Immunogenicity and Safety of Extended-Interval 2-Dose Regimens of 9vHPV Vaccine.

BACKGROUND: Nine-valent human papillomavirus (9vHPV) vaccines can be administered in 2 doses 6 to 12 months apart in adolescents. The impact of extended dose intervals is unknown. We report immunogenicity and safety data in adolescents of a second 9vHPV vaccine dose administered ≥1 year after the first. METHODS: This open-label safety and immunogenicity study (NCT04708041) assessed extended-interval 2-dose regimens of 9vHPV vaccine among adolescents (10 to 15 years) who received 2 9vHPV vaccine doses: the first ≥1 year before enrollment, and second, at enrollment (day 1). We measured serologic responses to vaccine-targeted human papillomavirus (HPV) types at enrollment day 1 (pre-dose 2) and 1 month post-dose 2 (month 1) using a competitive LuminexV® immunoassay. We estimated effects of dose interval on geometric mean titers (GMTs) using regression modeling. Participants reported adverse events (AEs) through 15 days after vaccination. RESULTS: We enrolled 146 adolescents (mean age 13.3 years) with median 25 months since first 9vHPV vaccine dose (range: 12-53 months). Across vaccine-targeted HPV types, GMTs increased from day 1 to month 1; seropositivity at month 1 was 100%. Anti-HPV GMTs at month 1 were not affected by differences in dose interval of 12 to 53 months, based on regression modeling. The most common AEs were mild-to-moderate injection site reactions; no serious AEs were reported. CONCLUSIONS: Extending the interval between first and second 9vHPV vaccine doses to 12 to 53 months did not affect antibody responses, with favorable safety profile. These results support feasibility of extended interval regimens for 9vHPV vaccine.

Assessing the long-term implications of age 9 initiation of HPV vaccination on series completion by age 13-15 in the US: projections from an age-structured vaccination model.

Introduction: Routine human papillomavirus (HPV) vaccination in the US is recommended at ages 11 or 12 years and can be given at age 9. Vaccination completion rates among adolescents 13-15 years in the US remain below the 80% goal. This study evaluated the long-term effects of increasing proactive HPV vaccination initiation rates at age 9 years in completion rates of adolescents. Methods: An age-structured vaccination model was developed and parametrized based on the National Immunization Survey-Teen (NIS-Teen) survey data. The model projected vaccination coverage (by vaccination status and age group), for 20 years, for a routine initiation scenario (no increase in initiation rates of 9-year-olds) and different proactive initiation (increased age 9 initiation) scenarios. The time to reach a completion rate of 80% for 13-15-year-olds was estimated. The model also generated projections stratified for subgroups of interest. Results: Results indicated that vaccine completion rates of 80% in 13-15-year-olds may not be achieved by 2040 under current trends of routine initiation at ages 11 or 12 years. However, increasing initiation rates in 9-year-olds by 1% and 3% annually could shorten the time to achieve 80% completion by 4 and 8 years, respectively. Stratification analyses showed that increasing initiation rates in 9-year-olds can also reduce disparities across subgroups in the time to achieve vaccination completion targets. Discussion: Increasing HPV vaccination initiation rates in 9-year-olds by as little as 1%-3% annually may be an effective strategy to improve HPV vaccination completion rates in adolescents by age 15 and reach the Healthy People goal of 80% completion much earlier.

Cost-effectiveness of nonavalent HPV vaccination in the Netherlands.

BACKGROUND: A bivalent human papillomavirus vaccine (2vHPV) is currently used in the Netherlands; a nonavalent vaccine (9vHPV) is also licensed. RESEARCH DESIGN AND METHODS: We compared the public health and economic benefits of 2vHPV- and 9vHPV-based vaccination strategies in the Netherlands over 100 years using a validated deterministic dynamic transmission metapopulation model. RESULTS: Compared to 2vHPV, the 9vHPV strategy averted an additional 3,245 cases of and 825 deaths from 9vHPV-strain-attributable cancers, 4,247 cases of and 190 deaths from recurrent respiratory papillomatosis (RRP), and 1,009,637 cases of anogenital warts (AGWs), with an incremental cost-effectiveness ratio (ICER) of €4,975 per quality-adjusted life year (QALY) gained. The ICER increased in a scenario with increased HPV vaccination coverage rates and was relatively robust to one-way deterministic sensitivity analyses, with variation in the disease utility parameter having the most impact. When catch-up vaccination for individuals ≤26 years of age was added to the model, vaccinating with 9vHPV averted additional cancers and AGWs compared to 2vHPV vaccination. CONCLUSION: Our analyses predict that transitioning from a 2vHPV- to a 9vHPV-based vaccination strategy would be cost-effective in the Netherlands.

