The cost-effectiveness of male HPV vaccination in the United States

Introduction

The objective of this study was to estimate the cost-effectiveness of adding human papillomavirus (HPV) vaccination of 12-year-old males to a female-only vaccination program for ages 12-26 years in the United States.

Methods

We used a simplified model of HPV transmission to estimate the reduction in the health and economic burden of HPV-associated diseases in males and females as a result of HPV vaccination. Estimates of the incidence, cost-per-case, and quality-of-life impact of HPV-associated health outcomes were based on the literature. The HPV-associated outcomes included were: cervical intraepithelial neoplasia (CIN); genital warts; juvenile-onset recurrent respiratory papillomatosis (RRP); and cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers.

Results

The cost-effectiveness of male vaccination depended on vaccine coverage of females. When including all HPV-associated outcomes in the analysis, the incremental cost per quality-adjusted life year (QALY) gained by adding male vaccination to a female-only vaccination program was $23,600 in the lower female coverage scenario (20% coverage at age 12 years) and $184,300 in the higher female coverage scenario (75% coverage at age 12 years). The cost-effectiveness of male vaccination appeared less favorable when compared to a strategy of increased female vaccination coverage. For example, we found that increasing coverage of 12-year-old girls would be more cost-effective than adding male vaccination even if the increased female vaccination strategy incurred program costs of $350 per additional girl vaccinated.

Conclusions

HPV vaccination of 12-year-old males might potentially be cost-effective, particularly if female HPV vaccination coverage is low and if all potential health benefits of HPV vaccination are included in the analysis. However, increasing female coverage could be a more efficient strategy than male vaccination for reducing the overall health burden of HPV in the population.     

Impact of vaccinating boys and men against HPV in the United States

We assessed the public health impact and value of vaccinating boys and men with the quadrivalent HPV vaccine in the United States. We used mathematical population models, accounting for both the direct and indirect protective effects of vaccination. Inputs for the models were obtained from public data sources, published literature, and analyses of clinical trial data. Compared with a program of vaccinating girls and women only, including boys and men 9–26 years of age would further decrease the cumulative mean number of genital wart cases, cervical intraepithelial neoplasia 2/3 cases, cancer cases, and cancer deaths by 5,146,000, 708,000, 116,000, and 40,000, respectively, within 100 years. The mean cost-effectiveness ratio (2008 US $) of this strategy was $25,700 (range: 13,600–48,800) per QALY gained if vaccination protects against all HPV 6/11/16/18-associated diseases, and $69,000 (range: 37,700–152,300)/QALY if it only protects against diseases currently in the vaccine indication. Vaccinating boys and men age 9–26 against all HPV 6/11/16/18-associated diseases provides substantial public health benefits and is cost-effective at commonly cited thresholds.     

Cost-effectiveness of HPV vaccination for adults through age 45 years in the United States: Estimates from a simplified transmission model

IntroductionThe objective of this study was to assess incremental costs and benefits of a human papillomavirus (HPV) vaccination program expanded to include “mid-adults” (adults aged 27 through 45 years) in the United States.MethodsWe adapted a previously published, dynamic mathematical model of HPV transmission and HPV-associated disease to estimate the incremental costs and benefits of a 9-valent HPV vaccine (9vHPV) program for people aged 12 through 45 years compared to a 9vHPV program for females aged 12 through 26 years and males aged 12 through 21 years.ResultsA 9vHPV program for females aged 12 through 26 years and males aged 12 through 21 years was estimated to cost < $10,000 quality-adjusted life year (QALY) gained, compared to no vaccination. Expanding the 9vHPV program to include mid-adults was estimated to cost $587,600 per additional QALY gained when including adults through age 30 years, and $653,300 per additional QALY gained when including adults through age 45 years. Results were most sensitive to assumptions about HPV incidence among mid-adults, current and historical vaccination coverage, vaccine price, and the impact of HPV diseases on quality of life.ConclusionsMid-adult vaccination is much less cost-effective than the comparison strategy of routine vaccination for all adolescents at ages 11 to 12 years and catch-up vaccination for women through age 26 years and men through age 21 years.     

