Proceedings of the Modeling Evidence in HPV Pre-Conference Workshop in Malmö, Sweden, May 9–10, 2009

doi:10.1016/j.clinthera.2010.06.017

Clinical Therapeutics

Volume 32, Issue 8, August 2010, Pages 1546-1564

https://doi.org/10.1016/j.clinthera.2010.06.017 Get rights and content

Abstract

Background: Prominent published and active human papillomavirus (HPV) modelers from around the world were invited to participate in the inaugural Modeling Evidence in HPV (MEHPV) Pre-Conference Workshop on May 9–10, 2009, in Malmö, Sweden. The workshop took place directly before the 25th International Papillomavirus Conference.

Objectives: The aim of the workshop was to develop an international network of investigators engaged in HPV modeling and to facilitate open discussion about the structure and parameterization of models, as well as other methodologic concerns.

Methods: Thirty-four participants from more than a dozen countries and a variety of settings, representing the authors or coauthors of 82% of the HPV modeling literature, exchanged ideas on fundamental questions in the field. These proceedings, based on the 217-page transcript, were assembled by the Scientific Committee to summarize the ideas of workshop participants in a deidentified, readable fashion. They represent the work and recorded opinions of session participants and do not constitute the official positions of participants as a whole or individually, the Scientific Committee, or any sponsoring organization or entity.

Results: In charting a path forward, 3 topics emerged as most pressing: best practices for HPV modeling, comparative modeling, and modeling in developing countries.

Conclusion: This summary of the proceedings of the preconference workshop on HPV modeling characterizes many of the prominent contemporary issues in the field.

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Cited by (10)

