National implementation of HPV vaccination programs in low-resource countries: Lessons, challenges, and future prospects.

More than 90% of cervical cancer deaths occur in low- and middle-income countries (LMICs), which have limited capacity to mount the comprehensive national screening and precancer treatment programs that could prevent most of these deaths. The development of vaccines against the human papillomavirus (HPV) has dramatically altered the landscape of cervical cancer prevention. As of mid-2020, 56 LMICs (41% of all LMICs) have initiated national HPV vaccination programs. This paper reviews the experience of LMICs that have introduced HPV vaccine into their national programs, key lessons learned, HPV vaccination sustainability and scale-up challenges, and future mitigation measures. As international guidance evolved and countries accumulated experience, strategies for national introduction shifted with regard to target groups, delivery site and timing, preparation and planning, communications and social mobilization, and ultimately monitoring, supervision and evaluation. Despite the successes that LMICs have been able to achieve in reaching large proportions of eligible girls, there are still considerable challenges countries encounter in overcoming rumors, reaching out-of-school girls, completing the vaccine series, estimating target populations, monitoring program performance, and assuring vaccination sustainability. New opportunities, such as the entry of additional vaccine manufacturers and ongoing studies to evaluate one-dose delivery, could help overcome the outstanding barriers to higher coverage and financial sustainability. Effective use of the experience to date and advances on the horizon could enable all LMICs to move towards the coverage levels that are needed to achieve eventual elimination.

Prevention of cervical and breast cancer mortality in low- and middle-income countries: a window of opportunity.

Breast and cervical cancer are the two most common women's cancers worldwide. Countries have invested for decades in early detection programs for breast and cervical cancer through screening, community education, and opportunistic case detection by health professionals. However, effectiveness in low- and middle-income countries (LMICs) has been limited due to low coverage, insufficient laboratory capacities for diagnosis, health information systems (HIS) that are not designed to track patients or monitor program performance, barriers that inhibit women's uptake of services, and inadequate treatment options. Even where some screening activities exist, there has not been sufficient attention to ensuring completion of appropriate diagnosis and treatment after women receive a positive screening test result or report symptoms suggesting cervical or breast cancer. Because of this failure to provide adequate follow-up care, these women miss the potential benefit from early detection and have a higher than average risk to develop cancer or progress to more advanced cancer stages that could have been avoided. There are several critical steps in a woman's journey from good health to elevated cancer risk, then to cancer prevention or diagnosis, and finally to treatment. There is a window of opportunity that extends from the time a positive finding is identified-by a cervical or breast screening test or recognition of a breast abnormality-to the point when cervical precancer treatment is delivered or a treatment plan for diagnosed breast cancer is initiated. Building on existing health systems and adapting measurable, affordable, and culturally acceptable interventions can achieve a lasting impact. If women can successfully navigate this window of opportunity, they can avoid progression to cervical cancer or greatly reduce the need for invasive treatments for breast cancer and improve their chances for survival and improved quality of life. We propose several actions that can lead us on the path towards reduction of this cancer burden.

Lessons learned from HPV vaccine delivery in low-resource settings and opportunities for HIV prevention, treatment, and care among adolescents.

BACKGROUND: Human papillomavirus (HPV) vaccines to prevent cervical cancer have become available in recent years and presented a new challenge to health systems, since they prevent a sexually transmitted virus and are most effective if they are delivered to young adolescent girls, a group not widely served by other health programs. Demonstration and pilot HPV vaccination programs undertaken in the past 7-8 years in low-resource settings have produced lessons that may be more broadly applied to other adolescent health interventions, particularly to those that attempt to reduce human immunodeficiency virus (HIV) infection. METHODS: A systematic literature review was undertaken to identify formal and informal evaluations of HPV vaccine use in low- and middle-income countries. Special attention was devoted to the detailed evaluations carried out on large demonstration projects in India, Peru, Uganda, and Vietnam. RESULTS: These lessons fall into 2 main categories: service delivery operations and community outreach and mobilization. Operational issues included venue and timing of vaccinations, definition of target population, micro-planning and coordination, integration with other services, and training. Community issues included consent, messages and channels, endorsement and support, and timing of mobilization efforts. DISCUSSION: Careful planning, good coordination across sectors and levels, and sensitive attention to the expressed needs for information and preferences for communication channels among youth, parents, and communities more broadly were among the key lessons that are relevant for HIV interventions, but many of the smaller details were also important. CONCLUSIONS: Applying or adapting these lessons to adolescent HIV services could accelerate effective program design and enhance success.

