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Abstract 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.

Abstract 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 publication 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

Abstract 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.

Abstract Recent studies show declining trends in hysterectomy rates in several countries. The objective of this study was to analyse hysterectomy time trends in Germany over a fifteen-year period using an age-period-cohort approach. Using an ecological study design, inpatient data from Diagnoses Related Group on hysterectomies by subtype performed in Germany from 2005 to 2019 were retrieved from the German Statistical Office. Descriptive time trends and age-period-cohort analyses were then performed. A total of 1,974,836 hysterectomies were performed over the study period. The absolute number of hysterectomies reduced progressively from 155,680 (365 procedures/100,000 women) in 2005 to 101,046 (257 procedures/100,000 women) in 2019. Total and radical hysterectomy decreased by 49.7% and 44.2%, respectively, whilst subtotal hysterectomy increased five-fold. The age-period-cohort analysis revealed highest hysterectomy rates in women aged 45–49 for total and subtotal hysterectomy with 608.63 procedures/100,000 women (95% CI 565.70, 654.82) and 151.30 procedures/100,000 women (95% CI 138.38, 165.44) respectively. Radical hysterectomy peaked later at 65–69 years with a rate of 40.63 procedures/100,000 women (95% CI 38.84, 42.52). The risk of undergoing total or radical hysterectomy decreased over the study period but increased for subtotal hysterectomy. Although, overall hysterectomy rates have declined, subtotal hysterectomy rates have increased; reflecting changes in clinical practice largely influenced by the availability of uterus-sparing options, evolving guidelines and introduction of newer surgical approaches.

Abstract 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.

Abstract 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

Abstract Background Women’s empowerment is an important factor for HIV prevention, but the association with HIV-related indicators has never been quantified. In this study, we examined the association between women’s empowerment and selected HIV-related indicators. Methods We used the latest Demographic and Health Surveys that included HIV testing among other biomarkers of 31 countries in sub-Saharan Africa. Empowerment was measured by the Survey-based Women’s EmPowERment (SWPER) index and was compared to the HIV-related indicators: HIV status, HIV testing (ever and in the past 12 months), condom use at last high-risk sex, the ability to ask the partner to use a condom, and the ability to refuse sex. Results 208,947 women were included in the analysis, of whom 100,924 (48%) were considered highly empowered and 21,933 (10%) as lowly empowered. There was no association between empowerment and HIV status (OR = 1.12, 95% confidence interval [CI] 0.98–1.28). Highly empowered women were more likely to have ever been tested for HIV (OR = 1.67, 95% CI 1.60–1.74) but less likely to have been tested for HIV in the past 12 months (OR = 0.92, 95%CI 0.88–0.96). Highly empowered women were more commonly able to ask the partner to use a condom (OR = 1.69, 95% CI 1.63–1.75) and to refuse sex (OR = 1.78, 95%CI 1.72–1.85). Conclusions Women’s empowerment does not seem to be linked to HIV status, but it is strongly associated with a woman’s ability to make decisions about their sexual behavior. Empowering women and young girls has the potential to contribute toward achieving the United Nations’ goal of ending AIDS by 2030.

Abstract Background Adolescent and young adult (AYA) cancer survivors (CS) face unique psychosocial challenges, which may affect their mental health. However, there are inconsistencies in AYA definitions and varying prevalence data on psychological distress, anxiety, and depression. We aimed to synthesize published literature on prevalence, risk, longitudinal changes, and predictors for these outcomes and estimate pooled prevalences. Methods We searched for observational studies published in English before June 1 2022, in PubMed, PsycINFO, Scopus, and Web of Science. Two researchers extracted independently information on study characteristics, prevalence, and risk. The pooled prevalence (PP) of psychological distress, anxiety, and depression was estimated using random‐effects models. Geographical region, treatment status, and assessment instruments were considered in stratified meta‐analyses. Results Sixty‐eight studies were included in the systematic review and 57 in the meta‐analyses. We estimated an overall prevalence of 32% (n = 30; 4226/15,213 AYAs; 95% CI, 23%–42%; I2 = 99%) for psychological distress, 29% for anxiety (n = 24; 2828/8751 AYAs; 95% CI, 23%–36%; I2 = 98%), and 24% (n = 35; 3428/16,638 AYAs; 95% CI, 18%–31%; I2 = 98%) for depression. The range of PP of psychological distress varied across geographical regions, treatment status, and assessment instruments. The PP of anxiety varied significantly across continents, while no variations were seen for depression. Studies found higher risks for psychological distress, anxiety, and depression in AYAs compared to older cancer survivors or cancer‐free peers. Conclusions Our research found that one in three AYA‐CS experience psychological distress or anxiety and one in four are affected by depression, highlighting the need for specialized psychological services for AYA‐CS in oncology settings and AYA‐focused interventions.

