No Vacillation on HPV Vaccination.

Evidence of the safety and protective benefits of human papillomavirus virus (HPV) vaccines as an anti-cancer measure is overwhelming. However, vaccine uptake varies widely across countries and falls short of levels needed to achieve population immunity. We highlight policy measures that would help ensure greater worldwide coverage and save lives.

Estimation of self-funded human papillomavirus vaccine recipients from Japan's previously assumed "unvaccinated generation".

Precise vaccination data is essential to accurately estimate the effectiveness of the human papillomavirus (HPV) vaccine against HPV-related cancers. In Japan, the number of subsidized HPV vaccinations can be tracked through registries, but the number of self-funded vaccinations has not been tracked. The number of individuals who chose to receive the vaccine at their own expense, despite being ineligible for public subsidies due to their age, is unknown and has been nominally considered to be zero. Our aim is to produce a more accurate estimate of this number using recently released proprietary data. First, we estimated the total number of self-funded HPV vaccinations occurring from 2010 to 2012 using public data from the Ministry of Health, Labour and Welfare and our previously reported data on the number of HPV vaccinations eligible for public subsidy. Second, using proprietary data from the vaccine manufacturer, we calculated the distribution of self-funded vaccination shots by age. Finally, we combined these data to estimate the number of self-funded HPV vaccinations by birth fiscal year (FY) relative to a yearly reference population. We found that 78,264 individuals born in FY1993 and 58,190 born in FY1992 self-funded their vaccinations, representing 13.6% and 10.0% of the reference population, respectively. Additionally, we found that 5%-10% of individuals born from FY1986 to FY1991 self-funded their vaccinations. Our study revealed for the first time that a certain number of individuals from the "HPV unvaccinated generation," ineligible for subsidies due to age restrictions, chose to self-fund their vaccinations.

Expanding vaccination competencies to community pharmacists: modelling the organizational and economic impacts of new human papilloma virus (HPV) vaccine pathways in France.

BACKGROUND: The vaccine coverage rate (VCR) for human papillomavirus (HPV) in France is one of the lowest in Europe, well below the target of 80% announced in the French Cancer Plan 2021-2030. The extension of vaccination competencies (prescription and administration) to new health care providers, such as community pharmacists (CPs), was a decisive step by the French Health Authority (HAS) in 2022 to simplify access to vaccination and improve the VCR. This research assessed the economic and organizational impacts (OIs) of the extension of vaccination competencies in France. METHODS: A model was developed in Excel® to compare the current HPV vaccination pathway focused on general practitioners (GPs) to a mix of pathways (new and current) that extends pharmacists' competencies (prescription and/or injection). The simulated population corresponded to girls and boys targeted by the French recommendations. The model was run from 2023 to 2030. HAS guidelines were used to identify OIs related to these new pathways. Model inputs were collected from national data sources and an acceptability study. The results focused on three OIs (HPV vaccination ability [defined as the number of adolescents who could be vaccinated in each pathway], the VCR projection, and flows of activity between health care professionals]). The economic impact was evaluated from the National Health Insurance (NHI) perspective in 2022. RESULTS: With a mix of vaccination pathways, including an increasing role of pharmacists, the target of an 80% VCR could be reached in 2030 (versus 2032 with the current pathway) with lower investment than the current situation, resulting in cost savings for the NHI of €212 million. Expanding vaccination competencies will provide pharmacists with additional revenue (an average of €755,000/month for all vaccinating pharmacies) and will free up medical time for GPs (average of 603,000 consultations/year for all GPs). CONCLUSIONS: Expanding vaccination competencies to pharmacists has a positive impact on the entire ecosystem. From a public health perspective, the national VCR target can be achieved and better access to care can be provided, freeing up medical time. From an economic perspective, this approach can provide savings for the NHI and additional revenue for pharmacists.

Determinants of parental demand of human papillomavirus vaccination for adolescent daughters in China: Contingent valuation survey.

