Lack of selection of antimalarial drug resistance markers after intermittent preventive treatment of schoolchildren (IPTsc) against malaria in northeastern Tanzania.

OBJECTIVE: Intermittent Preventive Treatment of schoolchildren (IPTsc) is recommended by WHO as a strategy to protect against malaria; to explore whether IPTsc with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) cause a selection of molecular markers in Plasmodium falciparum genes associated with resistance in children in seven schools in Tanga region, Tanzania. METHODS: SNPs in P. falciparum genes Pfmdr1, Pfexo, Pfkelch13, and Pfcrt and copy number variations in Pfplasmepsin-2 and Pfmdr1 were assessed in samples collected at 12 months (visit 4, n=74) and 20 months (visit 6, n=364) after initiation of IPTsc and compared with the baseline prevalence (n=379). RESULTS: The prevalence of Pfmdr1 N86 and Pfexo 415G was >99% and 0%, respectively without any temporal differences observed. The prevalence of Pfmdr1 184F changed significantly from baseline (52.2%) to visit 6 (64.6%) (χ2=6.11, P=0.013), but no differences were observed between the treatment arms (χ2=0.05, P=0.98). Finally, only minor differences in the amplification of Pfmdr1 were observed; from 10.2% at baseline to 16.7% at visit 6 (χ2=0.98, P=0.32). CONCLUSIONS: The IPTsc strategy does not seem to pose a risk for the selection of markers associated with DP or ASAQ resistance. Continuously and timely surveillance of markers of antimalarial drug resistance is recommended.

Identifying psychosocial vulnerabilities in pregnancy: A mixed-method systematic review of the knowledge base of antenatal conversational psychosocial assessment tools.

BACKGROUND: Early identification of psychosocial vulnerability among expectant parents through psychosocial assessment is increasingly recommended within maternity care. For routine antenatal assessment, a strong recognition exists regarding conversational assessment tools. However, the knowledge base of conversational tools is limited, inhibiting their clinical use. OBJECTIVE: Synthesising existing knowledge pertaining to antenatal conversational psychosocial assessment tools, including identifying characteristics, acceptability, performance, effectiveness and unintended consequences. DESIGN: Mixed-method systematic review based on searches in CINAHL, PubMed, Embase, PsycINFO, Cochrane and Scopus. 20 out of 5394 studies were included and synthesised with a convergent integrated approach using a thematic analysis strategy. FINDINGS: We identified seven antenatal psychosocial assessment tools that partially or completely utilised a conversational approach. Women's acceptability was high, and tools were generally found to support person-centred communication and the parent-health care professional relationship. Evidence regarding effectiveness and performance of conversational tools was limited. Unintended consequences were found, including some women having negative experiences related to assessment of intimate partner violence, lack of preparation and lack of relevance. High acceptability was reported by health care professionals who considered the tools as valuable and enhancing of identification of vulnerability. Unintended consequences, including lack of time and competencies as well as discomfort when assessment is very sensitive, were reported. CONCLUSIONS: Evidence regarding conversational tools' effectiveness and performance is limited. More is known about the acceptability of conversational tools, which is generally highly acceptable among women and health care professionals. Some unintended consequences of the use of included conversational tools were identified.

Incidence and clearance of cervical and anal high-risk human papillomavirus in kidney transplant recipients: Results from a Danish prospective clinical study.

This study investigates the incidence and clearance of cervical and anal high-risk human papillomavirus (hrHPV) infection in kidney transplant recipients (KTRs) compared to immunocompetent controls. During 2016-2017, we enrolled 125 female KTRs and 125 female controls. Liquid-based cervical and anal cytology samples collected at enrollment and follow-up were tested for human papillomavirus (HPV) DNA using the CLART HPV2 test. All participants answered a questionnaire on lifestyle and sexual behavior at both examinations. KTRs had an increased age-adjusted risk of incident cervical hrHPV infection compared to controls (hazard ratio [HR] = 3.6, 95% CI = 1.2-11.2). Probability of cervical hrHPV clearance at 18 months was lower among KTRs (8.3%) than controls (66.7%). There was no statistically significant difference in anal hrHPV incidence between KTRs and controls (HR = 0.9, 95% CI = 0.4-2.0). Clearance of anal hrHPV was similar between KTRs and controls at 18 months. During the total follow-up, a lower anal hrHPV clearance, although not statistically significant, was observed among KTRs (HR = 0.3, 95% CI = 0.06-1.2). KTRs had higher incidence of cervical hrHPV and lower probability of clearance, especially of cervical hrHPV infections, than controls. Our findings support that KTRs are at increased risk of HPV infection and point to the need for targeted HPV prevention strategies, such as cervical cancer screening.

