9vHPV Vaccine Research Articles

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

IntroductionIn 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.MethodsThe 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.ResultsCompared 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%.ConclusionsThis 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.

Vaccine initiation and 3-dose series completion of 4vHPV vaccine among US insured males 2012–2016

ObjectiveThe quadrivalent human papillomavirus vaccine (4vHPV, GARDASIL®), was approved in the US in 2009 for use in males aged 9 to 26 for the prevention of HPV-related genital warts, and in 2010 for the prevention of certain HPV-related anogenital diseases. A regimen was approved in 2016 for those who initiate the vaccine series between the ages of 9 to 14 years. We describe patterns of 4vHPV administration among US males before this modification. MethodsThe study used a US health insurance claims database, and included males, age 9 to 26 years, who initiated 4vHPV between 2012 and 2016. Time from first dose to subsequent doses was estimated. Logistic regression identified factors associated with regimen completion. ResultsAmong 100,786 males who initiated 4vHPV (corresponding to ∼ 13% of male birth cohorts), 50,573 (50.2%) and 25,763 (25.6%) received a second and third dose, respectively. Annual administration was common, with 47% of males receiving 3 doses over 3 years (1 dose per year) as compared to 12% receiving the 3-dose series in the recommended 6-month timeframe. Receipt of 4vHPV was 2.2 (range 1.5 to 2.9) times as likely to occur in summer months compared to other times of the year. Individuals aged 18 to 21 years and those living in Western states or rural regions were less likely to complete the 3-dose regimen. ConclusionsThe real-world patterns of 4vHPV vaccination observed, particularly the low uptake and regimen completion, suggest that better strategies are needed for males to improve 4vHPV vaccine use in males.

Design of a phase III efficacy, immunogenicity, and safety study of 9-valent human papillomavirus vaccine in prevention of oral persistent infection in men

BackgroundSeven high-risk human papillomavirus (HPV) types (16/18/31/33/45/52/58) covered by the 9-valent HPV (9vHPV) vaccine cause >90% of HPV-related head and neck cancers (HNCs). An ongoing clinical trial (NCT04199689) was designed to evaluate 9vHPV vaccine efficacy against HPV oral persistent infection, a surrogate endpoint for HPV-related HNCs. MethodsIn this double-blind, placebo-controlled, international trial, men aged 20–45 years (N = 6000) are randomized 1:1 to receive 9vHPV vaccine or placebo on day 1, month 2, and month 6. The primary objective is to demonstrate whether 9vHPV vaccination reduces incidence of HPV16/18/31/33/45/52/58-related 6-month oral persistent infection. Incidence of HPV6/11-related 6-month oral persistent infection will be evaluated as a secondary endpoint. Oral rinse and gargle samples will be collected on day 1, month 7, month 12, and every 6 months thereafter for HPV detection by PCR. Primary analyses will be performed in per-protocol populations. Efficacy in this case-driven study will be analyzed upon accrual of ≥20 primary efficacy endpoint cases. Serum will be collected at day 1 and months 7, 12, 24, 36, and 42; anti-HPV antibody titers will be measured by competitive Luminex immunoassay. Data will be summarized as geometric mean titers and seropositivity rates. Injection-site and systemic adverse events (AEs) will be collected for 15 days post-any vaccination and serious AEs through 6 months after the last vaccination; deaths and vaccine-related serious AEs will be collected throughout the study. DiscussionThis trial is expected to generate important data regarding the potential for 9vHPV vaccine to prevent HPV-related head and neck disease.

Portrayals of 2v, 4v and 9vHPV vaccines on Chinese social media: a content analysis of hot posts on Sina Weibo

ABSTRACT Rather than receive the effective 2vHPV vaccines that are readily available in China, Chinese women usually wait to receive 4v and 9vHPV vaccines, which are difficult to acquire. This means that Chinese women miss the opportunity for optimal protection from cervical cancer. As social media platforms are the main channel by which Chinese women learn about HPV vaccines, this study aimed to explore how HPV vaccines are described on social media, and in particular how they discuss or distinguish 2 v, 4 v and 9vHPV vaccines. The Octopus Web crawler tool was used to capture hot Weibo posts from 2013–2021, and 1,164 valid data were obtained. Results suggested that there are very few posts with great influence on Weibo about HPV vaccines among 9 years and much of them are created by “lay people.” HPV-related topics lacked persistent popularity, comprised highly repetitive content and the spread of information was geographically diverse. There were significant differences in the media descriptions of different kinds of HPV vaccines. Price was mentioned more often in the descriptions of 2vHPV vaccines, whereas appointments were referred to most often in the descriptions of 9vHPV vaccines. There was little media attention paid to the safety and effectiveness of HPV vaccines. Chinese media should develop better collaborations with public health professionals, pay more attention to the originality of their news coverage of HPV vaccines and strive to promote HPV vaccination. Such collaboration will help news media to better understand the key points of HPV information that need to be disseminated.

