Bowenoid Papulosis

Bowenoid papulosis was described in 1977 by Kopf and Bart as papules on the penis. Bowenoid papulosis is now most commonly known to occur on the genitalia of both sexes in sexually active people. Bowenoid papulosis is manifested as papules that are induced virally by human papillomavirus (HPV) and demonstrate a distinctive histopathology (bowenoid dysplasia).[1] Many bowenoid papulosis lesions appear to run a benign course, although a number of case reports associate bowenoid papulosis with malignant invasive transformation (2.6%).

Bowenoid papulosis may be considered to be a transitional state between a genital wart and Bowen disease. The rate of transformation of bowenoid papulosis lesions is unknown. Clearly, bowenoid papulosis lesions have some malignant potential, but they may be treated with locally destructive modalities, sparing the surrounding tissues. Bowenoid papulosis lesions often are multifocal, and patients should be observed for recurrence and for the possibility of invasive or in situ malignancy.

Bowenoid papulosis is an asymptomatic focal epidermal hyperplasia and dysplasia induced by HPV infection[2, 3] (most commonly by HPV 16). The result can appear as a papule or multiple papules that sometimes coalesce, as patches, or as plaques. Histologically, they are composed of scattered atypical cells or full-thickness epidermal atypia that some view as analogous to squamous cell carcinoma in situ. This epidermal atypia is sometimes known as bowenoid dysplasia.

HPV, particularly HPV 16, has been linked closely to bowenoid papulosis.[4] Other HPV types implicated include 18, 31, 32, 33, 34, 35, 39, 42, 48, 51, 52, 53, and 54. Consequently, the risk of acquiring bowenoid papulosis is identical to that for other genital HPV-associated conditions via sexual contact or, possibly, via vertical transmission from mother to newborn.

Frequency

Bowenoid papulosis lesions are related clinically to genital warts. They share the same age of onset in patients and are transmitted sexually. Because bowenoid papulosis lesions frequently are treated destructively as warts and without histopathologic examination, the true frequency of bowenoid papulosis is unknown but is believed to be underestimated. With locally destructive therapy, the risk of invasive carcinoma in bowenoid papulosis appears to be low.

Race

Bowenoid papulosis affects all races equally.

Sex

The male-to-female ratio for bowenoid papulosis is equal.

Age

Bowenoid papulosis occurs primarily in young, sexually active adults, with a mean age of 31 years. However, reported cases show children as young as 2 years who are affected. One case of a 3-year-old girl[5] with bowenoid papulosis and another case of a 9-year-old girl with vertically acquired HIV and bowenoid papulosis[6] have been reported.

Prognosis for bowenoid papulosis is variable. Younger patients tend to have a self-limiting course lasting months. Patients who are older or immunocompromised can have a protracted course lasting years and, possibly, no resolution.

Cervical bowenoid papulosis lesions are associated with an increased incidence of abnormal cervical smears. Although bowenoid papulosis has a low rate of developing invasive characteristics (2.6%), yearly serial examinations are recommended because of the possibility of recurrence.

Educate patients regarding the malignant potential of bowenoid papulosis and the avoidance of direct sexual contact to decrease transmission of the disease.

Bowenoid papulosis typically occurs in young sexually active persons. Bowenoid papulosis tends to be benign with spontaneous regression occurring within several months.[7] A more protracted course is believed to occur in older patients and, possibly, with lesions consistent with certain HPV types. These lesions may last as long as 5 years, or they may never regress completely. The lesions tend to be asymptomatic but can be inflamed, pruritic, or painful.

Bowenoid papulosis presents as solitary or multiple, small, pigmented (red, brown, or flesh-colored) papules with a flat-to-verrucous surface. The bowenoid papulosis lesions can coalesce into larger plaques. Lesions occur most commonly on the shaft of the penis or the external genitalia of females (as shown in the image below), although they can occur anywhere on the genitalia and in the perianal region.[8] Of note, several cases of nongenital bowenoid papulosis have been reported. Extragenital cases have been reported as isolated bowenoid papulosis and others as extragenital bowenoid papulosis with concomitant anogenital involvement.[9, 10, 11] One such case has been reported in the oral cavity following oral-genital sex in a patient undergoing therapy for Hodgkin disease.[12] Another case describes a presentation on the nipple.[13]

Bowenoid papulosis has an increased potential to cause cervical neoplasia, vulvar neoplasia, Bowen disease, and invasive squamous cell carcinoma.

Select a typical bowenoid papulosis lesion for cutaneous biopsy, and send it for routine histologic evaluation. White vinegar (5% acetic acid) application may make subclinical bowenoid papulosis lesions visible within 5-10 minutes.