BACKGROUND: Several types of human papillomavirus (HPV) vaccines have been approved for use in adolescent girls in China. These vaccines are regulated as non-National Immunisation Program vaccines and are optional and generally fully self-paid by vaccinees. OBJECTIVE: To assess parents' demand for HPV vaccination by eliciting their willingness-to-pay for their adolescent daughters to be vaccinated against HPV and to examine the determinants of demand for HPV vaccination in China. METHODS: A contingent valuation survey was conducted across three cities in Shandong Province in eastern China. We selected 11 junior middle schools with different socioeconomic features and randomly selected 6 classes in each school, and questionnaires were distributed to all girls aged 12-16 in the 66 classes for their parents to complete. A payment card approach was used to elicit parental willingness-to-pay for HPV vaccination for their daughters. We also collected a wide array of socioeconomic and psychological variables and interval regressions were applied to examine the determinants of parental willingness-to-pay. RESULTS: A total of 1074 eligible parents who completed valid questions were included in analyses. Over 85% of parents believed HPV vaccines were, in general, necessary and beneficiary. However, only around 10% believed that their daughters would be infected by HPV. About 8% of parents would not accept HPV vaccine even if the vaccine were free mainly due to concerns about the potential side effects and vaccine safety and quality issues, and 27.37% would only accept the vaccine if it were free. The median willingness-to-pay was 300 CNY (42 USD). Several factors were positively correlated with higher willingness-to-pay: income, urban residence (relative to rural residence), mothers (relative to fathers), parents' beliefs about vaccine benefits, whether they should make decisions for their daughters, and whether their daughters would be susceptible to HPV. Though education-level was not significantly correlated with willingness-to-pay in the main regressions, a subgroup analysis revealed interesting dynamics in the relation between education and willingness-to-pay across different income-levels. CONCLUSIONS: There is a large gap between parents' willingness-to-pay and the market price of HPV vaccine for girls in China. Parents generally believed the HPV vaccines were beneficial and necessary but when asked for their daughters, most parents did not believe their daughters would be infected by HPV despite the high prevalence in China. Future focus should be on ensuring the provision of accurate health information about HPV prevalence, vaccine quality, and safety to promote vaccine uptake, and promotional efforts tailored to different income groups might yield better effects. Government involvement in negotiating more widely acceptable and affordable prices or subsidising may be necessary for protecting high-risk population groups.

Choosing the optimal HPV vaccine: The health impact and economic value of the nonavalent and bivalent HPV vaccines in 48 Gavi-eligible countries.

The human papillomavirus (HPV) vaccines may provide some level of cross-protection against high-risk HPV genotypes not directly targeted by the vaccines. We evaluated the long-term health and economic impacts of routine HPV vaccination using either the nonavalent HPV vaccine or the bivalent HPV vaccine in the context of 48 Gavi-eligible countries. We used a multi-modeling approach to compare the bivalent with or without cross-protection and the nonavalent HPV vaccine. The optimal, that is, most cost-effective, vaccine was the vaccine with an incremental cost-effectiveness ratio below the per-capita gross domestic product (GDP) for each country. By 2100 and assuming 70% HPV vaccination coverage, a bivalent vaccine without cross-protection, a bivalent vaccine with favorable cross-protection and the nonavalent vaccine were projected to avert 14.9, 17.2 and 18.5 million cumulative cases of cervical cancer across all 48 Gavi-eligible countries, respectively. The relative value of the bivalent vaccine compared to the nonavalent vaccine increased assuming a bivalent vaccine conferred high cross-protection. For example, assuming a cost-effectiveness threshold of per-capita GDP, the nonavalent vaccine was optimal in 83% (n = 40) of countries if the bivalent vaccine did not confer cross-protection; however, the proportion of countries decreased to 63% (n = 30) if the bivalent vaccine conferred high cross-protection. For lower cost-effectiveness thresholds, the bivalent vaccine was optimal in a greater proportion of countries, under both cross-protection assumptions. Although the nonavalent vaccine is projected to avert more cases of cervical cancer, the bivalent vaccine with favorable cross-protection can prevent a considerable number of cases and would be considered a high-value vaccine for many Gavi-eligible countries.

