Version May 2024
INTRODUCTION — Human papillomavirus (HPV) is a common cause of cutaneous and mucosal infection. Condylomata acuminata (CA; singular: condyloma acuminatum), also known as anogenital warts, are manifestations of HPV infection that occur in a subset of individuals with anogenital HPV infection. External CA typically manifest as soft papules or plaques on the external genitalia, perianal skin, perineum, or groin (picture 1A-H). HPV types 6 and/or 11 are detected in most cases of CA.
The etiology, epidemiology, clinical features, and diagnosis of external CA will be reviewed here. Greater detail on HPV infection and discussions of pediatric CA, treatment of CA, and the relationship between HPV infection and cancer are provided separately. (See "Human papillomavirus infections: Epidemiology and disease associations" and "Condylomata acuminata (anogenital warts) in children" and "Condylomata acuminata (anogenital warts): Treatment of vulvar and vaginal warts" and "Condylomata acuminata (anogenital warts): Management of external condylomata acuminata in adult males" and "Virology of human papillomavirus infections and the link to cancer".)
ETIOLOGY — Human papillomavirus (HPV) is a group of nonenveloped, double-stranded DNA viruses belonging to the family Papillomaviridae. Investigators have identified 200 types of HPV, more than 40 of which can be transmitted through sexual contact and infect the anogenital region [1,2]. The virology of HPV is reviewed in detail separately. (See "Human papillomavirus infections: Epidemiology and disease associations", section on 'Microbiology'.)
Genital HPV types are divided into low-risk and high-risk types based upon associated risk for cancer in any body area. The low-risk types HPV 6 and/or HPV 11 are detected in around 90 percent of anogenital warts, although coinfection with other low-risk or high-risk types of HPV is common. For example, in an analysis of 8800 women in the placebo arms of two randomized trials assessing the efficacy of a quadrivalent vaccine, 298 (3 percent) developed anogenital warts, and HPV 6 and/or HPV 11 were detected in 447 of 520 examined warts (86 percent) [3]. High-risk HPV types, such as HPV 16, 18, 52, and 56, were detected in 191 warts (31 percent). (See "Virology of human papillomavirus infections and the link to cancer", section on 'HPV Genotypes and risk of cancer'.)
TRANSMISSION — Human papillomavirus (HPV) is transmitted through contact with infected skin or mucosa. The virus invades the cells of the epidermal basal layer through microabrasions. Anogenital HPV infection is almost always acquired through sexual contact. Warts are not required for transmission but are highly infectious because of their high viral load.
Once acquired, HPV infection can enter a latent phase without signs or symptoms. In patients who develop CA, the usual incubation period is three weeks to eight months. In a cohort study of 603 female university students that identified 31 students who developed anogenital warts after incident HPV infection, the median time to detection of anogenital warts after detection of HPV 6 or HPV 11 was 2.9 months [4].
The risk for development of CA after incident HPV-6 or HPV-11 infection appears to be high. In a cohort study of 473 18- to 21-year-old sexually active men who underwent triannual genital examinations, the cumulative incidence of genital wart development over 24 months was 58 percent (95% CI 38 to 79 percent) among the 46 men with incident HPV-6 or HPV-11 infection [5]. The cohort study of 603 female university students also found a high rate of genital wart development; triannual gynecologic examinations detected a 36-month cumulative incidence for genital warts among women with incident HPV-6 or HPV-11 infection of 64 percent (95% CI 51 to 77 percent) [4].
Vertical transmission of HPV from pregnant women with anogenital warts to the fetus is possible and is reviewed separately. (See "Condylomata acuminata (anogenital warts): Treatment of vulvar and vaginal warts", section on 'Vertical transmission and mode of delivery'.)
EPIDEMIOLOGY — Human papillomavirus (HPV) infection is the most common sexually transmitted disease in the world [6]. At least 75 percent of sexually active adults in the United States have been infected with at least one genital HPV type at some time [7-16]. The estimated prevalence rate of HPV anogenital infection in the United States adult population is 10 to 20 percent among unvaccinated individuals [7-16]. HPV infection rates are trending downward in countries where HPV vaccination has been implemented [17-19]. Greater detail on the epidemiology of HPV infection is provided separately. (See "Human papillomavirus infections: Epidemiology and disease associations" and "Human papillomavirus infections: Epidemiology and disease associations", section on 'Impact of HPV vaccine'.)
