Benefits, harms and cost-effectiveness of cervical screening, triage and treatment strategies for women in the general population.

In 2020, the World Health Organization (WHO) launched a strategy to eliminate cervical cancer as a public health problem. To support the strategy, the WHO published updated cervical screening guidelines in 2021. To inform this update, we used an established modeling platform, Policy1-Cervix, to evaluate the impact of seven primary screening scenarios across 78 low- and lower-middle-income countries (LMICs) for the general population of women. Assuming 70% coverage, we found that primary human papillomavirus (HPV) screening approaches were the most effective and cost-effective, reducing cervical cancer age-standardized mortality rates by 63-67% when offered every 5 years. Strategies involving triaging women before treatment (with 16/18 genotyping, cytology, visual inspection with acetic acid (VIA) or colposcopy) had close-to-similar effectiveness to HPV screening without triage and fewer pre-cancer treatments. Screening with VIA or cytology every 3 years was less effective and less cost-effective than HPV screening every 5 years. Furthermore, VIA generated more than double the number of pre-cancer treatments compared to HPV. In conclusion, primary HPV screening is the most effective, cost-effective and efficient cervical screening option in LMICs. These findings have directly informed WHO's updated cervical screening guidelines for the general population of women, which recommend primary HPV screening in a screen-and-treat or screen-triage-and-treat approach, starting from age 30 years with screening every 5 years or 10 years.

Obstetrics risk Assessment: Evaluation of selection criteria for vaccine research studies in pregnant women.

Vaccines designed for use in pregnancy and vaccine trials specifically involving pregnant women are rapidly expanding. One of the key challenges in designing maternal immunization trials is that developing exclusion criteria requires understanding and quantifying the background risk for adverse pregnancy outcomes in the pregnancy being studied, which can occur independent of any intervention and be unrelated to vaccine administration. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project has developed and published case definitions and guidelines for data collection, analysis, and evaluation of maternal immunization safety in trials involving pregnant women. Complementing this work, we sought to understand how to best assess obstetric risk of adverse outcomes and differentiate it from the assessment of vaccine safety. Quantification of obstetric risk is based on prior and current obstetric, and maternal medical history. We developed a step-wise approach to evaluate and quantify obstetric and maternal risk factors in pregnancy based on review of published literature and guidelines, and critically assessed these factors in the context of designing inclusion and exclusion criteria for maternal vaccine studies. We anticipate this risk assessment evaluation may assist clinical trialists with study design decisions, including selection of exclusion criteria for vaccine trials involving pregnant women, consideration of sub-group classification, such as high or low risk subjects, or schedule considerations, such as preferred trimester of gestation for an intervention during pregnancy. Additionally, this tool may be utilized in data stratification at time of study analyses.

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline.

PURPOSE: To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. METHODS: The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. RESULTS: Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. RECOMMENDATIONS: In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus-related cancers and diseases. Basic settings: vaccinating boys is not recommended.It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Global alignment of immunization safety assessment in pregnancy - The GAIA project.

Immunization in pregnancy provides a promising contribution to globally reducing neonatal and under-five childhood mortality and morbidity. Thorough assessment of benefits and risks for the primarily healthy pregnant women and their unborn babies is required. The GAIA project was formed in response to the call of the World Health Organization for a globally concerted approach to actively monitor the safety of vaccines and immunization in pregnancy programs. GAIA aims to improve the quality of outcome data from clinical vaccine trials in pregnant women with a specific focus on the needs and requirements for safety monitoring in LMIC. In the first year of the project, a large and functional network of experts was created. The first outputs include a guidance document for clinical trials of immunization in pregnancy, a basic data collection guide, ten case definitions of key obstetric and neonatal health outcomes, an ontology of key terms and a map of pertinent disease codes. The GAIA Network is designed as an open and growing forum for professionals sharing the GAIA vision and aim. Based on the initial achievements, tools and services are developed to support investigators and strengthen immunization in pregnancy programs with specific focus on LMIC.

Key terms for the assessment of the safety of vaccines in pregnancy: Results of a global consultative process to initiate harmonization of adverse event definitions.

