The combined impact of implementing HPV immunisation and primary HPV screening in New Zealand: Transitional and long-term benefits, costs and resource utilisation implications.

BACKGROUND: In response to emergent evidence, many countries are transitioning from cytology-based to HPV screening. We evaluated the impact of an upcoming transition on health outcomes and resource utilisation in New Zealand. METHODS: An extensively validated model of HPV transmission, vaccination, natural history and cervical screening ('Policy1-Cervix') was utilised to simulate a transition from three-yearly cytology for women 20-69 years to five-yearly HPV screening with 16/18 genotyping for women 25-69 years, accounting for population growth and the impact of HPV immunisation. Cervical cancer rates, resources use (test volumes), costs, and test positivity rates from 2015 to 2035 were estimated. FINDINGS: By 2035, the transition to HPV screening will result in declines in cervical cancer incidence and mortality rates by 32% and 25%, respectively, compared to 2018. A potentially detectable 5% increase in cervical cancer incidence due to earlier detection is predicted for the year of transition. Annual numbers of women screened will fluctuate with the five-year screening interval. Cytology volumes will reduce by over 80% but colposcopy volumes will be similar to pre-transition rates, and program costs will be reduced by 16%. A 9% HPV test positivity rate is expected in the first round of HPV screening (2019-2023), with 2.7% of women referred for colposcopy. Transitioning from cytology to primary HPV cervical screening could avert 149 cancer cases and 45 deaths by 2035. CONCLUSION: Primary HPV screening and vaccination will reduce cervical cancer and resources use. A small transient apparent increase of invasive cancer rates due to earlier detection may be detectable at the population level, reflecting the introduction of a more sensitive screening test. These findings can be used to inform health services planning and public communications surrounding program implementation.

[Health economic evaluation of bivalent human papilloma virus vaccine in China: based on the dynamic model].

Objective: This study aims to evaluate the prevention effect and cost-effectiveness of a prophylactic bivalent human papilloma virus (HPV) vaccine. Methods: A multiple health status dynamic model was developed, including natural history of diseases and prevention strategies. We built 19 prevention strategies including visual inspection with acetic acid/lugol's iodine (VIA/VILI) and/or 3 does prophylactic bivalent HPV vaccine administered to adolescent girls at the age of 15 years old every year under the assumption that vaccine coverage and screening coverage were 70%. The incremental cost-effectiveness ratio (ICER), optimal price of 3 does vaccine and cost-effectiveness frontier of these strategies were analyzed compared with no-intervention. The ICER threshold is 152 087 CNY. Results: Compared with no-intervention, Routine vaccination reduced the incidence of cervical cancer by 69.5%, superior to 5 strategies including VIA/VILI screening only. The range of effect was between 9.0% and 69.2%, and the effect of strategy increased significantly with the increase of screening frequency. Combination vaccination with screening at ages of 35 reduced the incidence of cervical cancer by 72.0%, and the effect increased with the increase of screening frequency. Combination vaccination with screening every 3 years between (35-64) years old reduced the incidence by 89.4%. Compared with no-intervention, the ICER of combination vaccination with screening twice between 35 years and 64 years was 121 292 CNY/life-year, which was cost-effective. The price of vaccine had a significant impact on the ICER of the strategy; when the vaccine price was less than 600 CNY, only routine vaccination or supplementary vaccination between 16-39 years old after routine vaccination was cost-effective; when the vaccine price was less than 1 200 CNY, supplementary vaccination between 16-19 years old plus VIA/VILI was cost-effective. Conclusion: Ther prevention strategy was cost-effective, which could effectively reduce the incidence of cervical cancer by implementation of HPV vaccination combined with VIA/VILI in suitable aging females.

Human papillomavirus vaccine trials and tribulations: Vaccine efficacy.