Abstract Background Cervical cancer (CC) screening is generally recommended until age 65. The incidence of CC could be underestimated, particularly in older women, due to a lack of hysterectomy correction. Furthermore, elderly women (≥65 years) are more often diagnosed with late‐stage disease and have worse outcomes than younger patients. This study aims to provide an in‐depth overview of CC in Germany. Methods Incidence rates of CC (ICD‐10 C53) were determined using data from the German Centre of Cancer Registry data (ZfKD) of six federal state registries. Incidence was corrected by using hysterectomy prevalence values from a real‐world study. The distribution of treatment modalities (surgery, chemotherapy, radiation therapy) was assessed. Relative survival was calculated using the period approach (2011–2015). Survival was stratified by tumor (T) stage and histological type. Results In total, 14,528 CC cases were included, 27.6% of which occurred in elderly women. Cumulative (2001–2015) age‐standardized incidence rates were 12.5 per 100,000 women without hysterectomy correction and 15.5 per 100,000 women after hysterectomy correction (+24% relative change). A lower proportion of elderly women were treated, especially in advanced tumor stages. Younger women (20–64 years) had a higher 5‐year relative survival compared to elderly women: 76.7% versus 46.9%, respectively. Survival was worse with increasing stage and for glandular histological subgroups, particularly among elderly women. Conclusions CC incidence in elderly women is underestimated and survival is lower compared to younger women in Germany. Due to the high disease burden in elderly women, screening and treatment strategies need to be improved.

Abstract Background The national skin cancer screening (SCS) was introduced in Germany in 2008. However, public awareness and participation rates remain low. There are no campaigns or target group‐specific invitation strategies for SCS yet. Thus, our aim was to derive potential suggestions on how to best inform German residents about the possibility of SCS. Methods Semi‐structured, individual interviews with male and female German residents aged ≥35 years were conducted in Erlangen (Germany) to explore opportunities on raising awareness of SCS. Interviews were audiotaped, transcribed verbatim, and analyzed using qualitative content analysis. Results Overall, 39 persons were interviewed. About 79.5% (31/39) had already undergone at least one SCS. Numerous opportunities to raise awareness of the possibility of SCS were suggested which were categorized into three main topics: the role of public promotion, health‐related caregivers, and health insurance. Similar themes were identified for inviting entitled persons to undergo SCS after 2 years. Furthermore, age‐dependent communication approaches were proposed, that is, younger persons should be approached electronically, while the older generation should be targeted with traditional media like mail. Conclusions The results of this project will inform stakeholders to take appropriate actions. The findings may contribute to increase participation rates in SCS and thus lead to earlier detection of skin cancer.

Abstract 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).

Abstract 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.

Abstract 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.

Abstract 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.

Abstract 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.

Abstract 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.

Abstract 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.

In Germany, a biennial preventive health check-up has been available for individuals aged 35 and older since 1989. The check-up includes identification of cardiovascular disease risk factors and examinations for diabetes mellitus type 2 and kidney disease. Participation in preventive health check-ups among 19,351 women aged 35 to 74 in Germany in 2004 was investigated. Logistic regression was performed to examine associations between participation and age, marital status, education, socio-economic status (SES) and region of residence. In total, 53.4% of women attended at least every two years, 23.4% attended irregularly and 23.2% never attended. In adjusted models, single, divorced, separated or widowed women were less likely to have a preventive health check-up at least every two years compared to married women (OR 0.63, 95% CI 0.57–0.71), while women in eastern Germany were less likely to participate (OR 0.80, 95% CI 0.75–0.86) than women in western Germany. Education showed no association with having a preventive health check-up at least every two years; however, women with low SES were less likely to participate compared to those with high SES (OR 0.82, 95% CI 0.74–0.92). About half of eligible women reported participating in health check-ups at least every two years, with participation varying according to socio-demographic characteristics. Women who are less likely to participate may benefit from receiving invitation letters within the framework of an organised programme. The benefits of general health checks, however, need to be evaluated.