CA is relatively common. A systematic review of international studies reporting incidence and prevalence of CA in adults found annual incidence rates ranging from 160 to 289 per 100,000 individuals [7]. Reported prevalence rates based upon reviews of administrative databases or medical charts and prospective physician reports ranged from 0.13 to 0.56 percent, and reported prevalence rates based upon genital examinations ranged from 0.2 to 5.1 percent. CA is most common in young adults [20].
RISK FACTORS — Sexual activity, including merely skin to skin contact, is the primary risk factor for anogenital human papillomavirus (HPV) infection. The relationship between sexual activity and HPV infection is reviewed separately.
Immunosuppression is associated with the development of larger and more treatment-resistant CA, higher rates of recurrence, and malignant transformation of anogenital warts [21]. As examples, CA in patients with human immunodeficiency virus (HIV) infection, receiving immunosuppressive therapy, or with diabetes [22] can be challenging to treat. Extensive anogenital warts have been reported in patients with human T-lymphotropic virus type I (HTLV-I) infection [23] and in association with the immune reconstitution inflammatory syndrome [24].
Smoking has been associated with increased risk for CA [25-27]. Risk for CA may increase as the number of cigarettes smoked per day and number of pack-years increase [25]. Whether this is causal or correlation is not clear.
Male circumcision may reduce risk for HPV infection. The impact of male circumcision on risk for sexually transmitted infections is reviewed separately. (See "Prevention of sexually transmitted infections", section on 'Male circumcision'.)
CLINICAL MANIFESTATIONS — External anogenital warts are typically found on the vulva, penis, groin, perineum, anal skin, perianal skin, and/or suprapubic skin [28]. The CA can be single or multiple, flat, dome-shaped, cauliflower-shaped, filiform, fungating, pedunculated, cerebriform, plaque-like, smooth (especially on the penile shaft), verrucous, or lobulated (picture 1A-H). The color varies; warts may be white, skin-colored, erythematous (pink or red), violaceous, brown, or hyperpigmented. Anogenital warts are usually soft to palpation and can range from 1 mm to more than several centimeters in diameter. The warts are typically asymptomatic but can occasionally be pruritic.
External anogenital warts can be accompanied by involvement of the cervix or urethra (picture 2) [29]. CA may also develop in the anal canal, typically manifesting as small flat-topped to globoid-shaped papules, usually distal to the dentate line [30].
Extensive CA can cause marked disfigurement of the anogenital area and may interfere with defecation. Urethral warts may result in urethral bleeding (including bleeding during coitus) and, in rare cases, urinary obstruction [31,32].
The psychologic effects of CA should not be discounted. Patients with CA often experience stigmatization, social isolation, anxiety, depression, angst, and guilt, as well as concerns about future fertility and cancer risk [33,34]. The emotional impact on sexual partners is also substantial and can lead to conflict and relationship termination [35].
DERMOSCOPY — The dermoscopic features of CA have been described based upon morphologic patterns and vascular characteristics [36]. The morphologic features may vary from a knob-like pattern to a finger-like pattern, and the vascular pattern can be dotted to glomerular. There is always papillomatosis.
CLINICAL COURSE — After their initial appearance, anogenital warts may increase in number and size or regress spontaneously. It is estimated that approximately one-third of anogenital warts regress without treatment within four months [37,38].
Human papillomavirus (HPV) infection may persist despite resolution of visible warts and may result in wart recurrence. Recurrence rates are not well defined. Mechanical irritation, wounding, immunosuppression, inflammation, and other extracellular influences affect viral copy number in the latently infected cells and may predispose to reappearance [39].
ASSOCIATION WITH MALIGNANCY — Although human papillomavirus (HPV) 6 and HPV 11, low-risk HPV types, are responsible for most cases of CA, coinfection with high-risk HPV genotypes linked to anogenital and head and neck cancers is common [3]. A Danish study of 15,155 men and 32,933 women diagnosed with CA between 1978 and 2008 found increased risk for anogenital cancers and head and neck cancers, including anal (standardized incidence ratio [SIR] for men, 21.5; SIR for women, 7.8), vulvar (SIR 14.8), vaginal (SIR 5.9), cervical (SIR 1.5), penile (SIR 8.2), and head and neck cancers (SIR 2.8) [40]. The SIR for subsites of head and neck cancer with confirmed HPV association was 3.5 for men and 4.8 for women. (See "Virology of human papillomavirus infections and the link to cancer", section on 'HPV Genotypes and risk of cancer'.)
Malignant degeneration of anogenital warts can occur but is rare. Malignant transformation is more likely to occur in immunosuppressed individuals [21,41].
