Public health impact of 2-, 4-, and 9-valent HPV vaccination in females on cervical and noncervical diseases in men and women under different coverage scenarios in China: A simulation study.

The high prevalence of human papillomavirus (HPV) infection in China suggests there would be a substantial positive health impact of widespread vaccination against HPV. We adapted a previously described dynamic transmission model of the natural history of HPV infection and related diseases to the Chinese setting to estimate the public health impact in China of 2-valent (with and without cross-protection), 4-valent, and 9-valent HPV vaccination strategies. The model predicted the incidence and mortality associated with HPV-related diseases, including cervical and noncervical cancers, genital warts, and recurrent respiratory papillomatosis (RRP), based on the various vaccination coverage rate (VCR) scenarios, over a 100-year time horizon. The public health impact of the 4 vaccination strategies was estimated in terms of cases and deaths averted compared to a scenario with no vaccination. Under the assumption of various primary and catch-up VCR scenarios, all 4 vaccination strategies reduced the incidence of cervical cancer in females and noncervical cancers in both sexes, and the 4-valent and 9-valent vaccines reduced the incidence of genital warts and RRP in both sexes. The 9-valent vaccination strategy was superior on all outcomes. The number of cervical cancer cases averted over 100 years ranged from ~ 1 million to ~ 5 million while the number of cervical cancer deaths averted was ~ 345,000 to ~ 1.9 million cases, depending on the VCR scenario. The VCR for primary vaccination was the major driver of cases averted.

Effectiveness and cost-effectiveness of human papillomavirus vaccination strategies among men who have sex with men in China: a modeling study.

Introduction: The health and economic benefits of human papillomavirus (HPV) vaccination targeted at men who have sex with men (MSM) in developing settings have been rarely assessed. This study aimed to evaluate the effectiveness and cost-effectiveness of different HPV vaccination strategies among MSM in China. Methods: A Markov model was developed to simulate HPV transmission dynamics among a total of 30.73 million MSM in China. The corresponding natural history included 6 states: susceptible, infected with low-risk subtypes, high-risk subtypes, anogenital warts and anal cancer, and deaths from anal cancer. MSM were divided into three age groups with cut-off points of 27 and 45 years. Alternative vaccination strategies were built by allocating bivalent, quadrivalent, nine-valent, or no vaccine to each of the groups. We generated the prevented infections and deaths by vaccination compared with baseline (no vaccination) and calculated incremental cost-effectiveness ratios (ICERs) to determine the optimal strategy. Results: The model showed that in 10 years, at baseline, the existing cases of anogenital warts would reach 5,464,225 (IQR, 4,685,708-6,174,175); that of anal cancer would reach 1,922.95 (1,716.56-2,119.93), resulting in 940.55 (732.27-1,141.87) deaths. Under 50% vaccination coverage among one age group, the prevented cases of anogenital warts were maximized with quadrivalent vaccines allocated to MSM aged 27-45 years; that of anal cancer were maximized when offering nine-valent vaccines to the same group. Under 50% vaccination coverage among all groups, the lowest ICER (34,098.09 USD/QALY, 31,146.54-37,062.88) was reached when only quadrivalent vaccines were provided. Based on this strategy, when the annual vaccination rate increased by 30%, the ICER (33,521.75 USD/QALY, 31,040.73-36,013.92) would fall below three times China's per capita GDP. When the vaccine price decreased by 60%, the ICER was reduced to 7,344.44 USD/QALY (4,392.89-10,309.23), indicating good cost-effectiveness taking China's per capita GDP as a threshold. Conclusions: HPV vaccination can effectively reduce the prevalence and mortality of related diseases among MSM in China, especially quadrivalent vaccines for anogenital warts and nine-valent vaccines for anal cancer. MSM aged 27-45 years were the optimal group for vaccination. Annual vaccination and appropriate adjustment of vaccine price are necessary to further improve the cost-effectiveness.

Real-world impact and effectiveness assessment of the quadrivalent HPV vaccine: a systematic review of study designs and data sources.

