Random forests for the analysis of matched case-control studies.

BACKGROUND: Conditional logistic regression trees have been proposed as a flexible alternative to the standard method of conditional logistic regression for the analysis of matched case-control studies. While they allow to avoid the strict assumption of linearity and automatically incorporate interactions, conditional logistic regression trees may suffer from a relatively high variability. Further machine learning methods for the analysis of matched case-control studies are missing because conventional machine learning methods cannot handle the matched structure of the data. RESULTS: A random forest method for the analysis of matched case-control studies based on conditional logistic regression trees is proposed, which overcomes the issue of high variability. It provides an accurate estimation of exposure effects while being more flexible in the functional form of covariate effects. The efficacy of the method is illustrated in a simulation study and within an application to real-world data from a matched case-control study on the effect of regular participation in cervical cancer screening on the development of cervical cancer. CONCLUSIONS: The proposed random forest method is a promising add-on to the toolbox for the analysis of matched case-control studies and addresses the need for machine-learning methods in this field. It provides a more flexible approach compared to the standard method of conditional logistic regression, but also compared to conditional logistic regression trees. It allows for non-linearity and the automatic inclusion of interaction effects and is suitable both for exploratory and explanatory analyses.

Incidence trend of type 2 diabetes from 2012 to 2021 in Germany: an analysis of health claims data of 11 million statutorily insured people.

AIMS/HYPOTHESIS: The aim of the study is to describe the time trend of type 2 diabetes incidence in the largest state of Germany, Bavaria, from 2012 to 2021, and to compare the incidence rates during the pandemic period (2020-2021) to the pre-pandemic period (2012-2019). METHODS: This secondary data analysis uses health claims data provided by the Bavarian Association of Statutory Health Insurance Physicians (KVB), covering approximately 11 million insurees, accounting for 85% of the total population of Bavaria, Germany. Newly diagnosed type 2 diabetes cases in adults (≥20 years) coded as E11 (Diabetes mellitus, Type 2) or E14 (Unspecified diabetes mellitus) under ICD-10, German modification (ICD-10-GM) for the study period 2012 to 2021 were included. Annual and quarterly age-standardised incidence rates (ASIR) stratified by sex, age and region were calculated using the European standard population. Sex-specific crude incidence rates (CIR) were calculated using 10-year age groups. Regression analyses adjusted for time trends, seasonal effects, and pandemic effects were used to analyse the incidence trend and to assess the effect of the pandemic. RESULTS: Overall, 745,861 new cases of type 2 diabetes were diagnosed between 2012 and 2021: 50.4% (376,193 cases) in women. The male/female ratio remained stable over the observation period, while the median age at diagnosis decreased from 61 to 58 years in men and from 66 years to 61 years in women. ASIR were consistently higher for men compared with women, with the yearly difference remaining stable over time (2012: 18%; 2021: 20%). An overall decreasing trend in ASIR was observed during the study period, with a strong decrease from 2012 to 2017, followed by a less pronounced decline from 2018 to 2021 for both sexes. For men, ASIR decreased from 1514 per 100,000 person-years in 2012 to 995 per 100,000 person-years in 2021 (4.6% average annual reduction), and for women from 1238 per 100,000 person-years in 2012 to 796 per 100,000 person-years in 2021 (4.8% average annual reduction). This downward trend was also observed for age groups above 50 years. Regression analyses showed no significant change in incidence rates during the pandemic period (2020 and 2021) compared with the pre-pandemic period. CONCLUSIONS/INTERPRETATION: For the first time, a 10-year incidence trend of type 2 diabetes is reported for Germany, showing a strong decline from 2012 to 2017, followed by a less pronounced decline from 2018 to 2021. The incidence trend of type 2 diabetes appears not to have been affected by the first 2 years of the COVID-19 pandemic. Despite an overall increasing prevalence, the incidence is decreasing, potentially resulting from robust screening by family physicians, reducing the median age at diagnosis by 3 to 5 years. However, further investigation is needed to fully identify the reasons for the declining incidence trend. Continued incidence monitoring is necessary to identify the long-term trend and the potential effect of the pandemic on diagnoses of type 2 diabetes.