Integration of Cell-Free DNA End Motifs and Fragment Lengths Can Identify Active Genes in Liquid Biopsies.

Multiple studies have shown that cell-free DNA (cfDNA) from cancer patients differ in both fragment length and fragment end motif (FEM) from healthy individuals, yet there is a lack of understanding of how the two factors combined are associated with cancer and gene transcription. In this study, we conducted cfDNA fragmentomics evaluations using plasma from lung cancer patients (n = 12) and healthy individuals (n = 7). A personal gene expression profile was established from plasma using H3K36me3 cell-free chromatin immunoprecipitation sequencing (cfChIP-seq). The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression. Furthermore, distinct GC-rich FEMs were enriched after cfChIP. Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001). An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001). This study expands the knowledge regarding cfDNA fragmentomics and sheds new light on how gene activity is associated with both cfDNA fragment lengths and distinct FEMs.

Identification of the PfK13 mutations R561H and P441L in the Democratic Republic of Congo.

OBJECTIVES: Partial artemisinin resistance, mediated by Plasmodium falciparum K13 (PfK13) mutations, has been confirmed in certain areas of East Africa that are historically associated with high-level antimalarial resistance. The Democratic Republic of Congo (DRC) borders these areas in the East. This study aimed to determine the prevalence of resistance markers in six National Malaria Control Program surveillance sites; Boende, Kabondo, Kapolowe, Kimpese, Mikalayi, and Rutshuru. METHODS: The single nucleotide polymorphisms (SNPs) in P. falciparum genes PfK13, Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt were assessed using targeted next-generation sequencing of isolates collected at enrollment in therapeutic efficacy studies. RESULTS: PfK13 SNPs were detected in two samples: in Kabondo (R561H) and in Rutshuru (P441L), both areas near Uganda and Rwanda. The Pfdhps ISGEGA haplotype, associated with reduced sulfadoxine-pyrimethamine chemoprevention efficacy, ranged from 0.8% in Mikalayi (central DRC) to 42.2% in Rutshuru (East DRC). CONCLUSIONS: R561H and P441L observed in eastern DRC are a concern, as they are associated with delayed artemisinin-based combination therapies-clearance and candidate marker of resistance, respectively. This is consistent with previous observations of shared drug resistance profiles in parasites of that region with bordering areas of Rwanda and Uganda. The likely circulation of parasites has important implications for the ongoing surveillance of partial artemisinin-resistant P. falciparum and for future efforts to mitigate its dispersal.

Overweight and obesity as risk factors for cervical cancer and detection of precancers among screened women: A nationwide, population-based cohort study.

OBJECTIVE: Obesity is a known risk factor for many types of cancer. However, there is no clear evidence whether overweight and obesity increases the risk of cervical cancer. We investigated the association between body mass index (BMI) and detection of squamous and glandular cervical cancer and precancer. METHODS: Based on the Medical Birth Registry, we conducted a nationwide cohort study in Denmark of 384,559 women with BMI ≥18.5 kg/m2 (pre-pregnancy BMI reported at the start of the pregnancy) having a cervical cytology screening at age 23-49 years within 5 years following the date of childbirth. The cohort was followed for 10 years from the first cervical cytology screening after the childbirth. We assessed absolute risks of cervical lesions according to BMI with the Aalen-Johansen estimator. We conducted Cox proportional hazards regression analyses to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses were adjusted for age, calendar year, parity, oral contraception use, HPV vaccination, smoking, country of origin, and education. RESULTS: Overweight and obesity were associated with higher rates of cervical cancer (HR = 1.24, 95% CI 1.04-1.49 and HR = 1.14, 95% CI 0.91-1.43, respectively) and lower rates of cervical precancer detection (HR = 0.88, 95% CI 0.84-0.92 and HR = 0.67, 95% CI 0.63-0.71, respectively). CONCLUSIONS: Higher than normal BMI was associated with higher incidence rates of cervical cancer and lower rates of precancer detection, emphasizing the importance of further research in possible mechanisms behind this association.

