Unraveling the Complex Nexus of Human Papillomavirus (HPV) in Extragenital Keratinocyte Skin Tumors: A Comprehensive Analysis of Bowen's Disease and In Situ Squamous-Cell Carcinoma.

This comprehensive study delves into the intricate landscape surrounding the role of human papillomavirus (HPV) in extragenital keratinocyte skin tumors, specifically exploring Bowen's disease (BD) and in situ squamous-cell carcinoma (iSCC). Through a multifaceted examination, this research study elucidates the nuanced interplay of HPV, gender dynamics, anatomical site variations, and potential implications for the etiopathogenesis of these malignancies.

New 675 nm Laser Device: The Innovative and Effective Non-Ablative Resurfacing Technique.

Background and Objectives: Photo/chrono-aging is usually expressed as facial discolouration, wrinkles, redness, elastosis, laxity, and dehydration, thus representing major signs of ageing that often lead to a negative phycological impact on a patient's quality of life. Several types of treatment have been tested during the last decade, especially laser treatments. This article aims to share our experience in the treatment of photoaging with a new 675 nm laser source system on facial chrono-ageing. Materials and Methods: Thirty-five (35) patients were treated with the 675 nm laser device: 32 females (mean age 49 years) and 3 men (mean age 57 years), with Fitzpatrick skin types I-III (9% type I, 43% type II, 48% type III), facial wrinkles and hyperpigmented spots. The efficacy of this treatment was assessed using the Modified Fitzpatrick Wrinkles Scale (FWS), which was calculated before starting the treatment and after 6 months. The pain was evaluated using the VAS Pain Scale. Results: All 35 patients showed a significant improvement in facial wrinkles according to the FWS (from 1.96 to 1.73 at the 3-month follow-up, up to a value of 1.43 at 6 months). In a small group of patients, it was observed that 44% of them showed vascular moderate improvement and that 13% showed a vascular marked improvement after treatment. No side effects were detected except a mild erythematous rash in two patients, and the VAS Pain scale was assessed at 1.17. Conclusions: Red Touch allows a uniform and stable result to be achieved over time with minimum discomfort.

Actinic Keratoses: A Prospective Pilot Study on a Novel Formulation of 4% 5-Fluorouracil Cream and a Review of Other Current Topical Treatment Options.

BACKGROUND: Actinic keratosis (AK) is one of the most common skin diseases, with a low risk of progression into invasive squamous cell carcinoma. We aim to assess efficacy and safety of a novel formulation of 5-Fluorouracil (5-FU) 4% with once daily application for the treatment of multiple AKs. METHODS: A pilot study was performed on 30 patients with a clinical and dermoscopic diagnosis of multiple AKs, enrolled between September 2021 and May 2022 at the Dermatology Departments of two Italian hospitals. Patients were treated with 5-FU 4% cream once daily for 30 consecutive days. The Actinic Keratosis Area and Severity Index (AKASI) was calculated before starting therapy, and at each follow-up, to assess objective clinical response. RESULTS: The cohort analyzed included 14 (47%) males and 16 (53%) females (mean age: 71 ± 12 years). A significant decrease in AKASI score at both 6 and 12 weeks (p < 0.0001) was observed. Only three patients (10%) discontinued therapy, and 13 patients (43%) did not report any adverse reactions; no unexpected adverse events were observed. CONCLUSIONS: In the setting of topical chemotherapy and immunotherapy, the new formulation of 5-FU 4% proved to be a highly effective treatment for AKs and field cancerization.

Skin Thickening of the Scalp and High Signal Intensity of Dentate Nucleus in Multiple Sclerosis: Association With Linear Versus Macrocyclic Gadolinium-Based Contrast Agents Administration.

