Podophyllotoxin (PPT) is commonly used for genital warts due to its antimitotic properties and relatively good accessibility since it can be extracted from plants in low-economy countries. However, due to relatively high toxicity, it cannot be used in a systematic way (intravenously). Thus, there is a need to find or create an equally effective derivative of PPT that will be less toxic. Natural PPT is a suitable and promising scaffold for the synthesis of its derivatives. Many of them have been studied in clinical and preclinical models. In this systematic review, we comprehensively assess the medical applications of PPT derivatives, focusing on their advantages and limitations in non-cancerous diseases. Most of the existing research focuses on their applications in cancerous diseases, leaving non-cancerous uses underexplored. To do that, we systematically reviewed the literature using PubMed, Embase, and Cochrane databases from January 2013 to January 2025. In total, 5333 unique references were identified in the initial search, of which 44 were included in the quantitative synthesis. The assessment of the quality of eligible studies was undertaken using the PRISMA criteria. The risk of bias was assessed using a predefined checklist based on PRISMA guidelines. Each study was independently reviewed by two researchers to evaluate bias in study design, reporting, and outcomes. Our analysis highlights the broad therapeutic potential of PPT derivatives, particularly in antiviral applications, including HPV, Dengue, and SARS-CoV-2 infections. Apart from their well-known anti-genital warts activity, these compounds exhibit significant anti-inflammatory, antimitotic, analgesic, and radioprotective properties. For instance, derivatives such as cyclolignan SAU-22.107 show promise in antiviral therapies, while compounds like G-003M demonstrate radioprotective effects by mitigating radiation-induced damage. To build on this, our review highlights that PPT derivatives, apart from anti-genital warts potential, exhibit four key properties-anti-inflammatory, antimitotic, analgesic, and radioprotective-making them promising candidates not only for treating viral infections such as HPV, Dengue, and SARS-CoV-2 but also for expanding their therapeutic potential beyond cancerous diseases. In conclusion, while PPT derivatives hold great potential across various medical domains, their applications in non-cancerous diseases remain limited by the scarcity of dedicated research. Continued exploration of these compounds is essential to unlock their full therapeutic value.

Giant condyloma acuminatum (GCA), alternatively referred to as a Buschke-Löwenstein tumor (BLT), is an uncommon, benign, but locally aggressive form of verrucous carcinoma. The condition usually affects the male population under the age of 50 years; however, there have been rare reports of pediatric cases. Various risk factors such as smoking, diabetes, promiscuous behavior, poor hygiene, immunosuppression, and others are linked to the development of this condition. We present the case of a 26-year-old male patient who came to the dermatology department with primary complaints of 10-year-old verrucous tumor formations located in the perigenital and perianal areas. Serological tests for AIDS, hepatitis B, hepatitis C, Chlamydia trachomatis, and syphilis were negative. The routine blood tests were slightly abnormal. Histological verification of condylomata acuminata of Buschke-Löwenstein was made. Given the sensitive areas, surgery was advised. With several fine undermining scalpel excisions, the lesions in the scrotal and perigenital areas were removed and the dartos muscle was preserved. Electrodissection and shave curettage were not performed. The postoperative period passed without complications and no recurrences in the perigenital area were reported. We believe that our case report represents the first documented surgical approach for scrotal Buschke-Löwenstein tumor using exclusively fine undermining scalpel surgery. A brief literature review of the condition is presented, focusing on the currently available treatment options and highlighting the potential effectiveness of the surgical approach.

Giant condyloma acuminata (GCA) is a rare, locally aggressive manifestation of human papillomavirus (HPV) infection, typically affecting the anorectal area. Patients with GCA often have a poor prognosis due to the high risk of malignant transformation. In this case report, we present a 39-year-old man with HIV who developed progressive and refractory anorectal GCA. Despite initially non-cancerous pathology results, there were concerns regarding a malignant component to the mass. Multidisciplinary discussions led to the decision to pursue definitive radiation therapy. This case report and review of the literature highlight the role of radiation in the management of GCA and the importance of a multidisciplinary approach in the treatment of complex cases.

Giant condyloma acuminatum (GCA) is an uncommon condition affecting the anogenital area.

Here, we report an 88-year-old male patient who presented with a 5-year history of a progressive appearance of multiple cauliflower-like warts over his penile shaft, pubis region, and groin as well as urine leakage along the distal penile shaft. Physical examination revealed an ulcerative skin perforation with pus discharge under the distal prepuce base, which was initially suspected to be a urethral fistula. However, during surgery, it was discovered that the perforation was caused by a giant condyloma lesion that had obliterated the prepuce opening, with infection and high pressure causing subsequent skin perforation. He underwent circumcision and wide excision with electrocauterization of the warts. He was discharged after the surgery, and the residual lesion was treated with imiquimod and low-dose oral tegafur-uracil.

Penile GCA can cause prepuce perforation and can be postoperatively treated with imiquimod and low-dose oral tegafur-uracil.