Initial programme theory development: The first step in a realist evaluation of a cross-sectoral intervention for expectant Danish parents living with psychosocial risks.

A distinct inequality in maternity care exists, and women with psychosocial risks are at a greater risk of adverse birth outcomes. In several high-income countries, a psychosocial risk assessment early in pregnancy is recommended so that expectant parents are offered an appropriate level of care which facilitates relevant, tailored interventions for those in need. In 2017, a cross-sectoral and interdisciplinary intervention for expectant parents with psychosocial risks was developed and implemented in the North Denmark Region. The development process of the intervention has not been reported and theory-based knowledge about how supportive interventions bring about change for expectant parents with psychosocial risks is scarce. Through the initial phase of a realist evaluation, we aimed to elicit key contexts and mechanisms of change regarding the intervention for expectant parents with psychosocial risks. Through an initial programme theory, this article illustrates how, for whom and in which contexts the intervention is intended to work. Data is comprised of intervention documents, 14 pilot observations and 29 realist interviews with key stakeholders. A thematic analytical approach inspired by retroductive thinking was applied to identify and analyse patterns related to the incentive of the intervention, its structure, intended outcomes, generative mechanisms and contextual matters. Generative mechanisms responsible for bringing about change in the intervention were identified as healthcare professionals' approach, continuity, trust, early intervention and social network. Cross-sectoral collaboration and healthcare professionals' competencies were assumed to be central stimulating contextual factors. The initial programme theory developed in this study will serve as the basis for further refinement via empirical testing in a later phase of the realist evaluation.

Factors associated with teenage pregnancy in the Scandinavian countries.

AIMS: Teenage pregnancy may have negative consequences for the mother and the infant. The aim of the study was to examine whether selected individual factors occurring early in life were associated with teenage pregnancy. METHODS: In a population-based, cross-sectional questionnaire study among 34,455 women from Denmark, Norway, and Sweden aged 20-45 years, who had first sexual intercourse (FSI) at age 13-19 years, we assessed the association between early smoking and drinking initiation (i.e., before the age of 13), contraceptive use at FSI, and teenage pregnancy. Log-linear binary regression models were fitted to estimate the relative risk (RR) with 95% confidence intervals (CIs) of teenage pregnancy according to the three exposure variables, overall and by age at FSI. Furthermore, the outcomes of the teenage pregnancies were examined according to age at FSI. RESULTS: Teenage pregnancy occurred in 11% of the population. Both early smoking initiation (RR: 1.6; 95% CI: 1.4-1.8), early drinking initiation (RR: 1.2; 95% CI: 1.0-1.4), and non-use of contraceptives at FSI (RR: 1.9; 95% CI: 1.8-2.0) were associated with teenage pregnancy. The associations for early smoking initiation and non-use of contraceptives remained when analyses were stratified by age at FSI. Almost 60% of all teenage pregnant women had an induced abortion and less than 30% gave birth. CONCLUSIONS: Individual factors, including early smoking and drinking initiation, and non-use of contraceptives at FSI, were associated with teenage pregnancy regardless of age at FSI. This emphasizes the necessity of focusing on early risk-taking behavior as a potential modifier to prevent teenage pregnancy.

Cervical human papillomavirus prevalence according to socioeconomic and demographic characteristics in a large Danish screening population.