Accelerating the reduction in cervical cancer: what can we learn from the Safe Motherhood movement?

As we move toward the post-2015 development agenda, we should reflect on the accomplishments of the Safe Motherhood movement and derive potential lessons to strengthen programs to reduce the burden of cervical cancer. Five key areas have been the focus of attention over the years: definition of the magnitude and distribution of maternal mortality; identification of effective and feasible clinical solutions; advocacy to increase attention, resources, and commitment; leadership through international coalitions; and development of a framework for accountability, with targets and indicators. While efforts have been made in each of these areas for cervical cancer prevention, progress has been constrained by inadequate resources. Data are of variable quality, with few cancer registries in the countries where cervical cancer is most prevalent. There has been substantial progress in identifying feasible and effective clinical and programmatic interventions, and a growing consensus around meaningful indicators. Advocacy on behalf of cervical cancer prevention has been gaining momentum but leadership is still fragmented. With so many of the basic elements for cervical cancer prevention in place, we must use the lessons learned from the Safe Motherhood movement to accelerate the pace of scaling-up cervical cancer prevention activities, saving millions of women's lives in the next decade.

Estimated global incidence of Japanese encephalitis: a systematic review.

OBJECTIVE: To update the estimated global incidence of Japanese encephalitis (JE) using recent data for the purpose of guiding prevention and control efforts. METHODS: Thirty-two areas endemic for JE in 24 Asian and Western Pacific countries were sorted into 10 incidence groups on the basis of published data and expert opinion. Population-based surveillance studies using laboratory-confirmed cases were sought for each incidence group by a computerized search of the scientific literature. When no eligible studies existed for a particular incidence group, incidence data were extrapolated from related groups. FINDINGS: A total of 12 eligible studies representing 7 of 10 incidence groups in 24 JE-endemic countries were identified. Approximately 67,900 JE cases typically occur annually (overall incidence: 1.8 per 100,000), of which only about 10% are reported to the World Health Organization. Approximately 33,900 (50%) of these cases occur in China (excluding Taiwan) and approximately 51,000 (75%) occur in children aged 0-14 years (incidence: 5.4 per 100,000). Approximately 55,000 (81%) cases occur in areas with well established or developing JE vaccination programmes, while approximately 12,900 (19%) occur in areas with minimal or no JE vaccination programmes. CONCLUSION: Recent data allowed us to refine the estimate of the global incidence of JE, which remains substantial despite improvements in vaccination coverage. More and better incidence studies in selected countries, particularly China and India, are needed to further refine these estimates.

Risk factors for high-risk human papillomavirus infection and cofactors for high-grade cervical disease in Peru.

OBJECTIVE: To evaluate the association between potential risk factors for high-risk human papillomavirus (HR-HPV) infection and cofactors for cervical intraepithelial lesions grade 2 or worse (CIN2+) in women attending cervical screening in Amazonian Peru. MATERIALS AND METHODS: Participants completed a risk factor questionnaire before screening. High-risk human papillomavirus infection was determined by Hybrid Capture II. Logistic regression was used to evaluate associations between potential risk factors for HR-HPV infection and between cofactors and risk of CIN2+ among women with HR-HPV infection. RESULTS: Screening and questionnaires were completed by 5435 women aged 25 to 49 years. The prevalence of HR-HPV was 12.6% (95% confidence interval [CI], 11.8%-13.6%) and decreased by age. Early age at first sexual intercourse and several lifetime sexual partners increased the risk of having HR-HPV (age-adjusted odds ratio [AOR] of age at first sexual intercourse <18 vs ≥20, 1.5; 95% CI, 1.2-2.0; AOR of ≥5 lifetime sexual partners vs 1, 2.1; 95% CI, 1.4-3.2). Among women with HR-HPV infection, those with no schooling (AOR relative to 1-5 years of schooling, 3.2; 95% CI, 1.3-8.3) and those with parity ≥3 (AOR relative to parity <3, 2.6; 95% CI, 1.4-4.9) were at increased risk of CIN2+. The effect of parity was stronger for cancer (AOR of parity ≥3 vs <3, 8.3; 95% CI, 1.0-65.6). Further analysis showed that the association between parity and CIN2+ was restricted to women younger than 40. Most women (83%) had previously been screened. Sixty-four percent of CIN2+ cases detected in this study occurred in women who reported having had a Papanicolaou test in the previous 3 years. Only 4 of 20 cancers were detected in women never screened before. Having had a previous abnormal Papanicolaou test increased the risk of CIN2+ (OR, 16.1; 95% CI, 6.2-41.9). CONCLUSION: Among women with HR-HPV, high parity (in young women), no schooling, lack of good-quality screening and of adequate follow-up care are the main risk factors for high-grade cervical disease in Peru.