HISTOPATHOLOGY — The primary histologic features of CA evident with hematoxylin-eosin (H&E) staining are papillomatosis, koilocytosis (multiple vacuolated cells with enlarged, irregular nuclei), and vascular distension (picture 3) [42]. Coarse keratohyaline granules may also be present. Flat anogenital warts show acanthosis in the epidermal spinous layer.
Additionally, the use of MIB1, an antibody targeting cell proliferation protein Ki-67, highlights cells infected with human papillomavirus (HPV) [43].
DIAGNOSIS — In most cases, clinicians familiar with the clinical manifestations of CA can diagnose CA based upon the physical examination. Examination with a bright light or a dermatoscope is helpful. (See "Overview of dermoscopy".)
Physical examination — Findings that suggest CA are single or multiple soft, smooth or papillated papules or plaques limited to the anogenital area. Select features that may suggest other disorders include umbilicated papules (molluscum contagiosum (picture 4)), keratotic plugs and hyperpigmentation (seborrheic keratosis (picture 5)), yellowish color (Fordyce spots (picture 6)), violaceous color (lichen planus (picture 7)), pinpoint papules (lichen nitidus (picture 8)), moist surface (condylomata lata of syphilis (picture 9)), and ulceration (other infection or malignancy). (See 'Differential diagnosis' below.)
Patients may have simultaneous infection of the genital area and perianal skin. Therefore, all areas of predilection for CA (lower abdomen, vulva, penis, perineum, perianal skin, mons pubis, and crural folds) should be examined. Of note, uncircumcised foreskin or hair can obscure warts, warranting more careful examination.
The physical examination should also include an assessment for other clinical signs that may suggest coexisting sexually transmitted diseases, such as ulcerations, vesicles, or discharge. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Clinical features' and "Clinical manifestations and diagnosis of Chlamydia trachomatis infections" and "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents" and "Syphilis: Screening and diagnostic testing".)
Biopsy — If there is uncertainty about the diagnosis, a biopsy should be performed. A shave or scissor procedure to remove a suspected wart or sample a large suspected wart is usually sufficient. (See "Skin biopsy techniques", section on 'Shave biopsy' and 'Histopathology' above.)
In addition, a biopsy to confirm the diagnosis and rule out malignancy is beneficial for CA that appear refractory to treatment, especially in immunosuppressed patients [44]. Other indications for biopsy include atypical features (eg, induration, fixation to underlying structures, bleeding, atypical pigmentation, or ulceration) [44].
Human papillomavirus (HPV) testing of warts is not routinely indicated for diagnosis. Testing does not confirm the diagnosis and does not influence management of CA [44].
Application of acetic acid has a low positive predictive value for diagnosing external anogenital warts [45,46]. Therefore, use cannot be advocated for diagnosis [47]. False-positive results commonly occur, resulting from parakeratosis in other pathologic processes (eg, psoriasis, candidiasis, squamous papilloma, healing epithelium, and lichen planus). The pain associated with acetic acid examination is another reason to avoid its use.
ADDITIONAL EVALUATION — The evaluation of patients with CA should include a review of the need for testing for other sexually transmitted diseases and concomitant internal involvement.
The assessment of sexual partners of patients with CA is reviewed separately. (See "Condylomata acuminata (anogenital warts): Treatment of vulvar and vaginal warts", section on 'Management of sex partners' and "Condylomata acuminata (anogenital warts): Management of external condylomata acuminata in adult males".)
Other sexually transmitted diseases — Testing for other sexually transmitted diseases is recommended [44,48], particularly for patients at risk for other sexually transmitted diseases, such as individuals with multiple sexual partners. In a retrospective study of 1015 new patients diagnosed with anogenital warts at a sexual health center in Australia between 2002 and 2007, approximately 5 percent also had chlamydia or gonorrhea [49]. (See "Screening for sexually transmitted infections" and "Sexually transmitted infections: Issues specific to adolescents", section on 'Dermatologic syndromes'.)
Internal involvement — Patients with external anogenital warts can have concomitant involvement of the anus, urethra, vagina, cervix, or rectum:
●Urethral involvement – Urethral CA occasionally occur and are most commonly found on the external meatus and distal urethra (picture 2) but may also develop in more proximal sites within the urethra [50]. Bladder obstruction is a rare complication [31,32]. The physical examination should include a visual assessment of the urethral orifice. Patients with warts at this site should be referred to a urologist for further evaluation.
