Placenta previa and placental abruption after assisted reproductive technology in patients with endometriosis: a systematic review and meta-analysis.

INTRODUCTION Recent evidence suggests that assisted reproductive technology (ART) increases the risk of adverse pregnancy outcomes, including placental disorders. Similarly, endometriosis resulted detrimental on placenta previa. However, up to 50% of women with endometriosis suffer from infertility, thus requiring ART. The aim of our metanalysis is to compare women with and without endometriosis undergoing ART in terms of placenta disorders events, to establish if ART itself or endometriosis, as an indication to ART, increases the risk of placenta previa. METHODS Literature searches were conducted in January 2018 using electronic databases (PubMed, Medline, Scopus, Embase, Science Direct, and the Cochrane Library Scopus). Series comparing pregnancy outcome after ART in women with and without endometriosis were screened and data on placenta previa and placental abruption were extracted. RESULTS Five retrospective case-control studies met the inclusion criteria. The meta-analysis revealed that endometriosis is associated with an increased risk of placenta previa in pregnancies achieved through ART (OR 2.96 (95% CI 1.25-7.03); p = 0.01, I=69%, random-effect model). No differences in placental abruption incidence were found (OR 0.44 (95% CI 0.10-1.87); p = 0.26, I= 0%, fixed-effect model). CONCLUSION Patients with endometriosis undergoing ART may have additional risk of placenta previa. Despite the inability to determine if endometriosis alone or endometriosis plus ART increase the risk, physicians should be aware of the potential additional risk that endometriosis patients undergoing ART harbor

Mathematical Models for Evaluating Effectiveness and Cost-Effectiveness of Cervical Cancer Control Policies in Populations Including Women Living With Human Immunodeficiency Virus: A Scoping Review.

OBJECTIVES Mathematical modeling is increasingly used to inform cervical cancer control policies, and model-based evaluations of such policies in women living with human immunodeficiency virus (HIV) are an emerging research area. We did a scoping review of published literature to identify research gaps and inform future work in this field. METHODS We systematically searched literature up to April 2022 and included mathematical modeling studies evaluating the effectiveness or cost-effectiveness of cervical cancer prevention strategies in populations including women living with HIV. We extracted information on prevention strategies and modeling approaches. RESULTS We screened 1504 records and included 22 studies, almost half of which focused on South Africa. We found substantial between-study heterogeneity in terms of strategies assessed and modeling approaches used. Fourteen studies evaluated cervical cancer screening strategies, 7 studies assessed human papillomavirus vaccination (with or without screening), and 1 study evaluated the impact of HIV control measures on cervical cancer incidence and mortality. Thirteen conducted cost-effectiveness analyses. Markov cohort state-transition models were used most commonly (n = 12). Most studies (n = 17) modeled the effect of HIV by creating HIV-related health states. Thirteen studies performed model calibration, but 11 did not report the calibration methods used. Only 1 study stated that model code was available upon request. CONCLUSIONS Few model-based evaluations of cervical cancer control strategies have specifically considered women living with HIV. Improvements in model transparency, by sharing information and making model code publicly available, could facilitate the utility of these evaluations for other high disease-burden countries, where they are needed for assisting policy makers

Cancer Screening in the Coronavirus Pandemic Era: Adjusting to a New Situation.

PURPOSE The coronavirus-induced pandemic has put great pressure on health systems worldwide. Nonemergency health services, such as cancer screening, have been scaled down or withheld as a result of travel restrictions and resources being redirected to manage the pandemic. The present article discusses the challenges to cancer screening implementation in the pandemic environment, suggesting ways to optimize services for breast, cervical, and colorectal cancer screening. METHODS The manuscript was drafted by a team of public health specialists with expertise in implementation and monitoring of cancer screening. A scoping review of literature revealed the lack of comprehensive guidance on continuation of cancer screening in the midst of waxing and waning of infection. The recommendations in the present article were based on the advisories issued by different health agencies and professional bodies and the authors' understanding of the best practices to maintain quality-assured cancer screening. RESULTS A well-coordinated approach is required to ensure that essential health services such as cancer management are maintained and elective services are not threatened, especially because of resource constraints. In the context of cancer screening, a few changes in invitation strategies, screening and management protocols and program governance need to be considered to fit into the new normal situation. Restoring public trust in providing efficient and safe services should be one of the key mandates for screening program reorganization. This may be a good opportunity to introduce innovations (eg, telehealth) and consider de-implementing non-evidence-based practices. It is necessary to consider increased spending on primary health care and incorporating screening services in basic health package. CONCLUSION The article provides guidance on reorganization of screening policies, governance, implementation, and program monitoring

Molecular triaging options for women testing HPV positive with self-collected samples

