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Purpose The aim of our study was to explore the impact of the COVID-19 pandemic on reported cancer cases in Bavaria, Germany, by comparing pre-pandemic (March 2019 to February 2020) and pandemic period (March 2020 to February 2021). Methods Data on incident cases were retrieved from the Bavarian Cancer Registry (until 22nd April 2022). We included patients with malignant and in situ neoplasms reported by pathology departments with consistent reporting. We calculated the number of incident cases during the COVID-19 pandemic and the pre-pandemic period with 95% confidence intervals (CI) with Bonferroni correction (α = 0.0018) based on a Poisson approach. We stratified for malignancy (malignant, in situ), tumor site, and month of year. Results Data was available for 30 out of 58 pathology departments (51.7%) from Bavaria. Incident malignant neoplasms dropped from 42,857 cases in the pre-pandemic period to 39,980 cases in the pandemic period (− 6.7%; 95% CI − 8.7%, − 4.7%). Reductions were higher for colon, rectum, skin/melanoma as well as liver (> 10.0% reduction) and less for breast cancer (4.9% reduction). No case reductions were observed for pancreas, esophagus, ovary, and cervix. Percent changes were largest for April 2020 (− 20.9%; 95% CI − 24.7%, − 16.8%) and January 2021 (− 25.2%; 95% CI − 28.8%, − 21.5%) compared to the previous year. Declines tended to be larger for in situ compared to malignant neoplasms. Conclusion Detection and diagnosis of cancer were substantially reduced during the COVID-19 pandemic. Potential effects, e.g. a stage shift of tumors or an increase of cancer mortality, need to be monitored.

BACKGROUND: The incidence of early-onset (diagnosis before age 50) colorectal cancer (EO-CRC) is increasing in some high-income countries. The present study analyzed this trend in Germany. METHODS: The epidemiological data on the incidence of colorectal cancer (ICD-10 C18–C20) in the federal states of Germany were obtained from the German Center for Cancer Registry Data (ZfKD). The regions included were those with adequate documentation, according to the ZfKD criteria, for the years 1999–2018. Cases identified from death certificates alone were excluded. The data on mortality were derived from the official cause of death statistics. Time trends for persons aged 20–49 years were expressed as the average annual percentage change (AAPC) with 95% confidence interval. The incidence was stratified by sex, site (proximal colon, distal colon, rectum), 10-year age group (20– 29, 30– 39, 40– 49), and tumor size (T). RESULTS: EO-CRC accounted for 5.1% (9529 cases) of all colorectal cancers in the selected German regions. The EO-CRC incidence rose annually by 1.16% [0.51; 1.81] in men and 1.32% [0.80; 1.84] in women. The incidence of proximal colon cancer increased in both sexes (men: AAPC 3.26 [2.00; 4.53]; women: AAPC 2.99 [2.17; 3.83]), while the incidence of distal colon cancer remained unchanged. CONCLUSION: The incidence of EO-CRC in Germany is rising. The reasons are probably multifactorial, reflecting the changing prevalence of risk and protective factors to which one is exposed in the early years of life.

Background To assess the hysterectomy probability by calendar period and age, the overall and the age-specific prevalence of hysterectomy in women aged 30–65 years. Methods Baseline data (2005–2007) from the population-based MARZY study conducted in Mainz and Mainz-Bingen, Germany, were analysed. 6429 women aged 30–65 years were asked whether they had undergone a hysterectomy and the date and indication of the procedure. We calculated the 5-year age-specific prevalence of hysterectomy and estimated the probability of undergoing a hysterectomy combining two approaches: 1) Kaplan–Meier and 2) Inverse probability weighting (IPW). We assessed potential changes over calendar periods by simulating survival curves, having hysterectomy as the event, employing a Cox proportional hazard model. Results Data on hysterectomy were available for 4719 women. Of these, 961 (20.4%) had undergone a hysterectomy between 1960 and 2006. The hysterectomy prevalence was highest among the 60–64 year-olds (40.7%). The IPW-corrected probability of having a hysterectomy up to the age of 65 years was 36.4%. The age-specific probability of hysterectomy increased from 0.1% (20–24 years), peaking at 45–49 years (7.8%) and declining thereafter to less than 5% among women aged 50 and older. Over time, women were hysterectomised at an increasingly older age. Most hysterectomies (86.7%) were done due to benign disease. Conclusions A shift to older age at hysterectomy with an advancing calendar period likely reflects changes in clinical practice in Germany. Trial registration Landesärztekammer Rheinland-Pfalz: 837.438.03 (4100).

Background Although the human papillomavirus (HPV) vaccine has been recommended in Germany for girls since 2007, no organised vaccination programme was introduced and HPV vaccine coverage remains low. We investigated the HPV vaccination rates from 2008 to 2018 and the effects of HPV vaccination on anogenital warts and precancerous lesions in young women in Bavaria, Germany, a state with low vaccination rates. Methods Retrospective analyses of claims data from the Bavarian Association of Statutory Health Insurance Physicians (KVB) on females born between 1990 and 2009 (9 to 28 years old in 2018) were conducted to calculate vaccination rates by birth cohort, proportion of vaccine types administered and incidence of anogenital warts and precancerous lesions of the cervix uteri. 942 841 Bavarian females 9 to 28 years old with available information on HPV vaccination were included to calculate vaccination rates. For the outcome analyses, data from 433 346 females 19 to 28 years old were analysed. Hazard ratios (HR) were computed from univariable and multivariable Cox regression models comparing vaccinated and unvaccinated women, considering type of vaccine used and contraceptive prescription. Results 40·9% of 18-year-olds and only 13·3% of 12-year-olds were fully vaccinated in 2018 in Bavaria. Gardasil® and Gardasil9® were most commonly administered. Vaccinated compared to unvaccinated women had a lower incidence of anogenital warts and cervical lesions, however only small differences were detected between fully and partially vaccinated women. Fully vaccinated women had a 63% (HR 0·37 (95% confidence interval (CI) 0·34 to 0·40) and 23% (HR 0·77, 95%CI 0·71 to 0·84) lower risk of anogenital warts and cervical lesions, respectively. Women who were prescribed contraceptives prior to vaccination had a 49% higher risk of developing anogenital warts (HR 1·49, 95%CI 1·25 to 1·79) or cervical lesions (HR 1·49, 95%CI 1·27 to 1·75) compared to vaccinated women without contraceptive prescription. Conclusions The evaluation of the effects of HPV vaccination in Bavaria showed a promising decline of anogenital warts and precancerous lesions in vaccinated young women. However, an increase in vaccination rates is necessary to achieve a greater population impact in preventing HPV-related diseases.

Due to the high burden of mental health issues among students at higher education institutions world-wide, animal-assisted interventions (AAIs) are being used to relieve student stress. The objective of this study was to systematically review of the effects of AAIs on the mental, physiological, and cognitive outcomes of higher education students. Randomized controlled trials using any unfamiliar animal as the sole intervention tool were included in this review. Study quality was assessed using the Cochrane Risk-of-Bias tool. Where possible, effect sizes (Hedges’ g) were pooled for individual outcomes using random-effects meta-analyses. Albatross plots were used to supplement the data synthesis. Of 2.494 identified studies, 35 were included. Almost all studies used dogs as the intervention animal. The quality of most included studies was rated as moderate. Studies showed an overall reduction of acute anxiety and stress. For other mental outcomes, studies showed smaller, but nonetheless beneficial effects. Studies showed no clear effect on physiological or cognitive outcomes. Strong methodological heterogeneity between studies limited the ability to draw clear conclusions.

