Acting on the call for cervical cancer elimination: Planning tools for low- and middle- income countries to increase the coverage and effectiveness of screening and treatment.

INTRODUCTION: Accessible planning tools tailored for low-and middle-income countries can assist decision makers in comparing implementation of different cervical cancer screening approaches and treatment delivery scenarios in settings with high cervical cancer burden. METHODS: The Cervical Precancer Planning Tool (CPPT) was developed by PATH for users to explore and compare the accuracy of screening approaches, what treatment equipment to procure, and how best to deploy treatment equipment in a given country. The CPPT compares four screening approaches: 1) visual inspection with acetic acid (VIA), 2) HPV testing, 3) HPV testing followed by a VIA triage, and 4) HPV testing followed by an enhanced triage test. Accuracy of screening outcomes (e.g., true positives, false positives) is based on published sensitivity and specificity of tests to detect cervical precancerous lesions. The CPPT compares five scenarios for deploying ablative treatment equipment: 1) cervical precancer equipment at every location a woman is screened (single visit approach), 2) equipment only at a hospital level, 3) a single unit of equipment in each district, 4) allowing two districts to share a single unit of equipment, and 5) equipment placed at select district hospitals paired with mobile outreach. Users can customize the CPPT by adjusting pre-populated baseline values and assumptions, including population estimates, screening age range, screening frequency, HPV and HIV prevalence, supply costs, and health facility details. RESULTS: The CPPT generates data tables and graphs that compare the results of implementing each of the four screening and five treatment scenarios disaggregated by HIV status. Outputs include the number and outcomes of women screened, cost of each screening approach, provider time and cost saved by implementing self-sampling for HPV testing, number of women treated, treatment equipment needed by type, and the financial and economic costs for each equipment deployment scenario. CONCLUSION: The CPPT provides practical information and data to compare tradeoffs of patient access and screening accuracy as well as efficient utilization of equipment, skilled personnel, and financial resources. Country decision makers can use outputs from the CPPT to guide the scale-up of cervical cancer screening and treatment while optimizing limited resources.

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.

Breast cancer early detection and diagnostic capacity in Uganda.

BACKGROUND: Greater than 80% of women presenting for breast cancer treatment in Uganda have late-stage disease, which is attributable to a dysfunctional referral system and a lack of recognition of the early signs and symptoms among primary health care providers, and compounded by the poor infrastructure and inadequate human capacity. Improving the breast health care system requires a systemic approach beginning with situational analysis to identify systematic gaps that prevent sustainable improvements in outcome. METHODS: The authors performed a situational analysis of the breast health care system using methods developed by the Breast Health Global Initiative. Based on their findings, they developed a series of recommendations for strengthening the health system for the early diagnosis of breast cancer based on clinical detection, referral, tissue sampling, and diagnosis. RESULTS: Deficits in the recognition of breast cancer signs and symptoms, the underuse of clinical breast examination as a diagnostic and/or screening tool, the centralization of diagnostic tests (radiology and pathology), reliance on excisional biopsies rather than needle biopsies, and a lack of trained professionals and knowledge of the referral system all contribute to significant health system delays. CONCLUSIONS: To strengthen referral networks and improve the early diagnosis of breast cancer in Uganda, national referral hospitals should provide educational programs to primary health care providers in community health centers (CHCs), at which the majority of women first present with symptoms. At secondary district-level facilities in which imaging and tissue sampling can be performed, the capacity for diagnostic testing could be increased through task shifting of basic interpretation (abnormal vs normal) from specialists to nonspecialists using networking technology to facilitate remote oversight from specialists at the national referral hospitals.

Health impact of delayed implementation of cervical cancer screening programs in India: A modeling analysis.