AIM: The aim of this study was to investigate high-risk human papillomavirus (hrHPV) prevalence according to socioeconomic and demographic characteristics in a Danish screening population. METHODS: We used data from HPV SCREEN DENMARK, which was an implementation study embedded into the routine cervical cancer screening programme. During 2017-2020, women aged 30-59 years screened in the Region of Southern Denmark were offered HPV testing or cytology. In the HPV group, liquid-based cytology samples were tested for 14 hrHPV types. We obtained registry information on socioeconomic and demographic characteristics and used log-binomial regression to estimate the prevalence ratio (PR) of hrHPV in three age groups (30-39, 40-49, 50-59 years), adjusting for age and marital status. RESULTS: We included 31,124 HPV unvaccinated women. In all age groups, the age-adjusted hrHPV prevalence was higher in women with basic versus higher education (e.g. age 30-39: 11.9% vs. 9.5%; PRage-adjusted=1.24; 95% confidence interval (CI): 1.02-1.50); women who were unemployed vs. employed (e.g. age 30-39: 11.6% vs. 10.4%; PRage-adjusted=1.11; 95% CI: 0.95-1.28); and in women with highest vs. lowest income (e.g. age 30-39: 11.6% vs. 9.5%, PRage-adjusted=1.18, 95% CI: 0.98-1.44). In models adjusted for marital status, these associations largely disappeared. CONCLUSIONS: We found slightly higher hrHPV prevalences in women with basic education, low income and unemployment. The differences largely disappeared when taking into account marital status as a potential proxy for sexual behaviour. Our findings support a need for targeted information on safe sexual practices and promoting socioeconomic equality in HPV vaccination and cervical cancer screening participation.

'It's about developing a trustful relationship': A Realist Evaluation of midwives' relational competencies and confidence in a Danish antenatal psychosocial assessment programme.

OBJECTIVE: to explore how contextual conditions influence midwives' relational competencies, ability and confidence to undertake psychosocial assessment of pregnant women and their partners during the first antenatal consultation that identifies expectant parents in vulnerable positions. DESIGN: a realist evaluation carried out through three phases: 1) development 2) testing and 3) refinement of programme theories. Data was generated through realist interviews and observations. SETTING: nine community-based and hospital-based midwife clinics in the North Region of Denmark. INTERVENTION: a dialogue-based psychosocial assessment programme in the the North Region of Denmark was evaluated. PARTICIPANTS AND DATA: 15 midwives were interviewed and 16 observations of midwives undertaking psychosocial assessment during the first antenatal consultation were conducted. FINDINGS: contextual conditions at multiple levels which supported midwives' relational competencies, autonomy and the power of peer reflection-and thus facilitation of a woman-centred approach and trust-were identified, i.e., being experienced, having interest, organisational prioritisation of peer reflection and flexibility. Where midwives lacked experience, competency development regarding psychosocial assessment, opportunities for peer reflection and autonomy to individualise care for expectant parents in vulnerable positions, the approach to assessment tended to become institution-centred which caused a distant dialogue and instrumental assessment which potentially harmed the midwife-woman/couple relationship. CONCLUSION: midwives' ability and confidence to undertake psychosocial assessment were affected by whether individual and organisational contextual conditions empowered them to assess and care for expectant parents within a philosophy of woman-centred care. Accordingly, development of trustful midwife-woman/couple relationships - which is essential for disclosure - was achievable. These conditions become fundamental for securing quality of antenatal care for expectant parents in vulnerable positions.

Trusting parent-professional relationships in interprofessional interventions for expectant and new parents in vulnerable positions: A realist evaluation.

Interprofessional collaboration and trusting parent-professional relationships can be key to delivering interprofessional care to meet the needs of expectant and new parents in vulnerable positions. This, however, presents challenges. This study aimed to gain deeper understanding of how and under what circumstances trusting parent-professional relationships develop and work within interprofessional team-based care for this group, from the professionals' perspectives. Realist evaluation was undertaken based on 14 semi-structured, realist interviews with midwives and health visitors and 11 observations. Multiple interrelated mechanisms were identified including patient/family-centered care, timely and relevant interprofessional involvement in care, gentle interprofessional bridging, transparency of intervention roles and purposes, and relational continuity. Good interprofessional collaboration was a primary condition for these mechanisms. Developed, trusting relationships supported parents' engagements with interprofessional care and constituted a supportive safety net that promoted parenting skills and coping abilities. We identified harmful mechanisms: distanced encounters, uncertainty of interprofessional involvement, and compromising the safe space. These mechanisms caused distrust and disengagement. Ensuring trusting parent-professional relationships within interprofessional team-based care demands each professional involved competently engages in relational work and interprofessional collaboration. Uncontrollability is thus influenced regarding interpersonal connection and potentially gives an explanation when trust-building efforts fail.