Age-Based Programs for Vaccination against HPV

Background:  The risk of infection with human papillomavirus (HPV) increases with age. Answering the question of which age groups are appropriate to target for catch-up vaccination with the newly licensed quadrivalent HPV vaccine (types 6/11/16/18) will be important for developing vaccine policy recommendations.
Objectives:  To assess the value of varying female HPV vaccination strategies by specific age groups of a catch-up program in the United States.
Methods:  The authors used previously published mathematical population dynamic model and cost-utility analysis to evaluate the public health impact and cost-effectiveness of alternative quadrivalent HPV (6/11/16/18) vaccination strategies. The model simulates heterosexual transmission of HPV infection and occurrence of cervical intraepithelial neoplasia (CIN), cervical cancer, and external genital warts in an age-structured population stratified by sex and sexual activity groups. The cost-utility analysis estimates the cost of vaccination, screening, diagnosis, and treatment of HPV diseases, and quality-adjusted survival.
Results:  Compared with the current screening practices, vaccinating girls and women ages 12 to 24 years was the most effective strategy, reducing the number of HPV6/11/16/18-related genital warts, CIN grades 2 and 3, and cervical cancer cases among women in the next 25 years by 3,049,285, 1,399,935, and 30,021; respectively. The incremental cost-effectiveness ratio of this strategy when compared with vaccinating girls and women ages 12 to 19 years was $10,986 per quality-adjusted life-year gained.
Conclusion:  Relative to other commonly accepted health-care programs, vaccinating girls and women ages 12 to 24 years appears cost-effective.     

The association between state Medicaid expansion and human papillomavirus vaccination

Increased vaccination against human papillomavirus (HPV) is recommended to reduce the incidence of anogenital and oropharyngeal cancers. This study aims to evaluate the impact of Medicaid expansion by states on HPV vaccination uptake among adolescents ages 13–17 in the United States. This study analyzed data from the National Immunization Survey (NIS) – Teen from 2011 to 2017 using a cross-sectional design. The adjusted difference-in-difference estimate of Medicaid expansion on HPV vaccine initiation was statistically significant (β = 0.031, 95% CI [0.016, 0.046]). There were significant increases in HPV vaccination after states expanded their Medicaid program. The largest increase occurred in those individuals below the federal poverty level and a modest increase occurred in those above the federal poverty level but below $75,000 of annual family income. Further research should be conducted to analyze the combined effect of multiple policies on HPV vaccination.     

Estimates of the timing of reductions in genital warts and high grade cervical intraepithelial neoplasia after onset of human papillomavirus (HPV) vaccination in the United States

Background

The objective of this study was to estimate the number of years after onset of a quadrivalent HPV vaccination program before notable reductions in genital warts and cervical intraepithelial neoplasia (CIN) will occur in teenagers and young adults in the United States.

Methods

We applied a previously published model of HPV vaccination in the United States and focused on the timing of reductions in genital warts among both sexes and reductions in CIN 2/3 among females. Using different coverage scenarios, the lowest being consistent with current 3-dose coverage in the United States, we estimated the number of years before reductions of 10%, 25%, and 50% would be observed after onset of an HPV vaccination program for ages 12–26 years.

Results

The model suggested female-only HPV vaccination in the intermediate coverage scenario will result in a 10% reduction in genital warts within 2–4 years for females aged 15–19 years and a 10% reduction in CIN 2/3 among females aged 20–29 years within 7–11 years. Coverage had a major impact on when reductions would be observed. For example, in the higher coverage scenario a 25% reduction in CIN2/3 would be observed with 8 years compared with 15 years in the lower coverage scenario.

Conclusions

Our model provides estimates of the potential timing and magnitude of the impact of HPV vaccination on genital warts and CIN 2/3 at the population level in the United States. Notable, population-level impacts of HPV vaccination on genital warts and CIN 2/3 can occur within a few years after onset of vaccination, particularly among younger age groups. Our results are generally consistent with early reports of declines in genital warts among youth.     