INTRODUCTION: Vaccine effectiveness and impact studies are typically observational, generating evidence after vaccine launch in a real-world setting. For human papillomavirus (HPV) vaccination studies, the variety of data sources and methods used is pronounced. Careful selection of study design, data capture and analytical methods can mitigate potential bias in such studies. AREAS COVERED: We systematically reviewed the different study designs, methods, and data sources in published evidence (1/2007-3/2020), which assessed the quadrivalent HPV vaccine effectiveness and impact on cervical/cervicovaginal, anal, and oral HPV infections, anogenital warts, lesions in anus, cervix, oropharynx, penis, vagina or vulva, and recurrent respiratory papillomatosis. EXPERT OPINION: The rapid growth in access to real-world data allows global monitoring of effects of different public health interventions, including HPV vaccination programs. But the use of data which are not collected or organized to support research also underscore a need to develop robust methodology that provides insight of vaccine effects and consequences of different health policy decisions. To achieve the WHO elimination goal, we foresee a growing need to evaluate HPV vaccination programs globally. A critical appraisal summary of methodology used will provide timely guidance to researchers who want to initiate research activities in various settings.

Trends in anogenital wart incidence among Tennessee Medicaid enrollees, 2006-2014: The impact of human papillomavirus vaccination.

INTRODUCTION: Evidence of human papillomavirus (HPV) vaccine impact on anogenital warts (AGWs) by race or urbanicity in the US is lacking. We evaluated HPV vaccine impact in Tennessee by assessing AGW trends among Tennessee Medicaid (TennCare) enrollees aged 15-39 years from 2006-2014. METHODS: Persons with incident AGWs were identified using diagnosis/pharmacy codes from TennCare billing claims. We calculated sex-specific annual AGW incidence by age group, race, and urbanicity; estimated annual percent changes (APCs) using log-linear models; and performed pairwise comparisons by race and urbanicity. RESULTS: AGW incidence decreased among females aged 15-19 (APC = -10.6; P < 0.01) and 20-24 years (APC = -3.9; P = 0.02). Overall trends were similar between Whites and Blacks, and between those living in metropolitan statistical areas (MSAs) and non-MSAs. Rates among males aged 15-19 years began decreasing after 2010. Among enrollees aged 25-39 years, rates increased or were stable. CONCLUSIONS: Following introduction of the HPV vaccine in 2006, AGWs decreased among age groups most likely to be vaccinated. The change in trend among young males after 2010 suggests early herd effects. Our findings indicate vaccine effects and support the importance of improving adherence to current vaccination recommendations for preventing AGWs and other HPV-related diseases.

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

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

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

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

Disparities in HPV vaccination rates and HPV prevalence in the United States: a review of the literature.

Human papillomavirus (HPV) is a common sexually transmitted infection which is the cause of several cancers, including cervical cancer, and genital warts. Although cervical cancer can be prevented through screening, this cancer persists in the US. More recently, HPV vaccination has the potential to decrease the burden of HPV-related disease among young HPV-unexposed adolescents. Several initiatives aimed to encourage HPV vaccination have been adopted. Unfortunately, uptake of the HPV vaccine remains modest, despite evidence that vaccine-type HPV prevalence is decreasing as a result of HPV vaccination. Further, geographic disparities in vaccination uptake across different US regions and by race/ethnicity may contribute to continuing disparities in HPV-related cancers. More data are needed to evaluate impact of HPV vaccination on HPV prevalence in smaller geographic areas. Further, more information is needed on the impact of individual vaccination programs and policy on population level vaccination and HPV prevalence.

Medical Care Costs Associated with Genital Warts for Commercially Insured US Patients.

INTRODUCTION: Genital warts are caused by infection with human papillomavirus (HPV) and are associated with significant morbidity. Primary prevention of genital warts is possible through HPV vaccination, but vaccination rates remain low in the USA. When deciding to implement HPV vaccination programs, public health officials and policy makers rely on cost-effectiveness studies that accurately reflect costs associated with morbidity and mortality. However, previous information on the cost of treating genital warts was outdated. OBJECTIVES: We estimated the mean direct medical care costs associated with genital warts in the USA. METHODS: This was a retrospective case-control study of patients diagnosed with genital warts and matched controls. We used commercial healthcare claims data from 2011 through 2014 to estimate total 1- and 2-year costs from date of diagnosis. We used a generalized linear model to identify factors associated with monthly costs. RESULTS: We identified 34,686 eligible cases of genital warts during the period 2011-2014. The first 2-year mean direct medical cost differences between cases and controls were US$6737 for the USA. Costs were significantly higher in the first 3 months following diagnosis and were higher among older individuals, women, those with co-morbidities or psychiatric illnesses, and those located in the south and southwest USA. CONCLUSIONS: The mean direct cost of treating genital warts is approximately US$6700 in the first 2 years after diagnosis in the USA. These data can assist policy makers in decisions with respect to allocation of resources to implement HPV vaccine programs.