Time trends in prevalence of p16 positivity and combined HPV/p16 positivity in a large cohort of Danish vulvar cancer patients.

Vulvar cancer is rare, but causes substantial morbidity in affected patients. A subset of vulvar cancers is caused by high-risk human papillomavirus (hrHPV), which primarily exerts its oncogenic effect through upregulation of tumor suppressor protein p16. Tumors positive for both hrHPV and p16 (double positive) are assumed to be HPV-driven, but only few large studies have investigated the combined prevalence of hrHPV and p16 positivity in vulvar cancer over time. In this Danish cross-sectional study, we assessed the prevalence of p16 positivity and double positivity for hrHPV and p16 in a large sample of vulvar squamous cell carcinomas (VSCCs) diagnosed during 1990 to 2017. In a nationwide register, we identified VSCCs from 13 hospitals across Denmark, and collected archival tumor tissue for hrHPV testing with INNO-LiPA and immunohistochemical p16 staining. We calculated the prevalence of hrHPV, p16 positivity and double positivity according to time, age and histological subtype and evaluated time trends through estimated annual percentage changes. We included 1278 VSCCs. Overall, 35.0% (95% confidence interval [CI]: 32.4-37.6) were positive for p16 and 31.0% (95% CI: 28.4-33.5) were positive for both hrHPV and p16. The prevalence of p16 positivity and double positivity increased over time, both in women aged ≤59 and ≥60 years. The double positive prevalence was higher in nonkeratinizing (60.7%) and warty/basaloid VSCCs (67.5%) than in keratinizing (16.1%) and verrucous VSCCs (5.0%). These results indicate that approximately one-third of vulvar cancers were caused by hrHPV infection, supporting a substantial preventive potential of the HPV vaccine.

Prevalence of cervical human papillomavirus and the risk of anal co-infection in kidney transplant recipients: Results from a Danish clinical study.

BACKGROUND: Kidney transplant recipients (KTRs) have increased risk of human papillomavirus (HPV)-related cancers, including cervical and anal cancer. In this cross-sectional clinical study, we investigated the prevalence of cervical high-risk HPV (hrHPV) and low-risk (lrHPV), risk factors for cervical hrHPV infection, and the prevalence of cervical and anal hrHPV co-infection in KTRs and immunocompetent controls. METHODS: During 2016-2017, we recruited 125 female KTRs and 125 female immunocompetent controls from one dermatology department (KTRs and controls) and five nephrology departments (KTRs) in Denmark. Liquid-based cervical and anal cytology samples were tested for HPV DNA using the INNO-LiPA test and participants answered a questionnaire on lifestyle. Odds ratios (ORs) were estimated using logistic regression, adjusting for age, lifetime sexual partners, smoking, and (in models concerning anal HPV) receptive anal sex. RESULTS: KTRs had higher prevalence of cervical hrHPV than controls (35.5% vs. 18.2; ORadjusted = 2.9, 95% CI, 1.5-5.5). In contrast, the prevalence of lrHPV was similar in KTRs and controls (25.6% vs. 23.1; ORadjusted = 1.2, 95% CI, 0.7-2.3). KTRs were more likely than controls to have cervical and anal hrHPV co-infection (27.3% vs. 6.6%, ORadjusted = 6.3, 95% CI, 2.7-15.0). CONCLUSIONS: Female KTRs had high prevalence of cervical hrHPV, and co-infection with anal and cervical hrHPV was common. Our results underline that KTRs are an important target group for preventive efforts against HPV-related diseases.

Quality Control of Biospecimens in a Danish Clinical Cytology Biobank.