As of December 2014, there were 3 approved vaccines for human papillomavirus (HPV): bivalent Cervarix (GlaxoSmithKline, New York, NY), quadrivalent Gardasil (Merck and Co, Kenilworth, NJ), and 9-valent Gardasil-9 (Merck and Co). The average cost per dose is $120, with a recommended 3-dose course. The quadrivalent vaccine is the most widely administered worldwide. As with the bivalent and 9-valent vaccines, the vaccine is considered safe, although concerns have been raised. In addition to immunization against the targeted HPV types, there is evidence that there is cross protection against other types of HPV. This continuing medical education review evaluates the differences in vaccines that are currently on the market; part II focuses on the cost-effectiveness of vaccination, the HPV vaccination programs currently instituted around the globe, efficacy, and safety.

Annual national direct and indirect cost estimates of the prevention and treatment of cervical cancer in Brazil.

OBJECTIVE: To estimate the annual direct and indirect costs of the prevention and treatment of cervical cancer in Brazil. METHODS: This cost description study used a "gross-costing" methodology and adopted the health system and societal perspectives. The estimates were grouped into sets of procedures performed in phases of cervical cancer care: the screening, diagnosis and treatment of precancerous lesions and the treatment of cervical cancer. The costs were estimated for the public and private health systems, using data from national health information systems, population surveys, and literature reviews. The cost estimates are presented in 2006 USD. RESULTS: From the societal perspective, the estimated total costs of the prevention and treatment of cervical cancer amounted to USD $1,321,683,034, which was categorized as follows: procedures (USD $213,199,490), visits (USD $325,509,842), transportation (USD $106,521,537) and productivity losses (USD $676,452,166). Indirect costs represented 51% of the total costs, followed by direct medical costs (visits and procedures) at 41% and direct non-medical costs (transportation) at 8%. The public system represented 46% of the total costs, and the private system represented 54%. CONCLUSION: Our national cost estimates of cervical cancer prevention and treatment, indicating the economic importance of cervical cancer screening and care, will be useful in monitoring the effect of the HPV vaccine introduction and are of interest in research and health care management.

Evaluation of human papilloma virus (HPV) vaccination strategies and vaccination coverage in adolescent girls worldwide.

STUDY OBJECTIVE: An analysis of HPV vaccination strategies and vaccination coverage in adolescent girls worldwide for the last eight years with regard to potential improvement of vaccination coverage rates in Poland. METHODS: Literature search, covering the period 2006-2014, was performed using Medline. Comparative analysis of HPV vaccination strategies and coverage between Poland and other countries worldwide was conducted. RESULTS: In the last eight years, a number of countries introduced HPV vaccination for adolescent girls to their national immunization programmes. Vaccination strategies differ, consequently affecting vaccination coverage, ranging from several percent to more than 90%. Usually, there are also disparities at national level. The highest HPV vaccination coverage rates are observed in countries where vaccines are administered in school settings and funded from the national budget. Poland is one of the eight EU countries where HPV vaccination has not been introduced to mandatory immunization programme and where paid vaccination is only provided in primary health care settings. HPV vaccination coverage in adolescent girls is estimated at 7.5-10%. CONCLUSIONS: Disparities in HPV vaccination coverage rates in adolescent girls worldwide may be due to different strategies of vaccination implementation between countries. Having compared to other countries, the low HPV vaccination coverage in Polish adolescent girls may result from the lack of funding at national level and the fact that vaccines are administered in a primary health care setting. A multidimensional approach, involving the engagement of primary health care and school personnel as well as financial assistance of government at national and local level and the implementation of media campaigns, particularly in regions with high incidence of cervical cancer, could result in an increase of HPV vaccination coverage rates in Poland.

Are current cost-effectiveness thresholds for low- and middle-income countries useful? Examples from the world of vaccines.

