Condylomas are usually benign lesions associated with human papillomavirus (HPV) infection, but extensive disease can cause substantial morbidity. Immunosuppression can contribute to disease progression.

BackgroundViral warts are a common skin infection, usually on the hands, feet, or face of children and young adults, and are caused by the human papillomavirus (HPV) due to lower immune resistance. The common types seen in Pakistan are common warts, plantar warts, and flat warts, which cause pain or cosmetic concern among patients.AimsTo compare and evaluate the efficacy of intralesional purified protein derivative (PPD) and vitamin D3 in the management of viral non-genital cutaneous warts.MethodsA retrospective, comparative study was conducted at Nishtar Medical University Hospital, Multan, Pakistan from January to July 2023. A total of 266 patients with 1-10 viral warts were divided into two groups: Group I was given intralesional PPD (0.1 mL of 10 TU), and Group II was given intralesional vitamin D3 (0.5 mL of 600,000 IU), each given at 2-week intervals for a maximum of four doses.SummaryThe mean age of participants was 42.84 ± 13.29 years, with a male predominance (67.3%). Complete clearance of warts was significantly higher in the PPD group (85.7%) compared to the vitamin D3 group (71.4%; P = .005). Subgroup analysis revealed better outcomes with PPD in younger patients with multiple warts and specific anatomical locations (palmar, plantar, trunk), while vitamin D3 showed superior clearance for limb warts. Intralesional PPD demonstrated superior efficacy compared to vitamin D3 in the treatment of viral warts. Both therapies were safe and well-tolerated. This study provides direct comparative evidence of distinct immunological mechanisms, offering practical insights for the management of recalcitrant warts.

Pure metaplastic squamous cell carcinomas (MSCC) of the breast are rare. We report the case of a 57-year-old woman who presented with a breast abscess in whom a papillomatous lesion was identified during incision and drainage. The initial biopsy demonstrated hyperplastic squamous epithelium with koilocytic atypia, raising the possibility of condylomata acuminata. Subsequent wide excision revealed extensive squamous metaplasia with invasive squamous cell carcinoma arising within a cystic papillary lesion consistent with pure MSCC of the breast. Immunohistochemistry revealed positivity for p63 and negativity for p16, estrogen receptor, progesterone receptor, and human epidermal growth receptor 2. The investigations excluded human papillomavirus infections, cutaneous origins, and extramammary primary squamous cell carcinomas. Following early local recurrence, the patient underwent mastectomy and axillary dissection. Adjuvant radiotherapy and chemotherapy were also administered. This case highlights the diagnostic challenges and aggressive behavior of pure MSCC and emphasizes the importance of clinicopathological correlations and multidisciplinary management.

Human papillomavirus types 6 and 11 are associated with mucosal condylomata acuminata, with rare reports of extragenital manifestations. We report a case of condyloma localized to the neck of an immunocompetent heterosexual man, without concurrent anogenital lesions. Our findings challenge theories of the site-specific tropism of these human papillomavirus types.

Condyloma acuminatum (CA) is a recurrent human papillomavirus (HPV)-associated lesion characterized by a locally immunosuppressive microenvironment. Although 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has been used as a local treatment option for CA and other HPV-related lesions, the mechanisms underlying its immunomodulatory effects remain incompletely understood. In this study, we investigated whether ALA-PDT-induced ferroptosis is associated with macrophage polarization and immune microenvironment-related changes in experimental CA models. HPV16-positive SiHa cells were used as an HPV-positive epithelial cell model to examine the cellular response to ALA-PDT, and the findings were further validated in an ex vivo CA tissue culture model. ALA-PDT significantly reduced the long-term clonogenic growth of SiHa cells in vitro, as demonstrated by colony formation assays. Mechanistically, ALA-PDT suppressed the GPX4/SLC7A11 antioxidant system and increased the accumulation of reactive oxygen species, malondialdehyde, and lipid peroxides in SiHa cells, indicating ferroptosis-associated cellular changes. In a Transwell co-culture system, ALA-PDT-treated SiHa cells promoted macrophage polarization toward an M1-like phenotype, as indicated by increased expression of CD86, iNOS, and IL-1β and decreased expression of CD206 and CD163. These effects were partially attenuated by ferrostatin-1. Consistently, ALA‑PDT reduced GPX4 and SLC7A11 expression in ex vivo condyloma acuminatum tissues, concomitant with an increase in CD86‑positive macrophages and a decrease in CD206‑positive macrophages. Collectively, these findings suggest that ALA-PDT suppress clonogenic growth, induce ferroptosis-associated changes, and modulate macrophage polarization in experimental CA-related models. Further studies are required to determine whether these effects contribute to lesion clearance and therapeutic responses in vivo.