OBJECTIVE: The aim of this study was to assess the presence of detectable changes of skin thickness on clinical brain magnetic resonance imaging (MRI) scans in patients with MS, history of multiple gadolinium-based contrast agents (GBCAs) administrations, and evidence of gadolinium deposition in the brain. MATERIALS AND METHODS: In this observational cross-sectional study, 71 patients with MS who underwent conventional brain MRI with an imaging protocol including enhanced 3D volumetric interpolated breath-hold examination (VIBE) T1-weighted with fat saturation were assessed. Patients with bilateral isointense dentate nucleus on unenhanced T1-weighted images were assigned to group A (controls without MRI evidence of gadolinium deposition), and patients with visually hyperintense dentate nuclei were assigned to group B. Qualitative and quantitative assessment of the skin thickness were performed. RESULTS: Group A included 27 patients (median age, 33 years [IQR, 27-46]; 20 women), and group B included 44 patients (median age, 42 years [IQR, 35-53]; 29 women). Qualitative and quantitative assessment of the skin revealed significant differences between group A and group B. The average skin-to-scalp thickness ratios was significantly higher in group B than in group A (mean ± standard deviation = 0.52 ± 0.02 in group B vs 0.41 ± 0.02 in group A, P < 0.0001) and showed a positive correlation with the total number of enhanced MRI scans ( r = 0.39; 95% confidence interval, 0.17-0.57, P < 0.01). CONCLUSIONS: Brain MRI detects increased skin thickness of the scalp in patients with MS and dentate nucleus high signal intensity on unenhanced T1-weighted images and shows positive association with previous exposures to linear GBCAs rather than macrocyclic GBCAs.

The role of HPV in keratinocyte skin cancer development: A systematic review.

Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for squamous cell carcinoma development in patients with epidermodysplasia verruciformis and organ transplant recipients, their role in non-melanoma skin cancer (NMSC) progression in the general population remains controversial. The aim of our review is to summarize current scientific data and to systematically analyse evidence regarding the role of HPV in keratinocyte skin cancers. A total of 2284 patients were included, of which 724 with actinic keratoses, 290 with Bowen's disease, 949 with cutaneous squamous cell carcinomas and 321 with keratoacanthomas. In the case of actinic keratoses, the majority were positive for beta (n = 372, 58.49%) and gamma HPV (n = 256, 40.25%) and only a few (n = 6, 0.94%) were positive for alpha subtypes. Similarly, most of the cutaneous squamous cell carcinomas were positive for beta (n = 248, 55.98%) and gamma HPV (n = 172, 33.82%) and 23 cases (2.42%) were positive for alpha subtypes. Bowen's disease lesions were mostly positive for beta (n = 43, 55.84%) and alpha HPV (n = 30, 38.96%), in contrast to the gamma genus (n = 4, 5.19%). Keratoacanthomas showed a high distribution among beta genus (n = 79, 50.31%) and an equal proportion between alpha (n = 39, 24.84%) and gamma (n = 39, 24.84%) genera. Studies published so far identifying HPV in keratinocyte skin cancers reflect the difference in detection methods rather than a type-specific tendency towards either actinic keratoses, Bowen's disease, squamous cell carcinoma or keratoacanthoma. On the other hand, recent evidence regarding the role of HPV vaccination in patients with non-melanoma skin cancer brings into perspective the idea of a beta-HPV vaccine or a combined alpha and beta-HPV vaccine that could be used as an adjuvant treatment measure in patients with recalcitrant non-melanoma skin cancer.

Carbon Peeling Laser Treatment to Improve Skin Texture, Pores and Acne Lesions: A Retrospective Study.

Carbon peel laser treatment has been described for the improvement of skin texture, with pore reduction and acne lesion treatment. The technique consists of applying a carbon mask to the face for about ten minutes followed by laser irradiation with a Q-switched 1064 nm laser. This mechanism of action seems to be related to small carbon molecules binding both the corneocytes and serum within the hair follicles; the effect of the laser eliminates carbon bound to skin particles and the high temperature generated reduces sebum production by sebaceous glands and inhibits Cutibacterium acnes replication. Although this method was described 20 years ago, scientific data supporting its efficacy and safety have only recently been reported in small case series. For this reason, we performed a retrospective study including patients treated from January to May 2022 in the context of a private practice. Even if this study is limited by the low number of patients and its retrospective nature, this is the first research to show that carbon peel laser, performed with a standardized technique, is an effective and safe treatment for patients with acne lesions, showing pores and wrinkles, and is able to improve the overall skin aspect.

The Role of p16/Ki-67 Immunostaining, hTERC Amplification and Fibronectin in Predicting Cervical Cancer Progression: A Systematic Review.