Cost-effectiveness analysis of active management of third-stage labour in Vietnam.

Active management of the third stage of labour (AMTSL) using oxytocin substantially reduces postpartum haemorrhage (PPH), a leading cause of maternal mortality. An economic analysis of the use of AMTSL was conducted as part of an intervention study in Thanh Hoa Province, Vietnam. A spreadsheet was used to calculate various scenarios and estimate the costs and outcomes of the routine use of AMTSL with oxytocin in Uniject compared with oxytocin in ampoules, and AMTSL compared with no AMTSL. We estimated the health outcomes from probabilities that were generated from the effectiveness portion of the AMTSL intervention project. The study also estimates the costs of treating PPH and the net incremental costs of AMTSL (costs and savings); examines the impact of different scenarios of PPH rate and Uniject cost; and estimates the potential cost per PPH case and PPH death averted. The additional net cost per woman of providing AMTSL with ampoules was just US dollar 0.20 in the base case; using Uniject devices added only US dollar 0.08 more per woman to the ampoule cost. Varying the rate of PPH had the biggest effect; if the underlying PPH rate were 8%, the incremental cost of AMTSL drops to just US dollar 0.07 per woman with ampoules and the cost to avert a case of PPH is US dollar 2.10 with ampoules and US dollar 4.52 with Uniject. The low net incremental cost of AMTSL suggests that the introduction of AMTSL in primary-level facilities in Vietnam can reduce the incidence of PPH and benefit women's health without adding much to national health care costs.

Does a novel prefilled injection device make postpartum oxytocin easier to administer? Results from midwives in Vietnam.

OBJECTIVE: to assess the acceptability of the Uniject prefilled injection device for delivery of oxytocin in the third stage of labour, and the effect of the device on overall willingness to perform active management of the third stage of labour (AMTSL). DESIGN: descriptive study that used baseline and post-intervention questionnaires. SETTING: three districts in northern Vietnam. The study population consisted of 52 midwives from two districts where AMTSL was already practiced, and 35 midwives from a district where AMTSL was introduced as part of the study. MEASUREMENTS AND FINDINGS: the majority of midwives reported that the Uniject device was easier to use and preferable compared with ampoules and standard syringes. They found the training materials easy to understand. KEY CONCLUSIONS: the use of a prefilled injection device overcame many of the barriers cited by midwives with regard to the use of oxytocin in ampoules, such as trying to break ampoules and fill syringes in a hurry. This device enabled midwives to deliver the correct dose of oxytocin in the third stage of labour in a safe and timely way, while attending to the other needs of the mother and her newborn baby. IMPLICATIONS FOR PRACTICE: use of a prefilled injection device for oxytocin may increase the acceptability and practice of AMTSL in primary level facilities, thus reducing maternal mortality due to postpartum haemorrhage.

Making the case for cervical cancer prevention: what about equity?

Cervical cancer is a major cause of suffering and premature death among women in the developing world, yet it is largely prevented in most higher-income countries. From an equity perspective, cervical cancer is unequally distributed globally in ways that are unnecessary, avoidable and unjust. Although cost-effectiveness analyses demonstrate that prevention measures are justified in low-resource countries, affordability and lack of prioritization have contributed to a lack of progress. This paper describes the inequities in cervical cancer disease burden, barriers in access to and utilisation of services, and the underlying conditions of poverty and low socio-economic status that put women in a disadvantaged position. These social disadvantages are aggravated by the disease itself, with serious consequences for women, their families and communities. Remedies are available in the form of new prevention and treatment approaches, including vaccines against human papillomavirus (HPV), rapid HPV testing, visual inspection of the cervix with acetic acid (VIA) and cryotherapy. These technologies could help to overcome the social, economic, and political disadvantages that contribute to disparities in cervical cancer incidence and mortality through an optimal combination of vaccination, screening and treatment. In the long run, however, increasing women's access to care will also require societies to address structural barriers related to health systems and poverty.

Is magnification necessary to confirm visual inspection of cervical abnormalities? A randomized trial in Peru.