AimWith the rapid advances in technology and data science, machine learning (ML) is being adopted by the health care sector; but there is a lack of literature addressing the health conditions targeted by the ML prediction models within primary health care (PHC). To fill this gap in knowledge, we conducted a systematic review following the PRISMA guidelines to identify the health conditions targeted by ML in PHC.MethodsWe searched the Cochrane Library, Web of Science, PubMed, Elsevier, BioRxiv, Association of Computing Machinery (ACM), and IEEE Xplore databases for studies published from January 1990 to January 2022. We included any primary study addressing ML diagnostic or prognostic predictive models that were supplied completely or partially by real-world PHC data. We performed literature screening, data extraction, and risk of bias assessment. Health conditions were categorized according to international classification of diseases. Extracted date were analyzed quantitatively and qualitatively.ResultsWe identified 109 studies investigating 42 health conditions. These studies included 273 ML prediction models supplied by the PHC data of 24.2 million participants from 19 countries. We found that 82% of the studies were retrospective. 76.6% of the studies reported diagnostic predictive ML models. 77% of all reported models aimed for models’ development without external validation. Risk of bias assessment revealed that 90.8% of the studies were of high or unclear risk of bias. The most frequently reported health conditions were Alzheimer’s disease and diabetes mellitus.ConclusionsTo the best of our knowledge, this is the first review to investigate the extent of the health conditions targeted by the ML prediction models within PHC settings. Our study provides an important summary on the presently available ML models in PHC, which can be used in further research and implementation efforts.

Background Caesarean sections account for roughly one third of all surgical procedures performed in low-income countries. Due to lack of standardised post-discharge follow-up protocols and practices, most of available data are extracted from clinical charts during hospitalization and are thus sub-optimal for answering post-discharge outcomes questions. This study aims to determine enablers and barriers to returning to the hospital after discharge among women who have undergone a c-section at a rural district hospital in Rwanda. Methods Women aged ≥ 18 years who underwent c-section at Kirehe District Hospital in rural Rwanda in the period March to October 2017 were prospectively followed. A structured questionnaire was administered to participants and clinical data were extracted from medical files between March and October 2017. At discharge, consenting women were given an appointment to return for follow-up on postoperative day 10 (POD 10) (± 3 days) and provided a voucher to cover transport and compensation for participation to be redeemed on their return. Study participants received a reminder call on the eve of their scheduled appointment. We used a backward stepwise logistic regression, at an α = 0.05 significance level, to identify enablers and barriers associated with post-discharge follow-up return. Results Of 586 study participants, the majority (62.6%) were between 21–30 years old and 86.4% had a phone contact number. Of those eligible, 90.4% returned for follow-up. The predictors of return were counselling by a female data collector (OR = 9.85, 95%CI:1.43–37.59) and receiving a reminder call (OR = 16.47, 95%CI:7.07–38.38). Having no insurance reduced the odds of returning to follow-up (OR = 0.03, 95%CI:0.03–0.23), and those who spent more than 10.6 Euro for transport to and from the hospital were less likely to return to follow-up (OR = 0.14, 95%CI:0.04- 0.50). Conclusion mHealh interventions using calls or notifications can increase the post-discharge follow-up uptake. The reminder calls to patients and discharge counselling by a gender-matching provider had a positive effect on return to care. Further interventions are needed targeting the uninsured and patients facing transportation hardship. Additionally, association between counselling of women patients by a female data collector and greater return to follow-up needs further exploration to optimize counselling procedures.

Background: Some countries have implemented stand-alone human papillomavirus (HPV) testing while others consider cotesting for cervical cancer screening. We compared both strategies within a population-based study. Methods: The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years (n = 5,275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep), and HPV testing (Hybrid Capture2, HC2). Screen-positive participants [ASC-US+ or high-risk HC2 (hrHC2)] and a random 5% sample of screen-negatives were referred to colposcopy. Post hoc HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blotting. Sensitivity, specificity (adjusted for verification bias), and potential harms, including number of colposcopies needed to detect 1 precancerous lesion (NNC), were calculated. Results: In 2,627 screened women, cytological sensitivities (Pap, LBC: 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Cotesting demonstrated higher sensitivities (HC2 cotesting: 99%; PCR cotesting: 84%), but at the cost of lower specificities (92%–95%) compared with HPV stand-alone (HC2: 95%; PCR: 94%) and cytology (97% or 99%). Cotesting versus HPV stand-alone showed equivalent relative sensitivity [HC2: 1.06, 95% confidence interval (CI), 1.00–1.21; PCR: 1.07, 95% CI, 1.00–1.27]. Relative specificity of Pap cotesting with either HPV test was inferior to stand-alone HPV. LBC cotesting demonstrated equivalent specificity (both tests: 0.99, 95% CI, 0.99–1.00). NNC was highest for Pap cotesting. Conclusions: Cotesting offers no benefit in detection over stand-alone HPV testing, resulting in more false positive results and colposcopy referrals. Impact: HPV stand-alone screening offers a better balance of benefits and harms than cotesting. See related commentary by Wentzensen and Clarke, p. 432

Summary Background HIV enhances human papillomavirus (HPV)-induced carcinogenesis. However, the contribution of HIV to cervical cancer burden at a population level has not been quantified. We aimed to investigate cervical cancer risk among women living with HIV and to estimate the global cervical cancer burden associated with HIV. Methods We did a systematic literature search and meta-analysis of five databases (PubMed, Embase, Global Health [ CABI.org ], Web of Science, and Global Index Medicus) to identify studies analysing the association between HIV infection and cervical cancer. We estimated the pooled risk of cervical cancer among women living with HIV across four continents (Africa, Asia, Europe, and North America). The risk ratio (RR) was combined with country-specific UNAIDS estimates of HIV prevalence and GLOBOCAN 2018 estimates of cervical cancer to calculate the proportion of women living with HIV among women with cervical cancer and population attributable fractions and age-standardised incidence rates (ASIRs) of HIV-attributable cervical cancer. Findings 24 studies met our inclusion criteria, which included 236 127 women living with HIV. The pooled risk of cervical cancer was increased in women living with HIV (RR 6·07, 95% CI 4·40–8·37). Globally, 5·8% (95% CI 4·6–7·3) of new cervical cancer cases in 2018 (33 000 new cases, 95% CI 26 000–42 000) were diagnosed in women living with HIV and 4·9% (95% CI 3·6–6·4) were attributable to HIV infection (28 000 new cases, 20 000–36 000). The most affected regions were southern Africa and eastern Africa. In southern Africa, 63·8% (95% CI 58·9–68·1) of women with cervical cancer (9200 new cases, 95% CI 8500–9800) were living with HIV, as were 27·4% (23·7–31·7) of women in eastern Africa (14 000 new cases, 12 000–17 000). ASIRs of HIV-attributable cervical cancer were more than 20 per 100 000 in six countries, all in southern Africa and eastern Africa. Interpretation Women living with HIV have a significantly increased risk of cervical cancer. HPV vaccination and cervical cancer screening for women living with HIV are especially important for countries in southern Africa and eastern Africa, where a substantial HIV-attributable cervical cancer burden has added to the existing cervical cancer burden. Funding WHO, US Agency for International Development, and US President's Emergency Plan for AIDS Relief.