Anti-HPV16 Antibody Titers Prior to an Incident Cervical HPV16/31 Infection

The goal of this study was to investigate the serological titers of circulating antibodies against human papillomavirus (HPV) type 16 (anti-HPV16) prior to the detection of an incident HPV16 or HPV31 infection amongst vaccinated participants. Patients were selected from a prospective post-HPV vaccine longitudinal cohort at Mount Sinai Adolescent Health Center in Manhattan, NY. We performed a nested case–control study of 43 cases with incident detection of cervical HPV16 (n = 26) or HPV31 (n = 17) DNA who had completed the full set of immunizations of the quadrivalent HPV vaccine (4vHPV). Two control individuals whom had received three doses of the vaccine (HPV16/31-negative) were selected per case, matched on age at the first dose of vaccination and follow-up time in the study: a random control, and a high-risk control that was in the upper quartile of a sexual risk behavior score. We conducted an enzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin G (IgG) antibodies specific to anti-HPV16 virus-like particles (VLPs). The results suggest that the average log antibody titers were higher among high-risk controls than the HPV16/31 incident cases and the randomly selected controls. We show a prospective association between anti-HPV16 VLP titers and the acquisition of an HPV16/31 incident infection post-receiving three doses of 4vHPV vaccine.

HPV and Cytology Testing in Women Undergoing 9-Valent HPV Opportunistic Vaccination: A Single-Cohort Follow Up Study.

Background: This study evaluates the possible effect of 9-valent (9vHPV) vaccination on the results of HPV and cytological tests in a cohort of adult women. Methods: This study is a retrospective, single-cohort, monocentric study. Sexually active women aged 14–70 years, who underwent 9vHPV vaccination, were enrolled. Dose administration dates, side effects and data on Pap smears and HPV tests performed before and after the first vaccine dose were collected. Subjects were considered “unexposed” to the vaccine for all time intervals before the first dose administration, and “exposed” to the first, second and third vaccine doses in all time intervals following each specific dose. Results: A total of 512 women underwent the first 9vHPV dose administration and were enrolled in the study. Median age at vaccination was 30.5 (14–70). Log-rank tests and Cox regression analyses showed a highly statistically significant (p < 0.0001) difference in the time to negativization after the exposure to the third vaccine dose in the 207 women starting with a Pap+ smear (HR (95% C.I.), 2.66 (1.83–3.86)) and in the 198 women starting with an HPV HR+ test (HR (95% C.I.), 7.80 (4.83–12.60)). Conclusions: 9vHPV vaccination may play a role in shortening the clearance time of HPV HR+ or Pap positivity in sexually active adult women.

Elimination of Cervical Cancer: Challenges Promoting the HPV Vaccine in China.

ObjectiveCervical cancers present major threats to women’s health in China. Eliminating cervical cancer in China is a huge challenge, with application of the HPV vaccine, which is an important part.MethodsThere are currently four HPV vaccines available in China: E-coli bv-HPV (Wantai, China), bv-HPV, qv-HPV (GSK, UK), and 9v-HPV (MSD, USA). To observe the immunogenicity, efficacy, and safety of these four vaccines in China, we formed the "Chinese Expert Consensus on the Clinical Application of HPV Vaccine."ResultsAt 7 months after vaccination, all vaccinated subjects had the same immunogenic response to either HPV16 or HPV18, ranging from 96 to 100%, and antibody production in girls aged 9–14 years was 2–3 times higher than that in adult women. Efficacy of the four vaccines against CIN2 + ranged from 87.3% to 100%, with prevention of HPV-associated infection reaching 96% ~ 97% at 12 months. Clinical trials showed bv-HPV and qv-HPV vaccine were also safe in women aged 18–45 years. Clinical trials of the 9v-HPV vaccine are underway. HPV vaccination is currently voluntary and self-paid in China. The "Chinese Expert Consensus on the Clinical Application of HPV Vaccine" will work to promote the application of HPV vaccine in China.ConclusionsIn clinical studies, the available HPV vaccines showed excellent efficacy, safety, and immunogenicity in Chinese women. We will continue strengthening screening and encouraging HPV vaccination.

