Introduction

Perceptions about program costs may be one reason why about 50% of low- and middle-income countries have not yet introduced HPV vaccination nationwide. While studies have estimated the program costs of HPV vaccine delivery to inform country decision-making, most were conducted during demonstration projects or in the initial years of vaccine introduction, which may not reflect the ongoing costs of mature programs. We conducted a multi-country study to estimate the ongoing financial and economic costs of HPV vaccine delivery for mature programs.

Methods

Micro-costing methods were used to retrospectively collect data to estimate the annual ongoing financial and economic costs of HPV vaccine delivery. Facility staff responsible for providing HPV vaccination services were interviewed using structured costing questionnaires. Vaccine dose and session data were extracted from program records in each facility. Stratified random sampling was used to select the health facilities in Guyana (n=43), Rwanda (n=42), and Uganda (n=66). The costing was done from the health system perspective with a 2019 reference year.

Results

Across the three countries, financial costs were a relatively small proportion of the total economic costs of HPV vaccine delivery (Table 1). Per diems were generally not paid for program activities. Cost of time for health workers accounted for the largest share of program costs, with the bulk of the time spent on service delivery. There was a wide range, within country and across countries, in the cost drivers and the estimated cost per dose.

Conclusions

When HPV vaccine programs mature, there are relatively low ongoing financial costs compared to nascent programs at the coverage levels currently being achieved. However, additional financial investments may be required to implement activities to increase coverage. Implementing single-dose schedules may further reduce HPV vaccine program costs making it more affordable and sustainable.

Introduction

Model-based cost-effectiveness analyses can inform optimal screening guidelines by quantifying consequences of alternative algorithms. Although actual screening adherence is <100%, incorporating non-adherence into analyses that aim to determine optimal guidelines, may impact the policy recommendations. It could lead to inefficient screening of compliant women. We evaluated the impact of alternative non-adherence assumptions on the optimal cervical cancer screening strategies in Norway.

Methods

We used an individual-based model of cervical carcinogenesis to project the long-term health and economic outcomes under alternative screening algorithms and adherence patterns for unvaccinated women. We compared 18 screening strategies involving primary HPV testing (5-yearly), that varied follow-up management of different HPV genotype groupings (16/18, 16/18/45, or 16/18/31/33/45/52/58) (Figure 1). We applied 12 analytic approaches to account for non-adherence: perfect compliance, eight high- and low-coverage ‘random-complier’ scenarios, and three ‘complier-profile’ scenarios that reflect conditional screening behavior over a lifetime. Non-adherence was incrementally applied across the entire screening pathway, including primary testing, follow-up, colposcopy and precancer treatment. We calculated incremental cost-effectiveness ratios (ICERs) and considered a strategy with the highest ICER below USD55,000/QALY as ‘optimal’.

Results

Under perfect compliance, the least intensive screening strategy, involving partial 16/18-genotyping, was optimal; in contrast, assuming any non-adherence resulted in a more intensive ‘optimal’ strategy (Table 1). Accounting for lower compliance resulted in both lower costs and health benefits, which allowed a more intensive ‘optimal’ strategy, but more harms for compliant women. For example, a woman screening according to guidelines informed by the ‘optimal’ strategy when assuming the lowest non-adherence rates, could increase colposcopies by up to 41% compared to if she followed her own ‘optimal’ guidelines.

Conclusions

Assuming non-adherence in analyses designed to inform national guidelines may lead to a relatively more intensive recommendation. Accounting for non-adherence in guideline development may lead to over-screening of compliant women.

Introduction

In Ontario, a population-based cytology screening program has been in place for multiple decades, underway to implement HPV-based screening in the future. The first cohorts of school-based HPV vaccinated individuals are currently starting cervical screening. We examined how screening strategies should be adjusted for these (partly) protected individuals in the future.