OBJECTIVES: Cervical cancer is the leading cause of cancer death among women in developing countries. This study was designed to evaluate whether visual inspection with acetic acid and magnification (VIAM) improved confirmation of cervical lesions as compared to confirmation with visual inspection with acetic acid (VIA) without magnification when used by physicians. METHODS: From April-December 2004, women in San Martin, Peru, who were referred as VIA-positive by an "obstetriz" (a professional midwife with 6 years of university training) were randomized into two groups for confirmatory screening by a physician using either VIA or VIAM with an AviScope, a hand-held 4x magnification scope with a green light source. The reference standard for the presence or absence of cervical neoplasia was colposcopy and directed biopsy, as required. RESULTS: A total of 358 women participated in the study; 161 had a confirmatory examination with VIAM and 159 with VIA. Sensitivity for low- or high-grade lesions was 68% with VIA and 77% with VIAM, and specificity was 62% with VIA and 63% with VIAM; however, these differences were not statistically significant. CONCLUSIONS: For settings where physician confirmation of cervical abnormalities identified through visual inspection is required and available, this study demonstrates that VIAM had no significant advantage over VIA.

Is magnification necessary to confirm visual inspection of cervical abnormalities? A randomized trial in Peru

OBJECTIVES: Cervical cancer is the leading cause of cancer death among women in developing countries. This study was designed to evaluate whether visual inspection with acetic acid and magnification (VIAM) improved confirmation of cervical lesions as compared to confirmation with visual inspection with acetic acid (VIA) without magnification when used by physicians. METHODS: From April-December 2004, women in San Martin, Peru, who were referred as VIA-positive by an "obstetriz" (a professional midwife with 6 years of university training) were randomized into two groups for confirmatory screening by a physician using either VIA or VIAM with an AviScope,TM a hand-held 4x magnification scope with a green light source. The reference standard for the presence or absence of cervical neoplasia was colposcopy and directed biopsy, as required. RESULTS: A total of 358 women participated in the study; 161 had a confirmatory examination with VIAM and 159 with VIA. Sensitivity for low- or high-grade lesions was 68 percent with VIA and 77 percent with VIAM, and specificity was 62 percent with VIA and 63 percent with VIAM; however, these differences were not statistically significant. CONCLUSIONS: For settings where physician confirmation of cervical abnormalities identified through visual inspection is required and available, this study demonstrates that VIAM had no significant advantage over VIA.

OBJETIVOS:En los países en desarrollo, el cáncer cervicouterino es la principal causa de muerte por cáncer en mujeres. Este estudio se diseñó para determinar si se puede mejorar la confirmación de lesiones cervicouterinas con la inspección visual con ácido acético y amplificación (VIAM) en comparación con la inspección visual con ácido acético (VIA) sin amplificación, cuando ambas las realizan médicos generales. MÉTODOS:Las mujeres de San Martín, Perú, con diagnóstico positivo mediante VIA realizado por una obstetriz (enfermera graduada con seis años de entrenamiento universitarios) entre abril y diciembre de 2004 se dividieron aleatoriamente en dos grupos para el diagnóstico confirmatorio realizado por médicos generales mediante VIA o VIAM, este último con un AviScopeTM, un dispositivo manual con lente monocular de amplificación 4X y fuente luz verde. Como método estándar de referencia para definir la presencia o ausencia de neoplasia cervicouterina se emplearon la colposcopia y la biopsia dirigida, según el caso. RESULTADOS:En el estudio participaron 358 mujeres, de ellas 161 pasaron la confirmación por VIAM y 159 por VIA. La sensibilidad para las lesiones de bajo y alto grados fue de 68 por ciento con VIA y de 77 por ciento con VIAM, mientras la especificidad fue de 62 por ciento por VIA y de 63 por ciento por VIAM; estas diferencias no tuvieron significación estadística. CONCLUSIONES:Se demostró que la VIAM no presentó ventajas significativas sobre la VIA en los casos en que se requiere y está disponible la confirmación de las lesiones del cuello uterino por un médico general.

Reducing postpartum hemorrhage in Vietnam: assessing the effectiveness of active management of third-stage labor.