Public health impact and cost-effectiveness of switching from bivalent to nonavalent vaccine for human papillomavirus in Norway: incorporating the full health impact of all HPV-related diseases.

AIM: The objective of this study was to estimate and compare the cost-effectiveness of switching from a bivalent to a nonavalent human papillomavirus (HPV) vaccination program in Norway, incorporating all nonavalent vaccine-preventable HPV-related diseases and in the context of the latest cervical cancer screening program. METHODS: A well-established dynamic transmission model of the natural history of HPV infection and disease was adapted to the Norwegian population. We determined the number of cases of HPV-related diseases and subsequent number of deaths, and the economic burden of HPV-related disease under the current standard of care conditions of bivalent and nonavalent vaccinations of girls and boys aged 12 years. RESULTS: Compared to bivalent vaccination, nonavalent vaccination averted an additional 4,357 cases of HPV-related cancers, 421,925 cases of genital warts, and 543 cases of recurrent respiratory papillomatosis (RRP) over a 100-year time horizon. Nonavalent vaccination also averted an additional 1,044 deaths over the 100-year time horizon when compared with bivalent vaccination. Total costs were higher for the nonavalent strategy (10.5 billion NOK [€1.03 billion] vs. 9.3-9.4 billion NOK [€915-925 million] for bivalent vaccination). A switch to nonavalent vaccination had a higher vaccination cost (4.4 billion NOK [€433 million] vs. 2.7 billion NOK [€266 million] for bivalent vaccination) but resulted in a savings of 627-694 million NOK [€62-68 million] in treatment costs. A switch to nonavalent vaccination demonstrated an incremental cost-effectiveness ratio of 102,500 NOK (€10,086) per QALY versus bivalent vaccination. CONCLUSIONS: Using a model that incorporated the full range of HPV-related diseases, and the latest cervical cancer screening practices, we found that switching from bivalent to nonavalent vaccination would be considered cost-effective in Norway.

Human papillomavirus (HPV) is a sexually transmitted infection that is common in Norway. Vaccination against HPV has substantially reduced the burden of HPV-related diseases globally. The HPV vaccine is available in bivalent, quadrivalent, and nonavalent forms. The bivalent vaccine is currently used in the Norwegian national immunization program, but the nonavalent vaccine is also licensed in Norway. In order to gain a more complete understanding of the benefits of nonavalent vaccination, it is necessary to evaluate the cost-effectiveness of switching from the bivalent vaccine to the nonavalent vaccine in light of the full array of vaccine-preventable diseases, including both cervical and noncervical cancers, genital warts, and recurrent respiratory papillomatosis (RRP). Our results show that, when the full range of HPV-related diseases is considered, nonavalent vaccination would be cost-effective relative to bivalent vaccination in Norway. Compared to bivalent vaccination, nonavalent vaccination averted an additional 4,357 cases of HPV-related cancers, 421,925 cases of genital warts, and 543 cases of RRP over a 100-year time horizon. Nonavalent vaccination also averted an additional 1,044 deaths over the 100-year time horizon when compared with bivalent vaccination. While total costs were higher for the nonavalent strategy (10.5 billion NOK [€1.03 billion] vs. 9.3-9.4 billion NOK [€915­925 million] for bivalent vaccination), switching to the nonavalent strategy resulted in a savings of 627­694 million NOK [€62­68 million] in treatment costs compared to the bivalent strategy.

Changes in vaccine administration trends across the life-course during the COVID-19 pandemic in the United States: a claims database study.