BackgroundDue to the high burden of mental health issues among students at higher education institutions world-wide, animal-assisted interventions (AAIs) are being increasingly used to relieve student stress. The objective of this study was to systematically review of the effects of AAIs on the mental and cognitive health outcomes of higher education students.MethodsRandomized controlled trials using any unfamiliar animal as the sole intervention tool were included in the systematic review. Study quality was assessed using the Cochrane Risk-of-Bias tool. Where possible, effect sizes (Hedges’ g) were pooled for individual outcomes using random-effects meta-analyses. Albatross plots were used to supplement the data synthesis.ResultsOf 2.401 identified studies, 35 were included. Almost all studies used dogs as the intervention animal. The quality of most included studies was rated as moderate. Studies showed an overall reduction of acute anxiety (g= -0.57 (95%CI -1.45;0.31)) and stress. For other mental outcomes, studies showed an overall small reduction of negative affect (g= -0.47 (95%CI -1.46;0.52)), chronic stress (g= -0.23 (95%CI -0.57;0.11)) and depression, as well as small increases in arousal, happiness and positive affect (g= 0.06 (95%CI -0.78;0.90)). Studies showed no effect on heart rate and heart rate variability, a small reduction in salivary cortisol and mixed effects on blood pressure. No effect on cognitive outcomes was found.ConclusionOverall, evidence suggests that AAIs are effective at improving mental, but not physiological or cognitive outcomes of students. Strong methodological heterogeneity between studies limited the ability to draw clear conclusions.

Hauptrisikofaktor fur die Entstehung eines invasiven Zervixkarzinoms ist eine persistierende Infektion mit humanen Papillomviren (HPV). Die beiden High-Risk-Typen HPV 16 und 18 sind in fast allen Zervixkarzinomfallen nachweisbar. Weltweit ist Gebarmutterhalskrebs die vierthaufigste Krebserkrankung bei Frauen. Im Jahr 2018 starben rund 311.000 Frauen weltweit an einem invasiven Zervixkarzinom. Zur primaren Pravention einer HPV-Infektion gibt es seit dem Jahr 2006 die Moglichkeit einer HPV-Impfung. In Deutschland empfiehlt die Standige Impfkommission (STIKO) eine HPV-Impfung fur alle Jungen und Madchen im Alter von 9–14 Jahren. Im Jahr 2015 waren deutschlandweit jedoch nur rund 31,2 % aller 15-jahrigen Madchen vollstandig geimpft. Weltweit weisen schulbasierte HPV-Impfprogramme die hochsten Immunisierungsraten auf. Die Einfuhrung einer schulbasierten HPV-Impfung konnte auch in Deutschland dazu beitragen, die HPV-Impfquoten zu steigern, und somit langfristig die Reduktion von HPV-Infektionen und daraus resultierenden Karzinomen unterstutzen.

Inpatient healthcare demand is influenced by demographic changes; however, existing research mainly focuses on age-related conditions among older age groups and lacks empirical evidence. We aimed to identify important indicator diagnoses by group, which best characterise age-specific conditions and their demand of inpatient services in Germany. Data stem from the general hospital diagnosis-related group (DRG) statistics in Germany from 2005 to 2010. To identify the indicator diagnosis groups, we used frequency analyses of individual diagnoses and combined them into common diagnosis groups, stratified by age and gender. We identified indicator diagnoses by the highest number of cases of inpatient hospital treatments in 2010 or the largest change in cases between 2005 and 2010. The most common diagnosis groups were then ranked using different weights. Changes were quantified using linear regression. Across all ages, 13 diagnosis groups were identified as frequently reported hospitalisations such as injuries to the head (S00-S09) among patients aged 0 to 17 years, and ischemic heart diseases (I20-I25) among patients aged 18 to 64 years. As the number of hospitals decreased, the demand in inpatient services increased. From 75 years and above, males were more frequently inpatients than females, and overall length of stay in hospitals appeared to decrease. We empirically identified 13 diagnosis groups, which best describe the inpatient services utilised among various age groups in a ranked order. Findings from this study can provide a platform for determining future demand of inpatient services as well as the demographic-specific diagnoses that need attention.

Background Survival of colorectal cancer (CRC) has improved markedly but risk of an independent second primary cancer (SPC) increases. We determined incidence and potential risk factors of SPC following CRC. Methods We obtained data from 217,202 CRC cases (ICD-10 C18-C20, aged ≥20 years) diagnosed between 1990-2013 from the German Centre for Cancer Registry Data. Cancers arising in a distinct site (excluding non-melanoma skin cancer) and/or of a different histology group were classified as SPCs. Standardised incidence ratios (SIR) and 95% confidence intervals compared the excess risk to the general population, stratified by age, sex and CRC sub-site. Cox proportional hazards models identified potential risk factors of SPC. Results Following CRC (median age 70 years), 18,751 SPCs occurred (8.63%; median age 69 years). SPC incidence increased by 36% in males (SIR: 1.36 [1.34-1.38]), 46% in females (SIR: 1.46 [1.43-1.49]) and doubled for cases Conclusions CRC survivors have an increased risk of SPC, particularly due to age, sex and tumour size. Key messages Colorectal cancer survivors have an increased risk of a SPC. Age, sex and tumour size are associated risk factors.

Background Cervical cancer screening can be conducted with cytology and Human Papillomavirus (HPV) testing but few studies have compared the latter directly to concomitant testing (co-testing). We compared these strategies to determine appropriate screening. Methods Within a randomised population-based cohort study conducted around Mainz, Germany, eligible women (≥30 years) were screened via Pap smear, liquid-based cytology (LBC) and HPV testing (HC2) and HPV genotyped post hoc (PCR). These tests formed three strategies: cytology (Pap or LBC) and HPV (HC2 or PCR) stand-alone and co-testing. Screen positives and 5% negative women were invited to colposcopy. Absolute and relative sensitivity, specificity, false positive rates (FPR) and number needed to colposcopy to detect one lesion (NNC) were calculated. Estimates were crude and verification bias-adjusted using stratified sampling with bootstrapped confidence intervals. Results Of 2,627 screened women, cytology stand-alone demonstrated lowest sensitivities (47%) and highest specificities (97%-99%) while HPV stand-alone demonstrated higher sensitivities (79%-95%) but lower specificities (94%-95%). Co-testing increased sensitivity (84%-99%) but not specificity (92%-95%). Relative sensitivities were similar between crude and adjusted estimates, with greater detection via HPV-based strategies. Specificity of co-testing with LBC relative to HPV stand-alone was near unity (0.99, 95% CI 0.99-1.00) but significantly lower than unity with Pap co-testing. FPR and NNC were greatest under co-testing. Conclusions HPV stand-alone screening in women over 30 years appears appropriate over co-testing as a screening strategy. Key messages Co-testing for cervical cancer does not appear to add any benefit in detection and may introduce unnecessary harms compared to HPV stand-alone screening.

Approximately 80% of lung cancer cases in Germany are attributable to smoking. Patients with a lung cancer diagnosis may remain at increased risk of developing smoking-related second primary cancers (SPCs).Anonymous data from 11 population-based cancer registries covering approximately 50% of the German population were pooled for the analysis. Included patients were diagnosed with having an index lung cancer between 2002 and 2013, aged 30 to 99 years old at diagnosis, and survived for at least 6 months. We calculated standardized incidence ratios (SIRs)-stratified by age, sex, region, and period-comparing the incidence of smoking-related and other SPCs to the general population.Of the 135,589 lung cancer survivors (68.2% male; mean follow-up 30.8 mo) analyzed, 5298 developed an SPC. In males, the risk was particularly high for SPCs of the larynx (SIR = 3.70, 95% confidence interval [CI]: 3.14-4.34), pharynx (3.17, 2.61-3.81), and oral cavity (2.86, 2.38-3.41). For females, SIRs were notably elevated for the esophagus (4.66, 3.15-6.66), oral cavity (3.14, 2.03-4.63), and urinary tract (2.68, 2.04-3.45). When combining all smoking-related cancer sites, SIR was 1.41 in males (95% CI: 1.36-1.47) and 1.81 in females (95% CI: 1.68-1.94). We observed that males had a 1.46-fold (95% CI: 1.37-1.56) and females a 1.33-fold (95% CI: 1.20-1.47) increased risk for smoking-related compared with other cancers.Patients with primary lung cancer were at increased risk for developing a smoking-related SPC. Therefore, the advantages of increased patient surveillance and the benefits of smoking cessation strategies should be considered.