Prevalence of Genital Human Papillomavirus by Age and Race/Ethnicity Among Males.

Genital and oral cancers are often caused by human papillomavirus (HPV) types that can be prevented through HPV vaccination. Since HPV is sexually transmitted, knowledge of penile prevalence of vaccine-type HPV among US males can help predict potential disparities in these cancers. This study examines penile HPV prevalence by age and race/ethnicity among males. This study was a secondary analysis of publicly available data from the National Health and Nutrition Examination Survey (NHANES). Using data from penile swab samples collected from males between 2013 and 2016, the prevalence of 4vHPV and 9vHPV vaccine types was examined across age groups and by race/ethnicity. Logistic regression models adjusting for demographics, sexual behavior, and circumcision were examined to determine whether associations remained after accounting for confounders. Among 2548 males evaluated, HPV infection prevalence differed by race/ethnicity, with Black males exhibiting a higher prevalence of HPV. Examination of 4vHPV type prevalence by age group showed that 18-26-year-old males had a lower prevalence than older age groups. After controlling for confounders, 4vHPV prevalence was only significantly elevated among 27-34-year-old males, those who were single, and males with ≥3 lifetime sex partners. In adjusted models, 9vHPV type prevalence remained elevated among Black males compared with White males. Variations in 9vHPV type prevalence between Black and White individuals indicate future disparities in HPV-related genital cancers may continue in the United States during the next decade. Revaccinating certain populations with the 9vHPV vaccine may be appropriate to help mitigate this.

Health Impact and Cost-Effectiveness of Implementing Gender-Neutral Vaccination With the 9-Valent Human Papillomavirus Vaccine in Belgium.

Background: Routine human papillomavirus (HPV) immunization in Belgium is currently regionally managed, with school-aged girls receiving the 9-valent HPV (9vHPV) vaccine in Flanders and Wallonia-Brussels with a national catch-up program for females only. This study will assess whether expanding these programs to gender-neutral vaccination (GNV) with the 9vHPV vaccine is a cost-effective strategy in Belgium. Methods: A validated HPV-type transmission dynamic model estimated the potential health and economic impact of regional vaccination programs, comparing GNV versus female-only vaccination (FOV) with the 9vHPV vaccine in individuals aged 11–12 years in Flanders, GNV with the 9vHPV vaccine versus FOV with the 2-valent HPV (2vHPV) vaccine in individuals aged 12–13 years in Wallonia-Brussels, and national catch-up GNV versus FOV with the 9vHPV vaccine for those aged 12–18 years. Vaccination coverage rates of 90, 50, and 50% in both males and females were used in the base cases for the three programs, respectively, and sensitivity analyses were conducted. All costs are from the third-party payer perspective, and outcome measures were reported over a 100-year time horizon. Results: GNV with the 9vHPV vaccine was projected to decrease the cumulative incidence of HPV 6/11/16/18/31/33/45/52/58-related diseases relative to FOV in both Flanders and Wallonia-Brussels. Further reductions were also projected for catch-up GNV with the 9vHPV vaccine, including reductions of 6.8% (2,256 cases) for cervical cancer, 7.1% (386 cases) and 18.8% (2,784 cases) for head and neck cancer in females and males, respectively, and 30.3% (82,103 cases) and 44.6% (102,936 cases) for genital warts in females and males, respectively. As a result, a GNV strategy would lead to reductions in HPV-related deaths. Both regional and national catch-up GNV strategies were projected to reduce cumulative HPV-related disease costs and were estimated to be cost-effective compared with FOV with incremental cost-effectiveness ratios of €8,062, €4,179, and €6,127 per quality-adjusted life-years in the three programs, respectively. Sensitivity analyses were consistent with the base cases. Conclusions: A GNV strategy with the 9vHPV vaccine can reduce the burden of HPV-related disease and is cost-effective compared with FOV for both regional vaccination programs and the national catch-up program in Belgium.