India has the highest burden of cervical cancer in the world. To estimate the consequences of delaying implementation of organized cervical cancer screening, we projected the avertable burden of disease under different implementation scenarios of a screening program. We used an individual-based microsimulation model of human papillomavirus (HPV) infection and cervical cancer calibrated to epidemiologic data from India to project age-specific cancer incidence and mortality reductions associated with screening (once-in-a-lifetime among women aged 30-34 years) with one-visit visual inspection with acetic acid (VIA) and one- and two-visit HPV DNA testing. We then applied these reductions to a population model to project the lifetime cervical cancer cases and deaths averted under different implementation scenarios taking place from 2017 to 2026: (1) immediate implementation of screening with currently available screening tests (one-visit VIA, two-visit HPV testing); (2) immediate implementation of screening with currently available screening tests, with a switch to point-of-care one-visit HPV testing in 5 years; and (3) 5-year delayed implementation of screening with current screening tests or point-of-care HPV testing. Immediate implementation of two-visit HPV testing with a switch to one-visit HPV testing averted 574,100 cases and 382,500 deaths over the lifetimes of 81.4 million 30- to 34-year-old women screened once between 2017 and 2026. Delayed implementation with a one-visit HPV test averted 209,300 cases and 139,100 deaths. Delaying implementation of screening programs in high-burden settings will result in substantial morbidity and mortality among women beyond the age for adolescent HPV vaccination.

Opportunities and challenges for introducing HPV testing for cervical cancer screening in sub-Saharan Africa.

To protect women against cervical cancer, the World Health Organization recommends that women aged 30 to 49 years be screened with tests that detect human papillomavirus (HPV). If the countries that have the greatest burden of this disease-especially those in sub-Saharan Africa-are not to be left behind, we must understand the challenges they face and identify measures that can help them take full advantage now of innovations that are transforming screening services in wealthier countries. We reviewed policy documents and published literature related to Kenya, Tanzania, and Uganda, and met with key personnel from government and nongovernmental organizations. National policy makers understand the value of HPV testing in terms of its superior sensitivity and the programmatic advantages that could result from using self-collected samples. However, while these countries have national cervical cancer prevention strategies, and some have national departments or units for cervical cancer prevention, screening is rare, funding scarce, and quality low. Age guidelines are not strictly followed, with scarce resources being used to screen many women younger than the recommended ages. Published evidence of the benefits of HPV testing-including performance, safety, and cost-effectiveness-must be provided to ministry of health leaders, along with information on anticipated costs for training personnel, purchasing supplies, providing facility space, and maintaining test kits. Despite the obstacles, a joint effort on the part of global and national stakeholders to introduce molecular screening methods can bring better protection to the women who need it most.

Resource-stratified implementation of a community-based breast cancer management programme in Peru.

Breast cancer incidence and mortality rates continue to rise in Peru, with related deaths projected to increase from 1208 in 2012, to 2054 in 2030. Despite improvements in national cancer control plans, various barriers to positive breast cancer outcomes remain. Multiorganisational stakeholder collaboration is needed for the development of functional, sustainable early diagnosis, treatment and supportive care programmes with the potential to achieve measurable outcomes. In 2011, PATH, the Peruvian Ministry of Health, the National Cancer Institute in Lima, and the Regional Cancer Institute in Trujillo collaborated to establish the Community-based Program for Breast Health, the aim of which was to improve breast health-care delivery in Peru. A four-step, resource-stratified implementation strategy was used to establish an effective community-based triage programme and a practical early diagnosis scheme within existing multilevel health-care infrastructure. The phased implementation model was initially developed by the Breast Cancer Initiative 2·5: a group of health and non-governmental organisations who collaborate to improve breast cancer outcomes. To date, the Community-based Program for Breast Health has successfully implemented steps 1, 2, and 3 of the Breast Cancer Initiative 2·5 model in Peru, with reports of increased awareness of breast cancer among women, improved capacity for early diagnosis among health workers, and the creation of stronger and more functional linkages between the primary levels (ie, local or community) and higher levels (ie, district, region, and national) of health care. The Community-based Program for Breast Health is a successful example of stakeholder and collaborator involvement-both internal and external to Peru-in the design and implementation of resource-appropriate interventions to increase breast health-care capacity in a middle-income Latin American country.