Estimation of the individual residual risk of cervical cancer after vaccination with the nonavalent HPV vaccine.

BACKGROUND: The nonavalent HPV (9vHPV) vaccine is indicated for active immunisation of individuals from the age of 9 years against cervical, vulvar, vaginal and anal premalignant lesions and cancers causally related to vaccine HPV high risk types 16, 18, 31, 33, 45, 52 and 58, and to the HPV low risk types 6 and 11, causing genital warts. OBJECTIVE: To estimate the lifetime risk (up to the age of 75 years) for developing cervical cancer after vaccinating a HPV naïve girl (e.g. 9 to 12 years old) with the 9vHPV vaccine in the hypothetical absence of cervical cancer screening. METHODS: We built Monte Carlo simulation models using historical pre-screening age-specific cancer incidence data and current mortality data from Denmark, Finland, Norway, Sweden and the UK. Estimates of genotype contribution fractions and vaccine efficacy were used to estimate the residual lifetime risk after vaccination assuming lifelong protection. RESULTS: We estimated that, in the hypothetical absence of cervical screening and assuming lifelong protection, 9vHPV vaccination reduced the lifetime cervical cancer and mortality risks 7-fold with a residual lifetime cancer risks ranging from 1/572 (UK) to 1/238 (Denmark) and mortality risks ranging from 1/1488 (UK) to 1/851 (Denmark). After decades of repetitive cervical screenings, the lifetime cervical cancer and mortality risks was reduced between 2- and 4-fold depending on the country. CONCLUSION: Our simulations demonstrate how evidence can be generated to support decision-making by individual healthcare seekers regarding cervical cancer prevention.

Annual prevalence and economic burden of genital warts in Korea: Health Insurance Review and Assessment (HIRA) service data from 2007 to 2015.

This study evaluated the annual prevalence of anogenital warts (AGW) caused by human papillomavirus (HPV) and analysed the trend in annual per cent changes (APC) by using national claims data from the Health Insurance Review and Assessment of Korea, 2007-2015. We also estimated the socio-economic burden and co-morbidities of AGW. All analyses were performed based on data for primary A63.0, the specific diagnosis code for AGW. The socio-economic cost of AGW was calculated based on the direct medical cost, direct non-medical cost and indirect cost. The overall AGW prevalence and socio-economic burden has increased during the last 9 years. However, the prevalence of AGW differed significantly by sex. The female prevalence increased until 2012, and decreased thereafter (APC + 3·6%). It would fall after the introduction of routine HPV vaccination, principally for females, in Korea. The male prevalence increased continuously over time (APC + 11·6%), especially in those aged 20-49 years. Referring to the increasing AGW prevalence and its disease burden, active HPV infection control surveillance and prevention in males are worth consideration.

Declines in Anogenital Warts Among Age Groups Most Likely to Be Impacted by Human Papillomavirus Vaccination, United States, 2006-2014.

OBJECTIVES: To detect decreases in anogenital warts (AGW) among sex and age groups likely to be affected by human papillomavirus vaccination. METHODS: We estimated annual AGW prevalence during 2006 to 2014 using health care claims among US private health insurance enrollees aged 15 to 39 years. We derived AGW diagnoses using 1 of the following: (1) condylomata acuminata diagnosis, (2) viral wart diagnosis combined with a benign anogenital neoplasm diagnosis or destruction or excision of an anogenital lesion, or (3) AGW medication combined with a benign anogenital neoplasm diagnosis or destruction or excision of an anogenital lesion. RESULTS: Prevalence decreased during 2008 to 2014 among females aged 15 to 19 years (annual percentage change [APC] = -14.1%; P < .001) and during 2009 to 2014 among women aged 20 to 24 years (APC = -12.9%; P < .001) and among women aged 25 to 29 years (APC = -6.0%; P = .001). We observed significant declines among men aged 20 to 24 years (APC = -6.5%; P = .005). Prevalence increased or was stable in all other sex and age groups. CONCLUSIONS: We observed AGW decreases among females in the age groups most likely to be affected by human papillomavirus vaccination and decreases in men aged 20 to 24 years. Decreased prevalence in young men is likely attributable to herd protection from vaccination among females.