Methods

The hybrid microsimulation model STDSIM-MISCAN-Cervix has been calibrated to the Ontario setting using observed demographic and screening data. Ten birth cohorts (1998-2007) who were recently offered vaccination were simulated over their entire lifetime. The efficiency of 309 different primary HPV screening strategies, varying by screening ages and triage methods, was assessed. Effects of screening were evaluated for the cohorts as a whole with a mixed vaccination status (i.e. unstratified screening) and separately for vaccinated individuals and for unvaccinated individuals within the vaccinated cohorts (i.e. stratified screening). Harms were measured as number of cervical tests and colposcopy referrals, benefits as cancers prevented and life years gained. A harms-benefits analysis and extensive sensitivity analyses were performed.

Results

In an unstratified screening scenario, five lifetime screens with HPV16/18 genotyping at ages 25, 30, 35, 40 and 55 along with one optional screen at age 45 was found to be optimal. In a stratified screening scenario, three lifetime screens with HPV16/18/31/33/45/52/58 genotyping at ages 30, 40 and 55 among vaccinated individuals, and 6 lifetime screens with HPV16/18 genotyping at ages 25, 30, 35, 40, 50 and 60 with two optional screens at ages 45 and 55 among unvaccinated individuals was found optimal. Sensitivity analyses showed that, in general, these results were robust.

Conclusions

To maintain the harms-benefits balance of screening, Ontario could consider reducing the number of lifetime screens in the future for vaccinated cohorts or for the population as a whole as more people in the screening ages are vaccinated.

Introduction

Experts have proposed an ‘EVEN FASTER’ concept involving intensifying concomitant screening and vaccination to age-groups maintaining human papillomavirus (HPV) infection circulation. Advocates suggest this approach could accelerate elimination of cervical cancer (CC) as a public health problem (currently projected in 2039 under existing policies) and the reduced need for screening. We explored the effects of these proposals on age-standardized incidence rate (ASR) and CC elimination timing in Norway.

Methods

We used a multi-modeling approach capturing HPV transmission and cervical carcinogenesis to estimate ASR associated with alternative vaccination and screening scenarios compared to the status-quo reflecting previous vaccination and screening policies. For cohorts ages 25–35 years, we examined 11 vaccination scenarios that incrementally increased vaccination coverage from current cohort-specific rates to 90% for girls and 89% for boys, with each scenario adding successive cohorts (e.g., increasing coverage to age 35 includes increasing coverage for ages 25–34). Each vaccination scenario was coupled with a screening scenario that lowered the age that women switch to HPV-based screening, if eligible (from age 34 years (status-quo) to age 30 or 25 in 2022) and varied the frequency of HPV-based screening (5-yearly (status-quo) or 10-yearly), resulting in a total of 56 scenarios.

Results

Twenty-one vaccination strategies coupled with de-intensified screening frequencies lowered ASR by 2050, but vaccination would have to be offered to additional cohorts and HPV screening-age would need to be lowered to accelerate CC elimination (Figure 1).

Conclusions

Increasing vaccination and decreasing HPV switch-age paired with less intensive screening frequencies can lead to greater benefits and accelerate CC elimination compared to current prevention policies, but changing screening for the youngest birth cohorts contributed the majority of declines rather than increasing vaccination age. Evaluations of HPV ‘EVEN FASTER’ need to estimate the full economic implications of these policies.

Introduction

Cervical Cancer Elimination efforts in low- and middle-income countries (LMICs) are being hampered because the cost of scaling-up screening and treatment programmes is unknown. To assist in programme planning and advocacy for additional funding, the SUCCESS project has developed an Excel-based tool for estimating the cost of scaling-up cervical cancer programmes. The tool builds upon a previously released costing tool: the WHO Comprehensive Cervical Cancer Costing and Planning (C4P) tool. The SUCCESS-C4P version aims to build costing capacity in LMICs by improving the user interface.

The tool and course package is undergoing field testing in four countries, Burkina Faso, Cote d’Ivoire, Guatemala, and the Philippines, as part of the SUCCESS Project to integrate recommended secondary prevention strategies into the national continuum of care.

