Incidence Patterns and Temporal Trends of Invasive Nonmelanotic Vulvar Tumors in Germany 1999-2011. A Population-Based Cancer Registry Analysis

<div><p>Objectives</p><p>Time trends on the incidence and characteristics of invasive vulvar cancer in Germany have so far been studied in few local population- and hospital based tumor registries. We aimed to provide an overview on recent developments of vulvar cancer in Germany, using population-based cancer registry data.</p><p>Methods</p><p>We analyzed the data on vulvar cancer of eight population-based German cancer registries for the period 1999-2011. ICD-10 codes and ICD-O-3 morphology codes were used to select site and histologic types. The annual percentage change was calculated on age-adjusted incidence rates with a joinpoint regression model.</p><p>Results</p><p>A total of 12,711 registered cases of invasive carcinoma of the vulva were included in the analyses, hereof were 12,205 of squamous cell origin. Age-standardized incidence rates of vulvar cancer annually increased by 6.7% (95% confidence limits: 5.6-7.9) from 1.7 per 100,000 women in 1999 to 3.6 per 100,000 women in 2011. An increase was observed among women of all ages, and especially between 30 and 69 years of age.</p><p>Conclusion</p><p>The annual incidence of invasive carcinoma of the vulva nearly doubled in the past decade in Germany, considerably exceeding the rates observed in other Western European countries. A combination of changes in risk factors, and documentation practice might have contributed to the observed substantial increase in vulvar cancer incidence.</p></div

Vulvar cancer incidence rates in Hamburg and Saarland from 1991–2011.

<p>Annual age-standardized vulvar cancer incidence rates per 100,000 women (old European Standard) by calendar year, all ages; DCO notified cases, histologically not further specified cases and melanoma excluded.</p

Women’s age at diagnosis and characteristics of the invasive vulvar tumors diagnosed from 1999–2011 (for topography up to 2009).

<p>Staging limited to data from 1999–2009 (TNM editions 4–6).</p><p>^aThe average annual percentage change (AAPC) from 1999–2011 of the age standardized (old European standard) incidence rate (ASIR).</p><p>Women’s age at diagnosis and characteristics of the invasive vulvar tumors diagnosed from 1999–2011 (for topography up to 2009).</p

Invasive vulvar cancer incidence rates from 1999–2011 in selected countries.

<p>Numbers represent annual age-standardized incidence rates per 100,000 women (old European Standard) of invasive vulvar cancer in selected national population-based cancer registries.</p><p>^aRegion Flamish only.</p><p>DCO cases, melanoma, and histologically not further specified cases included.</p

Patient characteristics.

<p>Patient characteristics.</p

Prevalence of deleterious variants within subgroups.

<p>Prevalence of deleterious variants within subgroups.</p

Histologic subtypes and prevalence of deleterious variants in patients with serous, endometrioid, mucinous or clear cell ovarian cancer.

<p>Histologic subtypes and prevalence of deleterious variants in patients with serous, endometrioid, mucinous or clear cell ovarian cancer.</p

Association of variants in small GTPase genes with epithelial ovarian cancer risk (p-value<10⁻⁴) and functional annotation.

<p>Association of variants in small GTPase genes with epithelial ovarian cancer risk (p-value<10⁻⁴) and functional annotation.</p

Association of rs2256787 in the <i>ARHGEF10L</i> gene with invasive endometrioid EOC risk by study site and combined.

<p>Squares represent the estimated per-allele odds ratio (OR) and are proportional to sample size for each study; lines indicate its 95% confidence interval (CI); source indicates contributing study;[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0197561#pone.0197561.ref011" target="_blank">11</a>] MAF, control minor allele frequency; PVal, per-allele p-value adjusted for age, site, and principal components to account for residual differences in European ancestry.</p

The most significant SNPs in the transport pathway genes and risk of EOC by histology, invasiveness, and race/ethnicity¹.

<p>¹ INV: all invasive EOC combined; LMP: low malignant potential / borderline tumors; SER: serous; CC: clear cell; End: endometrioid; Muc: mucinous. Statistically significant associations are indicated in bold (P<0.05). Data format is the following: OR (95% CI); p-value; FDR q-value (white-European women). Only significant FDRs (q<0.2) are shown (<i>HEPH</i>: INV and SER<i>; UGT1A</i>: End).</p><p>The most significant SNPs in the transport pathway genes and risk of EOC by histology, invasiveness, and race/ethnicity<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128106#t001fn001" target="_blank">¹</a>.</p