No abstract

In this updated systematic review and meta-analysis, we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN). PubMed, Embase and Cochrane Library databases were used to identify studies published between 1990 and 2015 and using a PCR-based or hybrid capture test to evaluate the presence of HPV DNA in vulvar cancer or VIN. Pooled estimates of the HPV prevalence with corresponding 95% confidence intervals (CI) were calculated based on a random effects model. The I statistic was used to describe the amount of heterogeneity. In meta-regression analyses, potential sources of heterogeneity were evaluated. We identified 92 eligible papers, comprising altogether 5,015 cases of vulvar cancer (64 papers) and 2,764 cases of VIN (48 papers). The pooled prevalence of HPV in vulvar cancer was 39.7% (95% CI: 35.1-44.4%). Overall, 76.3% (95% CI: 70.1-82.1%) of VIN lesions tested HPV-positive, while the HPV prevalence in new subcategories of VIN, uVIN and dVIN, was 86.2% (95% CI: 73.5-95.5%) and 2.0% (95% CI: 0-10.0%), respectively. Substantial between-study heterogeneity was observed (vulvar cancer: I = 88.4%; VIN: I = 90.7%) with the largest variation between geographical regions. Among HPV-positive cases, the predominant high-risk HPV type was HPV16, followed by HPV33 and HPV18. HPV6 was detected as a single infection in a small subset of VIN and vulvar cancer samples. Thus, HPV vaccination targeting these HPV types may prevent a substantial number of vulvar lesions.

Human papillomavirus (HPV) is essential for developing cervical cancer and precancerous lesions. Currently, three vaccines are available, which are effective as prophylaxis against HPV infection, however, limited knowledge exists about the possible effect of vaccinating women treated with conization to prevent recurrence. The aim of our study was to examine the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after conization according to HPV vaccination status. Using Danish nationwide registries, we identified women diagnosed with CIN3 on the cone (2006)(2007)(2008)(2009)(2010)(2011)(2012) and their HPV vaccination status. Vaccinees were defined as women vaccinated between 3 months before until 1 year after conization. The women were followed from 1 year after conization until diagnosis of CIN2+, conization, death, emigration or end of follow-up. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of CIN2+ comparing vaccinees with nonvaccinees. The HR was adjusted for age, histology on cone, education, year of conization, repeat conizations and CIN2+ lesions between conization and start of follow-up. Altogether 17,128 women were included (2,074 vaccinees). There was a statistically nonsignificant lower risk of CIN2+ among vaccinees (HR adjusted = 0.86, 95% CI: 0.67-1.09). Women vaccinated 0-3 months before tended to have a slightly lower HR of CIN2+ (HR adjusted = 0.77, 95% CI: 0.45-1.32) than women vaccinated 0-12 months after conization (HR adjusted = 0.88, 95% CI: 0.67-1.14), although not statistically significantly different. Our results add to the current knowledge about the potential clinical effect of vaccination as an adjunct to conization of high-grade cervical neoplasia to decrease risk of recurrence.

Many skin diseases can occur in pregnant women. However, a few pruritic dermatological conditions are unique to pregnancy, including pemphigoid gestationis (PG). As PG is associated with severe morbidity for pregnant women and carries fetal risks, it is important for the clinician to quickly recognize this disease and refer it for dermatological evaluation and treatment. Herein, we review the pathogenesis, clinical characteristics, and management of PG.

Tumor necrosis factor-alpha (TNF)-alpha inhibitors are licensed for patients with severe refractory psoriasis and psoriatic arthritis. However, TNF-alpha inhibitors have also been used off-label for various recalcitrant mucocutaneous diseases. This study aimed to evaluate the efficacy and safety of TNF-alpha inhibitors used for off-label dermatological indications. We retrospectively evaluated patient records of 118 patients treated off-label with TNF-alpha inhibitors in a dermatological university department. Patients presented with severe aphthous stomatitis/genital aphthous lesions (26), chronic urticaria (25), hidradenitis suppurativa (29), acne conglobata (11), dissecting cellulitis of the scalp (two), orofacial granulomatosis (four), sarcoidosis (four), granuloma annulare (two), granulomatous rosacea (one), granuloma faciale (one), subcorneal pustulosis (one), pyoderma gangrenosum (four), Sweet's syndrome (four), Well's syndrome (one), benign familial pemphigus (one), lichen planus (one), and folliculitis decalvans (one). A significant number of these patients went into remission during therapy with TNF-alpha inhibitors. A total of 11 patients (9%) experienced severe adverse effects during therapy. Off-label therapy with TNF-alpha inhibitors may be considered for selected patients with severe recalcitrant mucocutaneous diseases. The risk of severe adverse effects signals that a thorough benefit-risk assessment should be performed before initiating off-label treatment with TNF-alpha inhibitors for these conditions.