Emodin combined with 5-aminolevulinic acid photodynamic therapy inhibits condyloma acuminate angiogenesis by targeting SerRS.

Human papillomavirus (HPV) infection can cause condyloma acuminatum (CA), which is characterized by a high incidence and a propensity for recurrence after treatment. Angiogenesis plays an important role in the occurrence and development of CA. Seryl-tRNA synthetase (SerRS) is a newly identified, potent anti-angiogenic factor that directly binds to the vascular endothelial growth factor (VEGFA) promoter, thereby suppressing its transcription. Emodin is a natural anthraquinone derivative that can promote SerRS expression. This study aimed to investigate the effects of emodin on CA and explore combined treatment strategies. The HPV-infected cell line SiHa was treated with either DMSO, emodin, ALA-PDT or a combination of emodin and ALA-PDT. We observed the effects on cell proliferation, apoptosis and the SerRS-VEGFA pathway. Our findings demonstrated that emodin targets angiogenesis through the SerRS-VEGFA pathway, resulting in the inhibition of SiHa cell proliferation and promotion of apoptosis (p < 0.001). To verify the therapeutic effect of emodin combined with ALA-PDT on HPV-associated tumours in vivo, we established an animal xenograft model by subcutaneously inoculating mice with SiHa cells (n = 4). The results showed that the combination of emodin and ALA-PDT significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.001), thus showing an inhibitory effect on tumour (p < 0.001). Furthermore, we determined that the mechanism underlying the decrease in VEGFA expression after emodin combined with ALA-PDT in CA may be attributed to the promotion of SerRS expression (p < 0.001). The combination of emodin and ALA-PDT holds promise as a novel therapeutic target for CA by targeting neovascularization in condyloma tissues.

[Pedunculated Giant Condyloma Acuminatum of the Scrotum].

The patient was a 71-year-old male whose chief complaint was a scrotum mass. The mass had gradually increased in size without any associated symptoms. The physical examination revealed a pedunculated, radish brown, and elastic soft tumor (4. 5×3. 5×3. 0 cm) in the right scrotum. Blood chemical analysis of HbA1c and squamous carcinoma antigen were 8. 3% and 38. 4 ng/ml (≦1. 5), respectively. This tumor was successfully treated with surgical resection. Histopathological examination showed condyloma acuminatum without malignant findings. Giant condyloma acuminatum commonly affects the genital and perianal areas. An immunocompromised state generally exists in the background of the patients.

Correlation between super-high magnification (400x) dermoscopy and reflectance confocal microscopy for the diagnosis of melanosis and other pigmented genital lesions.

The clinical diagnosis of pigmented genital lesions is challenging. Reflectance confocal microscopy (RCM) is effective for diagnosis but is limited in its application due to elevated costs. A more affordable dermatoscope with a 400x magnification (D400) has recently been brought to market. The aim of our study was to compare these two imaging techniques for the analysis of pigmented genital tumours. An observational, prospective and mono-centric study was carried out from October 2017 to May 2019, in which clinical, dermatoscopic (20x and 400x) and RCM data from 207 pigmented genital lesions were collected. The images generated via D400 and RCM were analysed by three expert investigators. Similarities between the criteria observed using D400 and RCM were evaluated by each investigator. In total, 207 lesions were included: 183 melanosis, 19 nevi, one basal cell carcinoma (BCC), two condylomas and two melanomas in situ. Our series correlates well with data found in the literature especially for the distribution of different lesions, their topography, and their aspect using x20 dermatoscopy and RCM. Pattern and cell criteria defined using RCM largely paralleled those observed with D400 for all three investigators. Correlation between D400 and RCM was moderate to strong with regards to the identification of the ring pattern and clustered round cells, strong for dendritic and plump cells, and perfect for isolated round cells and spindle cells. D400 is an easy-to-use, cost-effective alternative for the analysis of pigmented genital lesions, particularly for melanosis.

Alteration of RNA m6A methylation mediates aberrant RNA binding protein expression and alternative splicing in condyloma acuminatum.

