Proportions and incidence of locally advanced cervical cancer: a global systematic literature review.

BACKGROUND: Optimal treatment of cervical cancer is based on disease stage; therefore, an understanding of the global epidemiology of specific stages of locally advanced disease is needed. OBJECTIVE: This systematic literature review was conducted to understand the global and region-specific proportions of patients with cervical cancer with locally advanced disease and to determine the incidence of the locally advanced disease. METHODS: Systematic searches identified observational studies published in English between 2010 and June 10, 2020, reporting the proportion of patients with, and/or incidence of, locally advanced stages of cervical cancer (considered International Federation of Gynecology and Obstetrics (FIGO) IB2-IVA). Any staging criteria were considered as long as the proportion with locally advanced disease was distinguishable. For each study, the proportion of locally advanced disease among the cervical cancer population was estimated. RESULTS: The 40 included studies represented 28 countries in North or South America, Asia, Europe, and Africa. Thirty-eight studies reported the proportion of locally advanced disease among populations with cervical cancer. The estimated median proportion of locally advanced disease among all cervical cancer was 37.0% (range 5.6-97.5%; IQR 25.8-52.1%); estimates were generally lowest in North America and highest in Asia. Estimated proportions of ≥50% were reported in nine studies from Asia, Europe, Brazil, and Morocco; estimates ≤25% were reported in six studies from Asia, United States, Brazil, and South Africa. Locally advanced disease was reported for 44% and 49% of women aged >70 and ≥60 years, and 5-100% of younger women with cervical cancer. A greater proportion of locally advanced disease was reported for Asian American (19%) versus White women (8%) in one United States study. Two of five studies describing the incidence of locally advanced disease reported rates of 2-4/100 000 women among different time frames. CONCLUSION: This review highlights global differences in proportions of locally advanced cervical cancer, including regional variance and disparities according to patient race and age.

Comparison of global treatment guidelines for locally advanced cervical cancer to optimize best care practices: A systematic and scoping review.

BACKGROUND: Survival outcomes for cervical cancer differ between countries and world regions. Locally advanced cervical cancer (LACC) is associated with poorer outcomes than early-stage disease. Country-specific variations in diagnostic and treatment recommendations might contribute to differences in LACC outcomes among countries. OBJECTIVE: We compared international and country-specific guidelines for LACC diagnostic imaging and treatment recommendations. METHODS: A systematic literature review and targeted search were used to identify cervical cancer treatment guidelines published between January 1999-August 2021. Guidelines were identified via literature databases, health technology assessment databases, disease-specific websites, and health organization websites. The targeted search included guidelines from countries in regions known to have high cervical cancer prevalence or mortality. Non-English guidelines were translated by native speakers or online translation services. RESULTS: Forty-six guidelines from 31 countries, regions, and international organizations were compared (41/46 using staging criteria, 27 of which used 2009 FIGO). Most guidelines recommended imaging tests for diagnosis and staging. Chest X-ray, intravenous pyelogram, CT, and MRI were commonly recommended for diagnosis and staging while MRI and PET-CT were recommended for the assessment of lymph node status and distant metastases, with a preference for PET-CT over MRI. There was global consensus for cisplatin-based concurrent chemoradiation as primary treatment for stages IIB to IVA, with few exceptions. Treatment recommendations for stages IB2 to IIA2 varied. Most guidelines agreed on adjuvant concurrent chemoradiation after radical hysterectomy when there is a high recurrence risk, and adjuvant radiotherapy when there is an intermediate recurrence risk. Recommendations for other adjuvant and neoadjuvant therapies varied among the guidelines. CONCLUSIONS: Differences among treatment guidelines by LACC stage might be influenced by staging criteria used, resource availability, and prevention program effectiveness. Addressing these areas may unify guidelines and improve global outcomes. Review and update of guidelines will be important as novel LACC therapies become available.

The National Sleep Foundation's Sleep Health Index.

OBJECTIVES: A validated survey instrument to assess general sleep health would be a useful research tool, particularly when objective measures of sleep are not feasible. Thus, the National Sleep Foundation spearheaded the development of the Sleep Health Index (SHI). DESIGN: The development of the SHI began with a task force of experts who identified key sleep domains and questions. An initial draft of the survey was created and questions were refined using cognitive testing and pretesting. The resulting 28-question survey was administered via random-sample telephone interviews to nationally representative samples of adults in 2014 (n=1253) and 2015 (n=1250). These data were combined to create the index. A factor analysis linked 14 questions to 3 discrete domains: sleep quality, sleep duration, and disordered sleep. These were assembled as sub-indices, then combined to form the overall SHI, with scores ranging from 0 to 100 (higher score reflects better sleep health). RESULTS: Americans earned an overall SHI score of 76/100, with sub-index scores of 81/100 in disordered sleep, 79/100 in sleep duration, and 68/100 in sleep quality. In regression analyses, the strongest independent predictors of sleep health were self-reported stress (ß=-0.26) and overall health (ß=0.26), which were also the strongest predictors of sleep quality (ß=-0.32 and ß=0.27 respectively). CONCLUSIONS: The current 12-item SHI is a valid, reliable research tool that robustly measures 3 separate but related elements of sleep health-duration, quality, and disorders-and assesses the sleep health status of adults in the United States.

Direct interaction of the mouse cytomegalovirus m152/gp40 immunoevasin with RAE-1 isoforms.

Cytomegaloviruses (CMVs) are ubiquitous species-specific viruses that establish acute, persistent, and latent infections. Both human and mouse CMVs encode proteins that inhibit the activation of natural killer (NK) cells by downregulating cellular ligands for the NK cell activating receptor, NKG2D. The MCMV glycoprotein m152/gp40 downregulates the surface expression of RAE-1 to prevent NK cell control in vivo. So far, it is unclear if there is a direct interaction between m152 and RAE-1 and, if so, if m152 interacts differentially with the five identified RAE-1 isoforms, which are expressed as two groups in MCMV-susceptible or -resistant mouse strains. To address these questions, we expressed and purified the extracellular domains of RAE-1 and m152 and performed size exclusion chromatography binding assays as well as analytical ultracentrifugation and isothermal titration calorimetry to characterize these interactions quantitatively. We further evaluated the role of full-length and naturally glycosylated m152 and RAE-1 in cotransfected HEK293T cells. Our results confirmed that m152 binds RAE-1 directly, relatively tightly (K(d) < 5 microM), and with 1:1 stoichiometry. The binding is quantitatively different depending on particular RAE-1 isoforms, corresponding to the susceptibility to downregulation by m152. A PLWY motif found in RAE-1beta, although contributing to its affinity for m152, does not influence the affinity of RAE-1gamma or RAE-1delta, suggesting that other differences contribute to the RAE-1-m152 interaction. Molecular modeling of the different RAE-1 isoforms suggests a potential site for the m152 interaction.