Human papillomavirus vaccination for adults aged 30 to 45 years in the United States: A cost-effectiveness analysis.

BACKGROUND: A nonavalent human papillomavirus (HPV) vaccine has been licensed for use in women and men up to age 45 years in the United States. The cost-effectiveness of HPV vaccination for women and men aged 30 to 45 years in the context of cervical cancer screening practice was evaluated to inform national guidelines. METHODS AND FINDINGS: We utilized 2 independent HPV microsimulation models to evaluate the cost-effectiveness of extending the upper age limit of HPV vaccination in women (from age 26 years) and men (from age 21 years) up to age 30, 35, 40, or 45 years. The models were empirically calibrated to reflect the burden of HPV and related cancers in the US population and used standardized inputs regarding historical and future vaccination uptake, vaccine efficacy, cervical cancer screening, and costs. Disease outcomes included cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as genital warts. Both models projected higher costs and greater health benefits as the upper age limit of HPV vaccination increased. Strategies of vaccinating females and males up to ages 30, 35, and 40 years were found to be less cost-effective than vaccinating up to age 45 years, which had an incremental cost-effectiveness ratio (ICER) greater than a commonly accepted upper threshold of $200,000 per quality-adjusted life year (QALY) gained. When including all HPV-related outcomes, the ICER for vaccinating up to age 45 years ranged from $315,700 to $440,600 per QALY gained. Assumptions regarding cervical screening compliance, vaccine costs, and the natural history of noncervical HPV-related cancers had major impacts on the cost-effectiveness of the vaccination strategies. Key limitations of the study were related to uncertainties in the data used to inform the models, including the timing of vaccine impact on noncervical cancers and vaccine efficacy at older ages. CONCLUSIONS: Our results from 2 independent models suggest that HPV vaccination for adult women and men aged 30 to 45 years is unlikely to represent good value for money in the US.

Informing Global Cost-Effectiveness Thresholds Using Country Investment Decisions: Human Papillomavirus Vaccine Introductions in 2006-2018.

OBJECTIVES: Cost-effectiveness analysis can guide decision making about health interventions, but the appropriate cost-effectiveness threshold to use is unclear in most countries. The World Health Organization (WHO) recommends vaccinating girls 9 to 14 years against human papillomavirus (HPV), but over half the world's countries have not introduced it. This study aimed to investigate whether country-level decisions about HPV vaccine introduction are consistent with a particular cost-effectiveness threshold, and to estimate what that threshold may be. METHODS: The cost-effectiveness of vaccinating 12-year-old girls was estimated in 179 countries using the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model, together with vaccine price data from World Health Organization's Market Information for Access to Vaccines database. In each year from 2006 to 2018, countries were categorized based on (1) whether they had introduced HPV vaccination, and (2) whether the incremental cost-effectiveness ratio for HPV vaccine introduction fell below a certain cost-effectiveness threshold. RESULTS: A cost-effectiveness threshold of 60% to 65% of GDP per capita has the best ability to discriminate countries that introduced vaccination, with a diagnostic odds ratio of about 7. For low-income countries the optimal threshold was lower, at 30% to 40% of GDP per capita. CONCLUSIONS: A cost-effectiveness threshold has some ability to discriminate between HPV vaccine introducer and non-introducer countries, although the average threshold is below the widely used threshold of 1 GDP per capita. These results help explain the current pattern of HPV vaccine use globally. They also inform the extent to which cost-effectiveness thresholds proposed in the literature reflect countries' actual investment decisions.

Effectiveness and Cost-Effectiveness of Human Papillomavirus Vaccination Through Age 45 Years in the United States.