Histology-specific standardized incidence ratio improves the estimation of second primary lung cancer risk.

BACKGROUND: Lung cancer (LC) survivors are at increased risk for developing a second primary cancer (SPC) compared to the general population. While this risk is particularly high for smoking-related SPCs, the published standardized incidence ratio (SIR) for lung cancer after lung cancer is unexpectedly low in countries that follow international multiple primary (IARC/IACR MP) rules when compared to the USA, where distinct rules are employed. IARC/IACR rules rely on histology-dependent documentation of SPC with the same location as the first cancer and only classify an SPC when tumors present different histology. Thus, SIR might be underestimated in cancer registries using these rules. This study aims to assess whether using histology-specific reference rates for calculating SIR improves risk estimates for second primary lung cancer (SPLC) in LC survivors. METHODS: We (i) use the distribution of histologic subtypes of LC in population-based cancer registry data of 11 regional cancer registries from Germany to present evidence that the conventional SIR metric underestimates the actual risk for SPLC in LC survivors in registries that use IARC/IACR MP rules, (ii) present updated risk estimates for SPLC in Germany using a novel method to calculate histological subtype-specific SIRs, and (iii) validate this new method using US SEER (Surveillance, Epidemiology, and End Results Program) data, where different MP rules are applied. RESULTS: The adjusted relative risk for lung cancer survivors in Germany to develop an SPLC was 2.98 (95% CI 2.53-3.49) for females and 1.15 (95% CI 1.03-1.27) for males using the novel histology-specific SIR. When using IARC/IACR MP rules, the conventional SIR underestimates the actual risk for SPLC in LC survivors by approximately 30% for both sexes. CONCLUSIONS: Our proposed histology-specific method makes the SIR metric more robust against MP rules and, thus, more suitable for cross-country comparisons.

Population-based age- and type-specific prevalence of human papillomavirus among non-vaccinated women aged 30 years and above in Germany.

BACKGROUND: A persisting high-risk human papillomavirus (HR-HPV) infection is causal for cervical cancer; however, there is limited population-based data on the prevalence of HPV infections in Germany. We assessed the age and type-specific HPV prevalence, and associated risk factors in HPV unvaccinated women aged 30 and above. METHODS: The MARZY prospective population-based cohort study was conducted between 2005 and 2012 in Mainz and Mainz-Bingen, Germany. Eligible women were randomly recruited from population registries and invited for cervical cancer screening (n = 5,275). A study swab (liquid-based cytology) was taken and HPV testing was performed with GP5+/6 + polymerase chain reaction (PCR) followed by genotyping. We assessed HPV types as HR-HPV, 'moderate' risk and low-risk (LR-HPV). Logistic regression was performed to identify factors associated with HPV infection, stratified by HPV types. RESULTS: 2,520 women were screened with a valid PCR result. Overall HPV prevalence was 10.6% (n = 266), with 6.5% HR-HPV positive (n = 165), 1.5% 'moderate' risk type (n = 38) and 3.3% LR-HPV type (n = 84) positive. 8.9% had a single infection (n = 225) and 1.6% had multiple types (n = 41). The most common HR-HPV types were 16, 56, 52 and 31 and LR-HPV 90 and 42. Of 187 HR-HPV infections detected (among 165 women), 55.1% (n = 103) were with HPV types not covered by available bivalent or quadrivalent HPV vaccines. About 23% (n = 43) were of types not covered by the nonavalent vaccine (HPV 35, 39, 51, 56, 59). The HR and LR-HPV prevalence were highest in the age group 30-34 years (HR 9.8%, 'moderate' risk 3.0% and LR 5.6%), decreasing with increasing age. HR-HPV prevalence in women with normal cytology was 5.5%. In women with a high-grade squamous intraepithelial lesion (HSIL), prevalence was 66.7%. Women currently not living with a partner and current smokers had increased chances of an HR-HPV infection. CONCLUSION: The overall population-based HPV prevalence was relatively high. An important share of prevalent HR-HPV infections constituted types not covered by current HPV vaccines. With the advent of HPV screening and younger vaccinated cohorts joining screening, HPV types should be monitored closely, also in older women who were not eligible for HPV vaccination.

