Vulvar cancer in Germany: increase in incidence and change in tumour biological characteristics from 1974 to 2013

<p><b>Background:</b> The incidence of vulvar cancer in Germany is increasing. Moreover, gynaecological oncologists reported observing increasing numbers of women presenting with small tumours. The aim of the present study is to validate this observation on a population level and to extend available incidence data.</p> <p><b>Material and methods:</b> Data from the population-based Saarland Cancer Registry were used and included 1136 women diagnosed with invasive vulvar cancer (ICD-9 codes: 181.1-181.4, ICD-10 code: C51) between 1974 and 2013. Multiple imputation methodology was used to overcome loss of precision and potential bias resulting from incomplete data. Incidence trends were investigated with regard to age at diagnosis, tumour size and clinical stage, morphology and histopathologic grade.</p> <p><b>Results:</b> The age-standardised incidence rate of vulvar cancer increased from 1.6 cases per 100,000 women per year in 1974–78 to 7.9 in 2009–13, representing an increase across all age groups. Since 1989–93, an almost exclusive increase in the incidence of small tumours ≤2 cm in the greatest dimension from 1.2 to 6.6 and of squamous cell carcinomas from 1.7 to 7.1 was observed, whereas the number of larger tumours and other invasive cancers remained rather constant. Patients aged ≥75 years generally suffered from more advanced tumours at the time of diagnosis.</p> <p><b>Conclusions:</b> An increase in vulvar cancer incidence of a size as observed in this study has not been reported thus far for any other European region. Furthermore, the analyses confirmed the observation of increasing numbers of women presenting with small tumours. The results of the age-specific analyses point to both human papillomavirus infection and non-infectious factors as explanations for the observed increase in squamous cell carcinomas.</p

Additional file 3: of Cancer-testis antigen cyclin A1 is broadly expressed in ovarian cancer and is associated with prolonged time to tumor progression after platinum-based therapy

Figure S1. Survival plot depicting the impact of Cyclin A1 expression (Affymetrix probe set 205899_at) on progression-free survival in the patient group with suboptimal debulking and platinum-based therapy using an online-accessible tool ( www.kmplot.com/ ), database version 2015 [n = 1648]. Case selection [n = 264]: survival: PFS, split patients by median; restrictions: FIGO II, III, IV; histology: serous; debulk: suboptimal; chemotherapy: contains platinum. Log-rank p = 0.0088. (PPTX 84 kb

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Serum Glycome Profiling: A Biomarker for Diagnosis of Ovarian Cancer

During the development of cancer, changes in cellular glycosylation are observed, indicating that alterations of the glycome occur in extracellular fluids as well as in serum and could therefore serve as tumor biomarkers. In the case of epithelial ovarian cancer (EOC), common tumor markers such as CA125 are known to have poor specificity; therefore, better biomarkers are needed. The aim of this work was to identify new potential glycan biomarkers in EOC-patients. N-Glycans were cleaved from serum glycoproteins from 63 preoperative primary EOC-patients along with 33 age-matched healthy women, permethylated, and analyzed using MALDI-TOF mass spectrometry. A value named GLYCOV was calculated from the relative areas of the 11 N-glycan biomarkers revealed by SPSS statistical analyses, namely four high-mannose and seven complex-type fucosylated N-glycans. GLYCOV diagnosed primary EOC with a sensitivity of 97% and a specificity of 98.4% whereas CA-125 showed a sensitivity of 97% and a specificity of 88.9%. Our study is the first one to compare glycan values with the established tumor marker CA125 and to give better results. Therefore, the N-glycome could potentially be used as a biomarker

Additional file 1: of Prediction of clinical response to drugs in ovarian cancer using the chemotherapy resistance test (CTR-test)

Percentage of viable cells and tumor cells. The percentage of viable cells and tumor cells of the different patient samples (Responder or Non-Responder for Monotherapy, Monotherapy plus Avastin or Combination Chemotherapy) is presented. (PDF 29 kb

Perioperative complications.

<p>Overall complications occurred in 74% of the patients. There was no difference between intervention and control group (p = 0.79). Major (Clavien Grade III and higher) perioperative complications occurred in 24% of the patients. There was no difference between the groups (p = 0.41).</p

Course of HRQoL.

<p>Comparing the baseline and follow-up values for health-related quality of life only for patients who survived and answered the 12 months questionnaire (n = 418), there were neither clinical relevant nor statistical significant differences between baseline and 12 months for HRQoL (intervention women: p = 0.58; men: p = 0.49; control women: p = 0.16; men = 0.29). Compared to age and gender-adjusted reference values for the German population [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0137824#pone.0137824.ref018" target="_blank">18</a>], men showed better global health-related quality of life than the reference population with clinical relevance. In contrast, women quoted a lower score of global HRQoL but without clinical relevance.</p

Short-term postoperative outcomes.

<p>OR: operating room, LOS: length of hospital stay, cardiopulmonary: respiratory insufficiency, angina, myocardial infarction, arrhythmia, lung edema, pulmonary embolism; excluded: pneumonia; SD: standard deviation, IQR: interquartile range.</p><p>#: χ2-Test</p><p>Short-term postoperative outcomes.</p

Median postoperative length of in-hospital stay.

<p><b>(A)</b> The median length of postoperative in-hospital stay was 9 (IQR 7) days in the intervention group and 9 (IQR 9) days in the control group (p = 0.99).</p

Study flow diagram.

<p>Study flow diagram.</p