Background: Condyloma acuminatum (CA) is caused by low-risk human papillomavirus, and is characterized by high recurrence after treatment. The RNA modification N6-methyladenosine (m6A) plays an important role during diverse viral infections, including high-risk HPV infection in cervical cancer. However, it is unclear whether low-risk HPV infection changes the RNA m6A methylation in CA. Methods: High-throughputm6A-sequencing was performed to profile the transcriptome-wide mRNA modifications of CA tissues infected by LR-HPVs and the paired normal tissues from CA patients. We further investigated the regulation of alternative splicing by RNA binding proteins (RBPs) with altered m6A modification and constructed a regulatory network among these RBPs, regulated alternative splicing events (RASEs) and regulated alternative splicing genes (RASGs) in CA. Results: The results show that the m6A level in CA tissues differed from that in the paired controls. Furthermore, cell cycle- and cell adhesion- associated genes with m6A modification were differentially expressed in CA tissues compared to the paired controls. In particular, seven RNA binding protein genes with specific m6A methylated sites, showed a higher or lower expression at the mRNA level in CA tissues than in the paired normal tissues. In addition, these differentially expressed RNA binding protein genes would regulate the alternative splicing pattern of apoptotic process genes in CA tissue. Conclusions: Our study reveals a sophisticated m6A modification profile in CA tissue that affects the response of host cells to HPV infection, and provides cues for the further exploration of the roles of m6A and the development of a novel treatment strategy for CA.

Argon Plasma Coagulation as Treatment for Anal Condylomas: A Narrative Review.

OBJECTIVES: Anal condylomas are a manifestation of anal human papillomavirus infection and can be associated with precancerous lesions and squamous cell carcinomas. Several methods have been described for treatment, including argon plasma coagulation. A narrative review of the evidence published on this topic was conducted. METHODS: A search was conducted using PubMed, Scopus, and Web of Science databases. RESULTS: Five studies reported on anal/perianal condyloma treatment with argon plasma coagulation. In 3 of these studies, there was a comparison with other treatment methods (addition of imiquimod, electrofulguration, and electrocautery, respectively). Argon plasma coagulation settings varied between studies. This type of treatment was effective for ablation. Recurrence rates and follow-up times varied largely between studies. No major complications, such as pain, scarring, sexual dysfunction, or severe bleeding were described. CONCLUSION: Studies indicate that argon plasma coagulation is an effective and safe therapy for anal and perianal condylomas.

Giant inflamed fibroepithelial scrotal polyp mimicking an anogenital wart.

We report the case of a young man who has never had any sexual contact presenting with a large scrotal lump with secondary bacterial infection. He reported no prior warts - genital or cutaneous. On examination, he had a large pink cauliform mass on the scrotum with four smaller but similar satellite lesions. Appearances were thought to be consistent with giant condyloma of Buschke and Lowenstein. Once superinfection was treated with oral antibiotics, he had a trial of imiquimod without success and was then referred to urology. After surgical excision, pathology concluded it was an inflamed fibroepithelial polyp with no malignant changes. To our knowledge, this is the first case report of a giant scrotal fibroepithelial polyp with characteristic gross warty features in an adult.

Risk factors of oncogenic HPV infection in HIV-positive men with anal condyloma acuminata in Shenzhen, Southeast China: a retrospective cohort study.

Background: Human immunodeficiency virus (HIV)-positive patients with anal condyloma acuminata (CA) present an increased risk of anal cancer progression associated with oncogenic human papillomavirus (HPV) infection. It is essential to explore determinants of anal infection by oncogenic HPV among HIV-positive patients with CA. Methods: A retrospective cohort study was performed in HIV-positive patients with CA between January 2019 to October 2021 in Shenzhen, Southeast China. Exfoliated cells were collected from CA lesions and the anal canal of HPV genotypes detected by fluorescence PCR. Unconditional logistic regression analysis was used to probe associations of independent variables with oncogenic HPV infection. Results: Among HIV-positive patients with CA, the most prevalent oncogenic genotypes were HPV52 (29.43%), HPV16 (28.93%), HPV59 (19.20%), and HPV18 (15.96%). Risk of oncogenic HPV infection increased with age at enrollment (COR: 1.04, 95% CI: 1.01-1.07, p = 0.022). In the multivariable analysis, age ≥ 35 years (AOR: 2.56, 95% CI: 1.20-5.70, p = 0.02) and history of syphilis (AOR: 3.46, 95% CI: 1.90-6.79, p < 0.01) were independent risk factors statistically associated with oncogenic HPV infection. History of syphilis (AOR: 1.72, 95% CI: 1.08-2.73, p < 0.02) was also an independent risk factor statistically associated with HPV16 or HPV18 infection. Conclusion: In clinical practice, HIV-positive CA patients aged ≥35 years or with a history of syphilis should carry out HR-HPV testing and even anal cancer-related examinations to prevent the occurrence of anal cancer.

"Free-Floating Anus": A Flap-Free Approach for Definitive Excision of Circumferential Giant Condyloma Acuminata.