BACKGROUND: This study provides an updated and expanded analysis of the impact of the COVID-19 pandemic on routine vaccinations across the life-course in the United States. RESEARCH DESIGN AND METHODS: Routine wellness visits and vaccination rates were calculated using structured claims data for each month during the impact period (January 2020 to August 2022) and compared to the respective baseline period (January 2018 to December 2019). Monthly rates were aggregated as annual accumulated and cumulative percent changes. RESULTS: The complete monthly rate interactive dataset can be viewed at https://vaccinationtrends.com. The greatest decrease in annual accumulated administration rates in the 0-2 and 4-6 years age groups was for the measles, mumps, and rubella vaccine; for adolescents and older adults, it was for human papillomavirus and pneumococcal vaccines, respectively. Routine in-person wellness visit rates recovered faster and more completely than vaccination rates in all age groups, indicating potential missed opportunities to administer vaccines during visits. CONCLUSIONS: This updated analysis reveals that the negative impact of the COVID-19 pandemic on routine vaccination continued through 2021 and into 2022. Proactive efforts to reverse this decline are needed to increase individual- and population-level vaccination coverage and avoid the associated preventable morbidity, mortality, and health care costs.

Health impact and cost-effectiveness of implementing gender-neutral vaccination with the 9-valent HPV vaccine in Hong Kong.

Human papillomavirus (HPV) can cause several diseases, including cancers, in both sexes. In January 2020, the Hong Kong government launched a school-based vaccination program for girls 10-12 years of age with the 9-valent HPV (9vHPV) vaccine for the prevention of HPV-related diseases; however, boys were not included. The current study estimated the potential health and economic impact of a routine gender-neutral vaccination (GNV) approach compared with the current female-only vaccination (FOV) strategy. We used a dynamic transmission model, adapted to Hong Kong. The model estimates changes in HPV-related disease incidence and mortality, treatment costs (in 2019 Hong Kong dollars), quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) over a 100-year time horizon. The base case analysis compared FOV with the 9vHPV vaccine with routine GNV (coverage rate 70%) for the prevention of HPV-related diseases. Compared with a FOV approach, routine GNV with the 9vHPV vaccine is predicted to provide greater reductions in cumulative HPV-related disease incidence and mortality, as well as lower HPV-related treatment costs. In the base case analysis, the ICER was $248,354 per QALY for routine GNV. As compared with FOV, routine GNV fell below the cost-effectiveness ceiling of $382,046/year for Hong Kong. These results highlight the potential value of a routine GNV program with the 9vHPV vaccine among 12-year-olds in Hong Kong to reduce the public health and economic burden of HPV-related diseases.

The Burden of Cervical Conization in Privately Insured Young and Mid-Adult Women in the United States.

In 2019, the United States (US) Advisory Committee on Immunization Practices (ACIP) recommended that healthcare providers engage in shared clinical decision making for adults aged 27-45 who may benefit from HPV vaccination. However, it is difficult to assess these benefits as there is a lack of data on HPV burden on young and mid-adult women. This analysis estimates the incidence of conization and the burden associated with treating pre-cancerous states related to HPV with a loop electrosurgical excision procedure (LEEP) or a cold knife conization (CKC) among commercially insured women aged 18-45. This retrospective cohort study used the IBM MarketScan commercial claims encounter database for women aged 18-45 treated with conization. We assessed the annual incidence of conization (2016-2019) and adjusted the two-year health care costs post-conization using a multivariable Generalized Linear Model (GLM)-accounting for follow-up time and other characteristics-stratified by the age groups, namely 18-26 and 27-45. The inclusion criteria were met by 6735 women, with a mean age of 33.9 years (SD = 6.2). Conization incidence was lowest for women aged 18-26 (41/100,000 to 62/100,000 women-years) and highest for women aged 31-35 (243/100,000 to 269/100,000). The GLM-adjusted, all-cause healthcare costs per patient per year were USD 7279 and USD 9249 in the 18-26 and 27-45 age groups, respectively. The adjusted costs for disease-specific care were USD 3609 and USD 4557 for women ages 18-26 and 27-45, respectively. The burden of conization and the associated costs were significant, indicating a potential healthcare benefit of HPV vaccination among young and middle-aged women.

Cost-effectiveness and budget impact of heat-stable carbetocin compared to oxytocin and misoprostol for the prevention of postpartum hemorrhage (PPH) in women giving birth in India.

