Economic analyses to support decisions about HPV vaccination in low- and middle-income countries: a consensus report and guide for analysts.

Low- and middle-income countries need to consider economic issues such as cost-effectiveness, affordability and sustainability before introducing a program for human papillomavirus (HPV) vaccination. However, many such countries lack the technical capacity and data to conduct their own analyses. Analysts informing policy decisions should address the following questions: 1) Is an economic analysis needed? 2) Should analyses address costs, epidemiological outcomes, or both? 3) If costs are considered, what sort of analysis is needed? 4) If outcomes are considered, what sort of model should be used? 5) How complex should the analysis be? 6) How should uncertainty be captured? 7) How should model results be communicated? Selecting the appropriate analysis is essential to ensure that all the important features of the decision problem are correctly represented, but that the analyses are not more complex than necessary. This report describes the consensus of an expert group convened by the World Health Organization, prioritizing key issues to be addressed when considering economic analyses to support HPV vaccine introduction in these countries

HPV-FRAME: A consensus statement and quality framework for modelled evaluations of HPV-related cancer control.

Intense research activity in HPV modelling over this decade has prompted the development of additional guidelines to those for general modelling. A specific framework is required to address different policy questions and unique complexities of HPV modelling. HPV-FRAME is an initiative to develop a consensus statement and quality-based framework for epidemiologic and economic HPV models. Its development involved an established process. Reporting standards have been structured according to seven domains reflecting distinct policy questions in HPV and cancer prevention and categorised by relevance to a population or evaluation. Population-relevant domains are: 1) HPV vaccination in pre-adolescent and young adolescent individuals; 2) HPV vaccination in older individuals; 3) targeted vaccination in men who have sex with men; 4) considerations for individuals living with HIV and 5) considerations for low- and middle-income countries. Additional considerations applicable to specific evaluations are: 6) cervical screening or integrated cervical screening and HPV vaccination approaches and 7) alternative vaccine types and alternative dosing schedules. HPV-FRAME aims to promote the development of models in accordance with an explicit framework, to better enable target audiences to understand a model's strength and weaknesses in relation to a specific policy question and ultimately improve the model's contribution to informed decision-making

The IARC perspective on cervical cancer screening

In May 2018, the World Health Organization (WHO) called for a global initiative to eliminate cervical cancer as a public health problem. To achieve this goal, global scale-up of effective vaccination against the human papillomavirus (HPV) as well as screening for and treatment of cervical cancer are required. Cervical cancer screening was evaluated in 2005 by the International Agency for Research on Cancer (IARC) Handbooks program,1 and a reevaluation was deemed to be timely given the major advances in the field since then. The new handbook provides updated evaluations of the effectiveness of screening methods, which were used as a basis for the update of the WHO Guideline for Screening and Treatment of Cervical Pre-cancer Lesions for Cervical Cancer Prevention.2 We convened an IARC Working Group of 27 scientists from 20 countries to assess the evidence on the current approaches to and technologies used in cervical cancer screening with the use of the newly updated Handbooks Preamble3 (Fig. 1) and Table 1).Fil: Bouvard, Véronique. International Agency For Research On Cancer; FranciaFil: Wentzensen, Nicolas. National Cancer Institute; Estados UnidosFil: Mackie, Anne. Public Health England; Reino UnidoFil: Berkhof, Johannes. University of Amsterdam; Países BajosFil: Brotherton, Julia. VCS Foundation; Australia. University of Melbourne; AustraliaFil: Giorgi Rossi, Paolo. Azienda Unità Sanitaria Locale Di Reggio Emilia; ItaliaFil: Kupets, Rachel. University of Toronto; CanadáFil: Smith, Robert. American Cancer Society; Estados UnidosFil: Arrossi, Silvina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bendahhou, Karima. Casablanca Cancer Registry; MarruecosFil: Canfell, Karen. The University Of Sydney; AustraliaFil: Chirenje, Z. Mike. University Of Zimbabwe; ZimbabueFil: Chung, Michael H.. University of Emory; Estados UnidosFil: del Pino, Marta. Hospital Clinico de Barcelona; EspañaFil: de Sanjosé, Silvia. Program for Appropriate Technology in Health; Estados UnidosFil: Elfström, Miriam. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Franco, Eduardo L.. McGill University; CanadáFil: Hamashima, Chisato. Teikyo University; JapónFil: Hamers, Françoise F.. French National Public Health Agency; FranciaFil: Herrington, C. Simon. University of Edinburgh; Reino UnidoFil: Murillo, Raúl. Hospital Universitario San Ignacio; ColombiaFil: Sangrajrang, Suleeporn. National Cancer Institute; TailandiaFil: Sankaranarayanan, Rengaswamy. Research Triangle Institute; Estados UnidosFil: Saraiya, Mona. Centers for Disease Control and Prevention; Estados UnidosFil: Schiffman, Mark. National Cancer Institute; Estados UnidosFil: Zhao, Fanghui. Chinese Academy of Medical Sciences & Peking Union Medical College; ChinaFil: Arbyn, Marc. Sciensano; BélgicaFil: Prendiville, Walter. International Agency For Research On Cancer; FranciaFil: Indave Ruiz, Blanca I.. International Agency For Research On Cancer; FranciaFil: Mosquera Metcalfe, Isabel. International Agency For Research On Cancer; FranciaFil: Lauby Secretan, Béatrice. International Agency For Research On Cancer; Franci

Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2):study protocol for an international multicenter patient-blinded randomized controlled trial

Background: Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design: The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion: The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration: ISRCTN27483786. Registered on August 2, 2023.</p

Criteria for second generation comparator tests in validation of novel HPV DNA tests for use in cervical cancer screening

While HC2 and GP5+/6+ PCR-EIA were pivotal in test validation of new HPV assays, they represent the first generation of comparator tests based upon technologies that are not in widespread use anymore. In the current guideline, criteria for second-generation comparator tests are presented that include more detailed resolution of HPV genotypes. Second-generation comparator tests should preferentially target only the 12 genotypes classified as carcinogenic (IARC-group I), and show consistent non-inferior sensitivity for CIN2+ and CIN3+ and specificity for ≤CIN1 compared to one of the first-generations comparators, in at least three validation studies using benchmarks of 0.95 for relative sensitivity and 0.98 for relative specificity. Validation should take into account used storage media and other sample handling procedures. Meta-analyses were conducted to identify the assays that fulfill these stringent criteria. Four tests fulfilled the new criteria: (1) RealTime High-Risk HPV Test (Abbott), (2) Cobas-4800 HPV test (Roche Molecular System), (3) Onclarity HPV Assay (BD Diagnostics), and (4) Anyplex II HPV HR Detection (Seegene), each evaluated in three to six studies. Whereas the four assays target 14 carcinogenic genotypes, the first two identify separately HPV16 and 18, the third assay identifies five types separately and the fourth identifies all the types separately

Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2): study protocol for an international multicenter patient-blinded randomized controlled trial

Background: Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design: The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion: The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration: ISRCTN27483786. Registered on August 2, 2023