Background: In the United States, the routine age for human papillomavirus (HPV) vaccination is 11 to 12 years, with catch-up vaccination through age 26 years for women and 21 years for men. U.S. vaccination policy on use of the 9-valent HPV vaccine in adult women and men is being reviewed. Objective: To evaluate the added population-level effectiveness and cost-effectiveness of extending the current U.S. HPV vaccination program to women aged 27 to 45 years and men aged 22 to 45 years. Design: The analysis used HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation), an individual-based transmission dynamic model of HPV infection and associated diseases, calibrated to age-specific U.S. data. Data Sources: Published data. Target Population: Women aged 27 to 45 years and men aged 22 to 45 years in the United States. Time Horizon: 100 years. Perspective: Health care sector. Intervention: 9-valent HPV vaccination. Outcome Measures: HPV-associated outcomes prevented and cost-effectiveness ratios. Results of Base-Case Analysis: The model predicts that the current U.S. HPV vaccination program will reduce the number of diagnoses of anogenital warts and cervical intraepithelial neoplasia of grade 2 or 3 and cases of cervical cancer and noncervical HPV-associated cancer by 82%, 80%, 59%, and 39%, respectively, over 100 years and is cost saving (vs. no vaccination). In contrast, extending vaccination to women and men aged 45 years is predicted to reduce these outcomes by an additional 0.4, 0.4, 0.2, and 0.2 percentage points, respectively. Vaccinating women and men up to age 30, 40, and 45 years is predicted to cost $830 000, $1 843 000, and $1 471 000, respectively, per quality-adjusted life-year gained (vs. current vaccination). Results of Sensitivity Analysis: Results were most sensitive to assumptions about natural immunity and progression rates after infection, historical vaccination coverage, and vaccine efficacy. Limitation: Uncertainty about the proportion of HPV-associated disease due to infections after age 26 years and about the level of herd effects from the current HPV vaccination program. Conclusion: The current HPV vaccination program is predicted to be cost saving. Extending vaccination to older ages is predicted to produce small additional health benefits and result in substantially higher incremental cost-effectiveness ratios than the current recommendation. Primary Funding Source: Centers for Disease Control and Prevention.

Cost and reimbursement of providing routine vaccines in outpatient obstetrician/gynecologist settings.

OBJECTIVE: To determine the costs and reimbursement associated with running a vaccine program in 5 obstetrics/gynecology practices in Colorado that had participated in a 3-year randomized, controlled trial focused on increasing vaccination in this setting. MATERIALS AND METHODS: This was a secondary analysis on costs from 5 clinics participating in a cluster-randomized controlled trial that assessed the effectiveness of a multimodal intervention to improve vaccination rates in outpatient obstetrics/gynecology clinics in central Colorado. The intervention included designation of an immunization champion within the practice, purchasing recommended vaccines for the practice, guidance on storage and management, implementing practices for routine identification of eligible patients for vaccination using the medical record, implementation of standing orders for vaccination, and vaccine administration to patients. Data on costs were gathered from office invoices, claims data, surveys and in-person observations during the course of the trial. These data incorporated supply and personnel costs for administering vaccines to individual patients that were derived from a combination of time-motion studies of staff and provider clinical activity, and practice reports, as well as costs related to maintaining the vaccination program at the practice level, which were derived from practice reports and invoices. Cost data for personnel time during visits in which vaccination was assessed and/or discussed, but no vaccine was given to the patient were also included in the main analysis. Data on practice revenue were derived from practice reimbursement records. All costs were described in 2014 dollars. The primary analysis was the proportion of costs for the program that were reimbursed, aggregated over all years of the study and combining all vaccines and practices, separated by obstetrics vs gynecology patients. RESULTS: Collectively the 5 clinics served >40,000 patient during the study period and served a population that was 16% Medicaid. Over the 3-year observation period, there were 6573 vaccination claims made collectively by the practices (4657 for obstetric patients, 1916 for gynecology patients). The most expensive component of the program was the material costs of the vaccines themselves, which ranged from a low of $9.67 for influenza vaccines, to a high of $141.40 for human papillomavirus vaccine. Staff costs for assessing and delivering vaccines during patient visits were minimal ($0.09-$1.24 per patient visit depending on the practice and whether an obstetrics or gynecology visit was being assessed) compared with staff costs for maintaining the program at a practice level (ie, assessing inventory, ordering and stocking vaccines; $0.89-$105.89 per vaccine dose given). When assessing all costs compared with all reimbursement, we found that vaccines for obstetrics patients were reimbursed at 159% of the costs over the study period, and for gynecology patients at 97% of the costs. Overall, the vaccination program was financially favorable across the practices, averaging 125% reimbursement of costs across the three study years. CONCLUSION: Providing routine vaccines to patients in the ambulatory obstetrics/gynecology setting is generally not financially prohibitive for practices, and may even be financially beneficial, though there is variability between practices that can affect the overall reimbursement margin.