Aims Annual opportunistic screening for cervical carcinoma has been done in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as this guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany. Methods With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline. Recommendations The second part of this short summary deals with the triage, treatment and follow-up care of cervical dysplasia. With regard to those women who do not participate in screening, the guideline authors recommend sending out repeat invitation letters or an HPV self-collection kit. Colposcopy should be carried out for further investigation if cytology findings are Pap II-p and HPV test results are positive or if the results of an HPV 16 or HPV 18 screening test are positive. A single abnormal Pap smear should be triaged and investigated using HPV testing or p16/Ki67 dual staining.

Objectives: The aim of this study was to assess penile cancer incidence, clinical characteristics, treatment options, transparency of clinical quality, and relative survival based on data from the clinical cancer registry. Subjects and Methods: A total of 898 patients with tumours of the penis were diagnosed and analysed in the period from 2000 to 2018; they were documented in the 4 regional clinical cancer registries and summarized in the Command Office of these 4 registries. Results: The standardized incidence rate increased from 0.86 in 2000 to 2.67 in 2018. Most tumours were located at the glans (42.9%) followed by the prepuce (19.5%) and corpus penis (6.9%); they were classified into pT1a/pT1b (20.0%/7.0%), pT2 (23.5%), pT3 (12.4%), and pT4 (0.8%). In only 32.0% of all documented cases, a stage-related lymphadenectomy (LND) was carried out. Negative surgical margins were found in only 70% and the Rx status in 15.1%. Primary metastasis was detected in pN1 (5.1%), pN2 (3.9%), pN3 (3.1%), and M1 status in 3.0%, respectively. The predominant therapy was surgery in 78.3%. The proportion of penile partial resections was significantly (p = 0.0045) regredient over the control period. Adjuvant chemotherapy was performed in 4.7%, adjuvant external-beam radiotherapy in 3.0%. The 5-year relative overall survival rate was 74.7% and ranged from 108.0% (stage 0) to 17.1% (stage IV). A total of 29 hospitals performed tumour operations. Conclusions: The multitude of clinical and epidemiological variables available in clinical cancer registries allows a safe assessment of tumour dynamics themselves, as well as good quality of transparency and broadly acceptable guideline adherence. Deviations from the accepted level of evidence were found in the grading definition, in the high quota of positive surgical margins, in the defensive indication position to the glans resurfacing/reconstruction and diagnostical LND. Based on these relevant findings in the database combined with the low frequency of the tumour in area/clinics/year, we recommended establishing SCCP reference clinics. This work is the first time that European standardized rate-based cancer registry data on penile cancer from Germany has been communicated.

Background: The contribution of HIV infection to cervical cancer burden at a population-level has not been systematically quantified. We aimed to investigate cervical cancer risk among women living with HIV (WLHIV), and to estimate the global cervical cancer burden associated with HIV. Methods: We conducted a systematic literature search and a meta-analysis to estimate the pooled risk ratio (RR) of cervical cancer among WLHIV. The RR was combined with country-specific UNAIDS estimates of HIV prevalence and GLOBOCAN 2018 estimates of cervical cancer, to calculate the proportion of WLHIV among women with cervical cancer, as well as population attributable fractions and age-standardized incidence rates (ASIR) of HIV-attributable cervical cancer. Findings: In all, 24 studies met our inclusion criteria including a total of 236 127 WLHIV, providing a pooled cervical cancer RR of 6·07 (95% CI, 4·40–8·37). Globally, 5·8% (33 000) of all cervical cancers in 2018 were diagnosed in WLHIV and 4·9% (28 000 cases) were attributable to HIV infection. The most affected regions were eastern and southern Africa, and western and central Africa where 35·5% (24 000) and 10·0% (4 300) of cervical cancers were diagnosed among WLHIV, respectively. ASIRs of HIV-attributable cervical cancer were over 20 per 100 000 in 6 countries, all in eastern and southern Africa. Interpretation: WLHIV have a significantly elevated risk of cervical cancer. HPV vaccination and cervical cancer screening for WLHIV are particularly critical for sub-Saharan African countries where a substantial HIV-attributable cervical cancer burden has added to the existing cervical cancer burden. Funding: Support for this project was provided by the World Health Organization (WHO) through funding made possible by United States Agency for International Development (USAID) under the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). The contents in this article are the sole responsibility of the authors, and do not necessarily represent the decisions, policy or views of WHO, IARC, USAID, PEPFAR or the United States Government. Conflict of Interest: DS: Nothing to declare LFT: Nothing to declare KKL: Nothing to declare IB: Nothing to declare AIK: Nothing to declare ASVS: Nothing to declare DAM: Nothing to declare SLG: Nothing to declare SJK: Nothing to declare ASW: Nothing to declare RB: Nothing to declare GC: Nothing to declare NB: Nothing to declare SD: Nothing to declare

Eine zytologische Untersuchung zur Fruherkennung des Zervixkarzinoms wird in Deutschland seit 1971 angeboten. Frauen ab einem Alter von 20 Jahren haben die Moglichkeit, jedes Jahr einen Pap-Abstrich durchfuhren zulassen. Ein organisiertes Screeningprogramm sowie personliche Einladungen fehlen bisher. Die Inzidenzrate des Zervixkarzinoms ist in den Jahrzehnten nach Einfuhrung der Krebsfruherkennungsuntersuchung (KFU) stark zuruckgegangen, in den letzten Jahren stagniert die Inzidenzrate jedoch. Ursachlich fur die Entstehung eines Zervixkarzinoms ist eine persistierende Infektion mit Hochrisikotypen des Humanen Papillomvirus (HPV). Seit einigen Jahren sind HPV-Tests fur das Zervixkarzinomscreening von der amerikanischen Food and Drug Administration (FDA) zugelassen. Des Weiteren wird seit 2006 eine HPV-Impfung zur Primarpravention angeboten. Im Rahmen des Nationalen Krebsplans wurde in Deutschland die Umsetzung der Europaischen Leitlinie fur das Zervixkarzinomscreening bearbeitet und 2013 im Krebsfruherkennungs- und -registergesetz gesetzlich verankert. Der Gemeinsame Bundesausschuss (G-BA) wurde mit der Umsetzung und Implementierung eines organisierten Zervixkarzinomscreenings beauftragt. Im April 2018 veroffentlichte der G‑BA aktualisierte Eckpunkte fur die Umsetzung eines organisierten flachendeckenden Screeningprogramms in Deutschland. Wahrend das jahrliche zytologische Screening fur Frauen zwischen 20 und 34 Jahren weitergefuhrt wird, erhalten Frauen ab 35 Jahren kunftig alle 3 Jahre eine Kombinationsuntersuchung, bestehend aus dem Pap-Abstrich und einem HPV-Test. Frauen zwischen 20 und 60 Jahren sollen alle 5 Jahre von ihrer Krankenkasse angeschrieben werden und eine Informationsbroschure erhalten. Nach einer Ubergangsphase von mindestens 6 Jahren soll das neue Programm evaluiert werden.