HPV Vaccination's Second Act: Promotion, Competition, and Compulsion

Developments regarding human papillomavirus (HPV) vaccines will transform HPV vaccination in the United States while simultaneously raising several new policy and ethical concerns.Policymakers, vaccine manufacturers, and the public health community must now respond to the presence of competing vaccines that are similar but distinct, particularly with respect to genital wart prevention and the benefits of vaccinating males. This work arises in the shadow of the contentious introduction of the HPV vaccine Gardasil (Merck & Co, Inc, Whitehouse Station, NJ) in 2006, particularly the opposition to efforts in many states to require the vaccine for school attendance.I review the current status of HPV vaccine policy in the United States and examine issues of public health ethics and policy central to ongoing and future HPV vaccination programs.Recent developments regarding human papillomavirus (HPV) vaccines signal the beginning of a new era in cervical cancer prevention. The October 2009 licensure of a second vaccine, Cervarix (GlaxoSmithKline, Philadelphia, PA), for females and the expanded approval of the first vaccine, Gardasil (Merck & Co, Inc, Whitehouse Station, NJ), for use by both genders create new opportunities to further reduce the burden of cervical cancer and other HPV-related diseases. However, as the introduction of Gardasil in 2006 revealed, HPV vaccine policy can be extremely contentious, and vaccination overall remains a source of considerable controversy.As this next phase of HPV vaccination efforts begins, policymakers, public health officials, and vaccine manufacturers have the opportunity to avoid repeating the mistakes that plagued the arrival of Gardasil while building on its successes. Doing so, and addressing the new ethical and policy challenges that result from having two similar yet distinct vaccines, will be critical to the long-term success of HPV vaccination programs in the United States and worldwide.     

Cost-effectiveness of nonavalent HPV vaccination among males aged 22 through 26 years in the United States

IntroductionIn the United States, routine human papillomavirus (HPV) vaccination is recommended for females and males at age 11 or 12 years; the series can be started at age 9 years. Vaccination is also recommended for females through age 26 years and males through age 21 years. The objective of this study was to assess the health impact and cost-effectiveness of harmonizing female and male vaccination recommendations by increasing the upper recommended catch-up age of HPV vaccination for males from age 21 to age 26 years.MethodsWe updated a published model of the health impact and cost-effectiveness of 9-valent human papillomavirus vaccine (9vHPV). We examined the cost-effectiveness of (1) 9vHPV for females aged 12 through 26 years and males aged 12 through 21 years, and (2) an expanded program including males through age 26 years.ResultsCompared to no vaccination, providing 9vHPV for females aged 12 through 26 years and males aged 12 through 21 years cost an estimated $16,600 (in 2016 U.S. dollars) per quality-adjusted life year (QALY) gained. The estimated cost per QALY gained by expanding male vaccination through age 26 years was $228,800 and ranged from $137,900 to $367,300 in multi-way sensitivity analyses.ConclusionsThe cost-effectiveness ratios we estimated are not so favorable as to make a strong economic case for recommending expanding male vaccination, yet are not so unfavorable as to preclude consideration of expanding male vaccination. The wide range of plausible results we obtained may underestimate the true degree of uncertainty, due to model limitations. For example, the cost per QALY might be less than our lower bound estimate of $137,900 had our model allowed for vaccine protection against re-infection. Models that specifically incorporate men who have sex with men (MSM) are needed to provide a more comprehensive assessment of male HPV vaccination strategies.     