Stopping the HPV vaccine crisis in Japan: Quantifying the benefits and risks of HPV vaccination in quality-adjusted life-years for appropriate decision-making.

BACKGROUND: The human papilloma virus (HPV) vaccination coverage rate in Japan has dropped dramatically from more than 70% to less than 1% since 2013. With conflicting information and a lack of quantification of the benefits and risks of the HPV vaccine, parents have been hindered in making their decision. We quantified the benefits and risks of the HPV vaccine in terms of quality-adjusted life-years (QALYs), to help their informed decision. METHOD: A literature search was performed to determine the incidence and burden of each outcome in a decision tree model. The benefits and the risks of the HPV vaccination were determined in QALY change with a sensitivity analysis. RESULT: The benefits of the HPV vaccine in terms of QALYs gained were 703.72, 14.45, and 30.83/100,000 persons for cervical cancer, cervical intraepithelial neoplasm 3 (CIN 3), and genital warts, respectively. The QALY loss due to acute adverse reactions, chronic adverse reactions without assistance needs, and chronic adverse reactions with assistance needs were 0.07, 5.83, and 5.82/100,000 persons, respectively. The risk/benefit ratio in QALY change in the base case was 0.0156. In all scenarios, the benefit of the HPV vaccine was significantly greater than the risk. CONCLUSION: The benefits are much greater than the risks, even if it is assumed that all reported adverse events were due to the vaccination. The Japanese government and health care providers should immediately recommend the HPV vaccine to all adolescent girls irrespective of any causal links between the vaccine and reported adverse events.

Assessing the epidemiological impact on cervical cancer of switching from 4-valent to 9-valent HPV vaccine within a gender-neutral vaccination programme in Switzerland.

BACKGROUND: An infection with high-risk human papillomavirus (HPV) is the obligatory aetiological factor for the development of cervical cancer. In Switzerland, the prevention strategy for cervical cancer is based on primary prevention via HPV vaccination and secondary prevention with an opportunistic screening programme for precancerous lesions. Vaccination is recommended to 11-26 years old male and female persons. The objective of the study was to assess the epidemiological impact on cervical cancer of switching from the currently implemented programme with the 4-valent vaccine to the 9-valent vaccine, in an 11-26 years old gender-neutral vaccination programme in Switzerland. METHODS: A previously validated dynamic transmission model of HPV infections was adapted and calibrated to the Swiss setting assuming an 80% coverage rate in HPV-vaccination and lifelong vaccine type-specific protection. A gender-neutral vaccination programme (males and females) for 11-26 years old with a 9-valent HPV vaccine was compared with the current 11-26 years old gender-neutral 4-valent vaccination programme. Sensitivity analyses were conducted in order to test the impact of lower vaccination coverage rates and a shorter duration of protection on the model outcomes. RESULTS: In Switzerland, a 9-valent gender-neutral vaccination programme would result in an additional prevention of 2979 cervical cancer cases, 13,862 CIN3 and 15,000 CIN2 cases, compared with the 4-valent gender-neutral vaccination programme over 100 years. These additional disease cases avoided would correspond to a 24, 36 and 48% cumulative incidence decrease in cervical cancer, CIN3 and CIN2 cases, respectively. It would also prevent additional 741 cervical cancer-related deaths over 100 years. A substantial additional reduction in cervical cancer and precancerous lesions burden is still observed when varying the vaccination coverage rate from 30 to 60% or reducing the duration of protection from lifelong to 20 years. CONCLUSIONS: The switch to the 9-valent vaccine in Switzerland to prevent cervical diseases showed an important contribution in terms of public health impact compared with the 4-valent vaccine in an 11-26 years old gender-neutral population, even with very conservative assumptions such as low coverage rates or low duration of protection and limiting analysis to only cervical disease.