●Vaginal and cervical involvement – Women with genital warts should undergo speculum examination to evaluate for vaginal or cervical involvement. Cervical cancer screening should be performed according to standard guidelines. (See "Condylomata acuminata (anogenital warts): Treatment of vulvar and vaginal warts", section on 'Cancer screening'.)
●Anal canal involvement – Clinicians should have a low threshold for performing anoscopy or referring patients to a gastroenterologist or colorectal surgeon for anoscopy to examine the anal canal. We suggest performing or referring patients for anoscopy whenever warts are present in the visible anal area.
DIFFERENTIAL DIAGNOSIS — In general, a trained health care provider performing a careful physical examination can distinguish CA from other disorders. In cases where the diagnosis is uncertain, a biopsy is helpful for confirming the diagnosis. (See 'Diagnosis' above.)
The differential diagnosis of CA includes common benign papular cutaneous conditions, such as seborrheic keratosis (picture 5), acrochordon (picture 10), pearly penile papules (picture 11), squamous papilloma, and Fordyce spots (picture 6).
In addition, sexually transmitted diseases such as molluscum contagiosum (picture 4), which typically manifests as umbilicated small papules, and condyloma latum of syphilis (picture 9), which typically manifests as single or multiple moist, gray-white papules or plaques, may enter the differential diagnosis. Inflammatory conditions, such as lichen nitidus and papulosquamous lesions of lichen planus may also be included. Lichen nitidus most commonly manifests as multiple flat-topped, pinhead-sized papules on the penis (picture 8). Papulosquamous lichen planus often manifests as violaceous polygonal or annular pruritic papules (picture 7).
Premalignant and malignant disorders, such as bowenoid papulosis and giant condyloma acuminatum (Buschke-Löwenstein tumor) may enter the differential diagnosis. Bowenoid papulosis is a premalignant focal epidermal dysplasia that usually manifests as multiple red to brown papules on the genitals and is most often associated with human papillomavirus (HPV) 16 (picture 12A-B). Giant condyloma acuminatum is a rare low-grade form of squamous cell carcinoma associated with HPV 6 and 11 that most commonly manifests on the glans penis, foreskin, and perianal regions (picture 13). Giant condyloma acuminatum can manifest in large cauliflower shapes and can form fistulas and/or abscesses with local neoplastic invasion.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sexually transmitted infections".)
SUMMARY AND RECOMMENDATIONS
●Etiology – Condylomata acuminata (CA), also known as anogenital warts, are a manifestation of anogenital human papillomavirus (HPV) infection. HPV 6 and HPV 11 are responsible for most cases of CA. Only a subset of anogenital HPV infections lead to CA. (See 'Etiology' above.)
●Transmission and risk factors – Anogenital HPV infection is almost always acquired through sexual activity. Immunosuppression increases risk for CA and may make CA more difficult to treat. (See 'Transmission' above and 'Risk factors' above.)
●Clinical manifestations – CA usually develops on the vulva, penis, groin, perineum, perianal skin, and/or suprapubic skin. The warts may be flat, dome-shaped, cauliflower-shaped, filiform, fungating, pedunculated, cerebriform, plaque-like, smooth (especially on the penile shaft), verrucous, or lobulated (picture 1A-H). The color is usually white, skin-colored, erythematous, violaceous, or brown. The size of individual warts ranges from 1 mm to more than several centimeters in diameter. Patients may have associated urethral, vaginal, cervical, or anal canal involvement. (See 'Clinical manifestations' above.)
●Clinical course – The usual incubation period for clinical warts is three weeks to eight months. After initial appearance, warts may continue to increase in number and size or may spontaneously regress. Up to 30 percent of warts spontaneously resolve within four months. Resolution of visible warts does not guarantee eradication of HPV infection. (See 'Clinical course' above.)
●Association with malignancy – Although HPV 6 and HPV 11 are associated with low risk for HPV-related malignancy, coinfection with high-risk types of HPV is common in patients with CA. Malignant transformation of anogenital warts is rare. Immunosuppressed patients have increased risk for malignant transformation. (See 'Association with malignancy' above.)
●Diagnosis – A diagnosis of CA usually can be made based upon the physical examination. If the diagnosis remains uncertain or atypical features are present, a biopsy is useful for confirming the diagnosis. (See 'Diagnosis' above.)
●Additional evaluation – Patients with CA may benefit from testing for additional sexually transmitted diseases as well as an evaluation for concomitant urethral, vaginal, cervical, or anal involvement. (See 'Additional evaluation' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Noah Scheinfeld, MD (deceased), who contributed to an earlier version of this topic review.
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