Global parental acceptance, attitudes, and knowledge regarding human papillomavirus vaccinations for their children: a systematic literature review and meta-analysis.

BACKGROUND: This systematic literature review aims to summarize global research on parental acceptance, attitudes, and knowledge regarding human papillomavirus vaccinations. METHODS: The literature search was conducted in PubMed, Web of Science and Scopus, and included publications from 2006 to 2023. Study quality was assessed using the Newcastle-Ottawa Scale. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to assess the strength of evidence for the primary outcome. Meta-analyses were performed using random-effects models to estimate pooled parental acceptance of HPV vaccinations. Studies were stratified by study years, and a subgroup analysis was conducted to estimate vaccine acceptance rates by world regions. Additionally, sensitivity analyses examined the role of parents in accepting HPV vaccinations for children of different sexes. RESULTS: Based on 86 studies, we found that parents generally supported HPV vaccinations for their children, yet HPV vaccine acceptance rates showed high variation (12.0 to 97.5%). The subgroup analysis revealed geographical variations in pooled parental HPV vaccine acceptance rates, with the highest rate observed in Africa (79.6%; 95% CI: 73.5-85.2; I² = 98.3%; p < 0.01) and the lowest in North America (56.7%; 95% CI: 49.3-64.0; I² = 99.4%; p < 0.01). Sensitivity analyses showed that acceptance was higher for daughters than for sons, with mothers more willing to get their daughters vaccinated. The proportion of parents reporting barriers or benefits regarding HPV vaccinations varied widely (0.3-95.8%) between study regions. Across all world regions, fear of adverse effects and concerns about vaccine safety were the main barriers, whereas the desire to protect their children from cancer was a significant predictor of vaccine acceptance. Knowledge levels varied widely (6.5 to 100%) between world regions and according to the questions asked. In most studies, knowledge e.g., that HPV is sexually transmitted, and that HPV vaccination provides protection against cervical cancer, ranged from moderate to high. CONCLUSIONS: The results indicated moderate parental acceptance of HPV vaccines. Public knowledge of HPV infection should be promoted, and special efforts should be made to minimize the existing barriers and increase vaccination accessibility and uptake.

Second primary cancer among 217702 colorectal cancer survivors: An analysis of national German cancer registry data.

With improvements in survival after colorectal cancer (CRC), more survivors are at risk of developing a second cancer, particularly in younger populations where CRC incidence is increasing. We estimated the incidence of second primary cancer (SPC) in CRC survivors and its potential risk factors. We identified CRC cases diagnosed between 1990 and 2011 and SPCs until 2013 from nine German cancer registries. Standardized incidence ratios (SIR) and absolute excess risk (AER) per 10 000 person-years were calculated and were stratified by index site: colon cancer (CC) and rectal cancer (RC), age and sex. Cox regression assessed potential SPC risk factors, including primary tumor-related therapy considering death as a competing risk. We included 217 202 primary CRC cases. SPC occurred in 18 751 CRC survivors (8.6%; median age: 69 years). Risk of cancer was significantly higher in CRC survivors than in the general population (SIR males 1.14, 95% confidence interval [CI] 1.12-1.17, AER = 24.7; SIR females 1.20, 95% CI 1.17-1.23, AER = 22.8). Increased risks of SPCs were observed for the digestive system, urinary system and female and male reproductive organs. CRC incidence increased in younger persons (<50 years) and SPC incidence was 4-fold in this group (SIR males 4.51, 95% CI 4.04-5.01, AER = 64.2; SIR females 4.03, 95% CI 3.62-4.48, AER = 77.0). Primary tumor-related factors associated with SPC risk were right-sided cancer and smaller primary tumor size. Treatment and risk of SPC differed for CC (no effect) and RC (lower risk after chemotherapy). CRC survivors have excess risk of developing SPC, with particular characteristics that could guide targeted surveillance.

Changes in the probability of hysterectomy in the city of Mainz and Mainz-Bingen region, Germany.

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).

Modelling the effect of demographic change and healthcare infrastructure on the patient structure in German hospitals - a longitudinal national study based on official hospital statistics.

