The patient presented on July 30, 2025, with a rapidly enlarging, painful vulvar mass that had developed over one month. Examination showed massive, bilaterally symmetrical, cauliflower-like enlargement of the labia majora, with marked edema obscuring the vaginal introitus. The urethral opening and perianal region appeared unaffected.

She had no significant comorbidities, history of immunosuppression, prior sexually transmitted infection or prior HPV vaccination. She was also highly concerned that treatment might involve disfiguring surgery with consequences for her body image and sexual function. Because the mass was extensive and rapidly enlarging, clinicians initially considered verrucous carcinoma as well as Buschke–Löwenstein tumor.

A wedge biopsy was taken from three quadrants of the lesion on August 21, 2025. Histopathology showed well-formed papillae with fibrovascular cores, marked verrucous hyperplasia, hyperkeratosis and koilocytosis, but no evidence of malignancy or stromal invasion. Immunohistochemistry found no p16 expression and a Ki-67 proliferative index of approximately 20%, largely confined to the basal layer.

Testing of vulvar tissue identified human papillomavirus type 11, while a concurrent cervical biopsy showed low-grade cervical intraepithelial neoplasia. These findings supported a diagnosis of Buschke–Löwenstein tumor, a histologically benign but locally aggressive HPV-associated lesion. Pelvic magnetic resonance imaging on September 3, 2025, identified a large, poorly defined mass confined to the labia majora and bilateral inguinal lymph nodes measuring as much as 1.6 cm, which were interpreted as inflammatory.

In view of the absence of invasive disease on biopsy and the anatomical changes that extensive vulvar resection could entail, the treating team selected a staged approach intended to reduce the tumor before conservatively removing the residual tissue. This was an individual treatment decision rather than a tested alternative to wide surgical excision, and its broader effectiveness cannot be inferred from the single case. On August 27, 2025, the patient began applying 5% topical imiquimod cream three times weekly and received the first dose of a nonavalent HPV vaccine.

Imiquimod stimulates innate and cell-mediated immune responses through Toll-like receptor 7 and has been used for HPV-related anogenital lesions, although its use for Buschke–Löwenstein tumors is off-label. The cream was applied directly to the lesions with a cotton swab and continued at the full dose until the day before the November 27 procedure, without tapering. The patient reported only minimal local irritation and no major discomfort.

A second vaccine dose followed on October 27, and a third was administered on January 23, 2026. Over the initial eight-week neoadjuvant period, the tumor regressed from involving nearly the entire bilateral vulva, including the clitoris and perineal body, while sparing the vagina and urethra, to a smaller residual lesion concentrated mainly on the inner labia majora and labia minora. The reduction allowed the surgical team to avoid radical vulvectomy.

The published discussion describes a 2025 systematic review that combined two randomized controlled trials and three prospective studies of HPV-related anogenital squamous lesions. It reported higher response rates for vulvar and perianal locations than for intra-anal disease, but the populations consisted predominantly of HIV-positive men who have sex with men. The immunocompetent woman in this report therefore differed substantially from those study populations.

The remaining lesion was treated on November 27, 2025, under general anesthesia with a Cavitron ultrasonic surgical aspirator, or CUSA. Operative settings were reported as 60% amplitude and aspiration, with irrigation at 6 mL per minute. The device fragmented and aspirated the friable residual tumor while preserving surrounding collagen-rich structures, producing minimal bleeding and maintaining the adjacent anatomy.

This approach differs from conventional excision because ultrasonic aspiration does not yield a solid specimen for margin assessment or routine postoperative histopathology. The authors therefore state that margin evaluation was inherently precluded, an important limitation of the procedure in an aggressive lesion that can recur. Pathology from the diagnostic biopsy described acanthosis, papillomatosis, hyperkeratosis and areas of parakeratosis, with koilocytosis in the upper epidermis and no malignancy.

After surgery, topical neomycin ointment was applied twice daily to the ablated region for about two weeks, alongside counseling on perineal hygiene. Topical imiquimod was resumed three times weekly as maintenance and stopped on February 23, 2026, the same day as the final HPV vaccine dose. Clinical examinations on December 3, December 12, December 27 and January 23 showed progressive re-epithelialization, no macroscopic recurrence and, by late December, restoration of normal vulvar anatomy with minimal scarring.

The patient did not develop severe erythema, ulceration, burning or systemic adverse effects during the reported course. On March 23, 2026, vulvar HPV DNA testing was negative and cervical cytology was normal. These were laboratory observations at that time, rather than evidence of durable virological control.

The case illustrates why treatment sequencing may matter in selected giant Buschke–Löwenstein tumors. Immediate wide excision of such an extensive lesion could require broad bilateral resection, while imiquimod alone may not eradicate bulky disease. Reducing the tumor first can make later ablation narrower and more anatomically precise.

The report also cautions against attributing the response to any single component. Imiquimod has an immunomodulatory role, but the HPV vaccine is prophylactic: it induces neutralizing antibodies against L1 virus-like particles and is intended to prevent infection or reinfection rather than treat an existing massive tumor. Its contribution as a therapeutic agent in this case is therefore unproven, and possible synergy, natural variation in host immunity and the effect of the procedure itself cannot be separated in a single-patient report.

Preserving vulvar anatomy was a central concern because radical surgery for an extensive lesion can produce anatomical alteration, functional impairment and psychological distress, particularly in young women. The case nevertheless remains preliminary. Buschke–Löwenstein tumors have a variable risk of recurrence and malignant transformation, and the report states that conservative cases require visual and colposcopic assessment every three to six months for at least two to five years.

Early healing, a negative HPV test and the absence of visible recurrence during short-term observation do not establish permanent cure. The most defensible conclusion is therefore narrow: in one carefully selected woman, neoadjuvant imiquimod followed by CUSA ablation achieved substantial tumor reduction, preserved vulvar structure and produced no evident recurrence during roughly four months of postoperative observation. Larger cohorts and extended follow-up are required before the sequence can be generalized or broadly adopted as a substitute for conventional oncologic management.

Subject of Research: Sequential immunomodulatory and ultrasonic treatment of a giant vulvar Buschke–Löwenstein tumor

Article Title: Anatomy-preserving sequential management of vulvar Buschke–Löwenstein tumor using immunomodulation and ultrasonic ablation: A case report

Article References: Looi, T. S., & Law, K.-S. (2026). Anatomy-preserving sequential management of vulvar Buschke–Löwenstein tumor using immunomodulation and ultrasonic ablation: A case report. Heliyon, 12(15), Article e45451. https://doi.org/10.1016/j.heliyon.2026.e45451

Image Credits: AI Generated

DOI: 10.1016/j.heliyon.2026.e45451

Keywords: Buschke–Löwenstein tumor, vulvar tumor, imiquimod, ultrasonic aspiration, CUSA, HPV type 11, tissue-sparing treatment, case report, vulvar anatomy, Anatomy-preserving, sequential, management