Design of a Phase III immunogenicity and safety study evaluating two-dose regimens of 9-valent human papillomavirus (9vHPV) vaccine with extended dosing intervals

HPV vaccines are widely licensed as two-dose regimens, 6–12 months apart, for adolescents. Extended intervals between doses may be necessary due to resource constraints or vaccination program disruption. This international, multicenter, open-label study (NCT04708041) will evaluate the safety and immunogenicity of two-dose 9vHPV vaccine regimens with extended intervals of 1–5 years between doses in boys/girls compared with a standard three-dose regimen in women. Participants (planned N = 700) will be enrolled into six cohorts; Cohort 0: boys/girls aged 10–15 years who received one 9vHPV vaccine dose ≥1 year before enrollment without completing the series will receive one study dose of 9vHPV vaccine at day 1; Cohorts 1–4: HPV vaccination-naïve boys/girls aged 9–14 years will receive two doses (day 1 and month 12, 24, 36, or 60); Cohort 5: HPV vaccination-naïve women aged 16–26 years will receive three doses (day 1, months 2 and 6). Primary analyses will be based on serological responses 1 month after final vaccine dose. Co-primary objectives will (1) evaluate non-inferiority of geometric mean titers in each of Cohorts 1–4 versus Cohort 5, and (2) characterize antibody responses in Cohort 0, accounting for the interval between commercial and study vaccine dose. Injection-site and systemic adverse events (AEs) will be collected for 15 days and serious AEs for 12 months post-vaccination; vaccine-related serious AEs and deaths will be collected throughout the study. Results will inform completion of vaccination in individuals who did not complete the recommended series and guide implementation of vaccination programs in resource-limited settings.

Immunogenicity and safety of a nine-valent human papillomavirus vaccine in Vietnamese males and females (9 to 26 years of age): an open-label, phase 3 trial

ABSTRACT This open-label, single-center, Phase 3 study (NCT03546842) assessed the immunogenicity and safety of the nine-valent human papillomavirus (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccine in Vietnamese males and females, with the aim to support 9vHPV vaccine licensure in Vietnam. Participants aged 9–26 years received three 9vHPV vaccine doses (Day 1, Month 2, Month 6). Serum samples were obtained on Day 1 (pre-vaccination) and at Month 7 (one month post-Dose 3) for the measurement of anti-HPV antibodies. Geometric mean titers (GMTs) and seroconversion percentages were obtained using the HPV-9 competitive Luminex immunoassay. Injection-site adverse events (AEs), systemic AEs, serious AEs (SAEs), and study discontinuations due to AEs were recorded. Of 201 participants enrolled, 200 (99.5%) received ≥1 vaccine dose. All participants who received the three-dose regimen (198/200, 98.5%) seroconverted for all 9vHPV vaccine types by Month 7. Robust anti-HPV GMT responses were also observed. Half of participants (50.5%) reported ≥1 AE; the majority were injection-site-related (45.0%) and mild (43.0%). There were no deaths, vaccine-related SAEs, or discontinuations due to AEs. Administration of three 9vHPV vaccine doses was highly immunogenic and resulted in acceptable seropositivity percentages for all vaccine HPV types. The 9vHPV vaccine was generally well tolerated among this study population. Region of origin: Vietnam Trial registration: clinicaltrials.gov Identifier NCT03546842

Association of Inadvertent 9-Valent Human Papillomavirus Vaccine in Pregnancy With Spontaneous Abortion and Adverse Birth Outcomes