Epidemiology of genital warts in the British population: implications for HPV vaccination programmes.

OBJECTIVES: To estimate the prevalence of, and describe risk factors for, genital warts (GWs) in the British population, following the introduction of the bivalent (human papillomavirus (HPV)-16/18) vaccination programme in girls, and prior to the switch to quadrivalent (HPV-6/11/16/18) vaccine (offering direct protection against GWs) and compare this with GW diagnoses in the prevaccination era. METHODS: Natsal-3, a probability sample survey in Britain, conducted in 2010-2012, interviewed 9902 men and women aged 16-44. Natsal-2, conducted in 1999-2001, surveyed 11 161 men and women aged 16-44. Both surveys collected data on sexual behaviour and sexually transmitted infection diagnoses using computer-assisted interview methods. RESULTS: In Natsal-3, 3.8% and 4.6% of sexually experienced men and women reported ever having a diagnosis of GWs, with 1.3% of men and 1.7% of woman reporting a GWs diagnosis in the past 5 years. GWs were strongly associated with increasing partner numbers and condomless sex. Diagnoses were more frequent in men who have sex with men (MSM) (11.6% ever, 3.3% past 5 years) and in women reporting sex with women (10.8% ever, 3.6% past 5 years). In the age group who were eligible for vaccination at the time of Natsal-3 (16-20 years), a similar proportion of same-aged women reported a history of GWs in Natsal-2 (1.9%, 1.1-3.4) and Natsal-3 (2.6%, 1.5-4.4). CONCLUSIONS: These data provide essential parameters for mathematical models that inform cost-effectiveness analyses of HPV vaccination programmes. There was no evidence of population protection against GWs conferred by the bivalent vaccine. Even with vaccination of adolescent boys, vaccination should be offered to MSM attending sexual health clinics.

Systematic review and evidence synthesis of non-cervical human papillomavirus-related disease health system costs and quality of life estimates.

BACKGROUND: Many economic evaluations of human papillomavirus vaccination should ideally consider multiple disease outcomes, including anogenital warts, respiratory papillomatosis and non-cervical cancers (eg, anal, oropharyngeal, penile, vulvar and vaginal cancers). However, published economic evaluations largely relied on estimates from single studies or informal rapid literature reviews. METHODS: We conducted a systematic review of articles up to June 2016 to identify costs and utility estimates admissible for an economic evaluation from a single-payer healthcare provider's perspective. Meta-analyses were performed for studies that used same utility elicitation tools for similar diseases. Costs were adjusted to 2016/2017 US$. RESULTS: Sixty-one papers (35 costs; 24 utilities; 2 costs and utilities) were selected from 10 742 initial records. Cost per case ranges were US$124-US$883 (anogenital warts), US$6912-US$52 579 (head and neck cancers), US$12 936-US$51 571 (anal cancer), US$17 524-34 258 (vaginal cancer), US$14 686-US$28 502 (vulvar cancer) and US$9975-US$27 629 (penile cancer). The total cost for 14 adult patients with recurrent respiratory papillomatosis was US$137 601 (one paper).Utility per warts episode ranged from 0.651 to 1 (12 papers, various utility elicitation methods), with pooled mean EQ-5D and EQ-VAS of 0.86 (95% CI 0.85 to 0.87) and 0.74 (95% CI 0.74 to 0.75), respectively. Fifteen papers reported utilities in head and neck cancers with range 0.29 (95% CI 0.0 to 0.76) to 0.94 (95% CI 0.3 to 1.0). Mean utility reported ranged from 0.5 (95% CI 0.4 to 0.61) to 0.65 (95% CI 0.45 to 0.75) (anal cancer), 0.59 (95% CI 0.54 to 0.64) (vaginal cancer), 0.65 (95% CI 0.60 to 0.70) (vulvar cancer) and 0.79 (95% CI 0.74 to 0.84) (penile cancer). CONCLUSIONS: Differences in values reported from each paper reflect variations in cancer site, disease stages, study population, treatment modality/setting and utility elicitation methods used. As patient management changes over time, corresponding effects on both costs and utility need to be considered to ensure health economic assumptions are up-to-date and closely reflect the case mix of patients.