Methods

We extensively reviewed the C4P tool with subject matter experts, previous users, and health economists to identify revisions needed to simplify the costing process. Special emphasis was placed on making data collection and input more streamlined for public health program managers and planners. Outputs were redesigned to facilitate report and presentation generation. We collaborated with program managers from the four countries to collect cost data and will be conducting validation workshops in each country. Online training materials for global use of the SUCCESS-C4P tool will incorporate learning experiences from these countries.

Results

Users demonstrated a greater understanding of how to estimate the cost of a cervical cancer elimination scale-up plan. The costing provided the prerequisite data for a sustainability analysis and financial gap analysis. Not least, country engagement strengthened collaborative ownership of the planned initiative by key participating organizations responsible for championing, supporting, and implementing it.

Conclusions

Cervical Cancer Elimination efforts in LMICs can be accelerated and strengthened through the use of a standardized scale-up costing process and tool developed by the SUCCESS Project.

Introduction

While no HPV vaccine is indicated for single dose administration, some evidence suggests that an off-label 1-dose (OLSD) regimen might reduce the risk of HPV infection and offer comparable levels of protection against HPV infection as two or three doses. This study estimated the potential impact of implementing an OLSD HPV vaccination program relative to a 2-dose program, with 9-valent vaccine (9vHPV) for adolescents in a low/middle income country, using Indonesia as a use case.

Methods

A previously published dynamic HPV transmission infection and disease model was adapted to the Indonesia population to compare the long-term health outcomes and cost-effectiveness of OLSD versus two-dose 9vHPV vaccination programs in girls and boys aged 9-14. A probabilistic sensitivity analysis was performed with uncertainty distributions for the vaccine model parameters for a single dose estimated from fitting data to interim KENSHE results. Scenarios analyses were run to show the impact of different coverage levels.

Results

2-dose girls only (GO) or GNV program may avoid 70,000-1.96 million additional cancer cases, over 100 years compared to an OLSD GO or GNV program. Compared to OLSD, a 2-dose GNV program has nearly 100% probability of being cost-effective at a WTP of 0.5x GDP ($1935/QALY). None of the 1-dose scenarios were likely to reach cervical cancer elimination. Dose price, coverage, and parameter uncertainty sensitivity analyses led to similar results.

Conclusions

Our modeling shows adoption of the one-dose 9vHPV vaccination program resulted in more vaccine-preventable HPV-related cancer cases, introduced substantial uncertainty in both health and economic outcomes, and had a low to zero probability of being cost-effective compared to the two-dose programs. The health impact on a low/middle income country is substantially larger and more uncertain due to differences in attributes related to disease burden, vaccine coverage (including historical HPV immunization program), lack of screening practices and parameters related to socio-economic conditions.

Introduction

Previous studies have reported significant disruption in well-child visits and in routine pediatric and adolescent vaccinations recommended by the Advisory Committee on Immunization Practices (ACIP) in the United States (US) between 2020 and early 2021; adolescent vaccination, including human papillomavirus (HPV), was shown to have the most significant disruption. We sought to provide an update on the trends in adolescent well-child visits and HPV vaccination up to August 2022.

Methods

We utilized the Merative^TM MarketScan Commercial Database (Early View) and analyzed enrolled individuals from January 1, 2018 until August 31, 2022. The monthly rates of in-person well-child visits and HPV vaccinations were calculated for the study period (January 2020 to August 2022) and compared to the respective monthly rates from the baseline period (January 2018 to December 2019). Monthly rates were aggregated over time as annual accumulated percent change.

Results

Relative to the baseline period, adolescent well-child visits (9-16 years of age) declined with the greatest decrease in April 2020 (-71.2%); some recovery was observed later in 2020 but declined again in early 2021 and remained low through August 2022. HPV vaccination rates followed a similar trend but with lower rates (Figure 1); there were 9.9% fewer vaccine administrations than expected in 2020 and 22.8% fewer in 2022 as of August (Figure 2). Those aged 17-18 years experienced even greater declines, suggesting these lost vaccinations were not made up in subsequent years.

