to the 

others, and no single treatment is ideal for all 

patients or all warts. Practitioners should be 

familiar with at least one patient-applied treatment 

and one provider-applied therapy. 6 No 

data suggest specific treatment modalities in 

the setting of concomitant human immunodeficiency 

virus (HIV) infection. 

Patient-applied Therapies 

Imiquimod.—Imiquimod/imidazoquinolinamine, 

5% cream, is an immune modifier 

that induces cytokines. 13,14 It has almost 

no systemic side effects, and is classified 

as pregnancy category C. It may also help 

to induce “immune memory” and prevent 

future recurrences. 15 It is indicated for use 

on external HPV infections, and contraindicated 

for occluded mucous membranes (eg, 

vagina, urethra, perianal area, cervix). Condoms 

and diaphragms should not be used 

during treatment, as imiquimod may damage 

latex. The patient should apply it three 

times a week, every other day, for up to 16 

weeks. The affected area should be washed 

with mild soap and water 6 to 10 hours after 

application. Side effects include erythema, 

erosion, itching, skin flaking, and edema. 

Clearance occurs within 16 weeks in 37% to 

54% of patients, with recurrences noted in 

13% to 19%. 9 

Podofilox.—Podofilox/podophyllotoxin, 

0.5% gel, solution, or cream, is the purified 

active component of podophyllin. It is 

contraindicated for use on occluded mucous 

membranes and during pregnancy. Podofilox 

is applied twice daily for 3 consecutive days 

followed by 4 consecutive days of no therapy 

(7 days total), repeated for a maximum of 4 

weeks. Trials have shown that 45% to 77% 

of patients attained clearance within 4 to 6 

weeks. Side effects include inflammation, 

irritation, erosion, burning, pain, and itching. 

Recurrences have been reported in 4% to 

38% of patients. Effective contraception such 

as condoms/diaphragms for women of 

childbearing age is advised until the warts 

are cleared. 9 

Sinecatechins.—Sinecatechins, 15% ointment, 

is a new botanical treatment derived 

from green tea, 16 and is FDA-approved for 

the treatment of external genital and perianal 

warts in patients aged 18 years or 

older. Catechins have shown chemopreventive 

properties against various cancers, 16 as 

well as antiangiogenic and anti-HPV activity 

and inhibition of tumor invasion. The ointment 

is applied by the patient three times 

a day for 16 weeks. Partial or total clearance 

has been reported in more than 77% 

of patients. Local skin reactions are mild to 

moderate, with rare instances of pain and 

inflammation. 17, 18 Sinecatechins is classified 

as pregnancy category C. 


Mayeaux 

Provider-administered Therapies 

Surgical Excision.—Surgical excision directly 

removes wart tissue. Studies demonstrate clearance 

in 35% to 72% of patients, with recurrence 

in 19% to 29% at 1 year. 9 

The loop electrosurgical excisional procedure 

(LEEP) is indicated for perineal condylomata; 

in skilled hands, it may be used for 

anal verge lesions. Late bleeding has been 

reported in 4% of patients, and can usually 

be controlled with Monsel’s solution or fulguration. 

In rare cases of infection, topical 

antibiotics can be applied. Hypopigmentation 

and hypertrophic scars are also rarely 

reported. Success rates range from 90% 

to 96%. 11 

Cryotherapy.—Cryotherapy with liquid 

nitrogen, nitrous oxide, or carbon dioxide 

cryoprobe is especially useful for discrete 

lesions. It is probably the safest therapy 

for use during pregnancy. The treated tissues 

slough after several days, followed by 

inflammation and then healing. Therapy is 

repeated every 1 to 2 weeks if necessary. 

Common complications include pain and 

local infection. The success rate is 71% to 

79%, and recurrence rates are 38% to 73% 

by 6 months. 9 

Trichloroacetic/bichloroacetic (dichloroacetic) 

Acid.—Topical acid is also safe for use 

during pregnancy, but should not be applied 

to the cervix or urinary meatus. Trichloroacetic 

acid (TCA) must be compounded at 

a pharmacy, but bichloroacetic acid (BCA) 

can be obtained in a standard preparation. A 

50% TCA solution is applied in a thin layer 

with a cotton-tipped applicator three times 

a week for a maximum of 4 weeks, or an 

80% solution can be applied twice a day for 

3 consecutive days per week for a maximum 

of 4 weeks. BCA may be applied to the wart 

weekly. Bicarbonate, talc, or soap and water 

may be used to neutralize any excess acid. 11 

Complications include ulceration, pain, and 

damage to adjacent skin. Response rates are 

50% to 81%, and recurrence rates are high 

but undefined. 9,11 

Podophyllin.—A solution of 10% to 25% 

podophyllin in tincture of benzoin is best 

suited for small external lesions. Its use in 

pregnancy is contraindicated, and it is not 

recommended for use in occluded mucous 

membranes. Systemic reactions and death 

can occur when application is extensive/prolonged 

or involves the mucous membranes. 

Adverse reactions include nausea, vomiting, 

fever, confusion, coma, renal failure, ileus, 

and leucopenia. Podophyllin is applied by 

trained personnel once or twice weekly for a 

maximum of 4 weeks. The solution should be 

washed off 1 to 4 hours after the first application, 

and 4 to 6 hours after subsequent applications. 

Complications include local erosion, 

ulceration, and scarring, as well as irritation 

of adjacent skin. Success rates range from 

20% to 77%, with recurrence rates of 23% 

19, 20 

to 65%. 