Mathematical Models for Evaluating Effectiveness and Cost-Effectiveness of Cervical Cancer Control Policies in Populations Including Women Living With Human Immunodeficiency Virus: A Scoping Review
2022, Value in Health Regional Issues
Citation Excerpt :
More than half of the studies in our review did not report whether they examined the concordance between their model outputs and external sources (external validation). More than a decade ago, the participants of a workshop on HPV modeling noted that scientific journal articles’ content and word limitations do not allow for a sufficiently detailed description of model-based evaluations.41 They suggested that comprehensive appendices should be published and that model code should be made available online.
Mathematical modeling is increasingly used to inform cervical cancer control policies, and model-based evaluations of such policies in women living with human immunodeficiency virus (HIV) are an emerging research area. We did a scoping review of published literature to identify research gaps and inform future work in this field.
We systematically searched literature up to April 2022 and included mathematical modeling studies evaluating the effectiveness or cost-effectiveness of cervical cancer prevention strategies in populations including women living with HIV. We extracted information on prevention strategies and modeling approaches.
We screened 1504 records and included 22 studies, almost half of which focused on South Africa. We found substantial between-study heterogeneity in terms of strategies assessed and modeling approaches used. Fourteen studies evaluated cervical cancer screening strategies, 7 studies assessed human papillomavirus vaccination (with or without screening), and 1 study evaluated the impact of HIV control measures on cervical cancer incidence and mortality. Thirteen conducted cost-effectiveness analyses. Markov cohort state-transition models were used most commonly (n = 12). Most studies (n = 17) modeled the effect of HIV by creating HIV-related health states. Thirteen studies performed model calibration, but 11 did not report the calibration methods used. Only 1 study stated that model code was available upon request.
Few model-based evaluations of cervical cancer control strategies have specifically considered women living with HIV. Improvements in model transparency, by sharing information and making model code publicly available, could facilitate the utility of these evaluations for other high disease-burden countries, where they are needed for assisting policy makers.
HPV-FRAME: A consensus statement and quality framework for modelled evaluations of HPV-related cancer control
2019, Papillomavirus Research
Citation Excerpt :
In general terms, model structures and parameterization should be as parsimonious as possible, while being able to capture the essential elements of the decision and mindful of the availability of data. Dynamic models should be used unless it can be demonstrated that herd effects are unimportant to the decision being informed [19–23]. This is because dynamic transmission models explicitly simulate changing (declining) HPV incidence and prevalence for vaccine-included types over time, and the consequently declining risk of new infections, after population-wide vaccination initiatives are introduced.
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 key role of mathematical modeling and health economics in the public health transitions in cervical cancer prevention
2019, Human Papillomavirus: Proving and Using a Viral Cause for Cancer
Mathematical modeling has played a key role in the implementation of major public health transitions in the prevention of cervical and other human papillomavirus (HPV)-related cancers. The natural history of HPV infection and cervical cancer is the most well understood of any cancer, and this has facilitated the development of comprehensive models. The main purpose of modeling is to support the policy-maker in complex areas where there are many options to consider. Clinical trial data for HPV vaccination and primary HPV screening have informed the development of models which have synthesized these findings with in-country information. These models yield predictions of the long-term health outcomes, resource utilization, costs and cost-effectiveness of interventions, and have been critical to the decisions by policy-makers to introduce HPV vaccination and primary HPV screening in many countries. Early models of cervical cancer natural history were reported in the 1980s and 1990s, and 25 years on, several groups around the world have developed comprehensive dynamic platforms of HPV transmission, infection and vaccination, and of cervical cancer natural history and screening. Comparative modeling, where multiple platforms using common input data sources are harnessed, is increasingly used for major evaluations. Looking forward, modeling will continue to play a key role in predicting and optimizing the complex interaction between HPV vaccination and cervical screening. In particular, modeling is critical to underpinning current strategic planning activities for the World Health Organization’s initiative to eliminate cervical cancer as a public health problem.
Health utilities lost and risk factors associated with HPV-induced diseases in men and women: The HPV Italian collaborative study group
2015, Clinical Therapeutics
A complete economic evaluation requires accurate data concerning the resources used, outcomes, and utilities (patient’s preferences) to properly value the cost utility of human papillomavirus (HPV) vaccination strategies. This study was designed to measure the utility loss in health states affected by a broad range of HPV-induced pathologies in both sexes in Italy. As a secondary objective, risk factors influencing the viral transmission and development of HPV infections were also investigated.
Patients with a diagnosis of several HPV-induced pathologies including atypical squamous cells of undetermined significance (ASC-US), cervical intraepithelial neoplasia (CIN), cervical and anal-colorectal cancer, head and neck squamous cell carcinoma (HNSCC) and anogenital warts (AWs) were evaluated. Utilities, quality of life, and risk factors were elicited using a standardized and computer-guided administration of time trade-off, European Quality of Life 5 Dimensions (EQ-5D), 3 levels, and risk factor questionnaires. Utilities were measured at 6 clinical research centers across Italy. A group of healthy subjects was used as a control. A mean number of 20 healthy subjects was used as a control for each pathology group.
