Genital warts are caused by infection with human papillomavirus (HPV). They are common benign neoplasms that are significant because of their transmissibility, the association of some HPV types with the development of malignancy, and our current inability to eradicate latent HPV from infected tissue. In contrast with herpes simplex virus (HSV) where there are two viral types, HSV 1 and HSV 2, there are over 100 HPV types. These are usually divided on the basis of their oncogenic potential into low-risk and high-risk groups. Anogenital infection may occur with viruses from either of these groups.

As noted above, genital warts may resolve spontaneously, especially in children and young adults. Contrarily, those occurring in immunosupressed patients are likely to remain in place indefinitely. In spite of the potential for resolution, nearly all anogenital warts should be treated to reduce contagion through sexual activity. This is particularly important because it is not possible to determine clinically which warts contain high-risk HPV types.

Before considering treatment options, clinicians should consider whether or not biopsy of one or more lesions should be undertaken. As indicated above, flat-topped warts (regardless of color) and large globular warts should be biopsied because of the possibility that in situ or invasive squamous cell carcinoma may be present. Shave biopsy is acceptable for flat-topped warts, whereas shave excision is preferred for large globular warts because of the greater risk of sampling error in these large lesions. Filliform lesions and those mimicking hand warts (see above) may be treated without biopsy due to the very low likelihood that dysplasia will be present.

Multiple approaches to treatment are available (8,9). Treatment needs to be individualized for each patient as no single therapy is universally preferable. One of the first priorities in the treatment process is the education of patients regarding the contagious aspects of the viral infection, the likelihood of recurrence after therapy, and, in some instances, the potential for malignant transformation. After this has been accomplished, input from the patient should be sought as to whether the treatment is to be undertaken by the patient (patient-based therapy) or by the clinician (clinician-based therapy).

There are three medications available for patient-based therapy: application of 0.5% podofilox, 5% imiquimod, or green tea polyphenon E. Podofilox (Condylox) solution or gel is applied to the warts twice daily for 3 days followed by 4 to 7 days without treatment. Imiquimod (Aldara) cream is applied once daily three times per week on alternate days. For both products, the cycle is repeated as necessary. A meta-analysis comparing these two products found that they were approximately equal in efficacy with clinical cure rates of 50% to 55% (10). However, the severity of adverse effects was slightly greater with podofilox (10). The Food and Drug Administration (FDA) has recently approved a green tea extract (Veregen), marketed as 15% ointment, to be applied to warts t.i.d. Data to support Veregen’s use are limited. Three randomized, double-blind, placebo-controlled studies have been carried out with complete clearance rates of 50% to 60% (11). Adverse effects of redness, burning, pain, and erosion occur with all three of these products though possibly to a slightly lesser degree with the green tea extract.

Clinician-based therapy can be either medical or procedural. Two medical approaches are available. With the
first, 25% podophyllin is applied to the warts once weekly or every other week. This approach is less used today than it was in the past due to nonstandardized podophyllin preparations, highly variable cure rates, and significant problems with irritation and pain. With the second, trichloroacetic acid can be applied (carefully!) in the office at 2- or 3-week intervals. Clearance rates of 70% to 80% have been reported after six applications (9). Burning on application is troublesome for patients but it is a reasonable approach when the warts are relatively nonkeratotic and the number and size of the lesions are small (12).

Clinician-based procedural therapy includes cryotherapy, electrosurgical destruction, laser destruction, and surgical excision. With cryotherapy, liquid nitrogen is sprayed (or applied with cotton-tipped applicators) at 2- to 3-week intervals. Clearance rates of about 80% are achieved with three to six treatments (9,13). Electrosurgical destruction (electrofulguration, electrodessication) is usually carried out using the ConMed Hyfrcator under local anesthesia. Other electrosurgical approaches using loop excision or a bipolar Bovie-type apparatus can also be used. Laser therapy, generally with a CO₂ laser, can also be considered but the cost of this equipment, and thus the treatments, is very high. Surgical excision is most often accomplished with a shave or scissors-snip technique; rarely elliptical excision might be considered. All three of these ablative approaches result in clearance rates of somewhat over 80% (9,14). Drawbacks, however, are the requirement for local anesthesia, the possibility of secondary infection, and potentially long healing times.

The choice of which medical or procedural approach is taken depends on patient preference and on the experience level of the clinician. For most patients, I prefer either electrosurgical destruction or shave removal with very light electrosurgery to the base. These two approaches are time honored, inexpensive, and do not depend on patient compliance. Moreover, only a single clinic visit is generally necessary and the patient leaves the clinic with the knowledge that he or she is free of all of the visible lesions. Of course, if the number and size of the warts are large, staged eradication at monthly intervals may be necessary.

The recurrence rate with all forms of therapy is very high, running generally in the 25% to 45% range. This presumably is the result of latent virus left in the perilesional skin after clinical visible lesions have been successfully treated.

Anogenital warts in children present a special problem because of the concern that sexual abuse may have taken place. However, for children under the age of two, it is very unlikely that the transmission occurred through sexual contact (7). Anogenital warts in these very young children may have arisen through normal parental contact or by way of contagion from an infected birth canal. A greater level of concern exists for those over the age of four and, in any case, inquiry by an experienced clinician or by other skilled interviewers must be carried for all children with anogenital warts.