The healthcare costs of treating human papillomavirus-related cancers in Norway.

BACKGROUND: Public health efforts to prevent human papillomavirus (HPV)-related cancers include HPV vaccination and cervical cancer screening. We quantified the annual healthcare cost of six HPV-related cancers in order to provide inputs in cost-effectiveness analyses and quantify the potential economic savings from prevention of HPV-related cancers in Norway. METHODS: Using individual patient-level data from three unlinked population-based registries, we estimated the mean healthcare costs 1) annually across all phases of disease, 2) during the first 3 years of care following diagnosis, and 3) for the last 12 months of life for patients diagnosed with an HPV-related cancer. We included episodes of care related to primary care physicians, specialist care (private specialists and hospital-based care and prescriptions), and prescription drugs redeemed at pharmacies outside hospitals between 2012 and 2014. We valued costs (2014 €1.00 = NOK 8.357) based on diagnosis-related groups (DRG), patient copayments, reimbursement fees and pharmacy retail prices. RESULTS: In 2014, the total healthcare cost of HPV-related cancers amounted to €39.8 million, of which specialist care accounted for more than 99% of the total cost. The annual maximum economic burden potentially averted due to HPV vaccination will be lower for vulvar, penile and vaginal cancer (i.e., €984,620, €762,964 and €374,857, respectively) than for cervical, anal and oropharyngeal cancers (i.e., €17.2 million, €6.7 million and €4.6 million, respectively). Over the first three years of treatment following cancer diagnosis, patients diagnosed with oropharyngeal cancer incurred the highest total cost per patient (i.e. €49,774), while penile cancer had the lowest total cost per patient (i.e. €18,350). In general, costs were highest the first year following diagnosis and then declined; however, costs increased rapidly again towards end of life for patients who did not survive. CONCLUSION: HPV-related cancers constitute a considerable economic burden to the Norwegian healthcare system. As the proportion of HPV-vaccinated individuals increase and secondary prevention approaches advance, this study highlights the potential economic burden avoided by preventing these cancers.

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.

The Joint Committee on Vaccination and Immunisation's Advice on Extending Human Papillomavirus Vaccination to Boys: Were Cost-Effectiveness Analysis Guidelines Bent to Achieve a Politically Acceptable Decision?

In July 2018, the UK Minister of Public Health announced that human papillomavirus vaccination would be extended to 12-year-old boys. This decision was informed by updated evidence from the Joint Committee on Vaccination and Immunisation (JCVI) published earlier that month. Vaccination of boys had been found not to be cost-effective in a series of analyses conducted for the JCVI, including the most recent assessment prior to the minister's announcement. These analyses were conducted under the standard methods for cost-effectiveness analysis recommended by the JCVI, which are primarily based on guidelines from the National Institute of Health and Care Excellence. Although the JCVI concluded they were unable to advise extending vaccination on the basis of standard appraisal methods, their most recent round of assessment also considered analyses using nonstandard appraisal methods. In particular, the JCVI noted that vaccination of boys was likely to be cost-effective when a lower discount rate of 1.5% is applied to costs and health effects, as opposed to the 3.5% rate usually employed. The JCVI stated that they were supportive of applying such alternative methods, and on this basis, they would advise extending vaccination to boys. This commentary explains the JCVI's application of nonstandard appraisal methods and considers whether it was justified. We conclude that the JCVI was not justified in applying the lower discount rate. We voice concerns that a willingness to endorse a politically popular intervention may have driven the JCVI to depart from a fair and consistent application of healthcare rationing.

Economic barriers, evidentiary gaps, and ethical conundrums: a qualitative study of physicians' challenges recommending HPV vaccination to older gay, bisexual, and other men who have sex with men.