To expand coverage, or increase frequency: Quantifying the tradeoffs between equity and efficiency facing cervical cancer screening programs in low-resource settings.

Cervical cancer is a leading cause of cancer death worldwide, with 85% of the disease burden residing in less developed regions. To inform evidence-based decision-making as cervical cancer screening programs are planned, implemented, and scaled in low- and middle-income countries, we used cost and test performance data from the START-UP demonstration project in Uganda and a microsimulation model of HPV infection and cervical carcinogenesis to quantify the health benefits, distributional equity, cost-effectiveness, and financial impact of either (1) improving access to cervical cancer screening or (2) increasing the number of lifetime screening opportunities for women who already have access. We found that when baseline screening coverage was low (i.e., 30%), expanding coverage of screening once in a lifetime to 50% can yield comparable reductions in cancer risk to screening two or three times in a lifetime at 30% coverage, lead to greater reductions in health disparities, and cost 150 international dollars (I$) per year of life saved (YLS). At higher baseline screening coverage levels (i.e., 70%), screening three times in a lifetime yielded greater health benefits than expanding screening once in a lifetime to 90% coverage, and would have a cost-effectiveness ratio (I$590 per YLS) below Uganda's per capita GDP. Given very low baseline coverage at present, we conclude that a policy focus on increasing access for previously unscreened women appears to be more compatible with improving both equity and efficiency than a focus on increasing frequency for a small subset of women.

Estimating the value of point-of-care HPV testing in three low- and middle-income countries: a modeling study.

BACKGROUND: Where resources are available, the World Health Organization recommends cervical cancer screening with human papillomavirus (HPV) DNA testing and subsequent treatment of HPV-positive women with timely cryotherapy. Newer technologies may facilitate a same-day screen-and-treat approach, but these testing systems are generally too expensive for widespread use in low-resource settings. METHODS: To assess the value of a hypothetical point-of-care HPV test, we used a mathematical simulation model of the natural history of HPV and data from the START-UP multi-site demonstration project to estimate the health benefits and costs associated with a shift from a 2-visit approach (requiring a return visit for treatment) to 1-visit HPV testing (i.e., screen-and-treat). We estimated the incremental net monetary benefit (INMB), which represents the maximum additional lifetime cost per woman that could be incurred for a new point-of-care HPV test to be cost-effective, depending on expected loss to follow-up between visits (LTFU) in a given setting. RESULTS: For screening three times in a lifetime at 100% coverage of the target population, when LTFU was 10%, the INMB of the 1-visit relative to the 2-visit approach was I$13 in India, I$36 in Nicaragua, and I$17 in Uganda. If LTFU was 30% or greater, the INMB values for the 1-visit approach in all countries was equivalent to or exceeded total lifetime costs associated with screening three times in a lifetime. At a LTFU level of 70%, the INMB of the 1-visit approach was I$127 in India, I$399 in Nicaragua, and I$121 in Uganda. CONCLUSIONS: These findings indicate that point-of-care technology for cervical cancer screening may be worthy of high investment if linkage to treatment can be assured, particularly in settings where LTFU is high.

Qualitative study of the feasibility of HPV vaccine delivery to young adolescent girls in Vietnam: evidence from a government-implemented demonstration program.

BACKGROUND: Introduction of human papillomavirus (HPV) vaccine in national programs has proceeded apace since 2006, mostly in high-income countries. Recently concluded pilots of HPV vaccination in low-income countries have provided important lessons learned for these settings; however, rigorous evaluations of the feasibility of these delivery strategies that effectively reach young adolescents have been few. This paper presents results from a qualitative evaluation of a demonstration program which implemented school-based and health center-based HPV vaccinations to all girls in grade 6, or 11 years of age, for two years in four districts of Vietnam. METHODS: Using semi-structured interviews of 131 health and education staff from local, district, province, and national levels and 26 focus-group discussions with local project implementers (n = 153), we conducted a qualitative two-year evaluation to measure the impact of HPV vaccinations on the health and education systems. RESULTS: HPV vaccine delivery at schools or health centers was made feasible by: a. close collaboration between the health and education sectors, b. detailed planning for implementation, c. clearly defined roles and responsibilities for project implementers, d. effective management and supervision of vaccinations during delivery, and e. engagement with community organizations for support. Both the health and education systems were temporarily challenged with the extra workload, but the disruptions were short-lived (a few days for each of three doses) and perceived as worth the longer-term benefit of cervical cancer prevention. CONCLUSION: The learning from Vietnam has identified critical elements for successful vaccine delivery that can provide a model for other countries to consider during their planning of national rollout of HPV vaccine.