Introduction: Based on the experience from a Swedish biobank, we established a clinical cervical cytology biobank and adapted it to a Danish setting. The aim of the present study was to validate the biobank material regarding quality and quantity, to determine the usefulness of the material for future diagnostics and biomarker testing. Methods: Cervical cytology samples collected in ThinPrep were analyzed before and after biobanking using p16/ki-67 dual staining, a human papillomavirus (HPV) DNA test (Cobas), and a test for HPV messenger RNA (mRNA; Aptima). The concordance of the test results before and after biobanking was assessed. We also evaluated the morphology before and after biobanking and did additional tests on the biobanked material to qualify the usefulness of the material (library preparation for next-generation sequencing [NGS], reverse transcription-polymerase chain reaction [RT-PCR], and the Inno-Lipa HPV genotyping test). Results: For the Cobas HPV test, the concordance was 92% (122/133), and for the Inno-Lipa test (30 samples), it was 100%. For the Aptima assay, the concordance was a little lower, 84% (42/50). The morphology of the cell was well preserved, and the concordance of the p16/ki-67 dual staining was 88% (37/42). The functional tests showed that DNA-based NGS libraries (TST15 panel; Illumina) had good quality parameters. However, with the RT-PCR, 12% of the samples showed poor quality and a too low input amount for the analysis. Conclusion: The quality of the biobanked samples is high, and the material is suitable for testing of DNA, RNA, and protein. However, for testing of specific biomarkers, pilot studies are recommended to ensure sufficient input amount and quality of the material, especially for RNA-based studies.

Incidence of cervical precancerous lesions and cervical cancer in Denmark from 2000 to 2019: Population impact of multi-cohort vaccination against human papillomavirus infection.

In Denmark, vaccination against human papillomavirus (HPV) has been implemented in the children's vaccination program (January 2009) and in multiple catch-up cohorts (October 2008 in girls 13-15 years and in August 2012 in women up to 27 years). In the present study we estimate incidence of cervical intraepithelial neoplasia grade 3 (CIN3), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (AC) during 2000-2019. All cases of CIN3 and AIS were identified from the nationwide Pathology Data Bank, while SCC and AC were identified from the Danish Cancer Registry. We calculated age-standardized incidence rates and estimated annual percentage change (EAPC) with corresponding 95% confidence interval (CI) for the periods before vaccination implementation (2000-2005), early after implementation of childhood HPV vaccination and the first catch-up vaccination program (2006-2012), and after implementation of the second catch-up program (2013-2019). For CIN3 and AIS, age-specific incidence rates and EAPCs were calculated. An increasing age-standardized incidence was observed before introduction of HPV vaccination (2000-2005) for CIN3 [EAPCCIN3 : 3.0 (95% CI 1.7 to 4.3)] and AIS [EAPCAIS : 3.5 (95% CI 0.7 to 6.4)]. In the most recent period (2013-2019), following implementation of the second catch-up program, a decrease was observed for both CIN3 [EAPCCIN3 : -6.5 (95% CI -8.3 to -4.8)], AIS [EAPCAIS : -8.7 (95% CI -12.3 to -5.1)] and for SCC [EAPCSCC : -3.9 (95% CI -7.5 to -0.2)]. In this study we document a decrease in the incidence of CIN3, AIS and SCC in the period after implementation of multi-cohort HPV vaccination in Denmark.

Comparison of human papillomavirus-based cervical cancer screening strategies in Tanzania among women with and without HIV.