The 9-valent human papillomavirus (9vHPV) vaccine is recommended for individuals through age 26 years and may be administered to women up to age 45 years. Data on 9vHPV vaccine exposures during pregnancy are limited. To evaluate the associations between 9vHPV vaccine exposures during pregnancy or peripregnancy and selected pregnancy and birth outcomes (spontaneous abortion [SAB], preterm birth, small-for-gestational age [SGA] birth, and major structural birth defect). This cohort study analyzed data from 7 participating health systems in the Vaccine Safety Datalink. The cohort comprised pregnancies among girls and women aged 12 to 28 years that ended between October 26, 2015, and November 15, 2018. Singleton pregnancies that ended in a live birth, stillbirth, or SAB were included. Vaccine exposure windows were distal (9vHPV or 4vHPV vaccine administered from 22 to 16 weeks before last menstrual period [LMP]), peripregnancy (9vHPV vaccine administered from 42 days before LMP until LMP), and during pregnancy (9vHPV vaccine administered from LMP to 19 completed weeks' gestation). Primary comparisons were (1) girls and women with 9vHPV vaccine exposures during pregnancy vs those with 4vHPV or 9vHPV distal vaccine exposures, (2) girls and women with vaccine exposures peripregnancy vs those with 4vHPV or 9vHPV distal vaccine exposures, and (3) girls and women with 9vHPV vaccine exposures during pregnancy or peripregnancy vs those with 4vHPV or 9vHPV distal vaccine exposure. Spontaneous abortions were confirmed based on medical record review and adjudication. Preterm and SGA births were identified from electronic health record and birth data. Major structural birth defects were based on diagnostic codes using a validated algorithm. Inverse probability weighting was used to balance the covariates. Time-dependent covariate Cox proportional hazards regression models and Poisson regression were used to estimate the associations between 9vHPV vaccine exposures and pregnancy and birth outcomes. The final cohort included 1493 pregnancies among girls and women with a mean (SD) maternal age of 23.9 (2.9) years. Of these pregnancies, 445 (29.8%) had exposures to the 9vHPV vaccine during pregnancy, 496 (33.2%) had exposures to the 9vHPV vaccine peripregnancy, and 552 (37.0%) had 4vHPV or 9vHPV distal vaccine exposures. The 9vHPV vaccine administered during pregnancy was not associated with increased risk for SAB (hazard ratio, 1.12; 95% CI, 0.66-1.93) compared with distal vaccine exposures. Findings were similar for 9vHPV vaccine exposures peripregnancy (relative risk [RR], 0.72; 95% CI, 0.42-1.24). Among live births (n = 1409), 9vHPV vaccine exposures during pregnancy were not associated with increased risks for preterm birth (RR, 0.73; 95% CI, 0.44-1.20) or SGA birth (RR, 1.31; 95% CI, 0.78-2.20). Results were similar regarding the association between 9vHPV vaccine exposures peripregnancy and preterm birth (RR, 0.72; 95% CI, 0.45-1.17) and SGA birth (RR, 1.10; 95% CI, 0.65-1.88). Birth defects were rare in all exposure groups, occurring in about 1% of live births with available infant data. This study found that 9vHPV vaccine exposures during or around the time of pregnancy were uncommon and not associated with SABs or selected adverse birth outcomes. These findings can inform counseling for inadvertent 9vHPV vaccine exposures.

Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27–45 years of age compared to women 16–26 years of age: An open-label phase 3 study

BackgroundEfficacy of the nine-valent human papillomavirus (9vHPV; HPV types 6/11/16/18/31/33/45/52/58) vaccine was demonstrated in a phase 3 study in women 16–26 years of age. We present a phase 3 immunogenicity and safety study of the 9vHPV vaccine in women 27–45 versus 16–26 years of age. MethodsThis international, open-label study (NCT03158220) was conducted in women 16–45 years of age. Participants (16–26 years, n = 570 and 27–45 years, n = 642) received a three-dose 9vHPV vaccination regimen (day 1, month 2, month 6). Month 7 geometric mean titers (GMTs) and seroconversion percentages to anti-HPV 6/11/16/18/31/33/45/52/58 were assessed. Participants were followed for safety throughout the study. ResultsAt month 7, anti-HPV 6/11/16/18/31/33/45/52/58 GMTs in women 27–45 years were compared to those in women 16–26 years of age. The primary hypothesis of non-inferiority of anti-HPV 16/18/31/33/45/52/58 GMTs in older versus younger women was met. The lower bound of the GMT ratio 95% confidence interval (27–45 years to 16–26 years) was 0.60–0.67 depending on HPV type, exceeding the non-inferiority margin of 0.5 for all HPV types. Month 7 seroconversion percentages in women 27–45 years of age were >99% for all HPV types. Injection-site and vaccine-related systemic adverse events (AEs) were observed in 87.5% and 25.1% of women 16–26 years, and 85.2% and 24.1% of women 27–45 years of age, respectively; no vaccine-related serious AEs were reported and no deaths occurred during the study. ConclusionsThe 9vHPV vaccine elicited non-inferior anti-HPV GMTs in women 27–45 years compared with women 16–26 years of age for HPV 16/18/31/33/45/52/58. The vaccine was generally well tolerated with a similar AE profile across the age groups. These data support bridging 9vHPV vaccine efficacy findings in women 16–26 years to women 27–45 years of age.Clinical trial registration NCT03158220.

Economic Value of Lost Productivity Attributable to Human Papillomavirus Cancer Mortality in the United States.