Giant condyloma acuminata (GCA), or Buschke-Löwenstein tumor, is a rare exophytic cauliflower-like growth in the anogenital region. The spectrum of treatment options is wide, ranging from the application of topical ointments to the performance of an abdominoperineal resection. Currently, wide local excision is the most common approach and may entail the creation of a protective loop ileostomy or implementation of flaps or grafts that facilitate closure. We describe a unique surgical approach for the management of circumferential GCA void of the use a protective loop ileostomy, flaps, or grafts. Our report highlights that the implementation of a radical, circumferential, wide excision resulting in "free-floating anus" and healing via secondary intention can ultimately lead to excellent functional and cosmetic results and therefore may be considered a minimally invasive surgical option for patients afflicted with a large, circumferential GCA.

Squamous Cell Carcinoma of perineal area developed from the Buschke-Löwenstein tumor.

The Buschke-Löwenstein tumor is a rare disease associated with human papillomavirus infection. The condition manifests with an ulcerative, exophytic tumor localized in the perineal area. Generally considered as non-cancerous, the growth may develop malignant transformation. Our manuscript highlights the importance of early diagnosis with histopathological analysis.

WTAP-mediated m6A modification of IFNE is required for antiviral defense in condyloma acuminata.

BACKGROUND: IFN-ε is essential in combating viral infections, particularly in epithelial cells and protected mucosal tissues. Its protective effects have been demonstrated against HSV2, Zika virus, HIV and SARS-COV2. However, the specific expression and role of IFN-ε in skin keratinocytes and HPV infection are still not fully understood and require further investigation. OBJECTIVE: In this study, we aimed to investigate the functions and expression mechanism of IFN-ε in keratinocytes during HPV infection and the progression of condyloma acuminata. METHODS: Keratinocytes isolated from biopsied CA warts and normal skins samples were analyzed by MeRIP-seq analysis. IFN-ε and WTAP in CA warts and normal skins were analyzed by immunostaining and qPCR. RESULTS: In this study, we identified IFN-ɛ was markedly upregulated in CA warts and HPV-infected keratinocytes. IFN-ɛ expression also showed negatively correlation with the size of CA warts (R=-0.4646, P = 0.009). IFN-ɛ suppressed the susceptibility of HPV infection directly. m6A analysis reveals WTAP is a key m6A writer promoting the m6A modification of IFNE mRNA. CONCLUSION: Our research suggests that IFN-ɛ is an important Type I IFN cytokine involved in the development of genital warts. Furthermore, we found that HPV infection affects the m6A modifications of IFNE through a mechanism dependent on WTAP. This study provides insights into the innate immune response of the host to HPV infection and may contribute to the development of future strategies for regulating innate immunity to treat genital warts.

Condyloma acuminata: An evaluation of the immune response at cellular and molecular levels.

Condyloma acuminata (CA) is a benign proliferative disease mainly affecting in non-keratinized epithelia. Most cases of CA are caused by low-risk human papillomavirus (HPV), mainly HPV 6 and 11. The aim of the current study was to highlight the candidate genes and pathways associated with immune alterations in individuals who did not spontaneously eliminate the virus and, thus, develop genital warts. Paraffin-embedded condyloma samples (n = 56) were analyzed by immunohistochemistry using antibodies against CD1a, FOXP3, CD3, CD4, CD8, and IFN-γ. The immunomarkers were chosen based on the evaluation of the innate and adaptive immune pathways using qPCR analysis of 92 immune-related genes, applying a TaqMan Array Immune Response assay in HPV 6 or HPV 11 positive samples (n = 27). Gene expression analysis revealed 31 differentially expressed genes in CA lesions. Gene expression validation revealed upregulation of GZMB, IFNG, IL12B, and IL8 and downregulation of NFATC4 and IL7 in CA samples. Immunohistochemical analysis showed increased FOXP3, IFN-γ, CD1a, and CD4 expression in CA than in the control tissue samples. In contrast, CD3 and CD8 expression was decreased in CA lesion samples. Increased levels of pro-inflammatory cytokines in HPV-positive patients compared with HPV-negative patients seem to reflect the elevated immunogenicity of HPV-positive CA lesions. Host defense against HPV begins during the early stages of the innate immune response and is followed by activation of T lymphocytes, which are mainly represented by CD4+ and regulatory T cells. The low CD8+ T cell count in CA may contribute to this recurrent behavior. Additional studies are needed to elucidate the mechanism of host defense against HPV infection in CA.

Bladder squamous cell carcinoma in situ in the background of condyloma acuminatum in a kidney transplant recipient.

Condyloma acuminatum with synchronous squamous cell carcinoma in situ (CIS) rarely occurs in the bladder. In developed countries, bladder squamous cell carcinoma (SCC) is uncommon. Among the various noninvasive squamous bladder lesions, there is significant morphological overlap, which further complicates accurate diagnosis. Immunosuppression and human papilloma virus increase the risk of bladder condyloma acuminatum, which has a strong association with bladder SCC. Herein, we describe a case of a 79-year-old man with a history of end-stage renal disease with kidney transplantation and anal SCC who presented with bladder squamous cell CIS arising in the background of condyloma acuminatum.

