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.

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.

Assessing the Level of Knowledge, Beliefs and Acceptance of HPV Vaccine: A Cross-Sectional Study in Romania.

(1) Background: The infection with Human papilloma virus (HPV) is the most common sexually transmitted infection and it has been associated with cervical cancer (CC) in 99.7% of the cases. In Romania, CC is the second most common, with incidence (22.6%000) and mortality rates (9.6%000) three times higher than any other European country. Our aim was to assess the level of knowledge regarding HPV infection among parents, highschool students, medical students and doctors, with an emphasis on their main source of information-the Internet. (2) Methods: We applied five questionnaires to six categories of respondents: parents of pupils in the 6th-8th grades, medical students, doctors, boys in the 11th-12th grades, girls in the 11th-12th grades and their mothers. (3) Results: We included a total of 3108 respondents. 83.83% of all respondents had known about HPV infection. The level of information about HPV infection and vaccination was either satisfactory, poor or very poor. Their main source of information varied depending on the respondent profile and professional activity. Medical students were informed by doctors and healthcare professionals (53.0%), doctors gathered their information from books, journals and specialized brochures (61.6%). For the other categories of respondents, the Internet was the main source of information. Most respondents answered that doctors and healthcare professionals should provide information on HPV infection and vaccination, but very few of them actually seeked information from their general practitioner. (4) Conclusions: Population adherence to the appropriate preventative programs, as well as relevant information disseminated by the medical staff are key elements towards reducing the risk of HPV-associated cancers. An important role could also be played by schools, where teachers and school doctors could provide relevant information on the general aspects of HPV infection. Additionally, sex education classes and parent-teacher meetings should cover the main characteristics of HPV infection and what preventative measures can be employed against it.

Alopecia Areata Universalis in the Onset of Autoimmune Polyendocrine Syndrome Type III C.

Alopecia areata (AA) is an organ-specific autoimmune disease which affects hair follicles. It usually presents as a transient patchy hair loss, but it can sometimes progress into more severe forms such as AA totalis or AA universalis (AAU). Different autoimmune diseases, as well as autoimmune polyglandular syndromes (APS), have been associated with AA, especially with Type I and Type II APS. Herein, we describe the case of a 16-year-old boy with a severe form of AAU and early onset of adult APS, Type III C. As far as we are aware, this combination of AAU, Hashimoto thyroiditis, and Type I diabetes in a teenager has not been previously described in the literature. Furthermore, the early onset of AAU followed by a premature debut of adult APS Type III is again unique, which is why we report this case.

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.

Acral Melanoma in an Elderly Patient with Congenital Ichthyosis Vulgaris.

Ichthyoses are a heterogeneous group of skin disorders featuring erythroderma and generalized scaling. The relationship between ichthyosis and melanoma has not been well-characterized. Herein we present a unique case of acral melanoma of the palm developing in an elderly patient with congenital ichthyosis vulgaris. Biopsy revealed a superficially spreading melanoma with ulceration. To the best of our knowledge, no acral melanomas have been reported so far in patients with congenital ichthyosis. Nevertheless, considering the potential for invasion and metastasis, patients with ichthyosis vulgaris should undergo regular clinical and dermatoscopic screening for melanoma.

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.

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.

Keratosis pilaris atrophicans faciei: An observational, descriptive, retrospective clinical study.