The best approach for genital warts is to prevent them for occurring in the first place. A quadrivalent vaccine (Guardasil) directed against HPV types 6, 11, 16, and 18 has been approved by the FDA for use in 9 to 26 year old children and adults of both sexes. The possibility of using this vaccine for women over the age of 26 is under consideration by the FDA currently. A bivalent (Cervarix) vaccine directed at HPV 16 and 18 has also been approved for girls and women 10 to 25 years of age. Clinical trials and almost 4 years of experience has documented that both of these vaccines are highly efficacious, safe, and durable. In addition both vaccines have some, but limited, crossover effect against HPV types other than those toward which the vaccines are primarily directed (15). The cost remains high and some parental objection exists. These two factors somewhat limit the use of these vaccines in many situations.

Both vaccines appear to be nearly 98% effective in preventing cervical and vulvar intraepithelial neoplasia (CIN 2 and 3) due to HPV types 16 and 18 for up to 3 years in those who were naïve to these types at the time of vaccination (15,16 and 17). Efficacy in older women aged 24 to 45 was slightly lower but still excellent at 90% (18).

Infection with molluscum contagiosum virus (MCV) is common and self-limited. It can be viewed as more of a nuisance than a threat to health or well-being.

Condyloma lata is the name used for the flat-topped papules and nodules that develop in the anogenital area during the secondary stage of syphilis. These lesions are uncommonly seen in conventional office practice but are, of course, encountered with some frequency in STD clinics. The primary coverage of syphilis is located in the section on chancre in Chapter 10 and only the clinical presentation and therapy of condyloma lata will be covered here.

Condylomata lata are sharply demarcated, large (1- to 2-cm), flat-topped, moist, skin-colored or pink papules (Fig. 12-16). When the lesions are located on a mucosal surface, they often exhibit a white surface because of retained moisture (Fig. 12-17). They are most commonly found on the vulva and the perianal area but can occur elsewhere on the genitalia and perigenital skin. As opposed to the other cutaneous lesions of secondary syphilis, the lesions of condyloma lata are teeming with spirochetes and pose a high risk for transmission to others. Condylomata lata are usually associated with other signs and symptoms of secondary syphilis such as fever, malaise, and generalized lymphadenopathy. Other skin findings such as slightly scaly red papules on the trunk, brown-red palmar and plantar papules, white patches on the oral mucous membranes, and patchy hair loss may also be present.

Patients with condylomata lata almost always exhibit a positive rapid plasma regain (RPR) or Venereal Disease Research Laboratory (VDRL) serologic test for syphilis. The only exceptions are those who are severely immunocompromised (e.g., HIV/AIDS) and those with such a high antibody titer that they exhibit the so-called prozone phenomenon. The lesions of condyloma lata can be confused with flat-topped HPV-induced warts and intraepithelial neoplasia of the vulva, penis, and scrotum. If there is any question about the correct identity, a serologic test for syphilis as well as a biopsy should be obtained. The treatment for secondary syphilis as recommended by the CDC is a single 2.4 million unit IM injection of benzathine penicillin G (Bicillin L-A) (30).

Until recently, lymphogranuloma venereum (LGV) was rarely encountered in Western countries. However, during the last 5 years, there has been a significant rise in the number of cases reported from the United Kingdom and Europe and a smaller rise in the United States. Nearly all of this increase is accounted for by infections occurring in MSM. Currently, the prevalence of LGV serovars in the rectum in UK MSM is about 1% (31). LGV occurs very rarely in women.

Nearly all (90% to 95%) of the patients with LGV have presented with proctitis and most of the others have had inguinal adenitis (31). Transient genital ulcers together with appreciable lymphadenopathy occur in a minority of patients (32).

A discussion of proctitis, with or without perianal ulcers, falls outside the scope of this textbook and the rarely encountered ulcers are not well described in the literature. The most striking feature is likely to be impressive lymphadenopathy (buboes). The inguinal lymph nodes are most commonly affected though in some cases femoral nodes are also involved. When both sets of nodes are affected, Poupart ligament (ligamentum inguinale) creates a characteristic grove between the two groups of nodes. The enlarged nodes are usually bilateral and they are exquisitely tender. In untreated patients, nodes that have been present for some time undergo liquefaction with attendant fluctuance. Eventually, breakdown of the overlying skin occurs, resulting in the presence of chronic purulent draining sinuses. Massive genital edema (elephantiasis) frequently develops. Patients with untreated proctitis develop rectal stenosis, strictures, and perianal abscess formation. The latter may be mistaken for Crohn disease.

LGV is caused by the L1, L2, or L3 serovars of the bacterium, Chlamydia trachomatis. Nearly all of the newly reported cases have been with the L2 serovar. The diagnosis is usually suspected on a clinical basis but similar adenopathy can occur in chancroid. Confirmation of the diagnosis requires identification of a LGV-type serovar from the site of infection. Previously, this had been accomplished primarily with bacterial cultures, but today molecular techniques are more widely used. In situations where these tests are not available, serologic techniques can be used but there are many problems with sensitivity and specificity.