Overall, 600 respondents were eligible for analysis: 465 patients (mean [SD] age, 44.0 [16.3] years) and 135 controls (mean [SD] age, 44.0 [13.2] years). With the exception of anal and HNSCC cancer, no statistically significant differences were observed between case and control groups, in terms of either age or quality of life at the time of interview. The patients’ perception of their health condition at baseline was equal to an EQ-5D score of 0.87 (0.22). The mean (SD) value of utilities associated with the HPV-induced pathologies corresponded to 0.83 (0.24), 0.78 (0.27), 0.83 (0.22), 0.81 (0.27), 0.58 (0.31), 0.51 (0.26), and 0.69 (0.30) for ASC-US, AWs, CIN 1 (mild), CIN 2–3 (moderate to severe), cervical cancer, anal cancer and HNSCC, respectively. Utility lost due to AWs was significantly higher in females compared with males (0.71 [0.29] vs 0.83 [0.25]; P = 0.018). Having >5 sexual partners increased the risk of acquiring HPV-induced infections as much as 2.52-fold (P = 0.004), whereas for smoking or the age at start of sexual activity younger than 18 years, the risk increased by ~1.62-fold (P = 0.034). High levels of education were associated with a statistically significant protective effect (P < 0.001).
Risk factors and utilities elicited in this study can be used as part of future economic assessments of other HPV vaccination strategies, including an immunization program for preadolescents of both sexes in Italy.
Development of a quality framework for models of cervical screening and its application to evaluations of the cost-effectiveness of HPV vaccination in developed countries
2015, Vaccine
Citation Excerpt :
A quality framework attempts to address poorly designed models, over-simplification, misinterpretation and failure to appreciate the degree of uncertainty in a decision process [15]. Although generic guidelines for health economic models are available, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) has recently published the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) Statement [77], and a broad consensus statement has been published on model aspects that need to be considered when modelling HPV infections [18–20], these do not address specific issues in modelling cervical screening and in general terms no guidelines or consensus statements have been published specifically for cervical screening models. Therefore, the aims of the current project were to: (i) adapt existing, broader frameworks to construct a specific quality framework for models of existing cervical screening processes; and (ii) to perform a systematic review of HPV vaccination cost-effectiveness assessments in developed countries and to apply the new quality framework to the assessment of the cervical screening models.
HPV vaccination has now been introduced in most developed countries, but this has occurred in the context of established cervical cancer screening mechanisms which provide population-level protection against the most common HPV-related cancer. Therefore, estimating the cost-effectiveness of HPV vaccination to further reduce HPV-related disease depends in large part on the estimation of the effectiveness of the cervical screening ‘background’. The aim of this study was to systematically review and assess methods for simulating cervical screening in decision analytic models used for evaluation of HPV vaccination.
Existing quality frameworks for economic models were extended to develop a specific quality framework for models of cervical screening. This involved domains for model structure, parameterisation (data sources) and validation (consistency). A systematic review of economic evaluations of HPV vaccination was then conducted, and assessment of cervical screening model components was then performed via application of the new quality framework.
Generally, models took into account population-level cervical screening participation, but were inconsistent in their approach to modelling abnormal smear management, diagnostic evaluation and treatment of precancerous disease. There was also considerable variability in the accuracy of modelling clinical pathways and the scope of validation performed for screening-related outcomes, with focus directed towards cervical cancer targets. Only a few models comprehensively validated against observed pre-cancerous abnormalities.
Models of HPV vaccination in developed countries can be improved by further attention to the ‘background’ modelling of secondary protection via cervical screening. The quality framework developed for this review can be used to inform future HPV vaccination evaluations, including evaluations of the cost-effectiveness of male vaccination and next generation HPV vaccines, and to assess models used to evaluate new cervical screening technologies and recommendations.
Cost-effectiveness of human papillomavirus vaccination in low and middle income countries: A systematic review
2013, Vaccine
The World Health Organization recommends establishing that human papillomavirus vaccination is cost-effective before vaccine introduction. We searched Pubmed, Embase and the Cochrane Library to 1 April 2012 for economic evaluations of human papillomavirus vaccination in low and middle income countries. We found 25 articles, but almost all low income countries and many middle income countries lacked country-specific studies. Methods, assumptions and consequently results varied widely, even for studies conducted for the same country. Despite the heterogeneity, most studies conclude that vaccination is likely to be cost-effective and possibly even cost saving, particularly in settings without organized cervical screening programmes. However, study uncertainty could be reduced by clarity about vaccine prices and vaccine delivery costs. The review supports extending vaccination to low income settings where vaccine prices are competitive, donor funding is available, cervical cancer burden is high and screening options are limited.

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Proceedings of the Modeling Evidence in HPV Pre-Conference Workshop in Malmö, Sweden, May 9–10, 2009

Abstract

Vaccine

Lancet

Computer modeling of diabetes and its complications: A report on the Fourth Mount Hood Challenge Meeting

Diabetes Care

for the Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices (ACIP). Quadrivalent human papillomavirus vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP)

MMWR Recomm Rep.

HPV vaccines prophylactic, not therapeutic

JAMA

Seroprevalence of human papillomavirus types 6, 11, 16, and 18 in the United States: National Health and Nutrition Examination Survey 2003–2004

J Infect Dis.

Primary and secondary prevention of cervical cancer—opportunities and challenges

J Natl Cancer Inst.

Anal human papillomavirus genotype diversity and co-infection in a community-based sample of homosexual men

Sex Transm Infect.

Anal human papillomavirus infection is associated with HIV acquisition in men who have sex with men

AIDS