Health and economic effects of introducing single-dose or two-dose human papillomavirus vaccination in India.

BACKGROUND: Cervical cancer is a major public health problem in India, where access to prevention programmes is low. The WHO-Strategic Advisory Group of Experts recently updated their recommendation for human papillomavirus (HPV) vaccination to include a single-dose option in addition to the two-dose option, which could make HPV vaccination programmes easier to implement and more affordable. METHODS: We combined projections from a type-specific HPV transmission model and a cancer progression model to assess the health and economic effects of HPV vaccination at national and state level in India. The models used national and state-specific Indian demographic, epidemiological and cost data, and single-dose vaccine efficacy and immunogenicity data from the International Agency for Research on Cancer India vaccine trial with 10-year follow-up. We compared single-dose and two-dose HPV vaccination for a range of plausible scenarios regarding single-dose vaccine protection, coverage and catch-up. We used a healthcare sector payer perspective with a time horizon of 100 years. RESULTS: Under the base-case scenario of lifelong protection of single-dose vaccination in 10-year-old girls with 90% coverage, the discounted incremental cost-effectiveness ratio (ICER) of nationwide vaccination relative to no vaccination was US$406 (₹INR30 000) per DALY (disability-adjusted life-years) averted. This lay below an opportunity-cost-based threshold of 30% Indian gross domestic product per capita in each Indian state (state-specific ICER range: US$67-US$593 per DALY averted). The ICER of two-dose vaccination versus no vaccination vaccination was US$1404 (₹INR104 000). The ICER of two-dose vaccination versus single-dose vaccination, assuming lower initial efficacy and waning of single-dose vaccination, was at least US$2282 (₹INR169 000) per DALY averted. CONCLUSIONS: Nationwide introduction of single-dose HPV vaccination at age 10 in India is highly likely to be cost-effective whereas extending the number of doses from one to two would have a less favourable profile.

Assessment of organization of cervical and breast cancer screening programmes in the Latin American and the Caribbean states: The CanScreen5 framework.

BACKGROUND: In the Community of Latin American and Caribbean States (CELAC), breast cancer and cervical cancer are the first and third causes of cancer death among females. The objectives are to assess the characteristics of the cervical and breast cancer screening programmes in CELAC, their level of organization, and the association of screening organization and coverage of essential health services. METHODS: Representatives of the Ministries of Health of 33 countries were invited to the CanScreen5 project. Twenty-seven countries participated in a "Train The Trainers" programme on cancer screening, and 26 submitted data using standardized questionnaires. Data were discussed and validated. The level of organization of the screening programmes was examined adapting the list of essential elements of organized screening programmes identified in a recently published IARC study. RESULTS: Twenty-one countries reported a screening programme for cervical cancer and 15 for breast cancer. For cervical cancer, 14 countries dedicated budget for screening (66.7%), and women had to pay in 3 countries for screening (14.3%), 9 for diagnosis (42.9%) and 8 for treatment (38.1%). Only 4 countries had a system to invite women individually (19.0%). For breast cancer, 8 countries dedicated budget for screening (53.3%), and women had to pay for screening in 3 countries (20.0%), diagnosis in 7 (46.7%) and treatment in 6 (40.0%). One country (6.7%) invited women individually. There was variability in the level of organization of both cancer screening programmes. The level of organization of cervical cancer screening and coverage of essential health services were correlated. CONCLUSION: Large gaps were identified in the organization of cervical and breast cancer screening services. CELAC governments need pragmatic public health policies and strengthened health systems. They should guarantee sustainable funding, and universal access to cancer diagnosis and treatment. Moreover, countries should enhance their health information system and ensure adequate monitoring and evaluation.

Costs and Benefits of Wax Production in the Larvae of the Ladybeetle Scymnus nubilus.

BACKGROUND: Larvae of the minute aphidophagous Scymnus nubilus Mulsant (Coleoptera: Coccinellidae) are common predators in apple orchards, covered by a wax layer that might act as a defense mechanism against natural enemies. However, the costs and benefits of protection conferred by wax remain to be assessed. We tested the following hypothesis: there is a trade-off in wax producing ladybeetles between the protection conferred by wax cover and the physiological or behavioral costs associated with its production. We predict that: (1) wax production is an efficient defensive mechanism (against intraguild predation), (2) wax production is associated with detrimental physiological (growth, reproduction) or behavioral effects (behavioral compensation: increased biomass consumption). RESULTS: Tests were carried out in the laboratory with wax and waxless larvae of S. nubilus, with and without lacewing larvae of Chrysoperla agilis (Neuroptera: Chrysopidae) being used as a potential intraguild predator of the coccinellid. Waxless individuals were more susceptible to intraguild predation by lacewing larvae. Adults originating from waxless larvae were lighter than the ones originating from wax larvae, suggesting a metabolic cost resulting from a constant need of wax production. Body-weight gain and conversion efficiency were lower in waxless larvae. Biomass consumption was similar, showing that waxless larvae did not compensate for the physiological cost by eating more aphid biomass. CONCLUSION: The results indicate the potential existence of a trade-off between growth and protection associated with wax production.