The World Health Organization's CHOosing Interventions that are Cost Effective (WHO-CHOICE) thresholds for averting a disability-adjusted life-year of one to three times per capita income have been widely cited and used as a measure of cost effectiveness in evaluations of vaccination for low- and middle-income countries (LMICs). These thresholds were based upon criteria set out by the WHO Commission on Macroeconomics and Health, which reflected the potential economic returns of interventions. The CHOICE project sought to evaluate a variety of health interventions at a subregional level and classify them into broad categories to help assist decision makers, but the utility of the thresholds for within-country decision making for individual interventions (given budgetary constraints) has not been adequately explored. To examine whether the 'WHO-CHOICE thresholds' reflect funding decisions, we examined the results of two recent reviews of cost-effectiveness analyses of human papillomavirus and rotavirus vaccination in LMICs, and we assessed whether the results of these studies were reflected in funding decisions for these vaccination programmes. We found that in many cases, programmes that were deemed cost effective were not subsequently implemented in the country. We consider the implications of this finding, the advantages and disadvantages of alternative methods to estimate thresholds, and how cost perspectives and the funders of healthcare may impact on these choices.

Sociodemographic factors predicting mother's cervical screening and daughter's HPV vaccination uptake.

BACKGROUND: Achieving high human papillomavirus (HPV) vaccine coverage may reduce inequalities in cervical cancer prevention by mitigating the inequalities seen in the cervical screening programme. This paper assesses whether the same sociodemographic factors are associated with both cervical screening and HPV vaccination. METHODS: Girls' HPV vaccination records were linked by address to cervical screening records for their mothers in the North West of England. Index of Multiple Deprivation scores (2010) and census ethnicity data (2001) were used to investigate the association between deprivation and ethnic composition of area of residence with HPV vaccination and cervical screening uptake, along with potential differences between Primary Care Trusts (PCTs), which were responsible for vaccine delivery. RESULTS: Deprivation was not associated with routine (12-13-year-olds) vaccination initiation, but girls living in the most deprived quintile were significantly less likely to complete the three vaccine doses (OR 0.75; 95% CI 0.63 to 0.88). Mother-daughter pairs failing to engage in either screening or vaccination were also more likely to live in deprived areas (routine vaccination OR for most deprived quintile: 2.35; 95% CI 2.00 to 2.77). There were differences between PCTs after controlling for demographic effects (OR 1.35; 95% CI 1.23 to 1.52). CONCLUSIONS: Ensuring completion of the vaccine schedule is critical for organisations responsible for vaccine delivery in order to reduce cancer risk among girls living in deprived areas. There remains a small minority of mothers and daughters from disadvantaged backgrounds who do not participate in either cervical screening or HPV vaccination.

Does India need an indigenous HPV vaccine and why?

Cervical cancer is the most common form of cancer in Indian women, causing high morbidity and mortality. Two effective and safe vaccines exist, but these remain out of reach of most people due to their high cost. It is imperative that an Human Papillomavirus (HPV) vaccine be affordable and cheap so that the target population can be vaccinated, to make a real impact in reducing the disease burden. We argue that in the long run India needs to develop and manufacture its own HPV vaccine in order to bridge this price gap. We also explore other strategies that can be adopted to increase the accessibility and affordability of this life-saving vaccine during the interim period.

Innovation in cervical cancer prevention and control in Mexico.

Disparities related to cervical cancer continue to exist in Mexico, including insufficient screening coverage, problems with quality control and a resulting greater risk of mortality among women from marginalized areas. A lack of opportunities and requirements for continuing education and accreditation of healthcare personnel involved in the screening program is also an issue. HPV DNA testing and HPV vaccines are recent technological innovations that offer a potential solution to the continued negative impact of cervical cancer among Mexican women. This essay attempts to answer questions such as: Why should HPV testing be integrated into the early detection program in Mexico? How can HPV testing best be integrated into the program in Mexico? How-from a public health perspective that seeks to reduce disparities-can HPV vaccination best be implemented in Mexico? HPV testing allows increased positive predictive value while also reducing costly and unnecessary overtreatment of low-grade abnormalities, and HPV vaccines offer the possibility of primary prevention of cervical cancer. The strategy proposed for Mexico includes primary prevention with HPV vaccination for girls aged between 12 and 16 years (before sexual initiation), Pap testing with excellent quality control for women 24-34 years of age and high-risk HPV DNA testing for women 35 years and older. HPV samples would be either clinically collected or self-collected and women with positive HPV test results would receive follow-up high-quality Pap testing. This approach is creative and focuses on reducing disparities and providing high-quality care that is also cost effective.