No association between HPV vaccination and infertility in U.S. females 18–33 years old

BackgroundHuman papillomavirus (HPV) vaccines have been recommended as primary prevention of HPV-related cancers for over 10 years in the United States, and evidence reveals decreased incidence of HPV infections following vaccination. However, concerns have been raised that HPV vaccines could decrease fertility. This study examined the relationship between HPV immunization and self-reported infertility in a nationally representative sample.MethodsData from the 2013–2016 National Health and Nutrition Examination Survey were analyzed to assess likelihood of self-reported infertility among women aged 20 to 33, who were young enough to have been offered HPV vaccines and old enough to have been queried about infertility (n = 1114). Two logistic regression models, stratified by marital history, examined potential associations between HPV vaccination and infertility. Model 1 assessed the likelihood of infertility among women who had never been pregnant or whose pregnancies occurred prior to HPV vaccination. Model 2 accounted for the possibility of latent and/or non-permanent post-vaccine infertility by including all women 20–33 years old who reported any 12-month period of infertility.Results8.1% reported any infertility. Neither model revealed any association between HPV vaccination at any age and self-reported infertility, regardless of marital status.ConclusionThere was no evidence of increased infertility among women who received the HPV vaccine. These results provide further evidence of HPV vaccine safety and should give providers confidence in recommending HPV vaccination. Further research should explore protective effects of HPV vaccines on female and male fertility.     

The accuracy of human papillomavirus vaccination status based on adult proxy recall or household immunization records for adolescent females in the United States: results from the National Immunization Survey-Teen

PurposeWe assessed the accuracy of human papillomavirus (HPV) vaccination status based on adult proxy recall and household immunization records for adolescent females in the United States.MethodsWe used data from the 2010 National Immunization Survey—Teen for females aged 13 to 17 years. The accuracy of HPV vaccination status (≥1 dose) based on adult proxy recall (unweighted n = 6868) and household immunization records (unweighted n = 2216) was assessed by estimating the sensitivity, specificity, and corresponding 95% confidence limits (CL) of these measures with provider-reported HPV vaccination status as the reference standard. Our analyses accounted for the complex survey design and population weights.ResultsThe sensitivity and specificity of adult proxy recall were 83.9% (95% CL: 81.2%, 86.6%) and 90.4% (95% CL: 88.9%, 92.0%), respectively. Conversely, the sensitivity and specificity of household immunization records were 74.2% (95% CL: 69.1%, 79.2%) and 98.0% (95% CL: 96.8%, 99.1%), respectively. The accuracy of both measures varied by race/ethnicity, proxy respondent, and maternal education.ConclusionsOur results suggest that adult proxy recall and household immunization records have reasonable accuracy for classifying HPV vaccination status for females aged 13 to 17 years in the United States, but these measures present a trade-off between sensitivity and specificity.     

Human papillomavirus (HPV) and influenza vaccine behavior among Muslim women in the United States

Abstract

In this study, we examined vaccination behaviors—single dose human papillomavirus (HPV) vaccination, triple dose HPV vaccination, and influenza vaccination—among Muslim women residing in the United States. Using logistic regression models, we analyzed self-reported survey. We found that respondents had lower rates of HPV vaccination and higher rates of influenza vaccination, relative to the general American population. The respondents in our sample who reported contraceptive use had higher odds of vaccination. In this study the authors provide a springboard for the enhancement of patient-centered care through better understanding of health behaviors and cultural preferences of underrepresented communities in research.     

Regional variation in human papillomavirus vaccination uptake and completion among adolescents 13–17 in the state of Texas

BackgroundHPV vaccination rates remain low in the United States despite efforts to increase them, although rates vary geographically both at the state and regional level within the United States. This study examines differences in teen HPV vaccination rates and associated sociodemographic factors among six regions in Texas to understand potential variation in smaller regions. These differences may inform planning of local public health interventions aimed at increasing vaccination uptake in teens.MethodsWe analyzed sociodemographic and vaccination data for a total of 2256 teens 13–17 years old from six regions in Texas using the 2017 National Immunization Survey--Teen (NIS-Teen). We used survey-weighted chi-squared tests to compare demographic characteristics and HPV vaccination initiation and series completion across regions and multivariable robust Poisson regression models to examine the association between region of residence and HPV vaccination outcomes.ResultsRates of initiation and completion of the HPV vaccine series varied significantly between six regions in Texas and were both highest in El Paso County and lowest in Dallas County (initiation 82.8% vs 52.5%, P < 0.001; completion 51.3% vs 30.2%, P < 0.001). Adjusted multivariable log binomial regression models demonstrated that teens in Dallas county were significantly less likely to initiate the HPV vaccine series than teens in Travis county (RR = 0.79, 95% CI: (0.65, 0.95), P = 0.01).DiscussionHPV vaccination uptake varied significantly between six regions in Texas, highlighting the importance of closely examining local regions in public health planning efforts. Intervention efforts should consider the variation in sociodemographic characteristics as well as policy at the regional level to best improve vaccination rates in communities across the nation.     