Human Papillomavirus Vaccine Effectiveness Against Incident Genital Warts Among Female Health-Plan Enrollees, United States.

We examined the effectiveness of human papillomavirus vaccination by dose number and spacing against incident genital warts in a cohort of 64,517 female health-plan enrollees in the United States during 2006-2012. Eligible recipients were classified into groups by regimen: 0, 1, 2 (<6 months apart), 2 (≥6 months apart), or 3 doses. They were followed until a genital wart diagnosis, loss to follow-up, or the end of study. Propensity score weights were used to balance baseline differences across groups. To account for latent genital warts before vaccination, we applied 6- and 12-month buffer periods from last and first vaccine dose, respectively. Incidence rates and hazard ratios were calculated using Poisson regression and Cox models. The propensity score-weighted incidence rate per 100,000 person-years was 762 among unvaccinated participants. Using 6- and 12-month buffer periods, respectively, incidence rates were 641 and 257 for 1 dose, 760 and 577 for the 2-dose (<6-month interval) regimen, 313 and 194 for the 2-dose (≥6-month interval) regimen, and 199 and 162 among 3-dose vaccinees; vaccine effectiveness was 68% and 76% for the 2-dose (≥6-month interval) regimen and 77% and 80% in 3-dose vaccinees compared with unvaccinated participants. Vaccine effectiveness was not significant among vaccinees receiving 1-dose and 2-dose (<6-month interval) regimens compared with unvaccinated participants. Our findings contribute to a better understanding of the real-world effectiveness of HPV vaccination.

UK healthcare professionals' uncertainties, barriers and facilitators to the introduction of targeted human papillomavirus vaccination for men who have sex with men.

BACKGROUND: Female-only human papillomavirus (HPV) vaccination will fail to protect men who have sex with men (MSM) against HPV and its sequelae (i.e. genital warts and anal cancers). In the absence of gender-neutral HPV vaccination, targeted vaccination at sexual health clinics for MSM offers a valuable preventive opportunity. This study aimed to identify sexual healthcare professionals' (HCPs) perceived barriers and facilitators for MSM-targeted HPV vaccination. METHODS: Nineteen telephone interviews with UK-based self-referred HCPs (13 doctors, three nurses, three health advisers) were conducted in October and November 2014. The interviews were recorded and transcribed verbatim. Data were analysed thematically by two researchers. RESULTS: HCPs were unsure about selection criteria, acceptable healthcare settings and the source of vaccination funding for the introduction of MSM-targeted HPV vaccination. Lack of political and public support, MSMs' limited access to HPV vaccination and disclosure of sexual orientation to HCPs, identification of eligible MSM, patients' poor HPV awareness and motivation to complete HPV vaccination were perceived as significant barriers. HCPs believed that the introduction of official guidelines on HPV vaccination for MSM, awareness campaigns and integrated clinic procedures could improve vaccination coverage. CONCLUSION: HCPs recognised a need to protect MSM against HPV. However, several challenges and obstacles associated with the introduction of MSM-targeted HPV vaccination in the UK were reported. HCPs' perspectives and concerns need to be addressed when developing policies and guidelines for a potential MSM-targeted HPV vaccination. Future research needs to examine whether negative views of HCPs towards MSM-targeted HPV vaccination are associated with lower HPV vaccine uptake and completion rates in MSM.

Health economic evaluation of Human Papillomavirus vaccines in women from Venezuela by a lifetime Markov cohort model.

BACKGROUND: Cervical cancer (CC) and genital warts (GW) are a significant public health issue in Venezuela. Our objective was to assess the cost-effectiveness of the two available vaccines, bivalent and quadrivalent, against Human Papillomavirus (HPV) in Venezuelan girls in order to inform decision-makers. METHODS: A previously published Markov cohort model, informed by the best available evidence, was adapted to the Venezuelan context to evaluate the effects of vaccination on health and healthcare costs from the perspective of the healthcare payer in an 11-year-old girls cohort of 264,489. Costs and quality-adjusted life years (QALYs) were discounted at 5%. Eight scenarios were analyzed to depict the cost-effectiveness under alternative vaccine prices, exchange rates and dosing schemes. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Compared to screening only, the bivalent and quadrivalent vaccines were cost-saving in all scenarios, avoiding 2,310 and 2,143 deaths, 4,781 and 4,431 CCs up to 18,459 GW for the quadrivalent vaccine and gaining 4,486 and 4,395 discounted QALYs respectively. For both vaccines, the main determinants of variations in the incremental costs-effectiveness ratio after running deterministic and probabilistic sensitivity analyses were transition probabilities, vaccine and cancer-treatment costs and HPV 16 and 18 distribution in CC cases. When comparing vaccines, none of them was consistently more cost-effective than the other. In sensitivity analyses, for these comparisons, the main determinants were GW incidence, the level of cross-protection and, for some scenarios, vaccines costs. CONCLUSIONS: Immunization with the bivalent or quadrivalent HPV vaccines showed to be cost-saving or cost-effective in Venezuela, falling below the threshold of one Gross Domestic Product (GDP) per capita (104,404 VEF) per QALY gained. Deterministic and probabilistic sensitivity analyses confirmed the robustness of these results.