Abstract Background Adequate coverage is key to the success of human papillomavirus (HPV) vaccination programmes. There is currently no organised HPV vaccination programme in Germany. The aim of this analysis was to determine HPV vaccine uptake as well as factors associated with uptake in nine to 17 year-old girls in Germany during the first year of vaccine availability. Methods This analysis is based on data from the Healthcare Access Panel, an established population-based household panel consisting of 55 000 representative households in Germany who were contacted between September and October 2007. A total of 4 747 households included at least one girl aged nine to 17 years. After reading a description of the HPV vaccine, these girls were asked, “Would you have yourself vaccinated against HPV?” Logistic regression analyses were performed to investigate associations between vaccination status and socio-demographic characteristics of the girls and their mothers. Results Of the 4 747 girls in the households who received questionnaires, 2 224 (46.9 %) participated in the study and 1 906 (40.2 %) answered the vaccination question. A total of 17.4 % of the girls were already vaccinated, 61.5 % felt positively about doing so, 4.7 % said they would not be vaccinated, and 16.3 % were not sure. The probability of a girl being vaccinated increased with each additional year of age (Odds Ratio (OR): 1.6, 95 % Confidence Interval (CI) 1.5–1.7). Among the 17 year-old girls, 38.5 % (95 % CI 32.6–44.4 %) had been vaccinated. Having a mother with high education (OR: 1.5, 95 % CI 1.0–2.3) or medium education (OR: 1.5, 95 % CI 1.1–2.1) versus basic education was a significant predictor for having been vaccinated. Similarly, medium (OR: 1.5, 95 % CI 1.0–2.4) versus low SES was significantly associated with having been vaccinated. Our analysis showed that during the first year of HPV vaccine availability in Germany, vaccination uptake was low. Conclusions Countries with organised HPV vaccination programmes showed much higher vaccination uptake, even in the first year after programme introduction. If vaccination uptake in Germany is to significantly improve in the future, an organised vaccination programme will need to be introduced.

Incidence and mortality rates of cervical cancer are higher in Germany than in other Western European countries. Type‐specific human papillomavirus (HPV) distribution was investigated for the first time in Germany in an epidemiological study including 8,101 women. Women above the age of 30 years, self‐referring for cervical cancer screening, were enrolled in two study centers in Hannover (Northern Germany) and Tübingen (Southern Germany). Participants were screened by the Pap smear and the hybrid capture 2 (HC2) test using the high‐risk probe. All samples that were positive by the HC2 test were genotyped using the prototype PGMY09/11 PCR line blot assay. Most women in the study population had a negative Pap smear (96.7%). Prevalence of high‐risk type HPV detected by HC2 was 6.4% and prevalence of carcinogenic types detected by PGMY09/11 was 4.3%. Of the PGMY09/11 PCR‐positive women, 70.2% had a single infection, 28.1% had multiple infections and 1.7% remained uncharacterized. 32 different HPV types were detected using PGMY09/11 PCR. HPV 16, 31, 52, 51, 18, and 45 were the most common carcinogenic types in the study population. Among women with histologically confirmed high‐grade lesions HPV 16, 45, 58, 18, 31, 33, and 52 were the predominant types. These results provide valuable information for the management of HPV infections in Germany, both in terms of future strategies of screening and vaccination. J. Med. Virol. 79:616–625, 2007. © 2007 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]

Objectives: To assess the risk of lung cancer mortality related to occupational exposure to titanium dioxide (TiO2). [ABSTRACT FROM AUTHOR]