Cervical cancer is the most common female cancer in Eastern Africa, and the World Health Organization (WHO) recommends human papillomavirus (HPV)-based screening as a key element to eliminate the disease. In this cross-sectional study from Tanzania, we compared nine HPV-based cervical cancer screening strategies, including HPV testing at standard cut-off; HPV testing at increased viral load cut-offs; HPV testing with partial/extended genotyping, and HPV testing with visual inspection with acetic acid (VIA). We pooled data collected during 2008 to 2009 and 2015 to 2017 from 6851 women aged 25 to 65. Cervical cytology samples were HPV tested with Hybrid Capture 2, and HPV positive samples were genotyped with INNO-LiPA Extra II. Human immunodeficiency virus (HIV) testing and VIA were done according to local standards. We calculated sensitivity, specificity, positive and negative predictive value of screening strategies, with high-grade cytological lesions as reference, separately for women with and without HIV. HPV testing at standard cut-off (1.0 relative light units [RLU]) had highest sensitivity (HIV+: 97.8%; HIV-: 91.5%), but moderate specificity (HIV+: 68.1%; HIV-: 85.7%). Increasing the cut-off for HPV positivity to higher viral loads (5.0/10.0 RLU) increased specificity (HIV+: 74.2%-76.5%; HIV-: 89.5%-91.2%), with modest sensitivity reductions (HIV+: 91.3%-95.7%; HIV-: 83.5%-87.8%). Limiting test positivity to HPV types 16/18/31/33/35/45/52/58 improved specificity while maintaining high sensitivity (HIV+: 90.2%; HIV-: 81.1%). Triage with VIA and/or partial genotyping for HPV16/18 or HPV16/18/45 had low sensitivities (≤65%). In conclusion, HPV testing alone, or HPV testing with extended genotyping or increased viral load cut-offs, may improve cervical cancer screening in Sub-Saharan Africa.

Sexual Health During COVID-19: A Scoping Review.

INTRODUCTION: The COVID-19 pandemic impacted profoundly on the wellbeing and social interactions of the world population, and all dimensions of sexual health were potentially affected by globally implemented preventive measures. OBJECTIVES: The scoping review aimed to compile existing research investigating possible effects of COVID-19 lockdowns on adult sexual health, that is, sexual behavior, functioning, and satisfaction. Further, studies on the interplay between mental health and sexual well-being during the pandemic were reviewed. METHODS: The review was conducted in accordance with guidelines established by the Joanna Briggs Institute and the Extension for Scoping Reviews (PRISMA-ScR) Checklist. On October 11-12, 2021, PubMed, Embase, PsycInfo, Cinahl, Cochrane, Sociological Abstracts and Scopus were systematically searched for relevant peer-reviewed papers employing quantitative methodology. Additionally, unpublished ("grey") research studies on the subject were retrieved. The screening, data extraction, and analysis of evidence were conducted by 4 independent reviewers using an iterative approach. RESULTS: Based on 107 studies included, the scoping review showed that the pandemic had had a wide impact on all dimensions of sexual health. Except for solo sex activities, mainly negative COVID-19 implications were identified, although findings were, in sum, characterized by complexity and unpredictability. Thus, sexual behavior, functioning, and satisfaction during the pandemic appeared to be mitigated by a broad range of sociodemographic and contextual factors. Finally, sexual health seemed deeply entwined with overall mental health. CONCLUSION: The scoping review revealed a broad range of COVID-19-related effects on sexual health, including an overall decline in partnered sex and a concurrent increase in solo sex activities. It also emphasized a need for future research to shed light on possible long-term consequences of the pandemic in various population groups and on all aspects of sexual health. Toldam NE, Graugaard C, Meyer R, et al. Sexual Health During COVID-19: A Scoping Review. Sex Med Rev 2022;10:714-753.

Changes in HPV prevalence in Danish women with vulvar cancer during 28 years - A nationwide study of >1300 cancer cases.

OBJECTIVE: A substantial proportion of vulvar cancers are caused by high-risk human papillomavirus (hrHPV), but hrHPV prevalence in vulvar cancer has mainly been investigated in smaller studies which did not evaluate time trends. Our aim was to assess hrHPV prevalence in >1300 Danish vulvar cancers diagnosed during 1990-2017, including changes in hrHPV prevalence over time. METHODS: In a nationwide pathology register, we identified women diagnosed with vulvar cancer at thirteen hospitals from all Danish regions. Archival tumor tissue was collected from local repositories and, upon pathology review, sent to a central laboratory for HPV testing using INNO-LiPA. We calculated hrHPV prevalence according to time, age and histology, and evaluated the overall and age-specific estimated annual percentage change (EAPC). RESULTS: We included 1308 vulvar cancer cases, with a median age of 72 years at diagnosis. The overall hrHPV prevalence was 52.0% (95% CI: 49.3-54.7). HPV types 16/18 were found in 39.6% of cases, whereas nine-valent HPV (9vHPV) vaccine types 16, 18, 31, 33, 45, 52, and 58 were found in 50.8%. The hrHPV prevalence showed an increasing trend over time, with an EAPC of 0.35% (95% CI: 0.00-0.71). The hrHPV prevalence was higher in younger women throughout the study period, and increasing trends over time were seen in both older (age ≥ 60) and younger (age < 60) women. The hrHPV prevalence was higher in non-keratinizing (71.0%) and warty/basaloid (78.0%) carcinomas than in keratinizing (39.4%) and verrucous (36.4%) carcinomas. CONCLUSIONS: Our results indicate that the 9vHPV vaccine could potentially prevent a substantial proportion of vulvar cancers in Denmark.