The Buschke-Löwenstein tumor (BLT) is an uncommon sexually transmitted ailment attributed to the human papillomavirus (HPV)-usually the 6 or 11 type (90%)-with male predominance and an overall infection rate of 0.1%. BLT or giant condyloma acuminatum is recognized as a tumor with localized aggressiveness, displaying distinctive features: the potential for destructive growth, benign histology, a rate of 56% malignant transformation, and a high rate of recurrence after surgical excision. There are several treatment choices which have been tried, including laser, cryotherapy, radiotherapy, electrocoagulation, immunotherapy, imiquimode, sincatechins, intralesional injection of 5-fluoruracil (5-FU), isolated perfusion, and local or systemic chemotherapy. In the case of an extensive tumor, preoperative chemotherapy or radiotherapy is used for tumor shrinkage, making the debulking procedure safer. HPV vaccines significantly decrease the incidence of genital warts, also decreasing the risk of BLT; HPV-6 and HPV-11 are included in these vaccines.

We present a 53-year-old heterosexual man, hospitalized in our department in June 2021 with a typical cauliflower-like tumor mass involving the perianal region, which progressively increased in size for almost 7 years. The perianal mass was completely removed, ensuring negative surgical margins. The large perianal skin defect which occurred was reconstructed with fascio-cutaneous V-Y advancement flap. There was no need for protective stoma. The literature review extended from January 1980 and December 2022, utilizing Pubmed and Google Scholar as search platforms.

Due to the disease's proximity to the anal verge and the limited number of reported cases, arriving at a definitive and satisfactory treatment strategy becomes challenging. The optimal approach entails thorough surgical removal of the lesion, ensuring well-defined surgical margins and performing a wide excision to minimize the likelihood of recurrence. In order to repair the large wound defects, various rotation or advancement flaps can be used, resulting in reduced recovery time and a diminished likelihood of anal stricture or other complications. Our objective is to emphasize the significance of surgical excision in addressing BLT through the presentation of a case involving a substantial perianal condyloma acuminatum, managed successfully with complete surgical removal and the utilization of a V-Y advancement flap technique. In the present case, after 5 months post operation, the patient came back with a buttock abscess, which was incised and drained. After another 5 months, the patient returned for difficult defecation, with an anal stenosis being diagnosed. An anal dilatation and sphincterotomy were carried out, with good postoperative results.

The surgical management of Buschke-Löwenstein tumors needs a multidisciplinary team with specialized expertise. The reconstruction techniques involved can be challenging and may introduce additional complications. We consider aggressive surgery, which incorporates reconstructive procedures, as the standard treatment for Buschke-Löwenstein tumors. This approach aims to achieve optimal surgical outcomes and prevent any recurrence.

Human papillomavirus (HPV) infection and related diseases are difficult clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating condyloma acuminata is remarkable, with high virus clearance and low recurrence rates. Podophyllotoxin (POD) is the first-line drug with a significant therapeutic effect on condyloma acuminata. However, no studies have determined whether POD-combined ALA-PDT improves high-risk (HR)-HPV-infected cell killing. We aimed to investigate whether POD-combined ALA-PDT could promote HPV-infected cell death more effectively than the single treatment and explore the underlying mechanism.

In HeLa and SiHa cells, flow cytometry, EdU assay and LDH release test were used to detect apoptosis, cell proliferation change and necrosis, respectively. To investigate whether the combined therapy might activate apoptosis and induce endoplasmic reticulum (ER) stress, flow cytometry was used to determine intracellular levels of ROS and calcium, and Western blotting was used to determine the expression of related proteins. Mitochondrial membrane depolarization was detected by JC-1 assay. Immunofluorescence staining and Western blotting were used to detect the activation of autophagy.

Podophyllotoxin -combined ALA-PDT inhibited the proliferation and promoted apoptosis and necrosis more effectively than the single treatment at the same intensity and concentration. The activation of the caspase-dependent apoptosis pathway, ER stress and autophagy was more substantial in POD-combined ALA-PDT than with single treatments.

Podophyllotoxin -combined ALA-PDT effectively promoted cell death through several pathways in HeLa and SiHa cells. This combination might be a promising therapeutic strategy for the HR-HPV infection.

Giant condyloma acuminatum (GCA), also called Buschke-Löwenstein tumor, presents as a verrucous infiltrating lesion and is caused by sexual transmission of human papilloma virus. The optimal treatment is controversial and there are no standard guidelines because of its rarity and frequent recurrence. It has a relatively high local recurrence rate.

We here report eight patients (six men and two women) with GCA whose lesions were successfully treated topically with traditional Chinese medicine (TCM) preparations, paiteling.

We administered topical TCM preparations to eight patients diagnosed with GCA who had refused surgery. The treatment process included three stages, their durations depending on the speed of resolution of the lesions and the results of visual inspection with acetic acid.

No significant complications occurred in any patient. The functional and esthetic outcomes were satisfactory. No recurrences were detected during follow-up.

Topical treatment with TCM preparations may be a good alternative to surgery or other traditional methods for the treatment of GCA. This treatment has the advantages of being non-invasive, painless, and having a low risk of recurrence, and may be a useful adjunct to mainstream medical treatments.