Bowenoid Papulosis

Back

Background

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.

Pathophysiology

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.

Etiology

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.

Epidemiology

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

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.

Patient Education

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

History

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.

Physical Examination

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]



View Image

Typical appearance of bowenoid papulosis in the female.

Complications

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

Laboratory Studies

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.

Other Tests

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.

Histologic Findings

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]



View Image

Bowenoid papulosa histopathology (hematoxylin and eosin, magnification 40X).



View Image

Bowenoid papulosa histopathology (hematoxylin and eosin, magnification 400X).

Medical Care

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]

Consultations

The following consultations may be warranted:

Activity

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.

Prevention

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]

Long-Term Monitoring

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.

Medication Summary

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

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

Clinical Context:  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)

Clinical Context:  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)

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

5-Fluorouracil cream (Efudex, Adrucil, Fluoroplex)

Clinical Context:  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.

Class Summary

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

Author

Mary V Kaldas, MD, Resident Physician in Anatomic Pathology, National Institutes of Health

Disclosure: Nothing to disclose.

Coauthor(s)

Mark P Eid, MD, Founder and Director, Virginia Dermatology and Skin Surgery Center

Disclosure: Nothing to disclose.

Specialty Editors

Michael J Wells, MD, FAAD, Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Disclosure: Nothing to disclose.

Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Mark W Cobb, MD, Consulting Staff, WNC Dermatological Associates

Disclosure: Nothing to disclose.

Acknowledgements

Edward A DiPreta, MD Dermatologist, DiPreta Dermatology

Edward A DiPreta, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for MOHS Surgery, and Medical Association of Georgia

Disclosure: Nothing to disclose.

Kurt Maggio, MD Director of Dermatologic Surgery and Cutaneous Oncology, Assistant Chief, Department of Dermatology, Walter Reed Army Medical Center

Disclosure: Nothing to disclose.