Objectives: To estimate years of potential life lost (YPLL) and present value of future lost productivity (PVFLP) associated with premature mortality due to HPV-attributable cancers, specifically those targeted by nonavalent HPV (9vHPV) vaccination, in the United States (US) before vaccine use.Methods: YPLL was estimated from the reported number of deaths in 2017 due to HPV-related cancers, the proportion attributable to 9vHPV-targeted types, and age- and sex-specific US life expectancy. PVFLP was estimated as the product of YPLL by age- and sex-specific probability of labor force participation, annual wage, value of non-market labor, and fringe benefits markup factor.Results: An estimated 7,085 HPV-attributable cancer deaths occurred in 2017 accounting for 154,954 YPLL, with 6,482 deaths (91%) and 141,019 YPLL (91%) attributable to 9vHPV-targeted types. The estimated PVFLP was $3.8 billion for cancer deaths attributable to 9vHPV-targeted types (84% from women). The highest productivity burden was associated with cervical cancer in women and anal and oropharyngeal cancers in men.Conclusions: HPV-attributable cancer deaths are associated with a substantial economic burden in the US, much of which could be vaccine preventable.

The epidemiologic and economic impact of a quadrivalent human papillomavirus vaccine in Thailand.

The human papillomavirus (HPV) vaccine was introduced into Thailand's national immunization program in 2017 for 11-12 year old school girls. The objectives of this study were to examine the epidemiological consequences and cost-effectiveness of a routine quadrivalent HPV (4vHPV) vaccination and the routine 4vHPV vaccination plus 5-year catch-up vaccination by comparing with cervical cancer screening only (no vaccination) in Thailand. A transmission dynamic model was used to assess the cost-effectiveness of the routine 4vHPV vaccination and the routine 4vHPV vaccination plus catch-up vaccination, compared with no vaccination (screening only) in Thai population. The vaccination coverage rate assumptions were 95% in 11-12-year-old girls for the routine vaccination and 70% in 13-24 year-old females for the 5-year catch-up vaccination. Vaccination costs, direct medical costs of HPV-related diseases, and the number of quality of life years (QALYs) gained were calculated for over a 100-year time horizon with discount rate of 3%. The model indicated that the routine 4vHPV vaccination and the routine plus catch-up 4vHPV vaccination strategies could prevent approximately 434,130 and 472,502 cumulative cases of cervical cancer, 182,234 and 199,068 cumulative deaths from cervical cancer and 12,708,349 and 13,641,398 cumulative cases of HPV 6/11 related genital warts, respectively, when compared with no vaccination over 100 years. The estimated cost per QALY gained (ICER) when compared to no vaccination in Thailand was 8,370 THB/QALY for the routine vaccination and 9,650 THB/QALY for the routine with catch-up vaccination strategy. Considering the recommended threshold of 160,000 THB/QALY for Thailand, the implementation of the routine 4vHPV vaccination either alone or plus the catch-up vaccination was cost-effective as compared to the cervical cancer screening only.

Public health impact and cost effectiveness of routine and catch-up vaccination of girls and women with a nine-valent HPV vaccine in Japan: a model-based study

BackgroundCombined with cancer screening programs, vaccination against human papillomavirus (HPV) can significantly reduce the high health and economic burden of HPV-related disease in Japan. The objective of this study was to assess the health impact and cost effectiveness of routine and catch-up vaccination of girls and women aged 11–26 years with a 4-valent (4vHPV) or 9-valent HPV (9vHPV) vaccine in Japan compared with no vaccination.MethodsWe used a mathematical model adapted to the population and healthcare settings in Japan. We compared no vaccination and routine vaccination of 12–16-year old girls with 1) 4vHPV vaccine, 2) 9vHPV vaccine, and 3) 9vHPV vaccine in addition to a temporary catch-up vaccination of 17–26 years old girls and women with 9vHPV. We estimated the expected number of disease cases and deaths, discounted (at 2% per year) future costs (in 2020 ¥) and discounted quality-adjusted life years (QALY), and incremental cost effectiveness ratios (ICER) of each strategy over a time horizon of 100 years. To test the robustness of the conclusions, we conducted scenario and sensitivity analyses.ResultsOver 100 years, compared with no vaccination, 9vHPV vaccination was projected to reduce the incidence of 9vHPV-related cervical cancer by 86% (from 15.24 new cases per 100,000 women in 2021 to 2.02 in 2121). A greater number of cervical cancer cases (484,248) and cancer-related deaths (50,102) were avoided through the described catch-up vaccination program. Routine HPV vaccination with 4vHPV or 9vHPV vaccine prevented 5,521,000 cases of anogenital warts among women and men. Around 23,520 and 21,400 diagnosed non-cervical cancers are prevented by catch-up vaccination among women and men, respectively. Compared with no vaccination, the ICER of 4vHPV vaccination was ¥975,364/QALY. Compared to 4vHPV, 9vHPV + Catch-up had an ICER of ¥1,534,493/QALY.ConclusionsA vaccination program with a 9-valent vaccine targeting 12 to 16 year-old girls together with a temporary catchup program will avert significant numbers of cases of HPV-related diseases among both men and women. Furthermore, such a program was the most cost effective among the vaccination strategies we considered, with an ICER well below a threshold of ¥5000,000/QALY.