Human papillomaviruses (HPVs) are common sexually transmitted infectious agents responsible for several anogenital and head and neck cancers. Cervical cancer (CC) is the fourth leading cause of death in women with cancer. The progression of a persistent HPV infection to cancer takes 15-20 years and can be preventable through screening. Cervical cytology (Pap smear) is the standard screening test for CC and precancerous lesions. For ASC-US and ASC-H lesions, a combination of Pap smear and HR-HPV analysis is recommended as a triage step before colposcopy. However, these tests cannot predict progression to CC. For this purpose, we summarized current scientific data on the role of p16/Ki-67 immunohistostaining, telomerase and fibronectin in predicting progression to CC. p16 and p16/Ki-67 dual staining (DS) were more specific than HR-HPV DNA testing for the detection of CIN2+/CIN3+ in women with ASC-US and LSIL. Similarly, hTERC FISH analysis significantly improved the specificity and positive predictive value of HPV DNA testing in differentiating CIN2+ from CIN2 cytological samples. In conclusion, p16 IHC, p16/Ki-67 DS and hTERC FISH amplification are all valid adjunctive biomarkers which significantly increase the sensitivity and specificity of cervical dysplasia diagnosis, especially when combined with HPV DNA testing. However, considering the global socioeconomic background, we can postulate that p16 and p16/ Ki-67 IHC can be used as a next step after positive cytology for ASC-US or LSIL specimens in low-income countries, instead of HPV DNA testing. Alternatively, if HPV DNA testing is covered by insurance, p16 or p16/Ki-67 DS and HPV DNA co-testing can be performed. In middle- and high-income countries, hTERC amplification can be performed as an adjunctive test to HPV DNA testing in women with ASC-US and LSIL.

Diagnostics of BAP1-Tumor Predisposition Syndrome by a Multitesting Approach: A Ten-Year-Long Experience.

Germline mutations in the tumor suppressor gene BRCA1-associated protein-1 (BAP1) lead to BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by high susceptibility to several tumor types, chiefly melanoma, mesothelioma, renal cell carcinoma, and basal cell carcinoma. Here, we present the results of our ten-year experience in the molecular diagnosis of BAP1-TPDS, along with a clinical update and cascade genetic testing of previously reported BAP1-TPDS patients and their relatives. Specifically, we sequenced germline DNA samples from 101 individuals with suspected BAP1-TPDS and validated pathogenic variants (PVs) by assessing BAP1 somatic loss in matching tumor specimens. Overall, we identified seven patients (7/101, 6.9%) carrying six different germline BAP1 PVs, including one novel variant. Consistently, cascade testing revealed a total of seven BAP1 PV carriers. In addition, we explored the mutational burden of BAP1-TPDS tumors by targeted next-generation sequencing. Lastly, we found that certain tumors present in PV carriers retain a wild-type BAP1 allele, suggesting a sporadic origin of these tumors or a functional role of heterozygous BAP1 in neoplastic development. Altogether, our findings have important clinical implications for therapeutic response of BAP1-TPDS patients.

Effective Intense Pulsed Light Protocol in the Treatment of Moderate to Severe Acne Vulgaris of the Chest and Back.

Background: Acne is defined as a chronic inflammatory disease of the pilosebaceous units, mainly affecting the face of young adults, but the chest and back can be involved as well. Oral antibiotics, topical retinoids, azelaic acid, benzoyl peroxide, and isotretinoin represent the most common treatment used for the treatment of acne, but several adverse effects and a lack of durable remission, with poor adherence by the patients, have been reported thus far. Lasers have been shown to be effective and safe to treat acne; intense pulsed light (IPL) demonstrates high efficacy rates, minimal discomfort, rapid recovery times, and excellent cosmetic and therapeutic outcomes. Objective: In this prospective study, we assessed the efficacy, safety, and reproducibility of a novel IPL protocol as a monotherapy in the treatment of acne of the chest and back. Methods: We included patients (N=50) aged 14 to 30 who presented with moderate papulopustular acne sited on the chest and back (Cook's Acne Grading Scale method 4-6, Pillsbury Scale III-IV). We performed four IPL sessions at two-week intervals on each patient. Results: An excellent outcome was achieved in 50 percent of the patients and a good outcome in the 35 percent of the patients. Patients experienced light erythema and mild burning as the most common side effects, which spontaneously resolved within 24 to 96 hours. Conclusion: Consistent with previous reports, our study demonstrated IPL to be a safe and effective treatment for severe cases of acne on the chest and back, providing excellent aesthetic and therapeutic results in 85 percent of treated patients.