BACKGROUND: The variability of terms and definitions of Adverse Events Following Immunization (AEFI) represents a missed opportunity for optimal monitoring of safety of immunization in pregnancy. In 2014, the Brighton Collaboration Foundation and the World Health Organization (WHO) collaborated to address this gap. METHODS: Two Brighton Collaboration interdisciplinary taskforces were formed. A landscape analysis included: (1) a systematic literature review of adverse event definitions used in vaccine studies during pregnancy; (2) a worldwide stakeholder survey of available terms and definitions; (3) and a series of taskforce meetings. Based on available evidence, taskforces proposed key terms and concept definitions to be refined, prioritized, and endorsed by a global expert consultation convened by WHO in Geneva, Switzerland in July 2014. RESULTS: Using pre-specified criteria, 45 maternal and 62 fetal/neonatal events were prioritized, and key terms and concept definitions were endorsed. In addition recommendations to further improve safety monitoring of immunization in pregnancy programs were specified. This includes elaboration of disease concepts into standardized case definitions with sufficient applicability and positive predictive value to be of use for monitoring the safety of immunization in pregnancy globally, as well as the development of guidance, tools, and datasets in support of a globally concerted approach. CONCLUSIONS: There is a need to improve the safety monitoring of immunization in pregnancy programs. A consensus list of terms and concept definitions of key events for monitoring immunization in pregnancy is available. Immediate actions to further strengthen monitoring of immunization in pregnancy programs are identified and recommended.

Immunizing school-age children and adolescents: experience from low- and middle-income countries.

OBJECTIVE: Given the increased attention on the need for booster immunizations of older children and adolescents, as well as new primary vaccine series that specifically target school-age children and adolescents, we reviewed the current state of vaccine delivery to school-age children and adolescents in low- and middle-income countries. METHODS: We searched the published literature and unpublished sources for articles, meeting presentations, technical reports and program documents related to immunization policies and programs for school-age children and/or adolescents between 6 and 19 years of age in low- and middle-income countries. FINDINGS: We found several examples of ongoing school-age children and adolescent immunization in low- and middle-income countries. Reasons to vaccinate this age group include vaccines specifically targeted for this age group, waning immunity from prior vaccination, "catch-up" vaccination, acceleration of disease control or elimination efforts, and age distribution shift in the incidence of vaccine-preventable diseases. Multiple delivery strategies are currently in use: routine immunization, supplementary immunization activities, and Child Health Days and similar activities. Vaccines can be delivered in fixed sites, or through outreach. Most immunization programs that target adolescents and school-aged children are providing boosters of infant vaccines at school entry age, with scant experience in delivery of primary vaccination series in adolescents. Few of these programs have been formally evaluated and dissemination of lessons learned is limited. CONCLUSIONS: This baseline description may facilitate immunization program planning in countries considering vaccinating this age group. Additionally, this summary may inform plans for operational research and program evaluation designed to expand vaccine delivery to school-age children and adolescents in low- and middle-income countries.

Longitudinal assessment of infecting serovars of Chlamydia trachomatis in Seattle public health clinics: 1988-1996.

BACKGROUND: There have been few longitudinal studies of fluctuations in the prevalence of Chlamydia trachomatis serovars in a given community; such studies could improve our understanding of the epidemiology and transmission of C trachomatis. STUDY DESIGN: This was a longitudinal study of 7110 female patients (62%) and 4344 male patients (38%) presenting with first-time infections to health department clinics between 1988 and 1996. GOAL: The goal was to ascertain trends in the proportion of infecting serovars over the 9-year study period and determine independent relationships between serovar and age, gender, race, and year of infection. RESULTS: Serovar E was the most prevalent (32%), followed by F (18%) and D (13%). Being female, African American, and infected with serovar B was associated with young age (P < 0.001, P < 0.001, and P = 0.09, respectively). Class C serovars were found in older patients (P < 0.001). Over the 9-year period, the percentage of infections with serovar types F and G increased (P = 0.007, P = 0.009), those with I and K decreased (P < 0.001, P = 0.008), and those with B, D, D-, E, H, Ia, and J remained stable. The age of those with positive Chlamydia cultures decreased (P < 0.001). CONCLUSION: In this population, while the major serovars appeared stable over 9 years, significant changes in the distribution of minor serovars, especially G, were observed over time.