Disease burden of human papillomavirus infection in the Netherlands, 1989-2014: the gap between females and males is diminishing.

PURPOSE: Besides cervical cancer, HPV infection is linked to a multitude of diseases in both males and females, suggesting that vaccination programmes should be re-evaluated, with a judicious assessment made of the disease burden stratified by sex, age, and genotype. Projections of burden into the near future are also needed to provide a benchmark for evaluating the impact of vaccination programmes, and to assess the need for scaling-up preventive measures. METHODS: Using the disability-adjusted life-years (DALY) measure, we estimated the total HPV-associated disease burden in the Netherlands. Annual cancer registrations over the period 1989-2014 for all cancers with an aetiological link to HPV infection were retrieved, supplemented by incidence data on high-grade cervical intraepithelial neoplasia (CIN) and anogenital warts. RESULTS: Over the recent period 2011-2014, the average annual HPV disease burden was 10,600 DALYs (95% credible interval (CrI):10,260-10,960) in females and 3,346 DALYs (95% CrI: 2,973-3,762) in males. Burden was dominated by cervical cancer, but its share amongst women decreased from 89% in 1989 to 77% in 2014. The male share of the total disease burden increased from 9.8% in 1989 to 26% in 2014. In 2023 (before the expected clinical impact from vaccinating girls), total burden is forecasted at 1.3-fold larger than in 2014. CONCLUSIONS: The HPV-associated disease burden is higher than that reported for any other infectious disease in the Netherlands, with a larger burden observed in women than in men. The rapidly rising male share of the total burden underlines the prioritization of male HPV-related disease in prevention programmes.

Vacuna del virus del papiloma humano: seguridad y eficacia / Human Papilloma Virus Vaccine: Safety and Efficacy