Planning cancer control in Latin America and the Caribbean.

Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.

Why the time is right to tackle breast and cervical cancer in low-resource settings.

The health concerns of women in their mid-adult years - when the prime age of reproduction has passed - have been traditionally given little or no attention by health systems and donors, despite the heavy burden that diseases such as breast and cervical cancer impose on women and their families. The risk of sexually transmitted infections that accompanies sexual relations and the risk of death and morbidity associated with pregnancy have long been recognized and have stimulated major control efforts that are finally yielding positive results. Much less attention has been focused, however, on how experiences in early life can affect women's health in adulthood. Breast and cervical cancers kill more women than any other types of cancer in all parts of the developing world. In most of Asia and Latin America and some African countries, deaths from these two forms of cancer now outnumber pregnancy-related deaths. There are five compelling reasons for focusing on these cancers now to try to reverse these epidemiologic trends: (i) the burden of breast and cervical cancer is large and is growing; (ii) effective screening and treatment are available; (iii) research is generating new knowledge; (iv) there are opportunities for synergy with other health programmes; and (v) noncommunicable diseases are the focus of much current interest.

Les problèmes de santé des femmes au milieu de l'âge adulte (une fois passé le premier âge de la reproduction) ont traditionnellement bénéficié de peu d'attention ou ont été ignorés par les systèmes de santé et les donateurs, malgré le lourd fardeau que constituent les maladies, comme le cancer du sein et du col de l'utérus pour les femmes et leurs familles. Le risque d'infections sexuellement transmissibles qui accompagne les relations sexuelles, et le risque de mortalité et de morbidité associé à la grossesse sont reconnus depuis longtemps et ont guidé d'importants efforts de lutte, qui finissent par donner des résultats positifs. Beaucoup moins d'attention a cependant été accordée à la façon dont les expériences en début de vie peuvent affecter la santé des femmes à l'âge adulte.Les cancers du sein et du col de l'utérus tuent plus de femmes que tout autre type de cancer dans tous les pays du monde en voie de développement. Dans la plupart des pays d'Asie, d'Amérique latine et dans certains pays d'Afrique, les décès résultant de ces deux formes de cancer sont maintenant plus nombreux que les décès liés à la grossesse. Il y a cinq raisons impérieuses de se concentrer maintenant sur ces cancers afin d'essayer d'inverser ces tendances épidémiologiques: (i) le fardeau du cancer du sein et du cancer du col de l'utérus est toujours plus lourd; (ii) un dépistage et des traitements efficaces sont disponibles; (iii) la recherche génère de nouvelles connaissances; (iv) il existe des possibilités de synergie avec d'autres programmes de santé; et (v) les maladies non transmissibles génèrent beaucoup d'intérêt actuellement.