Conclusions

The negative impact of the COVID-19 pandemic on adolescent well-child visits and HPV vaccinations in the US continues to be substantial through August 2022 with vaccination deficits worsening and little evidence of catching up of missed HPV vaccination. Concerted multi-stakeholder efforts to reverse these trends are urgently needed to prevent increase in HPV-related disease and economic burden.

Introduction

There is increasingly high confidence in the documented protection afforded by a single dose of the HPV vaccines. Durability of this protection is necessary to control cervical cancer. The Costa Rica HPV Vaccine Trial (CVT) provided evidence that antibody levels observed more than a decade following single-dose vaccination with the bivalent HPV vaccine were sufficient to confer very high vaccine efficacy. We extended this evaluation to assess HPV16/18 antibody levels up to 16 years after initial HPV vaccination.

Methods

In the HPV-vaccinated arm of CVT, 991 women were invited to continue follow-up after the 11-year visit, including 398 women who had received three-dose, 368 who had received two-doses and 193 who had received one-dose. More than 95% of these women completed the 14- and 16-year visits and blood collections. Antibody concentration was assessed by ELISA. HPV16 and 18 seropositivity and GMTs were calculated with 95% confidence intervals (CIs) by dose group.

Results

Regardless of number of doses, HPV16 and 18 seropositivity at 14 and 16 years remained close to 100% up to 16-years after HPV vaccination (Table). Between years 11 and 16, HPV16 antibody GMT levels declined 16% for women who received 3 doses, 20% for those who received 2 doses and 7% for those who received 1 dose. A similar pattern was observed for HPV18.

Conclusions

Sixteen years after HPV vaccination, almost 100% of HPV-vaccinated women remained seropositive irrespective of the number of HPV vaccine doses received. Minimal decline in the antibody concentration was observed over time, especially for the single-dose HPV vaccine group. These data confirm that a single dose of bivalent HPV vaccine induces durable antibodies, supporting the recent update to WHO recommendations.

Introduction

There is a global shift in the recommended primary cervical screening method from conventional cytology towards HPV testing. Because HPV testing is more sensitive, it has been suggested to extend screening intervals to every five years. Even longer screening intervals for HPV negative women may be feasible. The aim of this study was to examine the long-term negative predictive value of a cervical high-risk human papillomavirus (hrHPV) test in a young female population in a Danish setting.

Methods

During 1991-1993, a cohort of 11 088 Danish women aged 20 to 29 years was established. They all had a gynecological examination with cervical cytology and a swab for hrHPV DNA detection and genotyping using the Hybrid Capture 2 and InnoLiPa methods. The women were followed in the national Pathology Registry for diagnoses of CIN2+, CIN3+, and cervical cancer for up to nearly 30 years.

Results

Altogether 8.756 women had a negative hrHPV test at baseline. The absolute risk of CIN2+, CIN3+ and cervical cancer within 27 years of follow-up was low, 7.3%, 5.2% and 0.4%, respectively. The risk was slightly lower for women with an additional normal cytology at baseline. After 27 years, a lower risk of developing CIN2+/CIN3+ was seen for women older than 25 years at baseline compared to women 25 or younger: CIN2+ 6.1% (95% CI: 4.9-6.6) vs. 8.7% (95% CI: 7.8-9.7) and CIN3+ 4.1% (95% CI: 3.4-4.8) vs. 6.2% (95% CI: 5.4-7.0). In contrast, we observed no significant difference between the two age groups regarding the risk of subsequent cervical cancer.

Conclusions

In a Danish cervical cancer screening context, a negative hrHPV test in young women still shows a high negative predictive value for CIN2+, CIN3+ and cervical cancer after almost 30 years of follow-up.