Medical Care
The treatment of choice for giant condyloma of Buschke and Löwenstein (GCBL) is considered wide surgical excision. Surgery alone has resulted in a disease-free status in 45.5% of patients. [16] However, controlled trials comparing treatments are currently lacking. [17]
Several factors need to be considered in the selection of treatment, including the thickness and size of the lesions, quantity and anatomic location of the lesions, HPV classification, immunocompromised or immunocompetent status, preferences of the patient and provider, cost, and availability. No current treatment achieves complete eradication the HPV. [17]
In addition, oral and topical chemotherapeutic modalities have been used with mixed success as adjuvants to surgery or as treatment for recurrences. Topical therapy alone, such as with 5-fluorouracil, [18] podophyllin, or interferon (IFN), are generally insufficient to control disease or prevent progression of the giant lesions. One case report noted that intralesional bleomycin in the wound bed of an incompletely resected tumor was effective, with no recurrence at 2 years. Topical cidofovir gel 1.5% used for several months produced clinical improvement, even in cases refractory to conventional treatment. [19, 20]
The postulated viral origin of these tumors has led to the use of IFN with moderate success. One case of vaginal GCBL responded to 6 months of IFN 2-alfa, with apparent complete resolution. Although topical IFN lacked clinical efficacy, intralesional administration [21] has produced complete responses in 47-62% of cases; however, the recurrence rate is 40%. Large lesions may be candidates for systemic IFN. A deeply infiltrating giant condyloma acuminatum experienced a major response after 9 months of continuous IFN administration at 10 MU thrice weekly, although no change in the tumor could be observed in the first several months.
Imiquimod was effective in combination with carbon dioxide laser ablation in a patient unable to tolerate surgery, whose tumor was positive for HPV-6. [22]
Traditional systemic antitumor agents have also been used. One report described the use of bleomycin, cisplatin, methotrexate, and leucovorin in a patient with recurrence after multiple surgeries for GCBL. [23] An autopsy 1 year later showed no evidence of active disease. A separate report noted tumor shrinkage with mitomycin-C and 5-fluorouracil combined with fractionated radiotherapy; unfortunately, this patient manifested pulmonary metastases. [24] Etretinate and photodynamic therapy with intravenous porphyrins have been used with some success in vaginal GCBL.
Radiation therapy remains controversial. Extensive evidence supports anaplastic transformation in oral/plantar verrucous carcinoma, but data in GCBL are mixed. While some studies show evidence of new aggressive behavior after radiation therapy, more than a few case reports document resolution of small tumors after radiation. [25] One review recommended the avoidance of radiation if possible; but, if necessary, the use of a large dose of radiation to minimize chances of further mutation may be effective in a candidate who is a poor surgical risk. [24] To support this view, one report describes successful treatment of a recurrent tumor with radiation at 4500 cGy in 25 fractions; the patient remained disease free when reevaluated at 20 months.
Bulky tumors have been shrunk with preoperative chemoradiation, followed by radical surgery, in some instances followed by reconstructive surgery. One regimen that lead to a complete response consists of mitomycin C and 5-fluorouracil administered concomitantly with radiation therapy 50.4 Gy to the tumor bed and prophylactic irradiation of the regional nodes.
Autologous vaccination with a preparation of condyloma cells was well tolerated clinically and produced good responses in an initial and recurrent giant condyloma acuminata. After more than 1 year of follow-up in this series, recurrence rates with various treatments were 50% for excision alone and bichloracetic acid, 85% for podophyllin and IFN alfa, and only 4.6% after excision and vaccination. Mean follow-up was 13 months (range, 6-23 mo). [26]
Refractory disease that relapsed despite cryotherapy, imiquimod, topical sinecatechins, and surgical debulking was successfully treated with a combination of systemic interleukin 2 and topical cidifovir. [7]
Another biological treatment combination consisting of oral retinoid plus intramuscular interferon-gamma resulted in the complete clearance within 3 months of a GCBL in a 16-year-old girl. No recurrence was noted during two years of follow-up. The authors propose this treatment option in light of it being nonscarring and relatively painless. [27]
Surgical Care
Surgical excision is the treatment of choice. Its main advantage is the ability to histologically examine the entire specimen to ensure clear margins and to evaluate for foci of SCC. As a drawback, it typically requires at least a partial penectomy, but one series successfully used glansectomy only, with excellent functional and therapeutic results. [28, 29] Mohs surgery appears to be the most efficacious surgical treatment, allowing specimen examination and sparing most of the tissue.
Even extensive perineal giant condylomata acuminata can be successfully treated by extended surgical procedures, including colostomy and plastic reconstruction of resulting defects upon resection. [30]
In another report, very large lesions such as the one measuring 30 × 10 cm on each side of the vulva/perineum can be still excised and defects reconstructed. [31]
Excision of large genital lesions can be followed by long-term treatment with topical podophyllin. This approach, which was successfully used in one case by Akhavizadehan, allowed preservation of sexual function by limiting the depth of surgical resection. [32]
However, other experts favor conservative surgery, considering the patient’s quality of life. [33]
Recurrences of giant condyloma acuminatum can be successfully addressed with radical surgery. The cure rate with radical surgery reportedly is 61%, versus only 25% with chemoradiotherapy with or without local excision. Some authors recommend radical electrocautery surgical resection whenever possible. [34]
The substantial efficiency of surgery alone on patients in whom conservative measures failed was recently demonstrated in a series of 27 patients. The method of treatment consisted of radical excision with subsequent split-thickness skin graft. The advantages of this method consist of allowing a complete histological examination and having a rapid healing, which translates to an improvement in the patient’s quality of life. [35]
Resection with the carbon dioxide laser has also been effective, with the advantage of permitting a bloodless field, and it has been used effectively in a pregnant patient. Carbon dioxide and argon lasers are used for relapsing cases or as an alternative first-line therapy. [36] Cryosurgery has been effective in several case reports, primarily on small lesions, with normal anatomy resulting after tumor resolution. Close monitoring is required because destruction of the entire tumor cannot be ensured.
A combination of radiofrequency surgical dissection and oral acitretin (used for the treatment of erythrodermic psoriasis) was successfully used in the treatment of perianal Buschke-Löwenstein tumor, achieving an impressive disease-free status 26 months after the end of the treatment. The use of acitretin resulted in elimination of all the residual disease that was not removed by surgery. [37]
Complications
Most complications of GCBL are the result of the growth of the tumor or of the treatment. As the lesion progresses, fistulization, foul odor, and secondary infections are common. Extensive lesions, particularly leading to complex fistulous tracts and discharge, may require a temporary colostomy. Less radical approaches may lead to local recurrence. Therefore, abdominoperineal resection has been recommended for patients with rectal sphincter involvement. Malignant transformation to SCC occurs usually after several years.
Prevention
Early circumcision has been found to be extremely effective in preventing penile carcinoma. Given the association with HPV, condom use would probably be effective in decreasing the incidence of GCBL. The 9-valent HPV vaccine (9vHPV, Gardasil 9) is indicated for the prevention of condyloma acuminata caused by HPV subtypes 6 and 11. The 9vHPV vaccine is indicated to prevent HPV-associated dysplasias and neoplasias in males and females aged 9-45 years. [38] The vaccine is administered as three separate doses administered at 0, 2, and 6 months. In children aged 9-14 years, a two-dose regimen may be given. The availability of vaccinations against HPV infection is contributing to the decreasing incidence of this disease. [17]
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Giant condylomata acuminata of Buschke and Lowenstein of the perianal region, consisting of a slow-growing, ulcerated, cauliflowerlike mass.