Melasma treatment: a systematic review.

Melasma is a common chronic refractory disorder of pigmentation affecting people with darker skin types. Overall prevalence varies between 8.8% and 40%, depending on the ethnicity of the population and the geographical area. Therapeutic management of melasma is challenging, with high recurrence rates which significant impacts on the quality of life. No single treatment is universally efficacious. Systemic treatments with tranexamic acid and polypodium leucotmatous had promising results, although the former was related to systemic side effects. Microneedling and peeling were also efficacious, although their superiority to topical hydroquinone, the gold standard in melasma treatment, remains to be established. Similarly, laser and light devices have been beneficial. However, recurrence rates remain high in all treatment groups. Combination therapies, either in double or triple combinations yielded the best results when compared to single terapies. Treatment choice should be made after Wood's lamp examination, as well as dermatoscopic evaluation, in order to select the best treatment option, targeted at each melasma subtype.

Dupilumab as promising treatment for prurigo nodularis: current evidences.

Prurigo nodularis (PN) is a debilitating chronic disease characterized by intense itching and excoriated hyperkeratotic nodules distributed on the trunk and extremities, especially the extensor surfaces. The pathophysiology includes complex and not yet well-understood mechanisms involving inflammation and dysregulation of the nervous system. Currently, there are no approved therapies by the Food and Drug Administration (FDA) and the few treatment approaches for this condition are often ineffective and related to severe side effects. An emerging therapeutic option is dupilumab, a monoclonal antibody for adults and adolescents with moderate-to-severe atopic dermatitis, that inhibits interleukin-4 receptor alpha subunit (IL4-Rα) and the signaling pathways activated by interleukin (IL)-4 and IL-13. These cytokines seem to be involved in the development and perpetuation of PN and other type-2 inflammation diseases. Data on this topic are limited, but the emergent positive effects of this drug, reported in the literature and summarized in this review, suggest that it can be a safe and efficient therapy in PN.

Acne and diet: a review.

Acne is one of the most frequent dermatological afflictions especially for people in their first 30 years of age. Several studies have shown that nutrition is one of the key factors involved in acne pathogenesis. Data show that a high glycemic index diet may be a trigger in acne pathogenesis, while patients with a low glycemic index diet have fewer acne lesions. Milk and chocolate are also involved in the exacerbation of acne. However, foods rich in omega-3 fatty acids suppress the production of inflammatory cytokines with therapeutic effect. Additionally, docosapentaenoic acid and γ-linolenic acid have demonstrated improved acne lesions. The aim of this review was to summarize current knowledge on the association between acne and diet with special attention to the most frequently discussed factors involved in its pathogenesis: milk, chocolate, omega-3 fatty acids, hyperglycemia, hyperinsulinism, and IGF-1.

Spotlight on the treatment armamentarium of concomitant psoriasis and inflammatory bowel disease: a systematic review.

BACKGROUND: Psoriasis and inflammatory bowel diseases share common immunological pathomechanisms and therefore similar treatment options. OBJECTIVE: To assess already existing therapies and their efficacy versus adverse effects and paradoxical reactions in patients presenting with either disease or both. DATA SOURCES: A systematic search of the PubMed and Science.gov databases was performed for the period 2018-2020. Only articles in English were selected. Search terms included a combination of keywords: adalimumab, infliximab, etanercept, golimumab, certolizumab, ustekinumab, guselkumab, vedolizumab, secukinumab, ixekizumab, brodalumab, acitretin, cyclosporine, methotrexate, apremilast, mycophenolate mofetil, sulfasalazine, hydroxyurea, azathioprine, 6-thioguanine, tacrolimus, leflunomide and fumaric acid esters in combination with each of the following: paradoxical, psoriasis, psoriatic arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis. Other potentially relevant articles were identified by manually checking the references of the included literature. STUDY SELECTION: Recent reviews and meta-analyses, pooled analyses, cohort studies, observational studies, care reports were all included. CONCLUSIONS: Psoriasis and IBD can be treated concurrently as they share common inflammatory pathways. TNF-α inhibitors and IL-12/23 have been successful in treating both psoriasis and IBD. IL-17 inhibitors are recognized treatments for psoriasis but have the potential to exacerbate IBD. Newer molecules require further clinical trials and real-life studies in order to confirm their efficacy and safety.