INTRODUCTION: Low- and middle-income countries (LMICs) are committed to achieving the Sustainable Development Goal 3.1 to reduce maternal mortality. The Ministry of Health and Family Welfare of India recommends prophylactic uterotonic administration to every woman following delivery to reduce the risk of postpartum hemorrhage (PPH), as PPH is the leading cause of maternal mortality in LMICs, including India. In 2018, the World Health Organization first recognized heat-stable carbetocin for PPH prevention. Governments are now considering its introduction into their public health systems. METHODS: A decision-tree model was developed from the public healthcare system perspective to compare the value of heat-stable carbetocin versus oxytocin and misoprostol among women giving birth in public sector healthcare facilities in India. The model accounted for differences in PPH risk and costs based on mode of delivery and healthcare setting, as well as provider behavior to mitigate quality concerns of oxytocin. Model outcomes for each prophylactic uterotonic included the number of PPH events, DALYs due to PPH, deaths due to PPH, and direct medical care costs. The budget impact was estimated based on projected uterotonic uptake between 2022-2026. RESULTS: Compared to oxytocin, heat-stable carbetocin avoided 5,468 additional PPH events, 5 deaths, and 244 DALYs per 100,000 births. Projected direct medical costs to the public healthcare system were lowered by US $171,700 (₹12.8 million; exchange rate of ₹74.65 = US$1 from 2 Feb 2022) per 100,000 births. Benefits were even greater when compared to misoprostol (7,032 fewer PPH events, 10 fewer deaths, 470 fewer DALYs, and $230,248 saved per 100,000 births). In the budget impact analysis, India's public health system is projected to save US$11.4 million (₹849 million) over the next five years if the market share for heat-stable carbetocin grows to 19% of prophylactic uterotonics administered. CONCLUSIONS: Heat-stable carbetocin is expected to reduce the number of PPH events and deaths, avoid more DALYs, and reduce costs to the public healthcare system of India. Greater adoption of heat-stable carbetocin for the prevention of PPH could advance India's efforts to achieve its maternal health goals and increase efficiency of its public health spending.

Impact of the COVID-19 Pandemic on HPV Vaccinations in Switzerland and Greece: Road to Recovery.

The COVID-19 pandemic has caused significant disruptions to healthcare, including reduced administration of routinely recommended HPV vaccines in a number of European countries. Because the extent and trends of accumulated vaccine dose deficits may vary by country, decision-makers need country-specific information regarding vaccine deficits to plan effective catch-up initiatives. To address this knowledge gap in Switzerland and Greece, this study used a previously published COVID-19 recovery calculator and historical vaccine sales data to quantify the cumulative number of missed doses and the catch-up rate required to clear the deficit in Switzerland and Greece. The resultant cumulative deficit in HPV doses for Switzerland and Greece were 24.4% and 21.7%, respectively, of the total number of doses disseminated in 2019. To clear the dose deficit by December 2025, monthly vaccination rates must be increased by 6.3% and 6.0% compared to 2019 rates in Switzerland and Greece, respectively. This study demonstrates that administration rates of routine HPV vaccines decreased significantly among Swiss and Greek adolescents during the COVID-19 pandemic and that a sustained increase in vaccination rates is necessary to recover the HPV dose deficits identified and to prevent long-term public health consequences.

HPV vaccine initiation at 9 or 10 years of age and better series completion by age 13 among privately and publicly insured children in the US.

The US Advisory Committee on Immunization Practice recommends routine human papillomavirus (HPV) vaccination at 11-12 years of age, but states that vaccination may be initiated as early as 9 years. Our primary goal was to assess whether initiating HPV vaccination at 9-10 years of age, compared to 11-12, was associated with a higher rate of series completion by 13 years of age, and to identify factors associated with series completion by age 13. The study used vaccine claims and other data from the IBM MarketScan Commercial Claims and Encounters (privately insured) and IBM MarketScan Multi-State Medicaid (publicly insured) databases. Participants were 9-12 years of age and initiated HPV vaccination between January 2006 and December 2018 (publicly insured) or February 2019 (privately insured). Among 100,117 privately insured individuals, those initiating the HPV vaccination series at 9-10 years of age had a significantly higher series completion rate by 13 years of age than did those initiating at 11-12 years of age (76.2% versus 48.1%; p < .001). The same pattern was observed for 115,863 publicly insured individuals (70.4% versus 40.0%; p < .001). Provider and health care plan type, female sex, race/ethnicity, and wellness checks or non-HPV vaccinations during the baseline period were significantly associated with series completion by 13 years of age. Proactive initiation of HPV vaccination at 9-10 years of age was associated with higher rates of series completion by 13 years of age. These findings can inform provider education and other interventions to encourage timely HPV vaccination series completion.