Los problemas de salud de las mujeres de mediana edad, una vez han pasado la plenitud de la edad reproductora, han recibido tradicionalmente poca o ninguna atención por parte de los sistemas sanitarios y donantes, a pesar de la gran carga que enfermedades como el cáncer de mama o de cuello uterino representan para las mujeres y sus familias. El riesgo de enfermedades de transmisión sexual a través de relaciones sexuales, y el riesgo de muerte y enfermedad asociados con el embarazo han sido reconocidos y se han impulsado intentos de control a gran escala que al fin están dando resultados positivos. Sin embargo, se ha prestado mucha menos atención a cómo las experiencias en las primeras etapas de la vida pueden afectar la salud de las mujeres en la vida adulta. En el mundo desarrollado, los cánceres de mama y de cuello uterino matan a más mujeres que ningún otro tipo de cáncer. En la mayor parte de Asia y América Latina y algunos países africanos, las muertes por estos dos tipos de cáncer superan en número a las muertes relacionadas con el embarazo. Hay cinco razones de peso para centrar la atención en estos tipos de cáncer con objeto de intentar revertir estas tendencias epidemiológicas: (i) la carga de los cánceres de mama y de cuello uterino es muy elevada, y sigue creciendo; (ii) existen controles y tratamientos eficaces; (iii) la investigación está proporcionando conocimientos nuevos; (iv) existen oportunidades de sinergia con otros programas sanitarios y (v) las enfermedades no transmisibles reciben gran parte de la atención actual.

Health seeking behavior for cervical cancer in Ethiopia: a qualitative study.

BACKGROUND: Although cervical cancer is a leading cause of cancer related morbidity and mortality among women in Ethiopia, there is lack of information regarding the perception of the community about the disease. METHODS: Focus group discussions were conducted with men, women, and community leaders in the rural settings of Jimma Zone southwest Ethiopia and in the capital city, Addis Ababa. Data were captured using voice recorders, and field notes were transcribed verbatim from the local languages into English language. Key categories and thematic frameworks were identified using the health belief model as a framework, and presented in narratives using the respondents own words as an illustration. RESULTS: Participants had very low awareness of cervical cancer. However, once the symptoms were explained, participants had a high perception of the severity of the disease. The etiology of cervical cancer was thought to be due to breaching social taboos or undertaking unacceptable behaviors. As a result, the perceived benefits of modern treatment were very low, and various barriers to seeking any type of treatment were identified, including limited awareness and access to appropriate health services. Women with cervical cancer were excluded from society and received poor emotional support. Moreover, the aforementioned factors all caused delays in seeking any health care. Traditional remedies were the most preferred treatment option for early stage of the disease. However, as most cases presented late, treatment options were ineffective, resulting in an iterative pattern of health seeking behavior and alternated between traditional remedies and modern treatment methods. CONCLUSION: Lack of awareness and health seeking behavior for cervical cancer was common due to misconceptions about the cause of the disease. Profound social consequences and exclusion were common. Access to services for diagnosis and treatment were poor for a variety of psycho-social, and health system reasons. Prior to the introduction or scale up of cervical cancer prevention programs, socio-cultural barriers and health service related factors that influence health seeking behavior must be addressed through appropriate community level behavior change communications.

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.

Immunogenicity and reactogenicity of alternative schedules of HPV vaccine in Vietnam: a cluster randomized noninferiority trial.