Verrucous Carcinoma Arising in an Extended Giant Condyloma Acuminatum.

A 43-year-old heterosexual Tunisian man presented to the dermatology department with complaints of a genital friable mass. He had a past medical history of chronic hepatitis B. He was married and had a history of multiple sexual partners. The lesion had been present for over 10 years and gradually increased in size, disfiguring his genitalia. It had a major impact on his quality of life, preventing sexual intercourse and resulting in poor personal hygiene. On physical examination, the vegetative lesion presented as a giant cauliflower-like tumor (Figure 1) with a foul smell. The tumor involved the left inguinal region, the suprapubic genitalia, and was encircling the entire penile shaft. He also had inguinal lymphadenopathies. Under local anesthesia, a skin biopsy of the vegetative tumor was performed and sent for histopathologic examination. It revealed an exophytic epithelial tumor with papillomatosis, marked acanthosis, and many koilocytes, especially in the superficial layers of the epidermis. These signs along with the preservation of regular cytology were consistent with the diagnosis of condyloma acuminatum (Figure 2a). The histologic examination also showed clusters of atypical keratinocytes with high mitotic activity and keratinization, suggesting nests of squamous cell carcinoma (SCC) (Figure 2b and 2c). DNA-polymerase chain reaction (PCR) marker for Human papilloma virus (HPV) stains 11 was positive. Serology for hepatitis C, HIV, and syphilis non-reactive. Computed tomography scan of the abdomen and pelvis showed inguinal lymphadenopathies. The patient was referred to the oncologist for radiotherapy to reduce the size of the tumor followed by surgery. (SKINmed. 2023;21:53-54).

[Cystectomy of a young patient with squamous cell metaplasia of the bladder and manifestation of condyloma]. / Zystektomie einer jungen Patientin mit verhornter plattenepithlialen Metaplasie der Harnblase und ausgeprägtem Kondylombefall.

Interdisciplinary managed case of a 29-Year-old patient with massive condylomas of the vulva and papillary squamous cell metaplasia of the bladder, leads after years of chronic cystitis and obstruction with meatus plastic and laser treatment to cystectomy with conduit and partial vulvectomy. After long lasting HPV infection with condyloma we also found a squamous cell carcinoma (pT1 G1) of the vulva.

Successfully treated urethral condyloma acuminatum utilizing intraurethral self-application of 5-fluorouracil via Q-tip.

Condyloma acuminatum is a benign genital lesion associated with low-risk human papillomavirus subtypes. Approximately 20% of HPV-associated genital warts occur in the urethra. Topical treatment of urethral condyloma in women can be challenging to treat due to difficulty applying the medication such that it maintains contact with the urethra long enough to be effective. We present a case of a successfully cleared urethral condyloma acuminatum treated via self-application using a Q-tip.

Consensos em HPV Masculino da Sociedade Portuguesa de Andrologia, Medicina Sexual e Reprodução: Seguimento.

Patients with genital HPV lesion, as well as partners, usually present higher psychological stress, than the actual medical consequences of the lesion. Follow-up of these patients should be based on education and counseling. HPV molecular tests are not recommended as a follow-up test, or for screening partners. Development and implementation of protocols, by the centers or units, that follow these patients, are recommended.

Cryotherapy combined with photodynamic therapy for successful treatment of condyloma acuminatum in special sites such as the nipple and the nasal vestibule: A series of two case reports.

Condyloma acuminatum is a benign tumor principally resulting from a human papillomavirus type 6 or 11 infection. The lesions mostly damage the genital and perianal squamous epithelium and skin but occasionally emerge outside the perianal and genital regions. We studied the cases of a 29-year-old man with left nasal vestibule vegetation and a 22-year-old woman with left nipple vegetation. Each was diagnosed with condyloma acuminatum by histopathological examination and a human papillomavirus DNA test. The two patients received cryotherapy combined with 5-aminolevulinic acid photodynamic therapy and experienced no relapses during follow-up. These results suggest that physicians cannot ignore condyloma acuminatum outside the perianal and genital regions during diagnosis and treatment. Additionally, cryotherapy combined with 5-aminolevulinic acid photodynamic therapy is not only safe and effective for the treatment of condyloma acuminatum in special sites, but it is also less destructive to the affected regions. Thus, cryotherapy combined with 5-aminolevulinic acid photodynamic therapy may have more advantages than traditional therapy in the treatment of condyloma acuminatum in special sites.