The Clinical and Economic Impact of a Nonavalent Versus Bivalent Human Papillomavirus National Vaccination Program in Taiwan.

OBJECTIVES: This study aimed to estimate the epidemiologic and economic impact of a nonavalent human papillomavirus (HPV) vaccination program for 13- to 14-year-old females compared with that of the bivalent vaccine in Taiwan. METHODS: A previously developed dynamic transmission model for the nonavalent HPV vaccine was adapted to the Taiwan setting. The natural history of cervical cancer and genital warts was simulated by the HPV model assuming an 80% vaccination coverage rate in girls aged 13 to 14 years of age with a 2-dose schedule for the nonavalent and bivalent HPV vaccines. A lifetime duration of vaccine protection was assumed for the HPV vaccine types. RESULTS: The model estimated that the nonavalent HPV vaccine would prevent an additional 15 951 cervical cancer cases, 6600 cervical cancer-related deaths, 176 702 grade 2 or grade 3 cervical intraepithelial neoplasia cases, 103 959 grade 1 cervical intraepithelial neoplasia cases, and 1 115 317 genital warts cases compared with the bivalent HPV vaccine. The nonavalent HPV vaccination program was projected to cost an additional New Taiwan dollars (NTD) 675.21 per person and to produce an additional 0.00271 quality-adjusted life-year per person over 100 years compared with the bivalent HPV vaccine. Thus, the incremental cost-effectiveness ratio of the nonavalent HPV vaccine versus the bivalent HPV vaccine was NTD 249 462/quality-adjusted life-year. CONCLUSIONS: A nonavalent HPV vaccination program for 13- to 14-year-old girls would have additional public health and economic impacts and would be highly cost-effective compared with the bivalent HPV vaccine, relative to per capita gross domestic product, which is estimated at NTD 746 526 for Taiwan.

Burden of CIN2+ diagnoses and conizations in women aged 18-45 years-a retrospective secondary data analysis of German statutory health insurance claims data.

PURPOSE: High grade cervical intraepithelial neoplasia (CIN2+) may progress to cervical cancer. They may be detected by screening and are usually treated by conization. This study aimed at assessing annual proportions of screening, prevalent and incident CIN2+ diagnoses, as well as proportions of (re-)conizations during 24 months follow-up after conization in Germany. METHODS: A descriptive retrospective claims data analysis of the years 2013-2018 was conducted using the InGef Research Database. Women aged 18-45 years with CIN2+ diagnoses were identified by ICD-10-GM codes (N87.1, N87.2, D06.-, and C53.-). Cervical conizations were identified by OPS codes (5-671.0* or 5-671.1*). Screening participation was identified by EBM codes (01730, 01733, 32819 or 32820). Annual proportions were calculated as women with the respective documented codes divided by all women in the respective age group per calendar year. RESULTS: Overall annual proportions of screened women spanned from 60.01 to 61.33% between 2013 and 2018. The overall annual prevalence of CIN2+ diagnoses (regardless of screening participation) ranged from 0.72 to 0.84% between 2013 and 2018, with highest proportions observed in women aged 27-45 years. Also, CIN2+ incidence was highest in women 27-45 years. Annual proportion of women undergoing conization was 0.24% in 2013 and 0.21% in 2018. During a 24-month follow-up period after conization, 2.91% of women underwent a re-conization 3 months or later after the initial conization. CONCLUSION: This analysis demonstrates a considerable burden of CIN2+, conizations and re-conizations in Germany, especially in women aged 27-45 years. This highlights the need for intensified prevention efforts such as expanding human papillomavirus (HPV) vaccination.

Modeling the health and economic implications of adopting a 1-dose 9-valent human papillomavirus vaccination regimen in a high-income country setting: An analysis in the United Kingdom.

