(Genital Warts (Condyloma acuminatum) – Buschke-Löwenstein Tumors)

Artist/ Title/ Date

Christopher Alton, Female Genitalia with Diseased Tissue Spreading to Anus and Thighs, 1857. Watercolor. Wellcome Collection, London.

Description of Disease & Etiology

Condyloma acuminatum, or Buschke-Löwenstein tumors, are a rare complication of human papillomavirus (HPV) infection, most commonly associated with low-risk strains such as HVP-6 and HPV-11. To date, hundreds of HPV genotypes have been identified, and most humans are exposed to at least one type during their lifetime. These viruses infect the basal epithelial cells of skin and mucous membranes and are primarily transmitted through direct sexual contact, although transmission via fomites is also possible. Most HPV infections are asymptomatic and self-limiting. However, in rare cases, the virus persists, leading to chronic lesions, condylamatous growths, epithelial dysplasia, or, in some cases, neoplastic transformation.1

Signs/Signifiers of Illness

Buschke-Löwenstein tumors typically present as slow-growing masses in the genital and anorectal area, with potential to reach over 10 centimeters in diameter. These lesions are often described as “cauliflower-like”, and their development may occur gradually over a period of several years. Patients may report symptoms such as local discomfort, pain, discharge, or bleeding.

Although histologically benign, these tumors demonstrate locally aggressive behavior. On histological examination, these tumors can exhibit features such as hyperkeratosis and acanthosis, a thickening of the epithelial layers of the stratum corneum and stratum spinosum, respectively. Due to their aggressive growth, histological analysis is usually essential to rule out progression to squamous cell carcinoma.1-3

Pathology

The pathology of Buschke-Löwenstein tumors lies in disruption of normal cell cycle control caused by persistent HPV infection. In most cases, the virus remains in an episomal (non-integrated) form, but in rare instances, it integrates into chromosomal DNA, altering gene expression and promoting abnormal cell growth. Two key viral proteins, E6 and E7, promote degradation of the tumor-suppressor protein p53 and inactivate members of the retinoblastoma (Rb) protein family, respectively. This dysregulation impairs the cell’s ability to regulate growth and DNA integrity.

Although the immune system usually keeps HPV in check, individuals with weakened immunity (like those with HIV) are more likely to develop large or aggressive tumors. Histologically, Buschke-Löwenstein tumors show features typical of HPV-driven epithelial proliferation, including hyperkeratosis and acanthosis, as mentioned previously. These tumors grow with broad, pushing borders but typically lack evidence of metastasis. Despite their benign classification, these tumors carry a significant risk of malignant transformation, reported in up to 56% of cases, often occurring after several years of progression.1-3

Treatment

Treatment for these cases typically involves wide surgical excision with clear margins, aiming to remove the entire lesion and reduce the risk of recurrence. For early-stage, smaller lesions, topical or systemic therapies may be considered, including podophyllin (an antimitotic agent that inhibits cell division), imiquimod (an immune response modifier that stimulates cytokine production), interferon (a cytokine that enhances antiviral immunity), or CO2 laser therapy to ablate abnormal tissue may be used.

Although these treatments may help in selected cases, surgical excision remains the standard of care, especially for larger or invasive tumors. Preventive measures, such as HPV vaccination, are also crucial. Vaccines like Gardasil and Gardasil 9, which include antigens for HPV types 6 and 11, can reduce the risk of developing lesions associated with these low-risk strains.1, 3

Social Determinants of Illness

Development and progression of this condition are influenced by several social and structural factors that affect access to care, prevention, and early intervention. One of the most significant risk factors is immunosuppression, particularly in individuals living with HIV, where reduced immune surveillance allows for persistent HPV infection. Limited access to HPV vaccination also contributes to the disease burden, particularly in underserved populations.

Delays in diagnosis and treatment are also shaped by social stigma, limited health literacy, and barriers to healthcare access. Addressing public health challenges, such as sexual health education, vaccination availability, and comprehensive HIV care is critical for reducing incidence and severity of this condition.1-3

Author(s): Victoria Rhodes

Citations:

* 1) Purzycka-Bohdan, D., Nowicki, R. J., Herms, F., Casanova, J.-L., Fouéré, S., & Béziat, V. (2022). The Pathogenesis of Giant Condyloma Acuminatum (Buschke-Lowenstein Tumor): An Overview. International Journal of Molecular Sciences, 23(9), Article 9. https://doi.org/10.3390/ijms23094547 * 2) Egawa, N., & Doorbar, J. (2017). The low-risk papillomaviruses. Virus Research, 231, 119–127. https://doi.org/10.1016/j.virusres.2016.12.017 * 3) Manlubatan, S. I. T., Onglao, M. A. S., Tampo, M. M. T., & Lopez, M. P. J. (2022). Outcomes of surgical management of buschke-lowenstein tumor in a Philippine tertiary hospital. Annals of Coloproctology, 38(1), 82–87. https://doi.org/10.3393/ac.2020.00731.0104