INTRODUCCIÓN: Las infecciones del virus del papiloma humano (HPV) se transmiten principalmente por vía sexual, siendo su transmisión elevada; la mayor parte las infecciones son transitorias y benignas. Los tipos 6 y11 son responsables de las lesiones de bajo grado y del 80% de las verrugas genitales, mientras que la infección persistente en las mujeres por los tipos oncogénicos de HPV (casi siempre los 16 y 18) pueden provocar lesiones precancerosas que si no se tratan son susceptibles de progresar a cáncer de cuello uterino, También la infección por el HPV puede ser responsable del 90% de los cánceres de ano, 70% de los de vagina, 50% de pene, 40% de vulva y del 13 al 72% de los cánceres orofaríngeos. Con respecto a generaciones anteriores, cada vez es más precoz el inicio de las relaciones sexuales, con un número más elevado de compañeros sexuales. Estas nuevas conductas pueden contribuir al aumento de la prevalencia de la infección por el HPV. La familia del HPV cuenta con más de 120 tipos víricos que, en función de su patogenia oncológica, se clasifican en tipos de alto y bajo riesgo oncogénico. El paradigma de los primeros lo constituyen los tipos 16 y 18 y el de los segundos los tipos 6 y 11. Se estima que 527.624 nuevos casos de cáncer cervical se diagnostican anualmente en el mundo, y aproximadamente ocurren 265.672 muertes por año, siendo la segunda causa de muerte a nivel mundial entre los 15 a 44 años. En la Argentina se diagnostican 5.000 casos nuevos por año de neoplasias cervicales invasoras y 1.800 mueren por año por cáncer cervicouterino. En este contexto, se han introducidos las vacunas contra el HPV, con el propósito de disminuir la incidencia y mortalidad por cáncer cérvico-uterino. En la Argentina, la vacuna contra el virus del papiloma humano fue incorporada al calendario nacional de vacunación en el año 2011, destinada a las niñas de 11 años nacidas a partir del año 2000. Posteriormente, fue incluida también para los varones de 11 años de edad. OBJETIVO: Evaluar la eficacia y seguridad de las vacunas bivalente y cuadrivalente del HPV en la prevención de las infecciones y verrugas anogenitales, de la neoplasia epitelial cervical y del cáncer de cuello uterino. MATERIAL Y MÉTODO: Se llevó a cabo una búsqueda bibliográfica utilizando las siguientes palabras claves: Efficacy and safety of the human papillomavirus (HPV) vaccine Se exploraron las siguientes bases de datos: Cochrane library, Pub Med, Trip Database y se realizaron búsquedas secundarias. Se seleccionaron revisiones sistemáticas, meta-análisis e investigaciones clínicas controladas aleatorizadas publicadas en los últimos 5 años. Se incluyeron 14 estudios: 1 meta-análisis, 1 revisión sistemática, 7 ensayos clínicos controlados y 5 estudios de seguimiento de 5 ensayos controlados previos publicados entre los años 2012 y 2017, que evaluaran eficacia y seguridad de las vacunas bivalente y/o cuadrivalente para el virus del papiloma humano. RESULTADOS: Cortés (7) refiere que la Organización Mundial de la Salud (OMS) recomienda utilizar al CIN2+ y a la persistencia de la infección por HPV como variables subrogadas de eficacia ante la imposibilidad ética y metodológica de establecer el cáncer de cuello uterino como variable final de la eficacia en los ensayos. La medida del efecto utilizada para evaluar la eficacia de la vacuna fue la reducción del riesgo relativo (RRR) El concepto de infección persistente se basa en el momento del seguimiento, en el cual aparece el incremento significativo de riesgo de desarrollar CIN2+, que informaciones recientes lo sitúan por arriba de los 12 meses de infección. De acuerdo a estas recomendaciones, comentaremos fundamentalmente dichos puntos finales que evalúan la eficacia de los estudios incluidos en esta evaluación. CONCLUSIÓN: Los resultados de los estudios incluidos fueron notablemente consistentes entre ellos, mostrando una elevada eficacia en la prevención de lesiones asociadas a la infección por los tipos de HPV-6/11/16/18 y también una elevada inmunogenicidad, con tasas de seroconversión próximas al 100% y con títulos de anticuerpos superiores a los logrados a través de la infección natural27. Las vacunas demuestran un alto perfil de seguridad, con un balance riesgo beneficio positivo27. Estos resultados se traducen en la prevención de la infección, de lesiones precancerosas, de lesiones neoplásicas cervicales, vaginales, vulvares y de las verrugas anogenitales. Confiere además, cierta protección cruzada contra otros serotipos no incluidos en la vacuna.

Early impact of Ontario's human papillomavirus (HPV) vaccination program on anogenital warts (AGWs): A population-based assessment.

INTRODUCTION: This study aimed to evaluate the early population impact of Ontario's school-based human papillomavirus (HPV) vaccination program, implemented in September 2007 for grade 8 females, by comparing anogenital wart (AGW) health care utilization before and after vaccine program implementation, in program-eligible and program-ineligible cohorts, focusing on 15-26year olds. METHODS: Using a retrospective longitudinal population-based study design, health administrative data were used to identify incident AGWs and total health service utilization (HSU) for AGWs for Ontario residents 15years and older between April 1 2004 and March 31 2014. The study period was divided into two eras: the pre-vaccine program era and the vaccine program era. Negative binomial models were generated to analyze trends across time by age group and sex. We adjusted female rates for routine Papanicolaou (Pap) testing to address spillover effects of Pap smear policy changes on AGW diagnosis. RESULTS: Between fiscal years 2004 and 2013, AGW incidence decreased 2.6% on average per year in 15-17year old females, and total HSU for AGWs decreased an average of 4.8% and 2.2% per year in 15-17 and 18-20year old females. Comparing the vaccine era to the pre-vaccine era, AGW incidence decreased 6.5% in 18-20year old females, and AGW HSU decreased 13.8%, 11.1%, and 10.0% in 15-17, 18-20, and 21-23year old females respectively. In contrast, male AGW incidence rates increased an average of 4.1%, 2.8%, and 0.9% per year in 15-17, 21-23, and 24-26year old males respectively. AGW incidence rates increased 12.2% in 15-17year old males from the pre-vaccine to vaccine era. CONCLUSION: The decline in AGW incidence and HSU in program-eligible females suggests the school-based HPV vaccination program has had an early population impact in Ontario. The increasing AGW incidence in males suggests no early evidence of herd effects in males.