Three-Year Follow-up of 2-Dose Versus 3-Dose HPV Vaccine.

Human papillomavirus (HPV) antibody responses to the 9-valent human papillomavirus (9vHPV) vaccine among girls and boys (aged 9-14 years) receiving 2-dose regimens (months 0, 6 or 0, 12) were noninferior to a 3-dose regimen (months 0, 2, 6) in young women (aged 16-26 years) 4 weeks after last vaccination in an international, randomized, open-label trial (NCT01984697). We assessed response durability through month 36. Girls received 2 (months 0 and 6 [0, 6]: n = 301; months 0 and 12 [0, 12]: n = 151) or 3 doses (months 0,2, and 6 [0, 2, 6]: n = 301); boys received 2 doses ([0, 6]: n = 301; [0, 12]: n = 150); and young women received 3 doses ([0, 2, 6]: n = 314) of 9vHPV vaccine. Anti-HPV geometric mean titers (GMTs) were assessed by competitive Luminex immunoassay (cLIA) and immunoglobulin G-Luminex immunoassay (IgG-LIA) through month 36. Anti-HPV GMTs were highest 1 month after the last 9vHPV vaccine regimen dose, decreased sharply during the subsequent 12 months, and then decreased more slowly. GMTs 2 to 2.5 years after the last regimen dose in girls and boys given 2 doses were generally similar to or greater than GMTs in young women given 3 doses. Across HPV types, most boys and girls who received 2 doses (cLIA: 81%-100%; IgG-LIA: 91%-100%) and young women who received 3 doses (cLIA: 78%-98%; IgG-LIA: 91%-100%) remained seropositive 2 to 2.5 years after the last regimen dose. Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose.

5. Observational Study of Routine Use of 9-Valent Human Papillomavirus Vaccine: Safe in More Than 140,000 Individuals

BackgroundNine-valent human papillomavirus (HPV) vaccine (9vHPV vaccine, Gardasil®9) was licensed in the US in Dec-2014. Using a self-controlled risk interval design, we conducted a post-licensure retrospective cohort study within Kaiser Permanente in Northern California (KPNC) to assess 9vHPV safety following routine administration.MethodsWe included KPNC members 9-years or older who received 9vHPV as their first dose of HPV vaccine between Oct-2015 and Sep-2017. Post-vaccination emergency and hospitalization events were compared during risk intervals (days 1–60 and 0–14) with later self-comparison intervals using conditional logistic regression, following all 9vHPV vaccine doses combined, and by dose. We investigated significant findings by assessing post-vaccination timing and medical record reviews. We evaluated and reviewed medical records for all day 0 allergic reaction and syncope events, and all deaths during the study. An independent Safety Review Committee reviewed potential safety signals.ResultsWe studied 140,628 9vHPV-vaccinated individuals, including 69,027 (49%) who received 2 doses and 29,901 (21%) 3 doses, totaling 239,556 doses. Eight categories were significantly increased in at least one analysis (Table). On review, most findings were previously known, preceded vaccination, or were better explained by other medical history. Some day 0 allergic reactions and syncope were potentially related to vaccination. None of the 20 deaths were considered related to 9vHPV.Table. Elevated diagnosis categories comparing risk and self-comparison intervals.Diagnosis CategoriesORs (95% CI)Diabetes mellitus1.66 (1.01, 2.74)DeliriumNE (1.11, NE)Nervous system disorders+21.33 (1.02, 1.72)Digestive disorders+41.21 (1.03, 1.41)Male genital disease1.60 (1.04, 2.46)Skin disorders+11.88 (1.00, 3.53)Congenital anomalies, nervous system5.01 (1.10, 22.83)Symptoms, ill-defined+11.36 (1.13, 1.64) +n indicates number of elevated sub-categories, for a total of 16 categories. NE: not estimable.ConclusionThis large study of individuals who received only 9vHPV vaccine did not identify any new safety events related to 9vHPV administration and provides reassuring evidence of the favorable safety profile of the 9vHPV vaccine.DisclosuresSe Li, PhD, Merck & Co., Inc. (Employee, Shareholder) Christine Velicer, PhD, Merck & Co., Inc. (Employee, Shareholder) Patricia Saddier, MD, PhD, Merck & Co., Inc. (Employee, Shareholder) Nicola P. Klein, MD, PhD, GSK group of companies (Research Grant or Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Protein Science (now SP) (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)

