Background/Objectives: To systematically evaluate and compare the clinical efficacy and safety of non-cryotherapy modalities versus standard liquid nitrogen cryotherapy for the treatment of plantar warts, while exploring the influence of specific cryotherapy procedural parameters and intervention-related subgroup characteristics on treatment outcomes. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted according to PRISMA guidelines. We searched four major databases from inception until 1 July 2026. The primary outcome was complete clearance. Secondary outcomes included partial clearance, recurrence, and treatment-related adverse events. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models. Results: Thirty-one RCTs involving 2313 patients were included. No statistically significant difference was detected between non-cryotherapy modalities and cryotherapy in complete clearance rates (RR = 1.09, 95% CI: 0.98-1.20; p = 0.10; I2 = 0.00%) or recurrence outcomes (RR = 0.90, 95% CI: 0.56-1.44; p = 0.66). Partial clearance significantly favored cryotherapy (RR = 0.65, 95% CI: 0.44-0.95; p = 0.03), particularly in subgroup analyses using two freeze-thaw cycles and treatment intervals of every two weeks. Regarding safety, topical therapies demonstrated significantly lower erythema rates than cryotherapy, while no statistically significant differences were observed in blistering, scarring, or secondary bacterial infection. Conclusions: No statistically significant difference was detected between non-cryotherapy modalities and cryotherapy regarding complete clearance or recurrence of plantar warts. Cryotherapy may offer better partial clearance under optimized treatment parameters, whereas topical therapies may be better tolerated in selected patients.

Folk medicine played an important role in human history. Their sources were fed by experience, superstition and religiosity. In the following, we analyze traditions of wart therapy with a focus on Europe under medical-historical aspects. We focus on zootherapy, i.e. the use of animals to treat common skin warts. Both domestic and wild animals were used. Mollusks, reptiles, spiders, insects, fish, and mammals are mentioned. Often the animals used died an agonizing death within these rites. The cruelty of such procedures may be seen as a reflection of the hard living conditions of common people in history. In contrast to healing, in folk medicine terms such as 'drive away,' 'lose,' or 'disappear' are used. Successes were usually individualized. Suggestion and autosuggestion are important. Considering that the rate of spontaneous remissions is high (up to 2/3 within 2 years), the 'effect' of the procedures is probably mostly due to this circumstance, and we would not recommend any of them. Interestingly, recently some antimicrobial compounds have been isolated from snails and ants.

Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by persistent cutaneous β-human papillomavirus infection and increased risk of cutaneous squamous cell carcinoma (cSCC). The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway links cytosolic DNA sensing, genomic instability and innate immune activation, but its expression in EV-associated cSCC remains poorly defined. We quantified STING, p53 and BCL2 immunohistochemical expression in tissue microarrays containing 47 EV-associated and 83 non-EV cSCCs. Tumor H-scores were medians across valid cores; primary comparisons used patient-clustered generalized estimating equations (GEE). STING expression was higher in EV-associated tumors (median H-score 192.4 vs. 149.5); in grade-adjusted GEE, EV status was associated with a + 37.2-unit difference (95% confidence interval [CI] 23.4-51.0; p < 0.001). The EV-non-EV STING difference varied by histological grade (interaction p = 0.0067), with the largest estimated difference in grade 1 tumors. p53 expression was also higher in EV tumors (97.7 vs. 36.3; adjusted difference + 43.8, 95% CI 18.8-68.8; p < 0.001), and EV tumors had higher odds of belonging to a higher p53 tertile (odds ratio [OR] 3.54, 95% CI 1.98-6.32; p < 0.001). BCL2 remained low and was not significantly associated with EV (adjusted difference - 1.93, 95% CI - 4.84 to 0.98; p = 0.193). STING and p53 remained positively associated after adjustment for histological grade, EV status and patient clustering. These findings define an altered STING protein-expression phenotype in EV-associated cSCC, accompanied by increased p53 expression but no independent BCL2 association, and support functional investigation of cGAS-STING signaling.

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.