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.

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol.

INTRODUCTION: Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. METHODS AND ANALYSIS: Women aged 30-64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT01881659.

Low-concentration trypsin detection from a metal-enhanced fluorescence (MEF) platform: Towards the development of ultra-sensitive and rapid detection of proteolytic enzymes.

Proteolytic enzymes, which serve to degrade proteins to their amino acid building blocks, provide a distinct challenge for both diagnostics and biological research fields. Due to their ubiquitous presence in a wide variety of organisms and their involvement in disease, proteases have been identified as biomarkers for various conditions. Additionally, low-levels of proteases may interfere with biological investigation, as contamination with these enzymes can physically alter the protein of interest to researchers, resulting in protein concentration loss or subtler polypeptide clipping that leads to a loss of functionality. Low levels of proteolytic degradation also reduce the shelf-life of commercially important proteins. Many detection platforms have been developed to achieve low-concentration or low-activity detection of proteases, yet many suffer from limitations in analysis time, label stability, and ultimately sensitivity. Herein we demonstrate the potential utility of fluorescein derivatives as fluorescent labels in a new, turn-off enzymatic assay based on the principles of metal-enhanced fluorescence (MEF). For fluorescein sodium salt alone on nano-slivered 96-well plates, or Quanta Plates™, we report up to 11,000x enhancement for fluorophores within the effective coupling or enhancement volume region, defined as ~100 nm from the silver surface. We also report a 9% coefficient of variation, and detection on the picomolar concentration scale. Further, we demonstrate the use of fluorescein isothiocyanate-labeled YebF protein as a coating layer for a MEF-based, Quanta Plate™ enzymatic activity assay using trypsin as the model enzyme. From this MEF assay we achieve a detection limit of ~1.89 ng of enzyme (2.8 mBAEE activity units) which corresponds to a minimum fluorescence signal decrease of 10%. The relative success of this MEF assay sets the foundation for further development and the tuning of MEF platforms for proteolytic enzyme sensing not just for trypsin, but other proteases as well. In addition, we discuss the future development of ultra-fast detection of proteases via microwave-accelerated MEF (MAMEF) detection technologies.

Are two doses of human papillomavirus vaccine sufficient for girls aged 15-18 years? Results from a cohort study in India.

Extending two-dose recommendations of HPV vaccine to girls between 15 and 18 years will reduce program cost and improve compliance. Immunogenicity and vaccine targeted HPV infection outcomes were compared between 1795 girls aged 15-18 years receiving two (1-180 days) and 1515 girls of same age receiving three (1-60-180 days) doses. Immunogenicity outcomes in 15-18 year old two-dose recipients were also compared with the 10-14 year old three-dose (N = 2833) and two-dose (N = 3184) recipients. The 15-18 year old two-dose recipients had non-inferior L1-binding antibody titres at seven months against vaccine-targeted HPV types compared to three-dose recipients at 15-18 years and three-dose recipients at 10-14 years of age. Neutralizing antibody titres at 18 months in 15-18 year old two-dose recipients were non-inferior to same age three-dose recipients for all except HPV 18. The titres were inferior to those in the 10-14 year old three-dose recipients for all targeted types. Frequency of incident infections from vaccine-targeted HPV types in the 15-18 year old two-dose recipients was similar to the three dose recipients. None of the girls receiving two or three doses had persistent infection from vaccine-targeted types. These findings support that two doses of HPV vaccine can be extended to girls aged 15-18 years.

A cluster randomized controlled trial of visual, cytology and human papillomavirus screening for cancer of the cervix in rural India.

The impact of screening by visual inspection with acetic acid (VIA), cytology or HPV testing on cervical cancer incidence and mortality is investigated in a cluster randomized controlled trial in India. We report findings after the screening phase, when 52 clusters, with a total of 142,701 women aged 30-59 years in Osmanabad District, India, were randomized into 4 arms for a single round of screening by trained midwives with either VIA, cytology or HPV testing as well as a control group. All laboratory tests were done locally. Test-positive women underwent investigations (colposcopy/biopsy) and treatment in the base hospital. Data on participation, test positivity, positive predictive value and detection rates of cervical neoplasia were analyzed using cluster design methodology. Of the eligible women, 72-74% were screened. Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV. The detection rate of high-grade lesions was similar in all intervention arms (0.7% for VIA, 1.0% for cytology and 0.9% for HPV testing) (p = 0.06, Mann-Whitney test). While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing. Over 85% of women with high-grade lesions received treatment. Our results show that a high level of participation and good-quality cytology can be achieved in low-resource settings. VIA is a useful alternative but requires careful monitoring. Detection rates obtained by HPV testing were similar to cytology, despite higher investments.