Keratosis pilaris atrophicans faciei (KPAF) is a hereditary follicular disorder, an atrophicans subtype of keratosis pilaris (KP) with a highly elusive diagnosis. Clinically, it presents with follicular, horny papules surrounded by an erythematous halo of the cheeks, forehead, chin and eyebrows, and it is followed by a gradual hair loss on the lateral margins of the eyebrows. The onset is as early as a few months after birth, but it is mainly diagnosed in children and adolescents and it can persist through adulthood. At present, the natural progression of the disease is poorly understood, which makes a correct diagnosis highly unlikely. The aim of the present study was to describe the clinical characteristics of KPAF in patients encountered in daily practice, in order to find common characteristics that may aid in the earlier recognition of the disease. An observational, descriptive, retrospective study was performed on 14 patients diagnosed with KPAF between January 2000 and December 2020. The mean age at diagnosis was 17.04 years and the onset of clinical symptoms appeared at a mean age of 4.85 years. The first clinical symptom was KP involving either the upper or lower limbs, or both. Then, erythema of the face appeared at a mean age of 7.21 years, keratotic papules on the face at a mean age of 8.35 years and, finally, loss of hair on the lateral margins of the eyebrows at a mean age of 14 years. The patients also had concomitant xerosis cutis, multiple mole syndrome, acne, contact dermatitis and Laugier-Hunziker syndrome. Evidence of disease progression, associations, as well as efficacious treatment measures are lacking. An earlier diagnosis potentially allows for a more efficacious, targeted treatment option. Either topical emollients, systemic retinoids or laser therapy may prove effective for each patient individually.

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.

Effectiveness and tolerability of treatment for isolated actinic keratoses: A retrospective comparison between cryotherapy, CO2 laser and 5-fluorouracil 0.5%/salicylic acid 10.

Actinic keratoses (AK) have been described as either intraepithelial keratinocytic dysplasia that can evolve into invasive squamous cell carcinoma (SCC) or as in situ SCC that can progress into an invasive form. A retrospective study was conducted to compare outcomes of three different topical therapies for patients with single AK (<4): cryotherapy, CO2 laser and 5-fluorouracil 0.5%/salicylic acid 10%. We included 72 patients who presented at the Dermatology Clinic of Maggiore Hospital of Trieste between 1 November 2019 and 31 January 2020 for the treatment of AKs. All treatments led to a significant reduction in the average diameter of AK. Pain felt by patients was significantly lower after 5-FU 0.5%/SA 10%. Side effects appeared similarly distributed among the three groups, with erythema and crusts being the most frequent. Aesthetic outcomes were highest in the 5-FU 5%/SA 10% group, as evaluated by both the patient and the operator. Cryotherapy, CO2 laser and 5-FU 5%/SA 10% were all effective, with no significant efficacy differences among them. Additionally, 5-FU 5%/SA 10% was proved to have the best aesthetic result and to cause the least pain, while necessitating long-term administration. This should be taken into account for patients with low pain tolerance and low treatment adherence. Cryotherapy and CO2 laser have the advantage of requiring a single session, which might be more suitable for uncooperative patients.

Cutaneous Manifestations in Confirmed COVID-19 Patients: A Systematic Review.

There have been increasing reports of skin manifestations in COVID-19 patients. We conducted a systematic review and included manuscripts describing patients with positive RT-PCR coronavirus testing from nasopharyngeal swabs who also developed cutaneous manifestations. A total of 655 patients were selected, with different types of skin rashes: Erythematous maculopapular (n = 250), vascular (n = 146), vesicular (n = 99), urticarial (n = 98), erythema multiforme/generalized pustular figurate erythema/Stevens-Johnson syndrome (n = 22), ocular/periocular (n = 14), polymorphic pattern (n = 9), generalized pruritus (n = 8), Kawasaki disease (n = 5), atypical erythema nodosum (n = 3), and atypical Sweet syndrome (n = 1). Chilblain-like lesions were more frequent in the younger population and were linked to a milder disease course, while fixed livedo racemosa and retiform purpura appeared in older patients and seemed to predict a more severe prognosis. For vesicular rashes, PCR determined the presence of herpesviruses in the vesicle fluid, which raised the possibility of herpesvirus co-infections. The erythema-multiforme-like pattern, generalized pustular figurate erythema and Stevens-Johnson syndrome were most frequently linked to hydroxychloroquine intake. A positive PCR determination of SARS-COV-2 from conjunctival swabs suggest that eye discharge can also be contagious. These cutaneous manifestations may aid in identifying otherwise asymptomatic COVID-19 carriers in some cases or predict a more severe evolution in others.