BACKGROUND: Effects of demographic change, such as declining birth rates and increasing individual life expectancy, require health system adjustments offering age- and needs-based care. In addition, healthcare factors can also influence health services demand. METHODS: The official German hospital statistics database with odd-numbered years between 1995 and 2011 was analysed. This is a national comprehensive database of all general hospital inpatient services delivered. Official data from hospital statistics were linked at the district level with demographic and socio-economic data as well as population figures from the official regional statistics. Panel data regression, modelling case numbers per hospital, was performed for 13 diagnosis groups that characterised the patient structure. Socio-demographic variables included age, sex, household income, and healthcare factors included bed capacity, personnel and hospital characteristics. RESULTS: The median number of annual treatments per hospital increased from 6 015 (5th and 95th percentile [670; 24 812]) in 1995 to 7 817 in 2011 (5th and 95th percentile [301; 33 651]). We developed models characterising the patient structure of health care in Germany, considering both socio-demographic and hospital factors. Demographic factors influenced case numbers across all major diagnosis groups. For example, the age groups 65-74 and 75 + influenced cerebrovascular disease case numbers (p < 0.001). Other important factors included human and material resources of hospitals or the household income of patients. Distinct differences between the models for the individual diagnosis groups were observed. CONCLUSIONS: Hospital planning should not only consider demographic change but also hospital infrastructure and socio-economic factors.

HPV vaccination leads to decrease of anogenital warts and precancerous lesions of the cervix uteri in young women with low vaccination rates: a retrospective cohort analysis.

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.

Colposcopy non-attendance following an abnormal cervical cancer screening result: a prospective population-based cohort study.

BACKGROUND: A considerable proportion of cervical cancer diagnoses in high-income countries are due to lack of timely follow-up of an abnormal screening result. We estimated colposcopy non-attendance, examined the potential factors associated and described non-attendance reasons in a population-based screening study. METHODS: Data from the MARZY prospective cohort study were analysed. Co-test screen-positive women (atypical squamous cells of undetermined significance or worse [ASC-US+] or high-risk human papillomavirus [hrHPV] positive) aged 30 to 65 years were referred to colposcopy within two screening rounds (3-year interval). Women were surveyed for sociodemographic, HPV-related and other data, and interviewed for non-attendance reasons. Logistic regression was used to examine potential associations with colposcopy attendance. RESULTS: At baseline, 2,627 women were screened (screen-positive = 8.7%), and 2,093 again at follow-up (screen-positive = 5.1%; median 2.7 years later). All screen-positives were referred to colposcopy, however 28.9% did not attend despite active recall. Among co-test positives (ASC-US+ and hrHPV) and only hrHPV positives, 19.6% were non-attendees. Half of only ASC-US+ screenees attended colposcopy. Middle age (adjusted odds ratio [aOR] = 1.55, 95% CI 1.02, 4.96) and hrHPV positive result (aOR = 3.04, 95% CI 1.49, 7.22) were associated with attendance. Non-attendance was associated with having ≥ 3 children (aOR = 0.32, 95% CI 0.10, 0.86). Major reasons for non-attendance were lack of time, barriers such as travel time, need for childcare arrangements and the advice against colposcopy given by the gynaecologist who conducted screening. CONCLUSIONS: Follow-up rates of abnormal screening results needs improvement. A systematic recall system integrating enhanced communication and addressing follow-up barriers may improve screening effectiveness.

Enablers and barriers to post-discharge follow-up among women who have undergone a caesarean section: experiences from a prospective cohort in rural Rwanda.

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.

The Clinical Complexity of Penile Cancer: Current Clinical-Epidemiological Data from the Database of the Free State of Saxony/Germany.

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.

[HPV vaccination and the prevention of genital warts and precancerous lesions-current evidence and evaluation]. / HPV-Impfung zur Prävention von Genitalwarzen und Krebsvorstufen ­ Evidenzlage und Bewertung.