Although no human papillomavirus (HPV) vaccine is indicated for single-dose administration, some observational evidence suggests that a 1-dose regimen might reduce HPV infection risk to that achieved with 2 doses. This study estimated the potential health and economic outcomes associated with switching from a 2-dose HPV vaccination program for girls and boys aged 13-14 years to an off-label 9-valent (9vHPV), 1-dose regimen, accounting for the uncertainty of the effectiveness and durability of a single dose. A dynamic HPV transmission infection and disease model was adapted to the United Kingdom and included a probabilistic sensitivity analysis using estimated distributions for duration of protection of 1-dose and degree of protection of 1 relative to 2 doses. One-way sensitivity analyses of key inputs were performed. Outcomes included additional cancer and disease cases and the difference in net monetary benefit (NMB). The 1-dose program was predicted to result in 81,738 additional HPV-related cancer cases in males and females over 100 years compared to the 2-dose program, ranging from 36,673 to 134,347 additional cases (2.5% and 97.5% quantiles, respectively), and had a 7.8% probability of being cost-effective at the £20,000/quality-adjusted life years willingness-to-pay (WTP) threshold. In one-way sensitivity analyses, the number of additional cancer cases was sensitive to the median of the duration of protection distribution and coverage rates. The differences in NMBs were sensitive to the median of the duration of protection distribution, dose price and discount rate, but not coverage variations. Across sensitivity analyses, the probability of 1 dose being cost-effective vs 2 doses was < 50% at the standard WTP threshold. Adoption of a 1-dose 9vHPV vaccination program resulted in more vaccine-preventable HPV-related cancer and disease cases in males and females, introduced substantial uncertainty in health and economic outcomes, and had a low probability of being cost-effective compared to the 2-dose program.

Clinical and economic burden of HPV-related cancers in the US veteran population.

BACKGROUND: Human papillomavirus (HPV) is one of the most common sexually transmitted infection in the United States and can lead to cervical, vulvovaginal, anal, penile, and oropharyngeal cancers. Compared with the general population, US military members are at a higher risk of HPV-related conditions, yet vaccination rates are relatively low in this population. As many service members may not be diagnosed with HPV-related cancers until after they leave active service, the objective of this study was to determine the incidence, prevalence, and economic burden of HPV-related cancers among US veterans. METHODS: The study used the 2014-2018 Veterans Health Administration (VHA) database to identify newly diagnosed adult patients (cases) with HPV-related cancers, including cervical, vulvovaginal, anal, penile, and oropharyngeal cancers. Cases were matched by age, race, and sex to patients without HPV related cancer (controls). Outcome measures included annual incidence, prevalence, health care resource utilization (HCRU), and costs. These outcomes were calculated from the index date (first cancer diagnosis) through the earliest of 24 months, death, or end of study period. Adjusted results were examined using generalized linear models. RESULTS: The annual prevalence and incidence rates of HPV-related cancers ranged from 43 (anal) to 790 (oropharyngeal) cases per million (CPM), and four (anal) to 131 (cervical) CPM, respectively. Compared with controls, cases had significantly higher annual HCRU. Mean numbers of annual inpatient hospitalizations were several times higher compared to controls (cervical: 6.7-times (×); vulvovaginal: 2.7×; penile: 6.6×; oropharyngeal: 10.2×; and anal: 14.9×; all p < 0.01). Similarly, cases had significantly higher all-cause healthcare costs vs. matched controls across all cancer types: cervical ($24,252 vs. $10,402), vulvovaginal ($34,801 vs. $10,913), penile ($42,772 vs. $9,139), oropharyngeal ($82,763 vs. $10,017), and anal ($98,146 vs. $8,339); (all p < 0.01). CONCLUSIONS: HPV-related cancers may cause significant clinical and economic burden within the VHA system. Given the consequences of HPV-related cancers among veterans who did not have access to the vaccine, HPV vaccination of active military and eligible veterans should be considered a healthcare priority.

Healthcare Costs and Resource Use Associated With Cervical Intraepithelial Neoplasia and Cervical Conization: A Retrospective Study of German Statutory Health Insurance Claims Data.