926. Antibody Response to HPV Vaccination in Pediatric and Adolescent People Living with HIV (PLWH)

BackgroundImmune dysfunction related to HIV infection is associated with an inability to clear HPV infection and may compromise the immunogenicity of quadrivalent HPV vaccine Gardasil® (4v HPV).MethodsBetween 2005 and 2017, males and females 7 to 20 years old age, were offered 3-dose 4v HPV vaccine. Plasma IgG titers to HPV 6 (H6), 11 (H11), 16 (H16) and 18 (H18) were measured using multiplex VLP-based ELISA. For the 36 patients, median interval from 1st dose to 2nd and 3rd doses were 73 and 216 days. Plasma sample 1 was collected at median of 91 days after dose 1, sample 2, 169 and sample 3, 740 after respective vaccine doses. A 4th sample was available for 26 patients, median 2327 days after dose 1. Rank-sum test, Χ 2 or Fisher’s Exact Test were employed.ResultsBefore vaccination, 10 (28%) were seropositive to 1 or more HPV types. The baseline seropositives were older than seronegatives (16 years vs 11; p=0.007). After dose 3 all participants had an Ab response to at least 1 HPV type and 32 (89%) were seropositive for 4 HPV types. Seroconversions were H18, 87%; H16 97%; H11, 100%; H6, 97%. Seroconversions after 1 dose of 4v HPV among the baseline seronegatives were 61%, 90%, 86% and 86%, respectively and 22 became seropositive for all 4 types. The 4 baseline seronegative PLWH with partial seroconversion had higher median HIV viral load (VL) compared to baseline seronegative group with full seroconversion (12,920 vs 101 copies/ml; p = 0.052), but had comparable CD4 counts. The rate of post vaccination seropositivity and baseline to peak titer response for each HPV type was not significantly different for baseline sero-groups. Among baseline seronegative, all 19 sampled distant from vaccination remained seropositive to at least 1 HPV type (84% to 3 or more types) and 6 (32%) became seronegative (sero-reversion). Those showing sero-reversion had higher VL compared to the 14 who remained seropositive (9100 vs 48; p =0.015). Time from last dose of 4v HPV to sample 4, CD4%, age, gender, and race/ethnicity were similar between the groups.Bar Graphs representing Ab response to the 4 HPV types following each dose of 4v HPV vaccine ConclusionIn the complex environment of a pediatric HIV specialty clinic, most PLWH mounted Ab responses to 4v HPV that were durable. H18 was least immunogenic. Patients with higher HIV VL were less likely to seroconvert for all types and were more likely to sero-revert.Disclosures All Authors: No reported disclosures

Immunogenicity and Safety of the 9-Valent Human Papillomavirus Vaccine in Solid Organ Transplant Recipients and Adults Infected With Human Immunodeficiency Virus (HIV).

The burden of human papillomavirus (HPV) in human immunodeficiency virus (HIV)-infected persons and solid organ transplant (SOT) recipients is high. Clinical trials on HPV vaccines in persons living with HIV and particularly in SOT recipients have been sparse to date, included low numbers of participants, and none of them assessed the 9-valent HPV (9vHPV) vaccine. We investigated the immunogenicity with respect to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and the safety of the 9vHPV vaccine in persons living with HIV and recipients of a kidney, lung, or heart transplant. This is a phase III investigator-initiated study in 100 persons living with HIV (age 18-45 years) and 171 SOT recipients (age 18-55 years). The 9vHPV vaccine was administered at day 1, month 2, and month 6. Primary outcome was seroconversion rates to the 9vHPV types at month 7. Secondary outcomes were geometric mean titers (GMTs) and frequency of adverse events (AEs). All HIV-infected participants seroconverted for all HPV types, but seroconversion ranged from 46% for HPV45 to 72% for HPV58 in SOT recipients. GMTs ranged from 180 to 2985 mMU/mL in HIV-positive participants and from 17 to 170 mMU/mL in SOT recipients, depending on the HPV type. Injection-site AEs occurred in 62% of participants but were mostly mild or moderate in intensity. None of the reported serious adverse events were deemed vaccine related. No patients died during the study. Immunogenicity of the 9vHPV vaccine is high in persons living with HIV but suboptimal in SOT recipients. The vaccine is safe and well tolerated in both groups.