BACKGROUND: The human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide. Gay, bisexual, and other men who have sex with men (GBM), and GBM living with HIV in particular, are disproportionately impacted by HPV-associated cancers. The HPV vaccine, given early enough in life, may markedly reduce the likelihood of such cancers. In Canada, most provincial insurance programs only cover HPV vaccination for GBM up to the age of 26. Our objective was to understand physicians' everyday experiences and challenges in recommending HPV vaccination to older GBM patients. METHODS: As part of the HPV Screening and Vaccine Evaluation (HPV-SAVE) Study, we conducted semi-structured interviews with 25 HIV-positive GBM patients who had received anal cancer screening and 15 service providers, including 13 physicians, who had arranged for anal cancer screening in the Canadian provinces of Ontario and British Columbia. In this analysis, we draw upon the 13 physician interviews, which were coded following Grounded Theory. RESULTS: Physicians strongly supported the HPV vaccine for all GBM and considered it to be important for the management of HIV-related care. However, the overall support for HPV vaccination among physicians did not translate into consistent recommendation practices. There were two overarching factors that limited the strength/frequency of physicians' vaccine recommendation practices. First, cost/insurance coverage for some older patients impacted if and how the HPV vaccine was discussed. Second, physicians had diverse perspectives on both the prevention and therapeutic benefits of vaccinating older GBM and the reality that national guidelines are incongruent with publicly funded vaccine programs for vaccinating patients over 26 years old. These two interrelated factors have co-produced an apparent economic-evidentiary conundrum for many physicians regarding how and for whom to offer HPV vaccination. CONCLUSION: Economic barriers coupled with evidentiary and guideline gaps have created clinical practice challenges for physicians and has resulted in different messages being communicated to some older GBM patients about how important HPV vaccination is for their health.

Interdependency in vaccination policies among Japanese municipalities.

Economic theory predicts that vaccination policies at the local level can be negatively affected by the policies of neighboring regions because of free-riding motives, whereas positive dependency may exist due to policy diffusions among localities. By using the unique variations in the provision of vaccination subsidies in Japan, we assess how vaccination policies in a local government are affected by the decisions of neighboring governments. We find that the provision of vaccination subsidies is positively correlated with the decisions of neighboring localities. Moreover, a correlation is found with neighboring municipalities within the same prefecture but not with those in surrounding prefectures, indicating that the correlations are likely to arise because of mimicking behavior among localities within a prefecture. Our results show that vaccination policies tend to be formed following neighboring municipalities and do not necessarily aim to optimize community health, thus questioning the autonomy of local government authorities regarding vaccination policies.

Therapeutic Vaccines Against Human Papilloma Viruses: Achievements and Prospects.

Human papillomaviruses of high carcinogenic risk (HR HPVs) are major etiological agents of malignant diseases of the cervix, vulva, penis, anal canal, larynx, head, and neck. Prophylactic vaccination against HPV, which mainly covers girls and women under 25, does not prevent vertical and horizontal HPV transmission in infants and children and does not have a therapeutic effect. As a result, a significant proportion of the population is not protected from the HPV infection and development of HPV-associated neoplastic transformation and cancer, which indicates the need for development and introduction of therapeutic HPV vaccines. Unlike prophylactic vaccines aimed at the formation of virus-neutralizing antibodies, therapeutic vaccines elicit cellular immune response leading to the elimination of infected and malignant cells expressing viral proteins. The ideal targets for vaccine immunotherapy are highly conserved HR HPV oncoproteins E6 and E7 expressed in precancerous and tumor tissues. Here, we describe expression of these proteins during different stages of HPV infection, their antigenic and immunogenic properties, and T-cell epitopes, the response to which correlates with natural regression of HPV-induced neoplastic changes. The review describes patterns of E6 and E7 oncoproteins presentation to the immune system as components of candidate vaccines along with the results of the most promising preclinical trials and animal models used in these trials. Special attention is paid to vaccine candidates which have shown efficacy in clinical trials in patients with HPV-associated neoplastic changes.