Background Breast cancer remains the most common cancer among women worldwide. Autologous breast reconstruction may contribute toward restoring body image and improving quality of life after mastectomy. This systematic literature review describes differences in the quality and type of studies investigating autologous breast reconstruction techniques over time. Methods MEDLINE was searched for articles related to the surgical techniques, namely, TRAM, LADO, DIEP, and SGAP/IGAP, for the periods 1970 to 2007 and 2008 to 2010. The quality and type of studies were compared across the two time periods. Full-texts were evaluated according to prespecified quality criteria. Results The MEDLINE searches yielded 1,057 articles for review; of them, 517 articles were excluded, and 314 had a completed quality criteria checklist and hence were included; of these 314 articles, 206 articles investigated TRAM flaps, 85 investigated LADO flaps, 74 investigated DIEP flaps, and 6 investigated SGAP/IGAP flaps. A total of 218 articles were published between 1970 and 2007 compared to 96 articles published between 2008 and 2010. The comparison of quality scores between the two time periods showed a shift toward higher scores in the period 2008 to 2010. The DIEP technique was investigated more frequently between 2008 and 2010 than between 1970 and 2007, whereas the percentage of articles focusing on the TRAM flap decreased. The percentage of articles investigating the LADO and SGAP/IGAP techniques remained constant across the time periods. Conclusions Results relating to the methodological quality of articles on breast reconstruction with autologous tissue show that the quality of publications has improved with time, whereas research interests concerning the type of surgical technique investigated have changed in focus.

Background In 2008, a nationwide skin cancer screening (SCS) program was implemented in Germany. However, participation rates remain low. Objective The overall objective of the HELIOS study is to identify subgroup-specific invitation and communication strategies to increase informed SCS participation in Germany. Methods Focus group discussions will be performed in Erlangen, Germany, to explore potential invitation and communication strategies as well as possible barriers and motivating factors to participate in SCS. Male and female patients of different age groups who have already been diagnosed with skin cancer, as well as participants without a prior diagnosis of skin cancer, will be invited. Based on these results, an online questionnaire will be developed to identify subgroup-specific invitation strategies. A random sample of 2500 persons from the general population aged >35 years from the Munich area will be contacted to complete the questionnaire. Besides descriptive analysis, multinomial logistic regression will be performed. Additionally, a cluster analysis will be conducted to discover patterns or similarities among the participants. Results Recruitment for the focus group studies started in February 2021 and is ongoing. As of August 2021, we have enrolled 39 participants. We expect to end enrollment in the qualitative study in September 2021 and to finish the analysis in December 2021. The second part of the study will then start in January 2022. Conclusions The results of this project will enable us to derive improved and more efficient invitation and communication strategies for SCS. These may be implemented in the future to facilitate increased SCS uptake and early skin cancer detection. International Registered Report Identifier (IRRID) DERR1-10.2196/31860

BackgroundAbout 96.3 million children and adolescents aged 0–19 years reside in Nigeria, comprising 54% of the population. Without adequate access to surgery for commonly treatable diseases, many face disability and increased risk of mortality. Due to this population’s unique perioperative needs, increasing access to paediatric surgical care requires a situational evaluation of the distribution of paediatric surgeons and anaesthesiologists. This study’s aim is to identify the percentage of Nigerian youth who reside within 2 hours of paediatric surgical care at the state and national level.MethodsThe Association of Paediatric Surgeons of Nigeria and the Nigeria Society of Anaesthetists provided surgical and anaesthesia workforce data by state. Health facilities with paediatric surgeons were converted to point locations and integrated with ancillary geospatial layers and population estimates from 2016 and 2017. Catchment areas of 2 hours of travel time around a facility were deployed as the benchmark indicator to establish timely access.ResultsAcross Nigeria’s 36 states and Federal Capital Territory, the percentage of Nigeria’s 0–19 population residing within 2 hours of a health facility with a paediatric surgical and anaesthesia workforce ranges from less than 2% to 22.7%–30.5%. In 3 states, only 2.1%–4.8% of the population can access a facility within 2 hours, 12 have 4.9%–13.8%, and 8 have 13.9%–22.6%.ConclusionThere is significant variation across Nigerian states regarding access to surgical care, with 69.5%–98% of Nigeria’s 0–19 population lacking access. Developing paediatric surgical services in underserved Nigerian states and investing in the training of paediatric surgical and anaesthesia workforce for those states are key components in improving the health of Nigeria’s 0–19 population and reducing Nigeria’s burden of surgical disease, in line with Nigeria’s National Surgical, Obstetrics, Anaesthesia and Nursing Plan.

Prognosis of Her2-positive breast cancer has changed since the introduction of trastuzumab for treatment in metastatic and early breast cancer. It was described to be even better compared to prognosis of Her2-negative metastatic breast cancer. The purpose of this study was to evaluate the effect of trastuzumab in our cohort. Besides the effect of adjuvant pretreatment with trastuzumab on survival of patients with metastatic Her2-positive breast cancer was analyzed. All patients with primary breast cancer of the Regional Breast Cancer Center Dresden diagnosed during the years 2001–2013 were analyzed for treatment with or without trastuzumab in the adjuvant and in the metastatic treatment setting using Kaplan–Meier survival estimation and Cox regression. Age and tumor stage at time of first diagnosis of breast cancer as well as hormone receptor status, grading, time, and site of metastasis at first diagnosis of distant metastatic disease were analyzed. Of 4.481 female patients with primary breast cancer, 643 presented with metastatic disease. Her2-positive status was documented in 465 patients, including 116 patients with primary or secondary metastases. Median survival of patients with Her2-positive primary metastatic disease was 3.0 years (95% CI 2.3–4.0). After adjustment for other factors, survival was better in patients with Her2-positive breast cancer with trastuzumab therapy compared to Her2-negative metastatic disease (HR 2.10; 95% CI 1.58–2.79). Analysis of influence of adjuvant therapy with and without trastuzumab by Kaplan–Meier showed a trend for better survival in not pretreated patients. Median survival was highest in hormone receptor-positive Her2-positive (triple-positive) primary metastatic breast cancer patients with 3.3 years (95% CI 2.3–4.6). Prognosis of patients with Her2-positive metastatic breast cancer after trastuzumab treatment is more favorable than for Her2-negative breast cancer. The role of adjuvant chemotherapy with or without trastuzumab warrants further research. Survival is best in triple-positive metastatic breast cancer. This will effect counseling at the time of first diagnosis of metastatic breast cancer.

Eine persistierende Infektion mit humanen Papillomaviren (HPV) ist die Hauptursache fur die Entstehung eines Zervixkarzinoms. HPV-Impfstoffe schutzen durch den Aufbau einer Immunitat gegen bestimmte Typen der sexuell ubertragbaren humanen HPV und dienen der Krebspravention. Die Hochrisiko-HPV-Typen 16 und 18 sind weltweit fur etwa 60–70 % aller Falle von Gebarmutterhalskrebs verantwortlich. In Deutschland erkrankten im Jahr 2013 4610 Frauen neu an Gebarmutterhalskrebs; die Inzidenzrate lag bei 11,2 pro 100.000. Die Papillomaviren vom Typ 6 und 11 sind primar verantwortlich fur die Entstehung von Genitalwarzen. Aktuell sind drei HPV-Impfstoffe zugelassen: ein bivalenter Impfstoff, der gegen HPV 16 und 18 wirksam ist, ein tetravalenter Impfstoff, gegen HPV 6, 11, 16 und 18 und ein nonavalenter Impfstoff, welcher vor HPV 6, 11, 16, 18, 31, 33, 45, 52, und 58 schutzt. Klinische Studien zeigten, dass Infektionen, klinische Manifestationen hochgradiger Vorstufen des Zervixkarzinoms sowie genitale Warzen durch den Impfstoff grostenteils verhindert werden konnen, wenn HPV-naive Madchen vor dem ersten sexuellen Kontakt geimpft wurden. Die Impfstoffe wirken prophylaktisch; bereits bestehende Infektionen konnen nicht behandelt werden. Nach derzeitigem Wissensstand sind HPV-Impfstoffe gut vertraglich, sicher und hoch immunogen. Die Standige Impfkommission (STIKO) empfiehlt gegenwartig die Impfung von Madchen zwischen 9 und 14 Jahren mit dem Ziel, die Krankheitslast durch das Zervixkarzinom und seine Vorstufen zu verringern. In Deutschland erreicht die HPV-Impfung weniger als 50 % der anspruchsberechtigten Madchen. Die Vorsorgeuntersuchung zur fruhzeitigen Erkennung von Vorstufen des Zervixkarzinoms wird weiterhin empfohlen, da durch die Impfung nicht alle kanzerogenen HPV-Typen erfasst und demnach nicht alle Zervixkarzinome verhindert werden konnen.