HPV subtyping is not performed routinely in bowenoid papulosis. If subtyping the lesion is considered necessary, this can be accomplished via Southern blot hybridization, dot blot hybridization, reverse blot hybridization, or polymerase chain reaction.

Histopathologic findings with routine hematoxylin and eosin stain in bowenoid papulosis vary from those of a genital wart with a buckshot pattern to full-thickness epidermal atypia. Note the images below. This is characterized by a circumscribed epidermal proliferation composed of pleomorphic cells with clumped and irregular nuclei. Frequently, atypical mitoses and dyskeratotic cells can be present.[14] On low power, cells have nuclei that appear dark and are surrounded by a clear vacuolated cytoplasm. The integrity of the dermoepidermal border is preserved. The pattern occasionally has been described as windblown and may be identical to Bowen disease or squamous cell carcinoma in situ, occurring on nongenital skin.

Kaziouskaya et al studied the expression of p16 protein in bowenoid papulosis. After staining samples with an antibody to p16 protein, the researchers concluded that this immunostain has high sensitivity and specificity for detecting bowenoid papulosis.[15]

Conservative treatment is often considered, as bowenoid papulosis has been known to regress spontaneously.[5]

The most effective treatment for bowenoid papulosis is simple local destruction of the lesions. Various modalities have been used, although recurrences are common with all. The modalities include simple local excision, electrodesiccation, cryosurgery, laser surgery, and use of topical retinoic acid, podophyllum resin, and topical 5-fluorouracil.[16, 17]

Immunomodulators have been reported as effective treatment for bowenoid papulosis and may lengthen the remission period of lesions. Among immunomodulators, 2 of the agents include imiquimod 5%[18] and interferon.[19, 20, 21, 22] Application of interferon beta may decrease the relapse rate by reducing transcription of viral RNA oncogenes E6 and E7.

One report describes 2 cases of genital bowenoid papulosis successfully treated with tazarotene.[23] Another report shows an extensive case of bowenoid papulosis improving after 8 weeks of treatment with combined oral acitretin and topical 5% Imiquimod.[24]

Without treatment, regression can take up to 8 months.[14] However, treatment times may vary, with reported cases showing 2-6 months before regression.[18, 24]

The following consultations may be warranted:

• Dermatologist: Reexamine lesional skin serially every 3-6 months because of the possibility of transformation to Bowen disease or invasive squamous cell carcinoma. The risk of transformation is higher in patients who are immunocompromised and in elderly patients.

• Gynecologist: Female patients and women who have had sexual relations with male patients should be seen for a thorough cervical examination because of the increased risk of malignancy.

• Urologist: Patients with urethral involvement should consider receiving an examination by a urologist.

• Proctologist: Patients with perianal involvement should consider scheduling an examination with a proctologist.

Condom use may decrease the risk of bowenoid papulosis transmission.

Patients with HPV infection may be lifelong carriers of the virus. Partners should have regular evaluations. Female partners should be evaluated regularly using Papanicolaou smears.

In male partners, periodic anogenital examination may be of benefit.

Advise bowenoid papulosis patients to avoid direct contact with lesions.

Advise bowenoid papulosis patients to seek prompt treatment.

Bourgault Villada et al determined that regions from proteins E6 and E7 are strongly immunogenic, which may have implications for the development of an HPV-16 vaccine.[25]

Perform serial examinations. Bowenoid papulosis may show malignant change; therefore, follow-up treatment is warranted every 3-6 months if the lesions recur or do not resolve.

Destruction of the lesion is the treatment of choice for bowenoid papulosis. Most medications act to some degree as both destructive and immunomodulating agents.

Class Summary

These agents inhibit cell proliferation by blocking the progression of the cell cycle at specific stages.

Podophyllum resin (Pod-Ben, Podocon-25, Podofin)

Podophyllum resin is topical treatment for benign growths including external genital and perianal warts, papillomas, and fibroids. It arrests mitosis in the metaphase; the active agent is podophyllotoxin; the type of podophyllum resin used determines the strength. American podophyllum contains one fourth of the amount reported by an Indian source.

Trichloroacetic acid (Tri-Chlor)

Trichloroacetic acid cauterizes skin, keratin, and other tissues. Although caustic, it causes less local irritation and systemic toxicity than others in the same class; however, the response often is incomplete and recurrence occurs frequently.

Imiquimod (Aldara)

Imiquimod induces secretion of interferon alpha and other cytokines; the mechanisms of action are unknown.

5-Fluorouracil cream (Efudex, Adrucil, Fluoroplex)

5-Fluorouracil cream is for treatment-resistant bowenoid papulosis. It interferes with DNA synthesis by blocking the methylation of deoxyuridylic acid, and it inhibits thymidylate synthetase, which subsequently reduces cell proliferation.