BackgroundMultiple risk factors contribute jointly to the development and progression of cardiometabolic diseases. Therefore, joint longitudinal trajectories of multiple risk factors might represent different degrees of cardiometabolic risk.MethodsWe analyzed population-based data comprising three examinations (Exam 1: 1999-2001, Exam 2: 2006-2008, Exam 3: 2013-2014) of 976 male and 1004 female participants of the KORA cohort (Southern Germany). Participants were followed up for cardiometabolic diseases, including cardiovascular mortality, myocardial infarction and stroke, or a diagnosis of type 2 diabetes, until 2016. Longitudinal multivariate k-means clustering identified sex-specific trajectory clusters based on nine cardiometabolic risk factors (age, systolic and diastolic blood pressure, body-mass-index, waist circumference, Hemoglobin-A1c, total cholesterol, high- and low-density lipoprotein cholesterol). Associations between clusters and cardiometabolic events were assessed by logistic regression models.ResultsWe identified three trajectory clusters for men and women, respectively. Trajectory clusters reflected a distinct distribution of cardiometabolic risk burden and were associated with prevalent cardiometabolic disease at Exam 3 (men: odds ratio (OR)ClusterII = 2.0, 95% confidence interval: (0.9-4.5); ORClusterIII = 10.5 (4.8-22.9); women: ORClusterII = 1.7 (0.6-4.7); ORClusterIII = 5.8 (2.6-12.9)). Trajectory clusters were furthermore associated with incident cardiometabolic cases after Exam 3 (men: ORClusterII = 3.5 (1.1-15.6); ORClusterIII = 7.5 (2.4-32.7); women: ORClusterII = 5.0 (1.1-34.1); ORClusterIII = 8.0 (2.2-51.7)). Associations remained significant after adjusting for a single time point cardiovascular risk score (Framingham).ConclusionsOn a population-based level, distinct longitudinal risk profiles over a 14-year time period are differentially associated with cardiometabolic events. Our results suggest that longitudinal data may provide additional information beyond single time-point measures. Their inclusion in cardiometabolic risk assessment might improve early identification of individuals at risk.

With the advances in technology and data science, machine learning (ML) is being rapidly adopted by the health care sector. However, there is a lack of literature addressing the health conditions targeted by the ML prediction models within primary health care (PHC) to date. To fill this gap in knowledge, we conducted a systematic review following the PRISMA guidelines to identify health conditions targeted by ML in PHC. We 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 primary studies addressing ML diagnostic or prognostic predictive models that were supplied completely or partially by real-world PHC data. Studies selection, data extraction, and risk of bias assessment using the prediction model study risk of bias assessment tool were performed by two investigators. Health conditions were categorized according to international classification of diseases (ICD-10). Extracted data were analyzed quantitatively. We identified 106 studies investigating 42 health conditions. These studies included 207 ML prediction models supplied by the PHC data of 24.2 million participants from 19 countries. We found that 92.4% of the studies were retrospective and 77.3% of the studies reported diagnostic predictive ML models. A majority (76.4%) of all the studies were for models' development without conducting 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 diabetes mellitus (19.8%) and Alzheimer's disease (11.3%). Our study provides a summary on the presently available ML prediction models within PHC. We draw the attention of digital health policy makers, ML models developer, and health care professionals for more future interdisciplinary research collaboration in this regard.