Background Football training can be a primary prevention strategy to reach people who otherwise would not be physically active. This systematic review summarizes the evidence on the health effects of controlled recreational football training as an intervention in children, adolescents, adults and the elderly. Methods A systematic review (PROSPERO record CRD42018083665) of the literature was carried out in MEDLINE, Cochrane, Scopus, and SPORTDiscus databases to identify randomized and non-randomized intervention studies in which healthy individuals of any age participated in controlled football training and were investigated for health outcomes related to prevention of obesity, hypertension, diabetes mellitus, and cardiovascular disease. Results The studies included-14 randomized and three non-randomized intervention studies-have sample sizes too small for reliable statistical analysis and bear a considerable risk of systematic bias. The evidence of positive effects of playing football is limited to short-term loss of body fat and improvement in aerobic fitness. For all other health outcomes, no conclusive results were found. Conclusion A considerable number of intervention studies reporting on football-based intervention programs have been published, and there is a widespread assumption that such programs have positive health effects. However, this systematic review shows that the empirical evidence is insufficient to permit such a conclusion.

Background The safety and efficacy of influenza vaccination for the chronically ill are clearly supported by the evidence, yet vaccination rates in this vulnerable popu- lation remain low. This leads to many avoidable hospitalizations and deaths in Germany every year. The goal of this systematic review is to identify measures in primary care medicine that can be used to increase influenza vaccination rates among the chronically ill. Methods This review was carried out as recommended in the PRISMA statement. A systematic literature search was performed. Only randomized, controlled trials were included in the analysis. Details can be found in the study protocol (PROSPERO, CRD42018114163). Results 15 trials were included in the analysis. Training sessions for medical practice teams focusing on a particular disease raised the vaccination rates by as much as 22%. A financial incentive had the greatest effect (relative risk [RR]: 2.79; 95% confidence interval: [1.18; 6.62]). Reminders via text message yielded a maximum 3.8% absolute increase in vaccination rates. Complex interventions were not found to be of any greater benefit than simple ones. Conclusion A variety of approaches can be effective. Focusing training sessions for medical practice teams on certain diseases may be of greater benefit than vacci- nation-centered training sessions. Reminder systems for doctors should be more reliably implemented. Simple strategies are perhaps the most suitable ones in the heterogeneous population of chronically ill persons. The limitations of this system- atic review include the heterogeneity of the studies that we examined and the small number of studies in each category.

Folgen der Infektion mit humanen Papillomaviren (HPV) konnen Tumorerkrankungen und deren Vorstufen, aber auch Genitalwarzen sein. Regionen der inneren und der auseren Genitale, des Anus, der Haut, der Schleimhaut sowie des Mund- und Rachenraums konnen mit HPV infiziert werden. Insbesondere das Zervixkarzinom und dessen Vorstufen stellen schwerwiegende Folgen der HPV-Infektion dar. Daher wurden Impfstoffe entwickelt, die vor der Ansteckung mit bestimmten HPV-Typen schutzen und somit HPV-assoziierte Erkrankungen verhindern sollen. Im Jahr 2006 wurde der erste HPV-Impfstoff, Gardasil®, der vor einer Infektion mit den HPV-Typen 6, 11, 16 und 18 schutzen soll, in den USA und Europa zugelassen. Ferner erfolgten 2007 die Zulassung von Cervarix®, eines HPV-Impfstoffs, der eine Infektion mit den HPV-Typen 16 und 18 verhindern soll. Kurzlich wurde Gardasil® 9, der gegen die 9 HPV-Typen 6, 11, 16, 18, 31, 33, 45, 52 und 58 schutzen soll, zugelassen. Da die Impfung keinen Schutz vor allen HPV-Typen bietet, die fur die Entstehung eines Zervixkarzinoms verantwortlich sind, ist die gynakologische Krebsfruherkennungsuntersuchung, die Frauen in Deutschland jahrlich in Anspruch nehmen konnen, nach wie vor unverzichtbar. Die HPV-Impfung selbst wird als sicher und wirksam angesehen. International wird sie in den einzelnen Landern unterschiedlich angeboten, in einigen Landern im Rahmen von organisierten Programmen. Dadurch schwanken die Impfraten stark. Die HPV-Impfung ist fur Madchen und Frauen zugelassen und wird fur diese auch in vielen Landern empfohlen. Sie ist ebenfalls fur Jungen und Manner zugelassen. Derzeit wird international kontrovers diskutiert, inwiefern eine Empfehlung zur HPV-Impfung von Jungen sinnvoll erscheint.

The effect of different invitation models on participation in cervical cancer screening (CCS) was investigated in a randomized population-based cohort study in Germany. Participants were randomly selected via population registries and randomized into intervention Arm A (invitation letter) and Arm B (invitation letter and information brochure) or control Arm C (no invitation). The intervention and control arms were compared with regard to 3-year participation and the two invitation models were compared between intervention arms. Of the 7,758 eligible women aged 30-65 years, living in the city of Mainz and in the rural region of Mainz-Bingen, 5,265 were included in the analysis. Differences in proportions of women attending CCS were investigated and logistic regression was performed to analyze various factors influencing participation. In the intervention group, 91.8% participated in CCS compared to 85.3% in the control group (p < 0.0001), with a 6.6 percentage point increase in participation [95% confidence interval (CI) 4.6-8.6] and an adjusted odds ratio (OR) of 2.69 (95% CI 2.15-3.37). Effect estimators increased to 21.9 percentage points (95% CI 16.7-27.1) and an OR of 3.64 (95% CI 2.74-4.82), respectively, when women who participated in screening annually were excluded from the analysis. The invitation letter was particularly effective among women with lower school education, migrant women and older women. No difference in participation was found between the intervention Arm A and Arm B. An accompanying information brochure did not motivate more women to undergo CCS. However, a written invitation statistically significantly increased participation in CCS in Germany.

Single nucleotide polymorphisms (SNPs) in angiogenesis-associated genes might play an important role in activity of the tyrosine kinase inhibitor sunitinib and could affect survival of cancer patients treated with this drug. The aim of this retrospective study was to elucidate the role of 10 known SNPs in VEGFA, VEGFR1, VEGFR2 and VEGFR3 as potential prognostic and predictive markers in an independent cohort of patients with metastatic renal cell carcinoma (mRCC). DNA from 121 mRCC patients treated with sunitinib was used to analyze SNPs by TaqMan genotyping assays. Disease control rate was evaluated according to RECIST. Adverse effects of sunitinib were registered from medical records. The results of Cox and logistic regression were verified by correction for multiple testing. Kaplan–Meier analysis revealed a reduced progression-free survival in patients with the wild-type (WT) allele of the VEGFA SNP rs699947 compared to variant alleles. Patients with the AA/AC-alleles of the VEGFR1 SNP rs9582036 had an improved median overall survival compared to those with the CC–WT allele what could be confirmed by multivariable Cox proportional hazard regression analyses. No statistically significant associations between the analyzed SNPs and higher risk for adverse effects were observed. The results of this study suggest that most of the selected SNPs in angiogenesis-related genes are not associated with survival of mRCC patients after sunitinib therapy or with adverse effects. Only the VEGFR1 SNP rs9582036 showed a statistically significant association with overall survival. The potential of SNPs as prognostic and predictive markers for sunitinib-treated mRCC patients should be finally assessed by prospective studies.