Human Papillomavirus Prevalence in Oropharyngeal Cancer before Vaccine Introduction,United States

We conducted a study to determine prevalence of HPV types in oropharyngeal cancers in the United States and establish a prevaccine baseline for monitoring the impact of vaccination. HPV DNA was extracted from tumor tissue samples from patients in whom cancer was diagnosed during 1995–2005. The samples were obtained from cancer registries and Residual Tissue Repository Program sites in the United States. HPV was detected and typed by using PCR reverse line blot assays. Among 557 invasive oropharyngeal squamous cell carcinomas, 72% were positive for HPV and 62% for vaccine types HPV16 or 18. Prevalence of HPV-16/18 was lower in women (53%) than in men (66%), and lower in non-Hispanic Black patients (31%) than in other racial/ethnic groups (68%–80%). Results indicate that vaccines could prevent most oropharyngeal cancers in the United States, but their effect may vary by demographic variables.     

“I Thought It Was Just For Teenagers”: Knowledge,Attitudes, and Beliefs about HPV Vaccination Among Women Aged 27 to 45

PurposeWe aimed to identify human papillomavirus (HPV) and HPV vaccine-related knowledge, attitudes, and beliefs among women aged 27–45 years, who became eligible for HPV vaccination in 2018.MethodsEight virtual focus groups were conducted with 52 unvaccinated cisgender women aged 27–45 years living in Southern California's Inland Empire. Themes related to women's knowledge, attitudes, and beliefs were systematically identified using the rigorous and accelerated data reduction technique.ResultsThe sample was diverse: 62% of participants were Hispanic, Black, or Asian; 17% identified as lesbian or bisexual; and annual household incomes ranged from $0 to $260,000 (median, $60,500). Key qualitative themes centered on 1) questions about HPV and HPV vaccination, 2) knowledge and beliefs about HPV and HPV vaccination, 3) concerns about vaccine side effects and safety, 4) low perceived benefits of vaccination, and 5) social factors influencing vaccine acceptance. Few participants were aware adults aged 27–45 years are eligible for HPV vaccination or that vaccination can still be beneficial after sexual debut. Many believed HPV vaccination caused serious side effects among adolescents and questioned whether safety had been adequately studied for newly eligible adults. Although many participants associated HPV vaccination with social stigma, some emphasized that vaccination was a way to exercise control over their health and prevent illness, given they could not always control the actions of their sexual contacts.ConclusionsFindings provide insight into knowledge, attitudes, and beliefs about HPV and HPV vaccination among women aged 27–45 years, which may be useful for informing interventions to promote shared clinical decision-making between patients and health providers.     

HPV Vaccination Practices Among Juvenile Justice Facilities in the United States

The juvenile justice setting provides a unique opportunity to administer the human papillomavirus (HPV) vaccine to a high-risk, medically underserved population. We examined current HPV vaccination practices in the United States. Most states (39) offer the HPV vaccine to females committed to juvenile justice facilities.     

Estimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus in the United States

Estimates of the direct medical costs attributable to human papillomavirus (HPV) can help to quantify the economic burden of HPV and to illustrate the potential benefits of HPV vaccination. The purpose of this report was to update the estimated annual direct medical costs of the prevention and treatment of HPV-associated disease in the United States, for all HPV types. We included the costs of cervical cancer screening and follow-up and the treatment costs of the following HPV-associated health outcomes: cervical cancer, other anogenital cancers (anal, vaginal, vulvar and penile), oropharyngeal cancer, genital warts, and recurrent respiratory papillomatosis (RRP). We obtained updated incidence and cost estimates from the literature. The overall annual direct medical cost burden of preventing and treating HPV-associated disease was estimated to be $8.0 billion (2010 U.S. dollars). Of this total cost, about $6.6 billion (82.3%) was for routine cervical cancer screening and follow-up, $1.0 billion (12.0%) was for cancer (including $0.4 billion for cervical cancer and $0.3 billion for oropharyngeal cancer), $0.3 billion (3.6%) was for genital warts, and $0.2 billion (2.1%) was for RRP.     

County-Level Factors Associated With HPV Vaccine Coverage Among 11-Year-Olds to 12-Year-Olds Living in Florida in 2019

BackgroundIn the United States, human papillomavirus (HPV) vaccine initiation and up-to-date (UTD) status are associated with multiple factors at the individual level such as racial/cultural (e.g., race, immigration status), socioeconomic status (e.g., living below poverty level, education), and healthcare access (e.g., insurance status/type). HPV vaccination rates differ dramatically by US geographic areas and within states. To tailor interventions to local areas, it is important to understand county-level characteristics associated with HPV vaccination rates.MethodsUsing linear regression, we assessed the association between county-level HPV vaccination initiation and UTD rates for 11-year-olds to 12-year-olds in Florida (collected from the Florida SHOTS immunization registry) and county-level variables. Factors found significant in bivariate analysis and with a variance influence factors <4 were included in multivariable models.ResultsIn 2019, county-level HPV vaccine coverage among Florida 11-year-olds to 12-year-olds ranged from 31% to 92% initiation and 3%–36% UTD. Counties with the lowest HPV vaccine coverage were concentrated in Florida's North-Central and Panhandle regions. In multivariable models, counties with primarily rural populations had lower vaccination initiation and UTD coverage. Above and beyond the association with rurality, UTD coverage was associated with family physicians per 100,000 residents and uninsured or Medicaid-enrolled populations.DiscussionWhile Florida county-level HPV vaccine initiation rates among 11-year-olds to 12-year-olds varied by county in 2019, UTD rates remained universally low despite recommendations. Tailoring interventions toward healthcare access in rural communities may increase HPV vaccine coverage.     

Human Papillomavirus Vaccination at a Time of Changing Sexual Behavior

Human papillomavirus (HPV) prevalence varies widely worldwide. We used a transmission model to show links between age-specific sexual patterns and HPV vaccination effectiveness. We considered rural India and the United States as examples of 2 heterosexual populations with traditional age-specific sexual behavior and gender-similar age-specific sexual behavior, respectively. We simulated these populations by using age-specific rates of sexual activity and age differences between sexual partners and found that transitions from traditional to gender-similar sexual behavior in women <35 years of age can result in increased (2.6-fold in our study) HPV16 prevalence. Our model shows that reductions in HPV16 prevalence are larger if vaccination occurs in populations before transitions in sexual behavior and that increased risk for HPV infection attributable to transition is preventable by early vaccination. Our study highlights the importance of using time-limited opportunities to introduce HPV vaccination in traditional populations before changes in age-specific sexual patterns occur.     

Primary care physician support for harmonizing HPV vaccination recommendations across genders — United States, 2018

In the United States, human papillomavirus (HPV) catch-up vaccination has been nationally recommended for women and men of different ages. We surveyed national networks of primary care physicians specializing in family medicine, pediatrics, and internal medicine to assess attitudes about HPV vaccination. Of 785 physicians, 730 (93.0%), were in favor of a change to harmonize the recommended catch-up vaccination age across genders; the most commonly cited reason was to simplify the immunization schedule (97.9%). After considering these and other data, the Advisory Committee on Immunization Practices updated national policy to recommend catch-up vaccination for all persons through age 26 years.