CONCLUSION 

External genital HPV infections 

are common in sexually 

active individuals. 

Although such infections 

are low-risk with regard to 

subsequent cancer, considerable 

psychological distress 

and social disruption can 

occur. Selection of treatment 

depends on the number, 

size, and location of 

lesions, as well as patient preference and the 

physician’s training. There is little evidence 

that one treatment option is more effective 

than any other. 

REFERENCES 

There is 

little evidence 

that one 

treatment option 

is more effective 

than any other. 

1. Revzina NV, DiClemente RJ. Prevalence and 

incidence of human papillomavirus infection in 

women in the USA: a systematic review. Int J STD 

AIDS. 2005;16(8):528-537. 

2. Weinstock H, Berman S, Cates W Jr. Sexually 

transmitted diseases among American youth: incidence 

and prevalence estimates, 2000. Perspect 

Sex Reprod Health. 2004;36(1):6-10. 

3. Chuang TY, Perry HO, Kurland LT, Ilstrup DM. 

Condyloma acuminatum in Rochester, Minn., 

1950-1978. I. Epidemiology and clinical features. 

Arch Dermatol. 1984;120(4):469-475. 

4. Winer RL, Lee SK, Hughes JP, Adams DE, Kiviat 

NB, Koutsky LA. Genital human papillomavirus 

infection: incidence and risk factors in a cohort of 

female university students. Am J Epidemiol. 2003; 

157(3):218-226. 

5. Winer RL, Hughes JP, Feng Q, et al. Condom 

use and the risk of genital human papillomavirus 


CME 


infection in young women. N Engl J Med. 2006; 

354(25):2645-2654. 

6. Centers for Disease Control and Prevention, 

Workowski KA, Berman SM. Sexually transmitted 

diseases treatment guidelines, 2006. Genital warts. 

MMWR Recomm Rep. 2006;55(RR-11):62-67. 

7. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk 

RD. Natural history of cervicovaginal papillomavirus 

infection in young women. N Engl J Med. 

1998;338(7):423-428. 

8. Brown DR, Shew ML, Qadadri B, et al. A longitudinal 

study of genital human papillomavirus 

infection in a cohort of closely followed adolescent 

women. J Infect Dis. 2005;191(2):182-192. 

9. Wiley DJ, Douglas JM, Beutner K, et al. External 

genital warts: diagnosis, treatment and prevention. 

Clin Infect Dis. 2002;35(Suppl 2):S210-S224. 

10. Von Krogh G, Lacey CJ, Gross G, Barrasso R, 

Schneider A. European course on HPV associated 

pathology: guidelines for primary care physicians 

for the diagnosis and management of anogenital 

warts. Sex Transm Inf. 2000;76(3):162-168. 

11. Mayeaux EJ, Harper MB, Barksdale W, Pope J. 

Noncervical human papillomavirus genital infections. 

Am Fam Physician. 1995;52(4):1137-1146. 

12. Gunter J. Genital and perianal warts: new treatment 

opportunities for human papillomavirus infection. 

Am J Obstet Gynecol. 2003;189(3 Suppl):S3-S11. 

13. Edwards L, Ferenczy A, Eron L, et al. Self-administered 

topical 5% imiquimod cream for external 

anogenital warts. HPV Study Group. Human papillomavirus. 

Arch Dermatol. 1998;134(1):25-30. 

14 Megyeri K, Au WC, Rosztoczy I, et al. Stimulation 

of interferon and cytokine gene expression by 

imiquimod and stimulation of Sendai virus utilize 

similar signal induction pathways. Mol Cell Biol. 

1995;15(4):2207-2218. 

15. Ferenczy A. Treatment of external genital warts. 

J Lower Genital Tract Dis. 2000;4(3):128-134. 

16. Beti H, Orasan R, Meyer KG, et al. Polyphenon-E 

ointment in the treatment of external genital wartsfirst 

phase III results. J European Acad Dermatol 

Vener 2004; 18(Suppl 2): P09.30, p.401. 

17. Beutner K, Tatti S, Rodriguez Donando A, et al. 

Polyhenon E ointment in the treatment of anogenital 

warts- completing phase 3 study results. 

Abstracts of the 22nd International Papillomavirus 

Conference 2005 Vancouver, Canada, Abstract 

z-104, p. 107. 

18. Stockfleth E, Beutner K, Thielert C, et al. Polyphenon 

E ointment in the treatment of external 

genital warts. J European Acad Dermatol Vener 

2005;19(Suppl 2): FC06.8, p.116. 

19. Greene I. Therapy for genital warts. Dermatol Clin 

1992; 10:253-67. 

20. Brown DR, Fife KH. Human papillomavirus infections 

of the genital tract. Med Clin North Am 

1990; 74:1455-85. 

DISCLAIMER 

The opinions expressed herein are those of the author 

and do not necessarily represent the views of the sponsor 

or the publisher. Please review complete prescribing 

information of specific drugs or combination of 

drugs, including indications, contraindications, warnings 

and adverse effects before administering pharmacologic 

therapy to patients. 

HPV RESOURCE 

A new, 36-page full-color brochure 

on HPV is available from the CDC. 

Titled, “Human Papillomavirus: 

HPV Information for Clinicians,” 

the brochure can be downloaded 

from the web at 

www.cdc.gov/std/HPV/common-clinicians/ClinicianBro-fp.pdf.

External Genital Warts: An Update

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