People with a first-degree relative with colorectal cancer (CRC) are recommended to start CRC screening at age 40. However, there is limited information on how many people in different age groups have a known family history of CRC and how many of them have had a colonoscopy.We set up a multicenter, cross-sectional, population-based study in Germany to determine what proportions of persons in age groups from 40 to 54 years old have a known family history of CRC. We invited 160,000 persons to participate in an online survey from 2015 through 2016. We investigated what proportions of persons in each age group reported a family history of CRC and what proportions of persons underwent a colonoscopy examination using descriptive statistics and multiple logistic regression models.Of 28,711 responders to the online questionnaire (8428 were age 40-44 years, 9879 were age 45-49 years, and 10,404 were age 50-54 years), 2705 stated that they had a first-degree relative with CRC (9.4%). The prevalence of a first-degree relative with CRC increased with age: 7.5%, 9.6%, and 10.9% for people 40 to 44 years old, 45 to 49 years old, and 50 to 54 years old, respectively. The prevalence of a first-degree relative who received a diagnosis of CRC at age 70 years or older increased steadily with each age group. Although a greater proportion of people with a family history of CRC had undergone a colonoscopy examination (54.5%) than people without a family history of CRC (25.7%; P .0001), large proportions of people within this risk group were not in compliance with the guidelines (54.8%, 47.6%, and 38.6% for ages 40-44 y, 45-49 y, and 50-54 y, respectively).One in 10 persons in Germany age 40 to 54 years old has a first-degree relative with CRC. Guidelines recommend initiation of screening at ages 40 to 45 years for people with a family history, yet at this age many people do not have a family history of CRC yet, and almost half of persons 40 to 54 years old with a family history of CRC have not yet received a screening colonoscopy.

Aims Annual opportunistic screening for cervical carcinoma has been carried out in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as the guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany. Methods With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline. Recommendations The first part of this short summary presents the pathological basis and considers various questions related to screening for cervical cancer. As also reported in earlier reviews, the meta-analysis by Kleijnen Systematic Reviews showed that HPV-based screening offers better protection against invasive cervical cancer compared to cytology-based screening. The authors of this guideline therefore recommend – in accordance with the guideline of the Joint National Committee of Germany (Gemeinsamer Bundesauschuss, G-BA) – that women aged 35 and above should be examined at regular intervals (at least every 3 years) and undergo HPV-based screening. Co-testing can also be carried out. Women between the ages of 20 and 35 should have cytological screening every 2 years.

IntroductionDespite an estimated one-third of the global burden of disease being surgical, only limited estimates of accessibility to surgical treatment in sub-Saharan Africa exist and these remain spatially undefined. Geographical metrics of access to major hospitals were estimated based on travel time. Estimates were then used to assess need for surgery at country level.MethodsMajor district and regional hospitals were assumed to have capability to perform bellwether procedures. Geographical locations of hospitals in relation to the population in the 47 sub-Saharan countries were combined with spatial ancillary data on roads, elevation, land use or land cover to estimate travel-time metrics of 30 min, 1 hour and 2 hours. Hospital catchment was defined as population residing in areas less than 2 hours of travel time to the next major hospital. Travel-time metrics were combined with fine-scale population maps to define burden of surgery at hospital catchment level.ResultsOverall, the majority of the population (92.5%) in sub-Saharan Africa reside in areas within 2 hours of a major hospital catchment defined based on spatially defined travel times. The burden of surgery in all-age population was 257.8 million to 294.7 million people and was highest in high-population density countries and lowest in sparsely populated or smaller countries. The estimated burden in children ConclusionThe study provides an assessment of accessibility and burden of surgical disease in sub-Saharan Africa. Yet given the optimistic assumption of adequare surgical capability of major hospitals, the true burden of surgical disease is expected to be much greater. In-depth health facility assessments are needed to define infrastructure, personnel and medicine supply for delivering timely and safe affordable surgery to further inform the analysis.

Objective We want to present information about response patterns obtained by Web-based survey in a large-scale epidemiological study. Study Design and Setting Within the RAPS (Risk Adapted Prevention Strategies for colorectal cancer [CRC]) study, we invited 160,000 randomly selected persons aged 40–54 years in three large German cities from 2015 to 2016 to complete a Web-based questionnaire on CRC risk factors and screening (97 items, average time for completion 15 minutes). Invitation letters and up to two reminder letters were sent to each individual. Results A total of 21.4% of women and 18.0% of men completed the questionnaire. Overall cumulative response rates were 7.5%, 14.3%, and 19.6% after the initial invitation letter, and the first and second reminder, respectively, with prevalence of and associations of key epidemiological parameters (such as family history of cancer, previous colonoscopy, etc.) being remarkably stable across waves of responses. For example, the sex and age distribution of the sample did not change with additional answers gained from additional letters. Conclusion Web-based questionnaires are feasible, cost-effective, and time effective in the setting of large-scale epidemiological studies. Although response patterns were remarkably stable over several rounds of reminders with substantially increasing cumulative response rates, future research should address possibilities to further enhance response rates.

A low birth rate in addition to an increasing life expectancy within the context of an aging population characterize the current demographic situation in Germany. Cancer is primarily a disease of old age and the frequency increases with an expanding older population. In 2013, cancer was the second most common cause of death in Germany. With the aid of screening examinations cancer should be detected in the early stages so that suitable therapeutic measures can be initiated. In Germany, screening is currently offered for breast, cervical, colorectal, skin and prostate cancer and is covered by the statutory health insurance. Mammography screening is the only organized screening program in Germany. Eligible women are regularly invited to attend this program, which is not the case for the other types of cancer screening. In accordance with the Cancer Screening and Registry Act (KFRG) of 2013, colorectal and cervical cancer screening will also be implemented as organized screening programs in the future. As is the case in the mammography screening program, those eligible to participate will receive an invitation letter and the new programs are to be continually monitored, documented and evaluated.

Clinical outcome of patients with stage IV breast cancer is dependent on tumor biology, extent, and localization of metastases. Routine imaging diagnostics for distant metastasis is not recommended by the national guidelines for breast cancer follow-up. In this study, we evaluated different patterns of metastases of cancer subtypes in order to generate hypotheses on individualization of follow-up after breast cancer in the adjuvant setting. Patients of the Regional Breast Cancer Center Dresden diagnosed within the years 2006-2011 were classified into the five intrinsic subtypes luminal A (ER+, Her2-, G1/2), luminal B/Her2 negative (ER+, Her2-, G3), triple positive (ER+, PR+, Her2+), Her2-enriched (ER-, Her2+), and triple negative (ER-, PR-, Her2-) and with a median follow-up of 45 months. Tumor stage at time of first diagnosis of breast cancer as well as time and site of metastasis at first diagnosis of distant metastatic disease was analyzed. Tumor specimen of 2284 female patients with primary breast cancer was classified into five subtypes. Distant recurrence-free survival at 3 years was most unfavorable in Her2-enriched (66.8 %), triple negative (75.9 %), and triple-positive breast cancer (81.7 %). The same subtypes most frequently presented with visceral metastases only at first presentation: Her2-enriched 46.9 %, triple negative 45.5 %, and triple-positive breast cancer 37.5 %. Longest median survival of 2.3 years was seen in luminal A and in Her2-enriched metastatic disease, respectively. Median survival was significantly better in the luminal A, Her2-enriched, and triple-positive subtype compared to triple-negative breast cancer (p < 0.005). Differences in time to metastatic disease, first localization of metastases, and overall survival after diagnosis of metastatic disease were shown. Considering new targeted therapies and the option of surgery of oligometastases, screening for visceral metastases might be reasonable after diagnosis of Her2-positive subtypes.