CONTEXT: Human papillomavirus (HPV) vaccine programs may decrease the morbidity and mortality due to cervical cancer seen among women in low-resource countries. However, the 3-dose schedule over a 6-month period is a potential barrier to vaccine introduction in such settings. OBJECTIVE: To determine the immunogenicity and reactogenicity of different dosing schedules of quadrivalent HPV vaccine in adolescent girls in Vietnam. DESIGN, SETTING, AND PARTICIPANTS: Open-label, cluster randomized, noninferiority study (conducted between October 2007 and January 2010) assessing 4 schedules of an HPV vaccine delivered in 21 schools to 903 adolescent girls (aged 11-13 years at enrollment) living in northwestern Vietnam. INTERVENTION: Intramuscular injection of 3 doses of quadrivalent HPV vaccine delivered on a standard dosing schedule (at 0, 2, and 6 months) and 3 alternative dosing schedules (at 0, 3, and 9 months; at 0, 6, and 12 months; or at 0, 12, and 24 months). MAIN OUTCOME MEASURES: Serum anti-HPV geometric mean titers (GMT) measured 1 month after the third dose of the HPV vaccine was administered; GMT was determined by type-specific competitive immunoassay. Noninferiority of each alternative vaccination dosing schedule was achieved if the lower bound of the multiplicity-adjusted confidence interval (CI) of the type-specific GMT ratio for HPV-16 and HPV-18 was greater than 0.5 (primary outcome). Safety outcomes were immediate reactions, local reactions, fever within 7 days after each dose, and serious adverse events up to 30 days following the last dose. RESULTS: In the intention-to-treat analysis, 809 girls who received at least 1 HPV vaccine dose had valid serum measurements 1 month after the third dose. After the third dose, the GMTs for those in the standard schedule group who received doses at 0, 2, and 6 months were 5808.0 (95% CI, 4961.4-6799.0) for HPV-16 and 1729.9 (95% CI, 1504.0-1989.7) for HPV-18; 5368.5 (95% CI, 4632.4-6221.5) and 1502.3 (95% CI, 1302.1-1733.2), respectively, for those whose received doses at 0, 3, and 9 months; 5716.4 (95% CI, 4876.7-6700.6) and 1581.5 (95% CI, 1363.4-1834.6), respectively, for those who received doses at 0, 6, and 12 months; and 3692.5 (95% CI, 3145.3-4334.9) and 1335.7 (95% CI, 1191.6-1497.3), respectively, for those who received doses at 0, 12, and 24 months. Noninferiority criteria were met for the alternative schedule groups that received doses at 0, 3, and 9 months (HPV-16 GMT ratio: 0.92 [95% CI, 0.71-1.20]; HPV-18 GMT ratio: 0.87 [95% CI, 0.68-1.11]) and at 0, 6, and 12 months (HPV-16 GMT ratio: 0.98 [95% CI, 0.75-1.29]; HPV-18 GMT ratio: 0.91 [95% CI, 0.71-1.17]). Prespecified noninferiority criteria were not met for the alternative schedule group that received doses at 0, 12, and 24 months (HPV-16 GMT ratio: 0.64 [95% CI, 0.48-0.84]; HPV-18 GMT ratio: 0.77 [95% CI, 0.62-0.96]). Pain at the injection site was the most common adverse event. CONCLUSIONS: Among adolescent girls in Vietnam, administration of the HPV vaccine on standard and alternative schedules was immunogenic and well tolerated. The use of 2 alternative dosing schedules (at 0, 3, and 9 months and at 0, 6, and 12 months) compared with a standard schedule (at 0, 2, and 6 months) did not result in inferior antibody concentrations. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00524745.

Evaluation of diagnostic ultrasound use in a breast cancer detection strategy in Northern Peru.

To evaluate the diagnostic impact of point-of-care breast ultrasound by trained primary care physicians (PCPs) as part of a breast cancer detection program using clinical breast exam in an underserved region of Peru. Medical records and breast ultrasound images of symptomatic women presenting to the Breast Cancer Detection Model (BCDM) in Trujillo, Peru were collected from 2017-2018. Performance was measured against final outcomes derived from regional cancer center medical records, fine needle aspiration results, patient follow-up (sensitivity, specificity, positive, and negative predictive values), and by percent agreement with the retrospective, blinded interpretation of images by a fellowship-trained breast radiologist, and a Peruvian breast surgeon. The diagnostic impact of ultrasound, compared to clinical breast exam (CBE), was calculated for actual practice and for potential impact of two alternative reporting systems. Of the 171 women presenting for breast ultrasound, 23 had breast cancer (13.5%). Breast ultrasound used as a triage test (current practice) detected all cancer cases (including four cancers missed on confirmatory CBE). PCPs showed strong agreement with radiologist and surgeon readings regarding the final management of masses (85.4% and 80.4%, respectively). While the triage system yielded a similar number of biopsies as CBE alone, using the condensed and full BI-RADS systems would have reduced biopsies by 60% while identifying 87% of cancers immediately and deferring 13% to six-month follow-up. Point-of-care ultrasound performed by trained PCPs improves diagnostic accuracy for managing symptomatic women over CBE alone and enhances access. Greater use of BI-RADS to guide management would reduce the diagnostic burden substantially.