We review developments in molecular triaging options for women who test positive for high-risk human papillomavirus (hrHPV) on self-collected samples in the context of cervical cancer elimination. The World Health Organization (WHO) recommends hrHPV screening as the primary test for cervical screening due to its high sensitivity compared to other screening tests. However, when hrHPV testing is used alone for treatment decisions, a proportion of women of childbearing age receive unnecessary treatments. This provides the incentive to optimize screening regimes to minimize the risk of overtreatment in women of reproductive age. Molecular biomarkers can potentially enhance the accuracy and efficiency of screening and triage. HrHPV testing is currently the only screening test that allows triage with molecular methods using the same sample. Additionally, offering self-collected hrHPV tests to women has been reported to increase screening coverage. This creates an opportunity to focus health resources on linking screen-positive women to diagnosis and treatment. Adding an additional test to the screening algorithm (a triage test) may improve the test’s positive predictive value (PPV) and offer a better balance of benefits and risks for women. Conventional triage methods like cytology and visual inspection with acetic acid (VIA) cannot be performed on self-collected samples and require additional clinic visits and subjective interpretations. Molecular triaging using methods like partial and extended genotyping, methylation tests, detection of E6/E7 proteins, and hrHPV viral load in the same sample as the hrHPV test may improve the prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and invasive cancer, offering more precise, efficient, and cost-effective screening regimes. More research is needed to determine if self-collected samples are effective and cost-efficient for diverse populations and in comparison to other triage methods. The implementation of molecular triaging could improve screening accuracy and reduce the need for multiple clinical visits. These important factors play a crucial role in achieving the global goal of eliminating cervical cancer as a public health problem

Cancer treatment and survival among cervical cancer patients living with or without HIV in South Africa.

Objective To compare cancer treatment and all-cause mortality between HIV-positive and HIV-negative cervical cancer patients in South Africa. Methods We assessed cancer treatment and all-cause mortality in HIV-positive and HIV-negative cervical cancer patients who received cancer treatment within 180 days of diagnosis using reimbursement claims data from a private medical insurance scheme in South Africa between 01/2011 and 07/2020. We assessed treatment provision using logistic regression and factors associated with all-cause mortality using Cox regression. We assigned missing values for histology and ethnicity using multiple imputation. Results Of 483 included women, 136 (28 %) were HIV-positive at cancer diagnosis (median age: 45.7 years), and 347 (72 %) were HIV-negative (median age: 54.1 years). Among 285 patients with available ICD-O-3 morphology claims codes, the proportion with cervical adenocarcinoma was substantially lower in HIV-positive (4 %) than in HIV-negative patients (26 %). Most HIV-positive patients (67 %) were on antiretroviral therapy at cancer diagnosis. HIV-positive patients were more likely to receive radiotherapy (adjusted odds ratio [aOR] 1.90, 95 % confidence interval [CI] 1.05-3.45) or chemotherapy (aOR 2.02, 95 %CI 0.92-4.43) and less likely to undergo surgery (aOR 0.53, 95 %CI 0.31-0.90) than HIV-negative patients. HIV-positive patients were at a higher risk of death from all causes than HIV-negative patients (adjusted hazard ratio 1.52, 95 %CI 1.06-2.19). Other factors associated with higher all-cause mortality included age > 60 years and metastases at diagnosis. Conclusions HIV-positive cervical cancer patients in South Africa had higher all-cause mortality than HIV-negative patients which could be explained by differences in tumour progression, clinical care, and HIV-specific mortality

Cervical precancer and cancer incidence among insured women with and without HIV in South Africa.

HIV infection increases the risk of developing cervical cancer; however, longitudinal studies in sub-Saharan Africa comparing cervical cancer rates between women living with HIV (WLWH) and women without HIV are scarce. To address this gap, we compared cervical precancer and cancer incidence rates between WLWH and women without HIV in South Africa using reimbursement claims data from a medical insurance scheme from January 2011 to June 2020. We used Royston-Parmar flexible parametric survival models to estimate cervical precancer and cancer incidence rates as a continuous function of age, stratified by HIV status. Our study population consisted of 518 048 women, with exclusions based on the endpoint of interest. To analyse cervical cancer incidence, we included 517 312 women, of whom 564 developed cervical cancer. WLWH had an ~3-fold higher risk of developing cervical precancer and cancer than women without HIV (adjusted hazard ratio for cervical cancer: 2.99; 95% confidence interval [CI]: 2.40-3.73). For all endpoints of interest, the estimated incidence rates were higher in WLWH than women without HIV. Cervical cancer rates among WLWH increased at early ages and peaked at 49 years (122/100 000 person-years; 95% CI: 100-147), whereas, in women without HIV, incidence rates peaked at 56 years (40/100 000 person-years; 95% CI: 36-45). Cervical precancer rates peaked in women in their 30s. Analyses of age-specific cervical cancer rates by HIV status are essential to inform the design of targeted cervical cancer prevention policies in Southern Africa and other regions with a double burden of HIV and cervical cancer