Objective Penile cancer is a rare disease in Europe and North America. Cancer registry data were used to estimate the incidence, mortality, and survival of penile cancer in Saxony, Germany. Methods Data on incidence were analyzed for the period 1961 to 2012 and mortality for the period 1990 to 2012. Trend analyses of incidence and mortality were performed using joinpoint regression. Survival rates for primary penile cancer (ICD-10 C60) were estimated; overall, by T stage, UICC stage, and by year of diagnosis for the years 1963 to 2012. Results Age-standardized incidence increased from 1.2 per 100,000 in 1961 to 1.8 per 100,000 in 2012, with a statistically significant increase between 2003 and 2012 (annual percent change: 4.66; 95% confidence interval, CI 0.62–8.86). There was a statistically significant negative trend in mortality between 1990 and 2012 (annual percent change: −3.46, 95% CI −5.21 to −1.67). A total of 430 new cases of penile cancer were registered between 2003 and 2012, with 63% of all penile cancers occurring in men aged 60 to 79 years. Almost half of those cases were located at the glans penis. The overall relative 5-year survival for the years of diagnosis 2003 to 2012 was 72.4% (95% CI 64.8%–80.0%). Relative 5-year survival decreased with higher UICC stages (I: 96%, 95% CI 84.7%–107.3%; II: 86.3%, 95% CI 71.0%–101.5%; III: 39.6%, 95% CI 19.9%–59.3%; IV: 20.3%, 95% CI 2.4%–38.2%). Conclusion The incidence of penile cancer in Saxony has increased in recent years, while mortality has decreased. However, survival rates have remained constant over time.

Gebarmutterhalskrebs ist weltweit mit etwa 529.000 Neuerkrankungen pro Jahr die dritthaufigste Tumorerkrankung bei Frauen. Deutschland gehort in Westeuropa zu den Landern mit den hochsten Inzidenzraten. Seit mehr als 40 Jahren haben Frauen ab einem Alter von 20 Jahren in Deutschland die Moglichkeit, einen kostenlosen Pap-Abstrich im Rahmen der Krebsfruherkennungsuntersuchung (KFU) zu erhalten. Nach Einfuhrung der KFU ergab sich eine deutliche Reduktion der Zervixkarzinominzidenz und -mortalitat. Allerdings fuhrten die geringe Sensitivitat des Pap-Abstrichs sowie die vorliegende Evidenz zur Rolle von humanen Papillomaviren (HPV) bei der Entstehung des Zervixkarzinoms dazu, dass die bisherige KFU mittlerweile kritisch hinterfragt wird. Zwischenzeitlich wurden neue Screeningmethoden entwickelt, und es sind verschiedene HPV-Tests, Dunnschichtzytologieverfahren sowie neue Biomarker auf den Markt gekommen. Zu diesen Verfahren liegen unterschiedliche Studienergebnisse und Evidenzen vor. Zum HPV-Test als primare Screeningmethode gibt es wissenschaftliche Evidenzen aus mehreren randomisierten Studien. Diese zeigen, dass der Test, vor allem in Kombination mit der zytologischen Untersuchung, aber auch als alleiniger Screeningtest die Fruherkennung des Zervixkarzinoms deutlich verbessert. Aktuell befindet sich die Fruherkennung des Zervixkarzinoms in Deutschland in einer Umbruchphase. Basis hierfur bildet der Nationale Krebsplan und das daraus resultierende Krebsfruherkennungs- und -registergesetz (KFRG). In den nachsten Jahren soll, basierend auf der Europaischen Leitlinie, eine Umstrukturierung der bisherigen Screeningmodalitaten fur das Zervixkarzinom erfolgen. Dabei soll in Deutschland ein organisiertes, bevolkerungsbezogenes und qualitatsgesichertes Screeningprogramm implementiert werden.

Quality assurance is required for all relevant instruments and procedures in epidemiological studies just like for clinical trials. The structure and complexity of the monitoring was developed based on the monitoring in clinical trials and applied to an epidemiological cohort study on early detection of cervical cancer (MARZY Study). Analyses of the on-site monitoring in participating gynaecological practices during the baseline investigation of the MARZY cohort were presented. The baseline investigation of the MARZY study was conducted between 2005 and 2007 in the city of Mainz, the rural district of Mainz-Bingen and surrounding areas. Women, who were randomly selected via population registries, were invited to attend cervical cancer screening at a gynaecologist's office of their choice. All study participants received a study swab in addition to their routine Pap smear. The on-site monitoring included equipment and support of all participating gynaecological practices during study recruitment. Each participant and physician signed an informed consent form. In addition, the participant completed an epidemiological questionnaire. The gynaecologist took the study swab and completed the study documentation form. Prior to recruitment, standardised processes and documentation forms were developed for the monitoring process. The monitoring visits were carried out every six to eight weeks. During the baseline investigation, participants were included in the study among 121 gynaecological practices. In total, 2,892 monitoring documentation forms from 390 on-site monitoring visits in 96 gynaecological practices from the study region and surrounding areas were analysed. On-site monitoring visits were more frequently conducted during the first year of the study. The average time needed for an on-site visit was 107 minutes (minimum 73 minutes, maximum 200 minutes). Problems such as incomplete study documentation forms or erroneous inclusion into the study occurred among 975 study participants (33.7%). 664 study participants (68.1%) did not fully complete the study forms, and 89 (9.1%) were included in the study despite the fact that they met the exclusion criteria such as hysterectomy or pregnancy. Most of these problems could be sufficiently corrected during the on-site monitoring. Monitoring in epidemiological studies performed at physicians' offices should be carried out in accordance with the monitoring in clinical trials. On-site monitoring helped to avoid missing data and to ensure adherence to exclusion criteria. On-site monitoring considerably contributed to the correct and complete study inclusion of all eligible participants and a high quality of study data.

Im April 2013 trat das Krebsfruherkennungs- und -registergesetz (KFRG) in Kraft. Damit wurde bundesweit ein weiterer wichtiger Schritt fur die Sicherung der Qualitat der onkologischen Versorgung unternommen. Flachendeckende klinische Krebsregister sollen deutschlandweit eingerichtet werden. In den ostdeutschen Bundeslandern sowie in Bayern bestehen bereits flachendeckende und bevolkerungsbezogene klinische Krebsregister. Am Beispiel Sachsen und Brandenburg werden die bestehenden Moglichkeiten zur Nutzung der Daten der klinischen Krebsregister zur Erhohung der Versorgungstransparenz und Qualitat der onkologischen Versorgung aufgezeigt. In Brandenburg und Sachsen liegt die Vollzahligkeit der klinischen Krebsregister uber 95 %. Die vorliegenden Daten konnen genutzt werden, um Trendentwicklungen auf Landesebene darzustellen, Klinikvergleiche vorzunehmen sowie um die Zertifizierung von Organkrebszentren zu unterstutzen. Die klinischen Krebsregister in Sachsen und Brandenburg registrieren die Daten der Tumorpatienten mit hoher Vollzahligkeit und konnen bereits heute die gesetzlichen Vorgaben zum grosten Teil erfullen.