The CDC guidelines recommend treatment with oral doxycycline 100 mg twice daily for 3 weeks (30). In an attempt to obtain better compliance, single dose or short course azithromycin has also been used but there is insufficient evidence of efficacy to support the use of this medication on a regular basis (30). Fluctuant lymph nodes should be aspirated.

Epidermal cysts are commonly, but erroneously, termed sebaceous cysts. They are the most common type of cysts found in the anogenital area. They occur as firm, slopeshouldered, smooth-surfaced, white, yellow-white, slightly pink or skin-colored papules or nodules (Fig. 12-18). Very small cysts (1 to 2 mm) are called milia but these are not commonly seen in the anogenital area. The average diameter for genital lesions is 0.5 to 2.0 cm. Noninflamed
cysts are asymptomatic. Epidermal cysts are primarily found on the hair-bearing aspects of the genitalia. They are most commonly located on the scrotum in men and the labia majora in women. One or several may be present; rarely there are 10 to 20 clustered lesions (Figs. 12-19 and 12-20). The diagnosis is usually made on the basis of clinical appearance. Confirmation, if necessary, can be obtained when white cyst contents are visualized after incising and gently squeezing the lesion. Syringomas arising on the labia majora may be confused with epidermal cysts. The lesions of molluscum contagiosum may mimic epidermal cysts but the lesions of molluscum contagiosum are more superficial and appear to sit on the surface, rather than within the skin. Enlarged sebaceous glands (Fordyce spots) on mucosal aspects of the genitalia may resemble milia.

So-called “inclusion cysts” arise when bits of epithelium are implanted in the skin during the course of a surgical procedure or as a result of trauma sufficient to break the surface of the skin. The much more common, typical epidermoid cyst found on the genitalia, develops from the remnant of an anatomically malformed pilosebaceous unit that lacks a fully adequate outlet to the surface of the skin. These cysts may have a black dot, representing a comedone (“blackhead”), at the summit of the cyst. The white material located within an epidermal cyst is keratin that is produced by keratinocytes located in the lining of the cyst wall.

Epidermal cysts are medically unimportant and cause no problems unless the cyst wall leaks or ruptures. If this occurs, cyst contents come into contact with the connective tissue surrounding the cyst where they engender a brisk foreign body inflammatory reaction. This inflammation causes the cyst contents to liquefy into pus-like material. In spite of the appearance and smell, this mixture of liquefied keratin and inflammatory cells almost always lacks pathogenic bacteria. Nevertheless, such lesions may clinically resemble a furuncle or an inflammatory pseudocyst as seen in hidradenitis suppurativa. No treatment is needed for uninflamed cysts. Inflamed cysts may be incised and drained. Most clinicians prescribe antibiotics for inflamed cysts but any beneficial effect that occurs is likely due to the anti-inflammatory, rather than the antimicrobial, properties of these antibiotics. Rarely, symptoms or patient insistence will result in a need for excisional removal of the entire cyst.

Mucinous vestibular cysts are commonly found within the vulvar vestibule. They develop from anatomic abnormalities or obstruction of the minor vestibular glands. A buildup of gland secretion forms these 0.5- to 2-cm cysts (Fig. 12-21). They can be skin colored, translucent, yellow, or blue. Although vestibular cysts can be
removed surgically, they are asymptomatic and therefore ordinarily require no treatment.

A median raphe represents the midline embryonic joining point of two symmetrical tissues. In the anogenital area of men, a median raphe extends from the anus forward through the perineum, along the scrotum extending onto the underside of the penis and ending at the urethral meatus on the tip of the glans. The raphe is visible and palpable as a slight ridge that is skin colored or light brown. Cyst or canals can develop anywhere along this raphe but occur most commonly on the underside of the penis. Usually, only a solitary papule, representing a single cyst, is present but in some cases multiple cysts are found along the raphe. The lesions appear as dome-shaped skin-colored, yellow, or tan hemispherical papules that are 2 to 15 mm in diameter (Fig. 12-22). Presumably these are present from birth but slow growth and lack of symptoms generally mean they are not discovered until later in life. Rarely, they become inflamed as a result of trauma or infection. Histologically they may be lined with either columnar or stratified squamous epithelium. No treatment is necessary for asymptomatic lesions; inflamed or otherwise symptomatic lesions can be excised.

Though often termed pilonidal cyst, these lesions lack an epithelial cyst wall and therefore are more appropriately identified as a pilonidal sinus. They arise as an acquired lesion wherein hairs, trapped in folded areas of tissue, forcibly penetrate the skin and create a foreign body inflammatory reaction. Pilonidal sinus is most commonly located in the sacrococcygeal area in men but locations in other sites such as the axillae, webspaces of the hands, and genitalia have been reported (33). It appears that only about a dozen cases have reported to have involved the vulva and penis (33,34). Most of the vulvar cases have been located in a periclitoral site where they may develop into a clitoral or periclitoral abscess. In uncircumcised men, penile lesions have been located in the coronal sulcus.