Human papillomaviruses (HPVs) can cause both benign and malignant tumors. To date, more than 200 HPV types have been discovered, of which 12 are currently classified as high risk for cervical cancer. HPV types that affect the anogenital tract are sexually transmitted. Since 2006, prophylactic HPV vaccines have been available and should be administered before first sexual contact.HPVs infect epithelial cells and are worldwide the most common sexually transmitted viruses. Apart from cervical cancer, HPVs cause other anogenital cancers such as vulvar, vaginal, and anal cancer but also oropharyngeal cancer (or head and neck cancers). HPV types 16 and 18 are also found at these sites. HPV types 6 and 11 are associated with genital warts; other HPV types can cause harmless skin warts.HPV vaccines are safe and highly effective, if they are administered before exposure to HPV. Systematic reviews and meta-analyses have shown that HPV vaccination effectively prevents HPV infection, but also precancerous lesions of the anogenital tract and genital warts. Recent vaccination data also demonstrate reductions in cervical cancer incidence.The uptake rates of HPV vaccination vary worldwide by program and acceptance. In comparison to other European countries, Germany has a low uptake rate. The Standing Committee on Vaccination (STIKO) recommends HPV vaccinations for all girls and boys ages 9 to 14 years in Germany. In 2018, only half of all 18-year-old girls in Germany were completely immunized against HPV.Organized vaccination programs, whether population-based or school-based, are necessary in order to increase vaccination uptake rates.

Prevalence of a First-Degree Relative With Colorectal Cancer and Uptake of Screening Among Persons 40 to 54 Years Old.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review.

BACKGROUND: Human papillomavirus (HPV) vaccination is safe and effective in preventing cervical cancer in females. As HPV infections can also induce cancers of the anus, penis and oral cavity, male vaccination is also advocated, but systematic reviews on efficacy and safety in males are lacking. METHODS: We performed a systematic review on the efficacy, effectiveness and safety of HPV vaccination in males of any age. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched from inception to April 2017. RESULTS: We identified 5196 articles and seven studies (four randomized controlled trials (RCTs), three non-randomized studies) were included, comprising a total of 5294 participants. Vaccine efficacy against at least 6-month persisting anogenital HPV 16 infections was 46.9% (95% confidence interval (CI) 28.6-60.8%), whereas efficacy against persisting oral infections was 88% (2-98%). A vaccine efficacy of 61.9% (21.4-82.8%) and 46.8% (- 20 to -77.9%) was observed against anal intraepithelial neoplasia grade 2 and grade 3 lesions, respectively. No meaningful estimates were available on vaccine efficacy or effectiveness against penile intraepithelial neoplasia grade 2 or 3, and no data were identified for anal, penile or head and neck squamous cell cancer. In participants who were HPV-seronegative and PCR-negative at enrolment, efficacy against all outcomes was higher as compared to seropositive and/or PCR-positive individuals. Risk of bias was low in three RCTs and high in one, while the three non-randomized studies were at serious to critical risk of bias. Grading of Recommendations Assessment, Development and Evaluation evidence quality was moderate to low for most outcomes. CONCLUSIONS: HPV vaccination in males is moderately effective against persistent anogenital HPV infection and high-grade anal intraepithelial lesions in studies where the population consists mainly of HPV-infected males. Vaccine effectiveness was high in study groups comprising HPV-naïve males. This supports a recommendation for vaccination of boys before the onset of sexual activity with the goal of establishing optimal vaccine-induced protection. Mathematical modelling studies will still be needed to assess the effects of adding males to existing HPV vaccination programs in females. TRIAL REGISTRATION: Prospective Register for Systematic Reviews (PROSPERO) registration CRD42016038965 .

Study protocol of the RaPS study: novel risk adapted prevention strategies for people with a family history of colorectal cancer.