Predicting the effect of successful human papillomavirus vaccination on existing cervical cancer prevention programs in the United States.

The development of a prophylactic human papillomavirus (HPV) vaccine that potentially may eliminate a majority of cervical cancers is a landmark in cancer prevention. Cervical screening, however, will continue to play an important role for the foreseeable future. Maintaining screening at the same intensity and simply adding on the expense of vaccination would result in redundancy of prevention efforts at enormously increased costs without necessarily further reducing cervical cancer mortality. Effectively integrating vaccination and screening efforts will be a critical and evolving challenge over the next decade; this will require understanding not only the impact of vaccination on reducing cervical abnormalities but also the influence of vaccination on screening test performance.

Modeling cervical cancer prevention in developed countries.

Cytology-based screening has reduced cervical cancer mortality in countries able to implement, sustain and financially support organized programs that achieve broad coverage. These ongoing secondary prevention efforts considerably complicate the question of whether vaccination against human papillomavirus (HPV) types 16 and 18 should be introduced. Policy questions focus primarily on the target ages of vaccination, appropriate ages for a temporary "catch-up" program, possible revisions in screening policies to optimize synergies with vaccination, including the increased used of HPV DNA testing, and the inclusion of boys in the vaccination program. Decision-analytic models are increasingly being developed to simulate disease burden and interventions in different settings in order to evaluate the benefits and cost-effectiveness of primary and secondary interventions for informed decision-making. This article is a focused review on existing mathematical models that have been used to evaluate HPV vaccination in the context of developed countries with existing screening programs. Despite variations in model assumptions and uncertainty in existing data, pre-adolescent vaccination of girls has been consistently found to be attractive in the context of current screening practices, provided there is complete and lifelong vaccine protection and widespread vaccination coverage. Questions related to catch-up vaccination programs, potential benefits of other non-cervical cancer outcomes and inclusion of boys are subject to far more uncertainty, and results from these analyses have reached conflicting conclusions. Most analyses find that some catch-up vaccination is warranted but becomes increasingly unattractive as the catch-up age is extended, and vaccination of boys is unlikely to be cost-effective if reasonable levels of coverage are achieved in girls or coverage among girls can be improved. The objective of this review is to highlight points of consensus and qualitative themes, to discuss the areas of divergent findings, and to provide insight into critical decisions related to cervical cancer prevention.

The Australian funding debate on quadrivalent HPV vaccine: a case study for the national pharmaceutical policy.

OBJECTIVES: To analyse the media and political reactions to the initial decision of the Pharmaceutical Benefits Advisory Committee (PBAC) to reject funding of the quadrivalent human papilloma virus (HPV) vaccine in Australia. METHODS: A case study, informed by media reports and government documents, was utilised to examine the reactions of key stakeholders; PBAC, consumers, consumer organisations, pharmaceutical industry, politicians, health professionals and the media to the initial decision to reject funding of HPV vaccine. RESULTS: The initial decision to reject funding of the HPV vaccine led to unprecedented public response with over 300 newspaper articles and calls by consumers, health professionals and politicians to intervene in the decision making process. Misunderstanding of the decision making process, particularly cost-effectiveness assessments, the need for an independent process, the legislated inability of a timely and transparent response from policy makers and the lack of a risk mitigation strategy all played a role in the public outcry. CONCLUSIONS: Despite 15 years of implementation of cost-effectiveness assessments there is still a need for improving stakeholder understanding of the decision making process and for timely transfer of complete information. Risk mitigation strategies should be considered as part of the communication plan for all decisions.

