The impact of p16(ink4a) positivity in invasive vulvar cancer on disease-free and disease-specific survival, a retrospective study

Purpose To evaluate HPV and p16(ink4a) status as prognostic factors in patients with invasive vulvar cancer. Methods Retrospective analysis of disease-free (DFS) and disease-specific survival (DSS) of patients with invasive vulvar cancer at a single tertiary care center. Histology, HPV and p16(ink4a) status were evaluated in the context of a global multicenter trial. Logistic regression models were performed to identify the impact of p16(ink4a) positivity. Results 135 patients were included in the analysis. 32 (23.7%) showed a p16(ink4a) expression of over 25%. Disease-free and disease-specific survival was longer in p16(ink4a) positive patients (23 vs. 10 months, p = 0.004, respectively, 29 vs. 21 months, p = 0.016). In multivariate analysis, p16(ink4a) positivity was an independent parameter for DFS (p = 0.025, HR: 2.120 (1.100-4.085)), but not for DSS (p = 0.926, HR: 1.029 (0.558-1.901), in contrast to age and tumor stage. Conclusions Age and tumor stage negatively affect survival. However, disease-free survival is significantly longer in patients with p16(ink4a) positive invasive vulvar cancer

HPV prevalence in vulvar cancer in Austria

Background Even if vulvar cancer is not common, over one hundred women are affected in Austria per year. There is strong evidence that basaloid and warty variants are associated with types of human papillomavirus (HPV). Methods The aim of this study is to analyze the types of HPV in vulvar cancer in Austria. This cross-sectional period-prevalence international collaborative study on archival specimens was performed in cooperation with the Institut Catalan di Oncologia in Barcelona, Spain. A total of 177 consecutive samples of Austrian women were analyzed to detect the presence of various HPV types using the SPF10 PCR/DEIA/LiPA25 system. Furthermore, the expression of the tumor suppressor protein p16INK4a was analyzed by immunohistochemistry (CINtec histology kit, ROCHE). A tumor was considered HPV-driven if an overexpression of p16INK4a was detected. Results In all, 41 cases of vulvar cancer tested positive for HPV DNA (23%) and 32 (18%) were p16 positive. Patients with warty and basaloid squamous cell cancer were significantly younger than those with keratinizing squamous cell cancer (63.3 years vs. 71.0 years, p = 0.021). In addition, 77.4% of all cases suffering from warty or basaloid squamous cell cancer tested positive for HPV, compared to 9.5% of the keratinizing squamous cell cancer cases (p < 0.001). The most commonly detected HPV strain was type 16, followed by 31 and 33. Conclusion Infection with HPV type 16 appears to be strongly correlated to the development of warty or basaloid squamous cell cancer. Vaccination against HPV can be expected to prevent this type of vulvar cancer.(VLID)356917

Bariatric Surgery–How Much Malabsorption Do We Need?—A Review of Various Limb Lengths in Different Gastric Bypass Procedures

The number of obese individuals worldwide continues to increase every year, thus, the number of bariatric/metabolic operations performed is on a constant rise as well. Beside exclusively restrictive procedures, most of the bariatric operations have a more or less malabsorptive component. Several different bypass procedures exist alongside each other today and each type of bypass is performed using a distinct technique. Furthermore, the length of the bypassed intestine may differ as well. One might add that the operations are performed differently in different parts of the world and have been changing and evolving over time. This review evaluates the most frequently performed bariatric bypass procedures (and their variations) worldwide: Roux-en-Y Gastric Bypass, One-Anastomosis Gastric Bypass, Single-Anastomosis Duodeno-Ileal Bypass + Sleeve Gastrectomy, Biliopancreatic Diversion + Duodenal Switch and operations due to weight regain. The evaluation of the procedures and different limb lengths focusses on weight loss, remission of comorbidities and the risk of malnutrition and deficiencies. This narrative review does not aim at synthesizing quantitative data. Rather, it provides a summary of carefully selected, high-quality studies to serve as examples and to draw tentative conclusions on the effects of the bypass procedures mentioned above. In conclusion, it is important to carefully choose the procedure and small bowel length excluded from the food passage suited best to each individual patient. A balance has to be achieved between sufficient weight loss and remission of comorbidities, as well as a low risk of deficiencies and malnutrition. In any case, at least 300 cm of small bowel should always remain in the food stream to prevent the development of deficiencies and malnutrition

Detection of Human Papillomavirus Infection in Patients with Vaginal Intraepithelial Neoplasia

<div><p>Introduction</p><p>Vaginal intraepithelial neoplasia (VAIN) is a pre-malignant lesion, potentially leading to vaginal cancer. It is a rare disease, representing less than 1% of all intraepithelial neoplasia of the female genital tract. Similar to cervical intraepithelial neoplasia (CIN), there are three different grades of VAIN. VAIN 1 is also known as a low-grade squamous intraepithelial lesion (LSIL), whereas VAIN 2 and VAIN 3 both represent high-grade squamous intraepithelial lesions (HSIL). Risk factors for the development of VAIN are similar to those for cervical neoplasia, i.e. promiscuity, starting sexual activity at an early age, tobacco consumption and infection with human papillomavirus (HPV). However, compared to other intraepithelial neoplasia such as CIN or VIN (vulvar intraepithelial neoplasia), there still is little understanding about the natural course of VAIN and its capacity for pro- or regression. Furthermore, there is controversial data about the HPV detection rate in VAIN lesions.</p><p>Patients and Methods</p><p>67 patients with histologically confirmed VAIN, who were diagnosed between 2003 and 2011 at the University Women´s Hospital of Heidelberg Germany, were included in this study. The biopsies of all participating patients were subjected to HPV genotyping. GP-E6/E7 Nested Multiplex PCR (NMPCR) was used to identify and genotype HPV. Eighteen pairs of type-specific nested PCR primers were assessed to detect the following "high-risk" HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, as well as the "low-risk" genotypes 6/11, 42, 43 and 44. The data was analyzed with the software SAS (Statistical Analysis System).</p><p>Results</p><p>All 67 cases were eligible for DNA analysis. The median age was 53 years. The largest group with 53% (n = 36) was formed by women, who were first diagnosed with VAIN between the age of 41 to 60 years. 50% (n = 37) of the patients presented a VAIN in the upper 1/3 of the vagina. 58 (87%) were diagnosed with HSIL (VAIN). The median age in patients with LSIL (VAIN) was 53 years and in patients with HSIL (VAIN) 53.5 years. 12 women (18%) had an immunosuppression. HPV positivity was confirmed in 37 patients (55%). Except for a single patient, who had a triple infection with HPV types 6/11, 16 and 68, only infections with one single HPV genotype were detected. An infection with the HPV genotypes 31, 39, 45, 51, 58, 59, 66, 42, 43 and 44 couldn’t be found in any of the patients. In 28 patients with diagnosed VAIN, an infection with HPV 16 could be shown, 24 (86%) of them were diagnosed with a HSIL (VAIN). 16 (24%) women presented condylomata and 13 of them (81%) had a positive HPV status. However, only 47% of the women without condylomata presented a positive HPV status, resulting in a significant correlation (p = 0.0164) between condylomata and HPV infection. In 28 of all 67 patients (42%), recurrence of the neoplasia occurred.</p><p>Conclusion</p><p>HPV 16 is the main virus-type to be associated with the development of a VAIN. Also, HPV 16 infection, VIN or condylomata acuminata in the past medical history seemed to be significant factors for early relapse.</p></div

HPV type distribution.

<p>HPV type distribution.</p

Patient characteristics.

<p>Patient characteristics.</p