Background: Cervical intraepithelial neoplasia (CIN) can be a consequence of human papillomavirus (HPV) infection. High-grade CIN (CIN2/CIN3) may develop from persistent HPV infection and progress to cervical cancer if left untreated. Management of CIN includes conservative surveillance or ablation and excision by conization. Internationally, CIN and its treatment generate a considerable economic burden, but no current data regarding costs and resource use from the perspective of the German statutory health insurance exist. Objectives: The aim of this study was to explore the health economic burden in women with CIN diagnoses who either underwent cervical conization or were managed conservatively. Methods: We conducted a retrospective claims data analysis using the InGef Research Database from 2013 to 2018. Healthcare costs and resource utilization in a 24-month observation period (1:1:1 matching) were compared in 18- to 45-year-old women with CIN (1-3) who underwent a conization procedure (study cohort 1) and in women with CIN (1-3) who did not undergo conization (study cohort 2) to women with neither CIN nor conization (control group). Results: For each group, 2749 women were identified. Mean total healthcare costs after 24 months were higher in study cohort 1 (€4446, P<.01) and study cohort 2 (€3754, P=.09) compared with the control group (€3426). Comparing study cohort 1 and 2 to controls, mean differences were highest in age groups 41-45 years (cohort 1: €5115 vs €3354, P<.01; cohort 2: €4152 vs €3354, P=.14). Significantly more women were hospitalized at least once in study cohort 1 (57.46%, P<.01) and study cohort 2 (38.74%, P<.01) compared with the control group (31.14%). Frequency of outpatient physician visits was significantly higher in both study cohorts (43.23 visits, P<.01 and 38.60 visits, P<.01) compared with the control group (32.07 visits). Conclusion: Our results revealed 30% and 10% increased total healthcare costs in women with CIN undergoing invasive treatment (study cohort 1) and conservative management (study cohort 2), respectively, compared with a control group of women with no CIN in a 2-year follow-up period.

The impact and cost-effectiveness of 9-valent human papillomavirus vaccine in adolescent females in Hong Kong.

INTRODUCTION: In Hong Kong (HK), a single-cohort vaccination program for 10-12-year-old girls with the 9-valent human papillomavirus (HPV) vaccine (9vHPV; types 6/11/16/18/31/33/45/52/58) has been launched. This study assessed the public health impact and cost-effectiveness of implementing routine 9vHPV vaccination (12-year-olds) with or without catch-up 9vHPV vaccination (13-18-year-olds) in HK. METHODS: The health impact and costs of implementing routine 9vHPV vaccination with or without catch-up vaccination over a 100-year time horizon were evaluated using a validated HPV-type transmission dynamic model adapted to the HK population; analyses were performed from a healthcare payer perspective. Routine vaccination (12-year-old girls) and catch-up vaccination (13-18 years) assumed vaccine coverage rates of 70% (base case) and 30%, respectively. The model also assumed herd immunity, lifelong vaccine protection, a discount rate of 3%, and a cost per dose of HK dollars (HKD) 858 [United States dollars (USD) 110] and HKD 1390 (USD 179) for the 2-valent HPV (2vHPV) and 9vHPV vaccines, respectively. HPV disease-related incidence and the incremental cost-effectiveness ratio (ICER) per quality-adjusted-life-year (QALY) were estimated. Cost-effectiveness was determined at a ceiling threshold of HK dollars (HKD) 382,046 (USD 49,142) or 1.0 times the gross domestic product per capita of HK. RESULTS: Compared with routine 9vHPV alone, routine plus catch-up 9vHPV is projected to reduce cervical cancer incidence by 3.4%. Routine plus catch-up 9vHPV will also reduce genital warts incident cases for males/females by 2.6%/5.4%. The incremental cost-effectiveness ratios were HKD 29,911 (USD 3847)/quality-adjusted life-year (QALY) for routine plus catch-up 9vHPV versus routine 9vHPV alone and HKD 25,524 (USD 3283)/QALY for routine 9vHPV alone versus screening only. Sensitivity analyses indicated that routine plus catch-up 9vHPV compared with routine 9vHPV alone remained cost-effective at coverage rates of 30% and 90%. CONCLUSIONS: This analysis predicts that the current HK vaccination strategy can be considered cost-effective and will provide maximum health benefit. These results support addition of the routine 9vHPV vaccine with or without catch-up 9vHPV vaccination to the regional vaccination program in HK.