Human papillomavirus (HPV) is a DNA virus that belongs to the Papillomaviridae family. Among the various types, high-risk strains are associated to malignancy, whereas low-risk types cause benign skin warts due to persistent infection. Unlike high-risk HPVs, low-risk HPV genomes remain in an episomal state while expressing E6/E7 proteins. These proteins exhibit a reduced ability to degrade pRb and p53, which finally leads to controlled epithelial hyperplasia instead of developing malignancy. Infection with low-risk HPV activates distinct host signaling pathways, ultimately promoting the proliferation of keratinocytes and formation of warts. Simultaneously, it triggers host innate and adaptive immune responses that often clear the lesion. This review focuses on low-risk types that cause skin warts by analyzing the molecular pathways, particularly the integrin-FAK-PI3K/AKT, Hippo-YAP/TAZ pathway along with MAPK-ERK pathways that promotes cutaneous benign wart formation. This article further studies clinical management strategies for HPV associated warts, including primary destructive treatment (cryotherapy, keratolytics, excision), immunotherapies (imiquimod, interferon injections or intralesional antigen), and novel adjunctive therapies with clinical evidence including photodynamic therapy, intralesional chemotherapeutics, and emerging HPV vaccination strategies. Among these, for benign skin warts, intralesional immunotherapy, particularly Candida antigen, and intralesional HPV vaccination have shown encouraging responses clinically. But extensive controlled clinical studies are necessary to establish their efficacy and clinical value as a standard medicine. This review therefore, generates a comprehensive overview of papilloma virus mediated skin warts and their management for both clinicians and researchers.

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.

Acquired epidermodysplasia verruciformis (aEV) is a skin condition caused by increased vulnerability to cutaneous human papillomaviruses. aEV disproportionately affects people who acquire HIV perinatally. There are no accepted diagnostic criteria for aEV. The lack of routine diagnosis has limited research into this condition. There are no community prevalence estimates, no evidence-based treatments and no cohort studies to understand the risk of skin malignancy. Most people with perinatally-acquired HIV, live in low-resource settings without access to specialist skin doctors or skin biopsies. There is therefore a need to develop diagnostic criteria that can be used by non-specialists and are applicable in low-resource settings.

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.

Vitamin D has been used in a gamut of medical conditions, including dermatology. Intralesional Vitamin D, however, is not a common therapeutic option in dermatological disorders. This review is an attempt to summarise the evidence available for using intralesional vitamin D in warts, molluscum, keloids, and vitiligo.

Mutations in genes controlling IFN-γ production or signaling underlie Mendelian susceptibility to mycobacterial disease (MSMD) and predispose affected individuals to mycobacterial and other infections. Autosomal dominant (AD) mutations in exon VI of IFNGR1, which encodes interferon-γ receptor 1 (IFN-γR1), have been associated with multifocal osteomyelitis. We report a Mexican male patient whose clinical course began with severe BCGitis at 2 years of age, followed by tuberculous lymphadenitis at age 3, disseminated tuberculosis with hepatitis at age 10, and disseminated Mycobacterium bovis infection with vertebral osteomyelitis at age 19. Subsequent manifestations included HPV-associated warts at age 21, pneumonia and vertebral osteomyelitis associated with M. colombiense at age 25, mesenteric fibrosis, hepatic abscesses, vertebral osteomyelitis associated with M. avium at age 28, and pneumonia associated with M. fortuitum at age 30. The patient responded to prolonged antimycobacterial therapy. Functional studies demonstrated deficient IL-12p40 production following BCG plus IFN-γ stimulation, impaired Stat-1 phosphorylation in response to IFN-γ, and increased cell-surface expression of CD119/IFN-γR1. Sanger sequencing identified the heterozygous IFNGR1 c.805delT (p.Tyr269Ilefs*8) variant in the patient but not in his parents, consistent with a de novo event. This truncating variant leads to cell-surface accumulation of a defective IFN-γR1 and exerts a dominant-negative effect on IFN-γ signaling. This case, together with our literature review, supports an association between impaired IFN-γ signaling due to AD IFNGR1 variants and susceptibility to recurrent infectious osteomyelitis.