Accuracy of screening tests for cervical pre-cancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia

Introduction: To provide evidence to improve cervical screening for women living with HIV (WLHIV), we assessed the accuracy of screening tests that can be used in low-resource settings and give results at the same visit. Methods: We conducted a paired, prospective study among consecutive eligible WLHIV, aged 18-65 years, receiving cervical cancer screening at one hospital in Lusaka, Zambia. The histopathological reference standard was multiple biopsies taken at two time points. The target condition was high-grade cervical intraepithelial neoplasia (CIN2+). The index tests were high-risk human papillomavirus detection (hrHPV, Xpert HPV, Cepheid), portable colposcopy (Gynocular, Gynius), and visual inspection with acetic acid (VIA). Accuracy of stand-alone and test combinations were calculated as the point estimate with 95% confidence intervals. A sensitivity analysis considered disease when only visible lesions were biopsied. Results: Among 371 participants with histopathological results, 27% (101/371) women had CIN2+ and 23% (23/101) was not detected by any index test. Sensitivity and specificity for stand-alone tests were: hrHPV, 67.3% (95% CI: 57.7-75.7) and 65.3% (59.4-70.7); Gynocular 51.5% (41.9-61.0) and 80.0% (74.8-84.3); and VIA 22.8% (15.7-31.9) and 92.6% (88.8-95.2), respectively. The combination of hrHPV testing followed by Gynocular had the best balance of sensitivity (42.6% [33.4-52.3]) and specificity (89.6% [85.3-92.7]). All test accuracies improved in sensitivity analysis. Conclusion: The low accuracy of screening tests assessed might be explained by our reference standard, which reduced verification and misclassification biases. Better screening strategies for WLHIV in low-resource settings are urgently needed. Registration number: The trial was registered prospectively at ClinicalTrials.gov (ref: NCT03931083 ). The study protocol has been previously published, and the statistical analysis plan can be accessed on ClinicalTrials.gov . Key messages: What is already known on this topic: The 2021 World Health Organization guidelines recommend that women living with HIV (WLHIV) receive screening for high risk human papillomavirus high-risk human papillomavirus (hrHPV) genotypes at three- to five-year intervals, followed by a triage test to determine whether treatment is needed but this is based on low and moderate certainty evidence.What this study adds: This study among WLHIV in Lusaka, Zambia evaluated three screening tests that allow same-day treatment; hrHPV test, portable colposcopy (Gynocular), and visual inspection with acetic acid (VIA), using strict methods to reduce verification and misclassification biases. The test accuracy of the different screening was poor, with sensitivities and specificity for stand-alone tests: hrHPV, 67.3% and 65.3%; Gynocular 51.5% and 80.0%; and VIA 22.8% and 92.6%; respectively.How this study might affect research, practice or policy: Our findings have implications for research and cervical cancer screening policies among WLHIV if test-accuracy in this high-risk population has been overestimated from a majority of exsisting studies that are affected by verification and misclassification biases. Methodologically robust studies are crucial to inform cervical cancer screening practices and policies for the successful implementation of a cervical cancer elimination plan in sub-Saharan Africa, where 85% of women with cervical cancer and HIV live

Vulvovaginal yeast infections during pregnancy and perinatal outcomes: systematic review and meta-analysis.