References

  1. Ambooken B, Asokan N, Philip P, Jisha KT. Bowenoid papulosis unveiling a rare cause of immunosuppression. Int J STD AIDS. 2019 Apr. 30 (5):522-525. [View Abstract]
  2. Zhou L, Kang D, Xu C, Zhao W, Tian B, Chen L. Expression of cyclin D1 and cyclin E significantly associates with human papillomavirus subtypes in Bowenoid papulosis. Acta Histochem. 2013 May. 115(4):339-43. [View Abstract]
  3. Paolino G, Muscardin LM, Panetta C, Donati M, Donati P. Linear ectopic sebaceous hyperplasia of the penis: the last memory of Tyson's glands. G Ital Dermatol Venereol. 2016 Sep 6. [View Abstract]
  4. Dubina M, Goldenberg G. Viral-associated nonmelanoma skin cancers: a review. Am J Dermatopathol. 2009 Aug. 31(6):561-73. [View Abstract]
  5. Halasz C, Silvers D, Crum CP. Bowenoid papulosis in three-year-old girl. J Am Acad Dermatol. 1986 Feb. 14(2 Pt 2):326-30. [View Abstract]
  6. Godfrey JC, Vaughan MC, Williams JV. Successful treatment of bowenoid papulosis in a 9-year-old girl with vertically acquired human immunodeficiency virus. Pediatrics. 2003 Jul. 112(1 Pt 1):e73-6. [View Abstract]
  7. Feng J, Wu F, Liu F, Deng D, Chen J, Zeng M, et al. Spontaneous regression of bowenoid papulosis. Dermatol Online J. 2013 May 15. 19(5):18185. [View Abstract]
  8. Shaw KS, Nguyen GH, Lacouture M, Deng L. Combination of imiquimod with cryotherapy in the treatment of penile intraepithelial neoplasia. JAAD Case Rep. 2017 Nov. 3 (6):546-549. [View Abstract]
  9. Rüdlinger R, Grob R, Yu YX, Schnyder UW. Human papillomavirus-35-positive bowenoid papulosis of the anogenital area and concurrent human papillomavirus-35-positive verruca with bowenoid dysplasia of the periungual area. Arch Dermatol. 1989 May. 125(5):655-9. [View Abstract]
  10. Fader DJ, Stoler MH, Anderson TF. Isolated extragenital HPV-thirties-group-positive bowenoid papulosis in an AIDS patient. Br J Dermatol. 1994 Oct. 131(4):577-80. [View Abstract]
  11. Johnson TM, Saluja A, Fader D, et al. Isolated extragenital bowenoid papulosis of the neck. J Am Acad Dermatol. 1999 Nov. 41(5 Pt 2):867-70. [View Abstract]
  12. Kratochvil FJ, Cioffi GA, Auclair PL, Rathbun WA. Virus-associated dysplasia (bowenoid papulosis?) of the oral cavity. Oral Surg Oral Med Oral Pathol. 1989 Sep. 68(3):312-6. [View Abstract]
  13. Lee HJ, Shin DH, Choi JS, Kim KH. A case of isolated bowenoid papulosis of the nipple. Ann Dermatol. 2014 Jun. 26(3):381-4. [View Abstract]
  14. Xu X, Erickson L, Chen L, Elder DE. Diseases Caused by Viruses. Lever's Histopathology of Skin. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2009. 65-7.
  15. Kazlouskaya V, Shustef E, Allam SH, Lal K, Elston D. Expression of p16 protein in lesional and perilesional condyloma acuminata and bowenoid papulosis: clinical significance and diagnostic implications. J Am Acad Dermatol. 2013 Sep. 69(3):444-9. [View Abstract]
  16. Wu YH, Qiao JJ, Bai J, Fang H. Aminolevulinic acid photodynamic therapy for bowenoid papulosis. Indian J Dermatol Venereol Leprol. 2015 Mar-Apr. 81 (2):219-20. [View Abstract]
  17. Kupetsky EA, Charles CA, Mones J. High-grade squamous intraepithelial lesion of the oral commissure (bowenoid papulosis). A case and review. Dermatol Pract Concept. 2015 Oct. 5 (4):39-42. [View Abstract]
  18. Shimizu A, Kato M, Ishikawa O. Bowenoid papulosis successfully treated with imiquimod 5% cream. J Dermatol. 2014 Jun. 41(6):545-6. [View Abstract]
  19. Goorney BP, Polori R. A case of Bowenoid papulosis of the penis successfully treated with topical imiquimod cream 5%. Int J STD AIDS. 2004 Dec. 15(12):833-5. [View Abstract]
  20. Lucker GP, Speel EJ, Creytens DH, et al. Differences in imiquimod treatment outcome in two patients with bowenoid papulosis containing either episomal or integrated human papillomavirus 16. J Invest Dermatol. 2007 Mar. 127(3):727-9. [View Abstract]
  21. Orengo I, Rosen T, Guill CK. Treatment of squamous cell carcinoma in situ of the penis with 5% imiquimod cream: a case report. J Am Acad Dermatol. 2002 Oct. 47(4 Suppl):S225-8. [View Abstract]
  22. Ricart JM, Cordoba J, Hernandez M, Esplugues I. Extensive genital bowenoid papulosis responding to imiquimod. J Eur Acad Dermatol Venereol. 2007 Jan. 21(1):113-5. [View Abstract]
  23. Shastry V, Betkerur J, Kushalappa. Bowenoid papulosis of the genitalia successfully treated with topical tazarotene: a report of two cases. Indian J Dermatol. 2009 Jul. 54(3):283-6. [View Abstract]
  24. Lim JH, Lim KS, Chong WS. Dramatic Clearance of HIV-Associated Bowenoid Papulosis Using Combined OralAcitretin and Topical 5% Imiquimod. J Drugs Dermatol. 2014 Aug 1. 13(8):901-902. [View Abstract]
  25. Bourgault Villada I, Moyal Barracco M, Berville S, et al. Human papillomavirus 16-specific T cell responses in classic HPV-related vulvar intra-epithelial neoplasia. Determination of strongly immunogenic regions from E6 and E7 proteins. Clin Exp Immunol. 2010 Jan. 159(1):45-56. [View Abstract]
  26. Grekin RC, Samlaska CP, Vin Christian K. Andrews Diseases of the Skin. 9th ed. Philadelphia, Pa: WB Saunders; 2000. 515.

Typical appearance of bowenoid papulosis in the female.

Bowenoid papulosa histopathology (hematoxylin and eosin, magnification 40X).

Bowenoid papulosa histopathology (hematoxylin and eosin, magnification 400X).

Bowenoid papulosa histopathology (hematoxylin and eosin, magnification 40X).

Bowenoid papulosa histopathology (hematoxylin and eosin, magnification 400X).

Typical appearance of bowenoid papulosis in the female.