Background Surgical site infections (SSIs) cause a significant global public health burden in low and middle-income countries. Most SSIs develop after patient discharge and may go undetected. We assessed the feasibility and diagnostic accuracy of an mHealth-community health worker (CHW) home-based telemedicine intervention to diagnose SSIs in women who delivered via caesarean section in rural Rwanda.Methods This prospective cohort study included women who underwent a caesarean section at Kirehe District Hospital between September 2019 and March 2020. At postoperative day 10 (±3 days), a trained CHW visited the woman at home, provided wound care and transmitted a photo of the wound to a remote general practitioner (GP) via WhatsApp. The GP reviewed the photo and made an SSI diagnosis. The next day, the woman returned to the hospital for physical examination by an independent GP, whose SSI diagnosis was considered the gold standard for our analysis. We describe the intervention process indicators and report the sensitivity and specificity of the telemedicine-based diagnosis.Results Of 787 women included in the study, 91.4% (n=719) were located at their home by the CHW and all of them (n=719, 100%) accepted the intervention. The full intervention was completed, including receipt of GP telemedicine diagnosis within 1 hour, for 79.0% (n=623). The GPs diagnosed 30 SSIs (4.2%) through telemedicine and 38 SSIs (5.4%) through physical examination. The telemedicine sensitivity was 36.8% and specificity was 97.6%. The negative predictive value was 96.4%.Conclusions Implementation of an mHealth-CHW home-based intervention in rural Rwanda and similar settings is feasible. Patients’ acceptance of the intervention was key to its success. The telemedicine-based SSI diagnosis had a high negative predictive value but a low sensitivity. Further studies must explore strategies to improve accuracy, such as accompanying wound images with clinical data or developing algorithms using machine learning.

BackgroundIn 2008, a nationwide skin cancer screening (SCS) program was implemented in Germany. However, participation rates remain low. ObjectiveThe overall objective of the HELIOS study is to identify subgroup-specific invitation and communication strategies to increase informed SCS participation in Germany. MethodsFocus 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. ResultsRecruitment 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. ConclusionsThe 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

Background About 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.Methods The 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.Results Across 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%.Conclusion There 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.

BackgroundWe investigated the uptake of opportunistic cervical cancer screening (CCS) and other risk factors and their association with cervical cancer in Germany in a case-control study.Methods and findingsWe recruited incident cases of cervical cancer (ICD-10 C53) diagnosed between 2012 and 2016 and matched with three population-based controls, based on age and region of residence. Cases and controls reported their CCS participation during the past ten years (frequent: every three years; no or infrequent: less than every three years) and other relevant variables. We fitted conditional logistic regression models, reporting odds ratios (OR) and 95% confidence intervals (95% CI). We report overall and stratified analyses by histologic group (squamous cell-SCC, and adenocarcinoma-AC), T category (T1 and T2+), and age (ConclusionAlthough women who frequently attended CCS were less likely to develop cervical cancer, especially larger tumours, the high proportion of cases who had been frequently screened prior to diagnosis underscores the need to investigate the quality of cytology and treatment of precancerous lesions in Germany.

Introduction Peripheral arterial tonometry (PAT) is an operator-independent and non-invasive measurement method to assess microvascular endothelial function in the fingertips. PAT-derived measures of endothelial function were associated with type 2 diabetes in cross-sectional studies. However, longitudinal studies are lacking. The study aims to investigate the association of two PAT-derived endothelial function parameters reactive hyperemia index (RHI) and mean baseline amplitude (MBA) with follow-up glucose and insulin parameters and the development of (pre)diabetes and type 2 diabetes.Research design and methods The study included 673 participants initially without diabetes (328 men and 345 women) aged 52–71 years from the prospective population-based Cooperative Health Research in the Region of Augsburg F4/FF4 cohort study conducted in Southern Germany (baseline examination F4: 2006–2008; follow-up FF4: 2013–2014). An oral glucose tolerance test was performed at baseline and follow-up to define type 2 diabetes, prediabetes, fasting glucose, fasting insulin, 2-hour glucose, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of beta-cell function and hemoglobin A1c.Results In multivariable adjusted logistic/linear regression models, a 1 SD increase in baseline RHI was inversely associated with incident type 2 diabetes (OR 0.69 (95% CI 0.48 to 0.97)) as well as with fasting insulin (β −0.069 (95% CI −0.131 to −0.007)) and HOMA-IR (β −0.072 (95% CI −0.133 to −0.010)) at follow-up in participants with initial normoglycemia. A 1 SD increase in baseline MBA was positively associated with incident (pre)diabetes (OR 1.62 (95% CI 1.25 to 2.11)) and fasting glucose (β 0.096 (95% CI 0.047 to 0.146)) at follow-up in participants with initial normoglycemia.Conclusions Microvascular endothelial dysfunction seems to be involved in the development of early derangements in glucose metabolism and insulin resistance and could thereby trigger the development of prediabetes and type 2 diabetes.

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