BACKGROUND: People aged 40-60 years with a family history (FH) of colorectal cancer (CRC) in 1st degree relatives (FDRs) have a 2- to 4-fold increased risk of CRC compared to the average risk population. Therefore, experts recommend starting CRC screening earlier for this high-risk group. However, information on prevalence of relevant colonoscopic findings in this group is sparse, and no risk adapted screening offers are implemented in the German health care system. For example, screening colonoscopy is uniformly offered from age 55 on, regardless of family history. Thus, we initiated a multicenter epidemiological study - the RaPS study (Risk adapted prevention strategies for colorectal cancer) - with the following aims: to determine the prevalence of having a FH of CRC in FDR in the German population aged 40-54 years; to investigate the prevalence of colorectal neoplasms among people with a FDR; and to develop risk-adapted prevention strategies for this high-risk group based on the collected information. METHODS/DESIGN: A random sample of 160.000 persons from the general population aged 40-54 years from the catchment areas of three study centers in Germany (Dresden, Munich and Stuttgart) are contacted to assess FH of CRC by an online-questionnaire. Those with a FH of CRC in FDRs are invited to the study centers for individual consultation regarding CRC prevention. Participants are asked to donate blood and stool samples and medical records of colonoscopies will be obtained. Prevalence of CRC and its precursors will be evaluated. Furthermore, genetic, epigenetic and proteomic biomarkers in blood and microbiomic biomarkers in stool will be investigated. Risk markers and their eligibility for risk adapted screening offers will be examined. DISCUSSION: This study will provide data on the prevalence of colorectal neoplasms among persons with a FH of CRC in the age group 40-54 years, which will enable us to derive evidence based screening strategies for this high-risk group. TRIAL REGISTRATION: This trial was registered retrospectively in the German Clinical Trials Register (DRKS) on 29th of December 2016: German Clinical Trials Register DRKS-ID: DRKS00007842 .

[Cervical cancer screening in Germany]. / Gebärmutterhalskrebsscreening in Deutschland.

Cytological examination for the early detection of cervical cancer (CCS) has been available in Germany since 1971. Women over the age of 20 are entitled to a Pap smear every year; however, thus far an organized screening program and personal invitations have been missing.The incidence rate of cervical carcinoma declined dramatically in the decades following the introduction of CCS, but the incidence rate has stagnated in recent years. The cause of cervical cancer is a persistent infection with high-risk types of human papillomavirus (HPV). HPV tests have been approved by the American Food and Drug Administration (FDA) for CCS for several years. Furthermore, since 2006, the HPV vaccination has been offered as a form of primary prevention.As part of the German National Cancer Plan, the European Guideline for Cervical Cancer Screening was implemented and adopted into the 2013 Law on Cancer Screening and Registration. The Federal Joint Committee (G-BA) was commissioned with the implementation of an organized cervical cancer screening program.In April 2018, the G­BA published updated key points for the implementation of an organized nationwide screening program in Germany. While annual cytological screening for women between the ages of 20 and 34 will continue, women over the age of 34 years will be given a co-test comprising a Pap smear and an HPV test, every three years. Women between the ages of 20 and 60 will be contacted by their health insurance provider every five years and receive an information leaflet. After a test phase of at least six years, the new program will be evaluated.

Cancer incidence in Germany attributable to human papillomavirus in 2013.

BACKGROUND: It is estimated that a total of 120,000 new cancer cases in men and in women in more developed countries could be avoided if exposure to HPV was prevented. We used the nationwide pool of German population-based cancer registry data to estimate the burden of HPV-attributable cancer in this population for the year 2013. METHODS: Incident cases of cervical cancer, squamous cell carcinoma of the anus, oropharynx (OP), as well as of the vulva, vagina and penis were classified as potentially HPV-associated and identified from the nationwide cancer registry data-pool. We calculated the incidence and proportions of cancer with potentially HPV-associated morphologies. Estimation of the HPV-attributable incidence was based on prevalence-estimates of viral DNA in tumor cells in the respective sites, as provided from the international literature. RESULTS: From the overall 15,936 incident cases of anogenital and OP cancers in 2013, 6239 female and 1358 male cancer cases were estimated to be attributable to HPV. The majority of HPV-attributable cases were contributed by cervical cancer (70.9% of female cancers) and oropharyngeal cancer (46.9% of male cancers). CONCLUSIONS: Even if most HPV-attributable cases were contributed by cervical cancer, anogenital cancer at sites other than the cervix, and oropharyngeal cancer substantially contribute to the burden of HPV-associated cancer. Our nationwide cancer registry data-analyses provide the baseline for long-term population-based monitoring of vaccination-effects on cancer incidence in Germany.

Trastuzumab and survival of patients with metastatic breast cancer.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.