A cost-effectiveness analysis of adding a human papillomavirus vaccine to the Australian National Cervical Cancer Screening Program.

BACKGROUND: The cost-effectiveness of adding a human papillomavirus (HPV) vaccine to the Australian National Cervical Screening Program compared to screening alone was examined. METHODS: A Markov model of the natural history of HPV infection that incorporates screening and vaccination was developed. A vaccine that prevents 100% of HPV 16/18-associated disease, with a lifetime duration of efficacy and 80% coverage offered through a school program to girls aged 12 years, in conjunction with current screening was compared with screening alone using cost (in Australian dollars) per life-year (LY) saved and quality-adjusted life-year (QALY) saved. Sensitivity analyses included determining the cost-effectiveness of offering a catch-up vaccination program to 14-26-year-olds and accounting for the benefits of herd immunity. RESULTS: Vaccination with screening compared with screening alone was associated with an incremental cost-effectiveness ratio (ICER) of $51 103 per LY and $18 735 per QALY, assuming a cost per vaccine dose of $115. Results were sensitive to assumptions about the duration of vaccine efficacy, including the need for a booster ($68 158 per LY and $24 988 per QALY) to produce lifetime immunity. Accounting for herd immunity resulted in a more attractive ICER ($36 343 per LY and $13 316 per QALY) for girls only. The cost per LY of vaccinating boys and girls was $92 052 and the cost per QALY was $33 644. The cost per LY of implementing a catch-up vaccination program ranged from $45 652 ($16 727 per QALY) for extending vaccination to 14-year-olds to $78 702 ($34 536 per QALY) for 26-year-olds. CONCLUSIONS: These results suggest that adding an HPV vaccine to Australia's current screening regimen is a potentially cost-effective way to reduce cervical cancer and the clinical interventions that are currently associated with its prevention via screening alone.

[HPV-infection]. / Ubertragungswege - Risikofaktoren -Testindikationen - Impffragen. Was der Hausarzt uber die HPV-Infektion wissen sollte.

Cervical carcinoma is worldwide the third most frequent carcinoma affecting women; regionally, it is sometimes even the most frequent form of female cancer. Moreover, anogenital dysplasia and genital warts represent a major health care problem. With the development of bivalent and quadrivalent prophylactic vaccines against HPV 16 and 18 or HPV 6, 11, 16 and 18, respectively, a very promising immunoprophylaxis is now available to prevent the development of HPV-associated diseases and in particular, cervical carcinoma.

Mathematical models for predicting the epidemiologic and economic impact of vaccination against human papillomavirus infection and disease.

Infection with human papillomavirus (HPV) is the primary cause of cervical cancer, other anogenital cancers, genital warts, and recurrent respiratory papillomatosis. Clinical studies have demonstrated that a prophylactic HPV vaccine can prevent infection, genital warts, and the precancerous lesions that lead to cervical cancer. Given the absence of data on the long-term effectiveness of HPV vaccination, a number of mathematical models have been developed to provide insight to policy makers by projecting the long-term epidemiologic and economic consequences of vaccination and evaluate alternative vaccination policies. This paper reviews the state of these models. Three types of HPV mathematical models have been reported in the literature: cohort, population dynamic, and hybrid. All have demonstrated that vaccination can significantly reduce the incidence of cervical cancer in the long term. However, only the cohort and hybrid models have evaluated the cost-effectiveness of vaccination strategies for preventing cervical cancer. These models have generally shown that vaccinating females can be cost-effective. None has accounted for the potential benefits of vaccinating the population to reduce the burden of recurrent respiratory papillomatosis and cancers of the vagina, vulva, anus, penis, and head/neck. Given that only the population dynamic model can account for both the direct and indirect (i.e., herd immunity effects) benefits of vaccination in the population, future research should focus on further development of dynamic models by expanding the range of epidemiologic outcomes tracked and including the ability to assess the cost-effectiveness of alternative vaccination policies.