Synthesis of the Data on COVID-19 Skin Manifestations: Underlying Mechanisms and Potential Outcomes.

The incidence of coronavirus disease 2019 (COVID-19)-related skin manifestations has progressively grown, in parallel with the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreading. The available evidence indicates that cutaneous signs are heterogeneous and can be divided as follows: a) erythematous rashes, b) lesions of vascular origin, c) vesicular rashes, d) urticarial rashes, and e) acute generalized exanthematous pustulosis (AGEP), erythema multiforme (EM) and other polymorphic/atypical reactions. Most cutaneous manifestations appear simultaneously or after respiratory and/or systemic symptoms such as fever, even if rarely urticaria has been reported as the first sign of the disease. It has been proposed that erythematous and vesicular rashes, as well as urticaria, are the result of immunological activation against Sars-CoV-2, similarly to other viral exanthems; alternatively, reactivation or co-infection of herpesviruses and drug hypersensitivity represent possible etiologic diagnosis that has to be considered. Regarding lesions of vascular origin, ischemic ones are the result of systemic hypercoagulability established in severe infections, whereas chilblains seem to be linked to the type I-interferon massively produced to halt virus replication. AGEP is triggered by drugs, whereas EM could represent a delayed immune response to the virus or a hypersensitivity reaction to drugs elicited by the inflammatory process built to fight the infection. A further pathogenic hypothesis is that the virus, or its particles detected in the skin (particularly in endothelium and eccrine glands), could be responsible for certain skin reactions, including chilblains and EM. From the available data, it appears that chilblains are correlated with younger age and less severe disease, while ischemic manifestations occur in the elderly with severe infection. In conclusion, larger studies are needed to confirm the suggested pathogenetic mechanisms of COVID-19-related skin reactions and to determine the potential prognostic significance of each one.

Basal cell carcinoma and dermal nevi of the face: comparison of localization and dermatoscopic features.

BACKGROUND: Basal cell carcinoma (BCC) and dermal nevi located on the face can easily be confused on clinical examination. Little is known about the different preferential localizations of these entities, and a systematic analysis of dermatoscopic features for differential diagnosis is lacking. METHODS: Clinical and dermatoscopic images of BCCs and dermal nevi were retrospectively evaluated to study their relation to various face anatomical areas, BCC histotype, classic and nonclassic dermatoscopic BCC criteria, as well as typical dermatoscopic criteria for dermal nevi. RESULTS: We examined 118 BCCs and 77 dermal nevi, all having histopathological confirmation. BCCs were most frequently located on the lateral side of the forehead (12.7%), nasal dorsum (10.2%) and nasal ala (9.3%), while dermal nevi were found predominantly on the buccal area (11.8%), scalp (11.8%), and perioral region (10.8%). The prevalent dermatoscopic criteria for BCC were the classic arborizing vessels (94.1%) and arborizing microvessels (89%). The most common BCC histotype on the face was sclerodermiform (47.5%), followed by nodular (28%) and superficial (24.6%). CONCLUSIONS: This study shows that BCCs are preferentially located on the lateral side of the forehead, nasal dorsum and nasal ala, while dermal nevi of the face are preponderantly located on the buccal area, scalp, and perioral region. The dermatoscopic features confirmed the frequency of classic and nonclassic criteria for BCCs already demonstrated in other studies. No significant site-specific features were observed for either BCCs or dermal nevi.

Neoadjuvant Therapy for Non-melanoma Skin Cancer: Updated Therapeutic Approaches for Basal, Squamous, and Merkel Cell Carcinoma.

OPINION STATEMENT: Recently introduced systemic therapies for locally advanced and metastatic non-melanoma skin cancers (NMSCs) are paving the way for neoadjuvant approach. Although none of the therapeutic options has currently gained indication in this setting, neoadjuvant approach for NMSCs is an open field and we are likely to see huge developments in the near future. Targeted therapy with sonic hedgehog pathway inhibitors is very effective in locally advanced or multiple basal cell carcinomas while immunotherapy with immune checkpoint inhibitors appears to be promising for advanced cutaneous squamous cell carcinoma and Merkel cell carcinoma. To date, targeted therapy and immunotherapy represent the frontiers in NMSC therapeutic management and, according to recent studies, good results can be achieved.