Impact of the COVID-19 pandemic on adolescent vaccinations: projected time to reverse deficits in routine adolescent vaccination in the United States.

OBJECTIVE: The COVID-19 pandemic has led to significant reductions in the administration of routinely recommended vaccines among adolescents in the US including tetanus, diphtheria, and acellular pertussis (Tdap); meningococcal (ACWY); and human papillomavirus (HPV) vaccines. The extent to which these deficits could persist in 2021 and beyond is unclear. To address this knowledge gap, this study estimated the cumulative deficits of routine vaccine doses among US adolescents during the COVID-19 pandemic and estimated the time and effort needed to recover from those deficits. METHODS: Monthly reductions in Tdap, meningococcal, and HPV doses administered to US adolescents during the COVID-19 pandemic were quantified using MarketScan Commercial Claims and Encounters data. The time and effort required to reverse the vaccination deficit under various catch-up scenarios were estimated. RESULTS: Annual doses administered of Tdap, meningococcus, and HPV vaccines decreased by 21.2%, 20.8%, and 24.0%, respectively, in 2020 compared to 2019. For 2021, the reduction in doses administered is projected to be 6%-21% compared to 2019 under different scenarios. The projected deficit of missed doses is expected to be cleared between winter 2023 and fall 2031. CONCLUSIONS: Administration rates of routine vaccines decreased significantly among US adolescents during COVID-19. Reversing these deficits to mitigate long-term health and economic consequences will require a sustained increase in vaccination rates over multiple years.

Incremental healthcare resource utilization and costs for patients with cervical, vaginal, vulvar, anal, and oropharyngeal cancer in the United States.

INTRODUCTION: Human papillomavirus (HPV) cause cancers in a variety of anatomic sites presenting at various stages of disease. Current economic assessments rely on HPV-related cancer cost estimates from data prior to the launch of the nonavalent HPV vaccine (2014). The goal of the present study was to assess and describe the current direct medical care burden of HPV-related cancers in the US. METHODS: Using Clinformatics Data Mart, patients in the US who were newly diagnosed with cervical, vulvar, vaginal, anal, and oropharyngeal cancers between 2012 and 2015 were compared to non-cancer matched (propensity score) controls. Health care resource utilization and direct medical cost (2020 USD) were assessed over a 2-year follow-up period following index diagnosis from a payer perspective. The cost for censored time was estimated using generalized linear model while adjusting for survival probability using cox-proportional hazard model. Confidence intervals were calculated with bootstrapping technique. RESULTS: The analyses included 4128 cervical, 1580 vulvar, 538 vaginal, 1827 anal, and 6106 oropharyngeal cancers and matched controls. Cases and controls had similar baseline clinical characteristics and length of follow-up. The 2-year incremental direct medical costs were $93,272, $81,676, $141,096, $129,366, and $134,045 for cervical, vulvar, vaginal, anal, and oropharyngeal cancers respectively. Outpatient care costs was the biggest driver of the total incremental medical costs. Most cancer costs were incurred during the first 6 months of follow-up and then stabilized during follow-up. CONCLUSION: HPV-related cancers are responsible for substantial health care expenditure each year.

Impact of reduced human papillomavirus vaccination coverage rates due to COVID-19 in the United States: A model based analysis.

The coronavirus disease 2019 (COVID-19) pandemic has significantly affected utilization of preventative health care, including vaccines. We aimed to assess HPV vaccination rates during the pandemic, and conduct a simulation model-based analysis to estimate the impact of current coverage and future pandemic recovery scenarios on disease outcomes. The model population included females and males of all ages in the US. The model compares pre-COVID vaccine uptake to 3 reduced coverage scenarios with varying recovery speed. Vaccine coverage was obtained from Truven Marketscan™. Substantially reduced coverage between March-August 2020 was observed compared to 2018-2019. The model predicted that 130,853 to 213,926 additional cases of genital warts; 22,503 to 48,157 cases of CIN1; 48,682 to 110,192 cases of CIN2/3; and 2,882 to 6,487 cases of cervical cancer will occur over the next 100 years, compared to status quo. Providers should plan efforts to recover HPV vaccination and minimize potential long-term consequences.