AIM: The study was undertaken to meet the need of the Ministry of Health to have local evidence on the effectiveness of active management of third-stage labor (AMTSL) in reducing the incidence of postpartum hemorrhage (PPH) > or = 500 mL and the need for PPH treatment. METHODS: Using a quasi-experimental design, AMTSL was introduced for all births attended by government midwives (at home, community, and district levels) in one district while standard practice without AMTSL was continued in three neighboring districts (with a 1:2 ratio of participants). Oxytocin (10 IU) was administered either by standard disposable syringe and needle or by a prefilled, single-use injection device. Postpartum blood loss was estimated using standard containers; other outcome measures included the duration of third stage, the need for additional treatments, and final maternal condition. A total of 3607 women participated (1236 in the intervention district and 2371 in the comparison districts). Multivariate logistic regression was used to control for age, parity, place of delivery, and first-stage oxytocin augmentation. RESULTS: AMTSL was associated with reduced risks for prolonged third stage beyond 30 min (odds ratio [OR] = 0.20, 95%; confidence interval [CI]: 0.11, 0.35), supplemental oxytocin (OR = 0.68, 95% CI: 0.49, 0.94), and bimanual compression (OR = 0.63, 95%; CI: 0.41, 0.98). When cases with first-stage oxytocin augmentation were excluded, AMTSL was associated with a 34% reduction in PPH incidence (OR = 0.66, 95%; CI: 0.45, 0.98). CONCLUSION: This study supports the value of AMTSL in reducing the incidence of PPH, shortening the third stage of labor, and reducing the need for additional treatments.

Breast cancer in limited-resource countries: health care systems and public policy.

As the largest cancer killer of women around the globe, breast cancer adversely impacts countries at all levels of economic development. Despite major advances in the early detection, diagnosis, and treatment of breast cancer, health care ministries face multitiered challenges to create and support health care programs that can improve breast cancer outcomes. In addition to the financial and organizational problems inherent in any health care system, breast health programs are hindered by a lack of recognition of cancer as a public health priority, trained health care personnel shortages and migration, public and health care provider educational deficits, and social barriers that impede patient entry into early detection and cancer treatment programs. No perfect health care system exists, even in the wealthiest countries. Based on inevitable economic and practical constraints, all health care systems are compelled to make trade-offs among four factors: access to care, scope of service, quality of care, and cost containment. Given these trade-offs, guidelines can define stratified approaches by which economically realistic incremental improvements can be sequentially implemented within the context of resource constraints to improve breast health care. Disease-specific "vertical" programs warrant "horizontal" integration with existing health care systems in limited-resource countries. The Breast Health Global Initiative (BHGI) Health Care Systems and Public Policy Panel defined a stratified framework outlining recommended breast health care interventions for each of four incremental levels of resources (basic, limited, enhanced, and maximal). Reallocation of existing resources and integration of a breast health care program with existing programs and infrastructure can potentially improve outcomes in a cost-sensitive manner. This adaptable framework can be used as a tool by policymakers for program planning and research design to make best use of available resources to improve breast health care in a given limited-resource setting.

Cervical dysplasia treatment: key issues for developing countries

Many developing countries face serious obstacles that have hindered establishent of successful cervical cancer contrl programs. Various countries are now seeking to strenthen cytology services and identify simple low-cost screening strategies; but any real gains in reducing cervical cancer incidence and mortality will also require effective treatment of women with preinvasive disease. Despite a trend toward conservative outpatient approaches for treating cervical dysplasia in industrialized countries, clinicians in many developing countries still rely primarily on invasive inpatient methods such as cone biopsy and hysterectomy. For woment who could be treated with less invasive methods, these procedures tend to pose unnecessary risks and entail high costs that put them beyond the reach of may patients. Outpatient therapy, employing methods such as cryotherapy and the loop electrosurgical excision procedure (LEEP), combined with proper follow-up, is appropriate for dealing with visible lesions on the ectocervix when invasive cancer and endocervical involvement have been ruled out. Cryotherapy and LEEP hold out particular promise for developing countries because of their effectiveness, lack of side-effects, simplicity, and low cost. Cure rates range form 80 percent to 95 percent, depending on the method used and the severity of the lesions. However, each method has advantages and disadvantages that demand consideration. Various ways of reducing the number of follow-up visits, including the two-visit see and treat approach, are also available for use in areas where women's access to health services may be limited. A recent survey by the Program for Appropriate Technology in Health (PATH) affirmed the tendency to rely on cone biopsy and hysterectomy. It also found that in many places all degrees of preinvasive disease were treated, rather than only high-grade or severe conditions; that respondents in Latin America, the Caribbean, and Asia tended to use cryotherapy and LEEP more widely than other low-cost methods; the LEEP was preferred over cryotherapy in Latin America; and the colposcopes and other basic equipment needed to provide treatment were nto consistently or widely available in some settings (AU)