Women with obesity participate less in cervical cancer screening and are more likely to have unsatisfactory smears: Results from a nationwide Danish cohort study.

Some studies found an association between obesity and increased cervical cancer risk, but potential mechanisms are unknown. In this nationwide register-based cohort study, we investigated the association between overweight/obesity and cervical cancer screening participation and risk of unsatisfactory smears. The study population was identified in the Danish Medical Birth Registry. We included 342,526 women aged 23-49 years with pre-pregnancy body mass index (BMI) registered during 2004-2013. Screening participation and unsatisfactory smears during up to four years after child birth were identified in a nationwide pathology register. We used absolute risk regression to estimate the relative absolute risk (RAR) with 95% confidence intervals (CIs) of screening participation according to BMI, adjusted for age, calendar year, sociodemographic characteristics, parity and previous high-grade cervical intraepithelial neoplasia. Among those who were screened (n = 295,482), we used log-binomial regression to investigate the relative risk (RR) of an unsatisfactory smear according to BMI, adjusted for age, year, parity, oral contraceptive use and pathology department. A lower proportion of obese women (79.3%) than women of normal weight (85.8%) were screened, and obese women had lower adjusted probability of being screened than women of normal weight (RARadjusted = 0.94, 95% CI, 0.93-0.95). A higher proportion of obese women (2.4%) than women of normal weight (1.7%) had an unsatisfactory smear, and this association remained after adjustments (RRadjusted = 1.28, 95% CI, 1.19-1.38). In conclusion, women with obesity were less likely to participate in cervical cancer screening and more likely to have an unsatisfactory smear than women of normal weight.

Anal Human Papillomavirus Infection in Kidney Transplant Recipients Compared With Immunocompetent Controls.

BACKGROUND: Kidney transplant recipients (KTRs) have increased risk of human papillomavirus (HPV)-related anogenital (pre)cancers, including anal high-grade intraepithelial lesions and cancer. Previous studies on anal high-risk HPV (hrHPV) among KTRs are sparse. METHODS: In a cross-sectional study, we included 247 KTRs and 248 controls from a dermatology department and 5 nephrology departments in Denmark during 2016-2017. All participants provided an anal cytobrush sample that was tested for HPV DNA. Participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of anal hrHPV in KTRs compared with controls and risk factors for anal hrHPV in KTRs. RESULTS: The anal hrHPV prevalence was higher in female KTRs (45.5%) than in controls (27.2%). Female KTRs had almost 3-fold higher adjusted odds of anal hrHPV than controls (adjusted OR, 2.87 [95% confidence interval, 1.57-5.22]). In contrast, among men we did not observe increased prevalence or odds of anal hrHPV in KTRs compared with controls (prevalence, 19.4% vs 23.6%; adjusted OR, 0.85 [95% 95% confidence interval, .44-1.64]). Among hrHPV-positive KTRs, 63% and 52% of men and women, respectively, were infected with hrHPV types covered by the nonavalent HPV vaccine (type 16, 18, 31, 33, 45, 52, or 58). Current smoking, >10 lifetime sexual partners, history of genital warts, and among men having had receptive anal sex were risk factors for anal hrHPV in KTRs. CONCLUSIONS: Female KTRs had an increased risk of anal hrHPV compared with immunocompetent controls. Our findings indicate that pretransplant HPV vaccination should be considered to prevent anal high-grade intraepithelial lesions and cancer caused by anal hrHPV infection in KTRs. CLINICAL TRIALS REGISTRATION: NCT03018327.