BACKGROUND Vulvovaginal yeast infections in pregnancy are common and can cause extensive inflammation, which could contribute to adverse pregnancy outcomes. Symptomatic yeast infections are likely to cause more inflammation than asymptomatic. The objective of this study was to investigate associations between symptomatic and asymptomatic vulvovaginal yeast infections in pregnancy and perinatal outcomes. METHODS We did a systematic review and searched eight databases until 01 July 2022. We included studies reporting on pregnant women with and without laboratory confirmed vulvovaginal yeast infection and preterm birth or eight other perinatal outcomes. We used random effects meta-analysis to calculate summary odds ratios (OR), 95% confidence intervals (CI) and prediction intervals for the association between yeast infection and outcomes. We described findings from studies with multivariable analyses. We assessed the risk of bias using published tools. RESULTS We screened 3909 references and included 57 studies. Only 22/57 studies reported information about participant vulvovaginal symptoms. Preterm birth was an outcome in 35/57 studies (49,161 women). In 32/35 studies with available data, the summary OR from univariable analyses was 1.01 (95% CI 0.84-1.21, I2 60%, prediction interval 0.45-2.23). In analyses stratified by symptom status, we found ORs of 1.44 (95% CI 0.92-2.26) in two studies with ≥ 50% symptomatic participants, 0.84 (95% CI 0.45-1.58) in seven studies with < 50% symptomatic participants, and 1.12 (95% CI 0.94-1.35) in four studies with asymptomatic participants. In three studies with multivariable analysis, adjusted ORs were greater than one but CIs were compatible with there being no association. We did not find associations between vulvovaginal yeast infection and any secondary outcome. Most studies were at high risk of bias in at least one domain and only three studies controlled for confounding. CONCLUSIONS We did not find strong statistical evidence of an increased risk for preterm birth or eight other adverse perinatal outcomes, in pregnant women with either symptomatic or asymptomatic vulvovaginal yeast infection. The available evidence is insufficient to make recommendations about testing and treatment of vulvovaginal yeast infection in pregnancy. Future studies should assess vulvovaginal symptoms, yeast organism loads, concomitant vaginal or cervical infections, and microbiota using state-of-the-art diagnostics. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020197564

Cervical cancer screening outcomes in Zambia, 2010-19: a cohort study.

BACKGROUND Globally, cervical cancer is the fourth leading cause of cancer-related death among women. Poor uptake of screening services contributes to the high mortality. We aimed to examine screening frequency, predictors of screening results, and patterns of sensitisation strategies by age group in a large, programmatic cohort. METHODS We did a cohort study including 11 government health facilities in Lusaka, Zambia, in which we reviewed routine programmatic data collected through the Cervical Cancer Prevention Program in Zambia (CCPPZ). Participants who underwent cervical cancer screening in one of the participating study sites were considered for study inclusion if they had a screening result. Follow-up was accomplished per national guidelines. We did descriptive analyses and mixed-effects logistic regression for cervical cancer screening results allowing random effects at the individual and clinic level. FINDINGS Between Jan 1, 2010, and July 31, 2019, we included 183 165 women with 204 225 results for visual inspection with acetic acid and digital cervicography (VIAC) in the analysis. Of all those screened, 21 326 (10·4%) were VIAC-positive, of whom 16 244 (76·2%) received treatment. Of 204 225 screenings, 92 838 (45·5%) were in women who were HIV-negative, 76 607 (37·5%) were in women who were HIV-positive, and 34 780 (17·0%) had an unknown HIV status. Screening frequency increased 65·7% between 2010 and 2019 with most appointments being first-time screenings (n=158 940 [77·8%]). Women with HIV were more likely to test VIAC-positive than women who were HIV-negative (adjusted odds ratio 3·60, 95% CI 2·14-6·08). Younger women (≤29 years) with HIV had the highest predictive probability (18·6%, 95% CI 14·2-22·9) of screening positive. INTERPRETATION CCPPZ has effectively increased women's engagement in screening since its inception in 2006. Customised sensitisation strategies relevant to different age groups could increase uptake and adherence to screening. The high proportion of screen positivity in women younger than 20 years with HIV requires further consideration. Our data are not able to discern if women with HIV have earlier disease onset or whether this difference reflects misclassification of disease in an age group with a higher sexually transmitted infection prevalence. These data inform scale-up efforts required to achieve WHO elimination targets. FUNDING US President's Emergency Plan for AIDS Relief

Ovarian reserve of women with and without BRCA pathogenic variants: A systematic review and meta-analysis.

INTRODUCTION Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women carrying BRCA mutations (BRCAm) have decreased ovarian reserve, in terms of Anti-Muellerian Hormone (AMH), compared to women without BRCAm (wild-type). MATERIAL AND METHODS Systematic searches of PubMed, Medline, Scopus, Embase, Science Direct and the Cochrane Library from inception until July 2020 were conducted. All studies comparing AMH level in fertile age women, with and without BRCA pathogenic variants were considered. Sub-analyses were performed according to age, presence of breast cancer, and type of mutation. RESULTS Among 64 studies, 10 series were included. For the entire cohort, a trend of reduced AMH level were found between BRCAm carriers and women without pathogenic variants. BRCAm carriers aged 41-years or younger had lower AMH levels compared to 41-years or younger wild type women (OR: 0.73 [95%CI-1.12;-0.35]; p = 0.0002). This finding was confirmed for BRCA1m carriers (OR: 1 [95%CI-1.96;-0.05]; p = 0.004) whereas no difference was observed between BRCA2m carriers and wild type women. The same analysis on breast cancer patients with and without BRCAm achieved the same results. CONCLUSION Young BRCA1m carriers seem to have lower AMH level compared with wild type women and therefore a potential decreased ovarian reserve