Human papillomavirus (HPV) infection is highly prevalent worldwide and is associated with a broad spectrum of anogenital diseases, including vulvar condylomas and malignancies. Immunosuppression plays a key role in HPV persistence, recurrence, and progression; however, data on the clinical course of vulvar condylomas in immunocompromised women remain limited. This retrospective cohort study evaluated clinical progression, treatment response, recurrence, and neoplastic outcomes in women diagnosed with vulvar condyloma between January 2008 and January 2021 at a tertiary referral center in Brazil. Immunosuppressed patients, including women living with HIV, those receiving immunosuppressive therapy for autoimmune diseases, and patients undergoing chemotherapy, were compared with an age-matched immunocompetent group. Among 294 women included, 41 (13.9%) were immunosuppressed. Lesion extent was significantly greater in immunosuppressed patients, although lesion number did not differ between groups. Clinical remission after first-line treatment was significantly lower among immunosuppressed women (21.9%vs55.0%; p < 0.0001; OR = 4.5) with a higher need for multiple treatment sessions. Similarly, the complete remission rate at the end of follow-up was higher for the immunocompetent patients (75.9% vs. 48.8%; p < 0.0001; OR = 3.3). Immunosuppressed women had a 2.3-fold increased risk of recurrence and a higher risk of progression to vulvar intraepithelial neoplasia (OR = 6.7) and invasive disease (OR = 8.5). In the HIV patients, recurrence was not associated with CD4T-lymphocyte count or HIV viral load. These findings indicate that immunosuppressed women with vulvar condylomas experience more extensive disease, poorer treatment response, higher recurrence rates, and an increased risk of neoplastic progression, highlighting the importance of closer surveillance and individualized management in this high-risk population.

Early prophylactic human papillomavirus (HPV) vaccination of girls and boys leads to long-lasting sterile immunity against the HPV types covered by the respective vaccine. Both in clinical trials and in population-based studies, virus-like particle (VLP)-based HPV vaccines have exceeded all expectations regarding immunogenicity and efficacy. In clinical trials, HPV vaccines induced protection rates of 95-100% against high-grade cervical intraepithelial neoplasia (CIN) caused by vaccine-covered types, and nearly 100% against HPV6/11-induced anogenital warts. Numerous studies have demonstrated that early age at vaccination is crucial for the effectiveness of HPV vaccination. The duration of vaccine-induced protection against high-grade CIN and cervical cancer, as documented by long-term studies, currently ranges between 15 and 18 years. In addition to cervical cancer and anogenital warts, early HPV vaccination can also prevent precursor lesions of anal cancer as well as vulvovaginal precancerous lesions at the population level. Several countries have already introduced a single-dose vaccination schedule in line with the WHO recommendation. Given the lack of long-term data and data on HPV infections outside the cervix, Germany and other countries are still maintaining a 2-dose vaccination schedule. The WHO aims to eliminate cervical cancer. To this end, all countries should achieve HPV vaccination rates of 90% among 15-year-old girls by 2030. Due to herd effects, vaccination rates of around 80% may also be sufficient. In Germany, currently only 55% of 15-year-old girls and 36% of boys have completed the full HPV vaccination series. To increase HPV vaccination rates, a national HPV vaccination year is planned to be held in Germany in 2028.

ObjectivesClinician-observed external genital lesions may be incorporated into syndromic STI management, yet their prevalence and morphology in antenatal populations are poorly characterized. We aimed to describe the prevalence and types of clinician-observed genital lesions among pregnant women in a high HIV/STI prevalence setting and examine their distribution by laboratory-confirmed HIV, syphilis, and Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis (CT/NG/TV) status.MethodsWe analyzed clinical and laboratory data from the Philani Ndiphile antenatal STI screening study (2021-2025), conducted across four primary healthcare clinics in the Eastern Cape, South Africa (ClinicalTrials.gov identifier: NCT04446611). Among 2,247 pregnant women attending their first antenatal visit, trained clinicians documented the presence and morphology of external genital lesions during routine pelvic examination. Lesions were categorized as warts, inflammatory/dermatitis-like, ulcerative/erosive, boils/abscesses, scarring, cystic swelling, or other/unclassified. HIV and syphilis were diagnosed using rapid antibody testing and rapid treponemal tests; CT/NG/TV was detected by GeneXpert® molecular assay. Analyses used counts and proportions to characterize lesion prevalence overall and by infection status, with comparisons performed separately for HIV, syphilis, and CT/NG/TV.ResultsOverall, 61 participants (2.7%) had a clinician-observed genital lesion. Lesion prevalence was significantly higher among women living with HIV than among women without HIV (6.1% vs. 1.3%; p<0.001) and among women with, versus women without syphilis (11.9% vs. 2.4%; p < 0.001), but did not differ significantly between women with versus without CT/NG/TV (3.5% vs. 2.4%; p = 0.16). Warts were the most common lesion type overall and were disproportionately observed among women living with HIV. Among lesion-positive women within each infection group, ulcerative lesions were observed in 40% of those with syphilis, 12.5% of those living with HIV, and 19% of those with CT/NG/TV.ConclusionsClinician-observed genital lesions were uncommon in this antenatal cohort, and most laboratory-confirmed STIs were not accompanied by visible lesions. These findings highlight their limited overlap and support current guidelines emphasizing laboratory-based antenatal screening for HIV and syphilis, with expanded STI testing where diagnostic capacity permits.