The value of male human papillomavirus vaccination in preventing cervical cancer and genital warts in a low-resource setting.

OBJECTIVE: To estimate health benefits and incremental cost-effectiveness of human papillomavirus (HPV) vaccination of pre-adolescent boys and girls compared with girls alone for preventing cervical cancer and genital warts. DESIGN: Model-based economic evaluation. SETTING: Southern Vietnam. POPULATION: Males and females aged ≥9 years. METHODS: We simulated dynamic HPV transmission to estimate cervical cancer and genital warts cases. Models were calibrated to epidemiological data from south Vietnam. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs): cost per quality-adjusted life-year (QALY). RESULTS: Vaccinating girls alone was associated with reductions in lifetime cervical cancer risk ranging from 20 to 56.9% as coverage varied from 25 to 90%. Adding boys to the vaccination programme yielded marginal incremental benefits (≤3.6% higher absolute cervical cancer risk reduction), compared with vaccinating girls alone at all coverages. At ≤25 international dollars (I$) per vaccinated adolescent (I$5 per dose), HPV vaccination of boys was below the threshold of Vietnam's per-capita GDP (I$2800), with ICERs ranging from I$734 per QALY at 25% coverage to I$2064 per QALY for 90% coverage. Including health benefits from averting genital warts yielded more favourable ICERs, and vaccination of boys at I$10/dose became cost-effective at or below 75% coverage. Using a lower cost-effectiveness threshold of 50% of Vietnam's GDP (I$1400), vaccinating boys was no longer attractive at costs above I$5 per dose regardless of coverage. CONCLUSION: Vaccination of boys may be cost-effective at low vaccine costs, but provides little benefit over vaccinating girls only. Focusing on achieving high vaccine coverage of girls may be more efficient for southern Vietnam and similar low-resource settings. TWEETABLE ABSTRACT: Limited cervical cancer reduction from including boys in HPV vaccination of girls in low-resource settings.

[Cost-effectiveness of quadrivalent vaccine against human papilloma virus in Argentina based on a dynamic transmission model]. / Costo-efectividad de la vacuna tetravalente contra VPH en Argentina, a partir de un modelo dinámico de transmisión.

OBJECTIVE: To assess the cost-effectiveness of the quadrivalent vaccine against human papillomavirus (HPV) in Argentina from the health system perspective. MATERIALS AND METHODS: A dynamic transmission model was used to estimate the impact of the vaccine on the incidence of cervical cancer, warts, and other HPV related diseases; in quality adjusted life years (QALYs); and in healthcare costs. RESULTS: Vaccination could reduce the risk of cervical cancer by 60% and by 67% the risk of genital warts. Compared to a non-vaccine scenario, the immunization strategy showed an incremental benefit of 0.00234 QALY per person at an incremental cost of US$2.36, resulting in an incremental cost-effectiveness ratio of US$1007.55 per QALY gained. Sensitivity analysis proved the robustness of these results. CONCLUSIONS: Immunization with the quadrivalent vaccine was a cost-effective intervention in Argentina, and it was far below the threshold of one gross domestic product per capita (US$15 009) per QALY gained.

Costo-efectividad de la vacuna tetravalente contra VPH en Argentina, a partir de un modelo dinámico de transmisión / Cost-effectiveness of quadrivalent vaccine against human papilloma virus in Argentina based on a dynamic transmission model

Objetivo. Evaluar la costo-efectividad (CE) de la vacuna tetravalente contra el virus de papiloma humano (VPH) en Argentina, desde la perspectiva del sistema de salud. Material y métodos. Se utilizó un modelo dinámico de transmisión para estimar el impacto en la incidencia de cáncer de cuello uterino (Cacu), verrugas y otras lesiones, en los años de vida ajustados por calidad (AVAC) y en costos sanitarios. Resultados. La vacuna podría reducir en 60% el riesgo de muerte por Cacu y en 67% el de padecer verrugas genitales. Comparada con no vacunar, la estrategia de vacunación mostró un beneficio incremental promedio de 0.00234 AVAC por persona a un costo incremental de 2.36 dólares, con una CE de 1007.55 dólares por AVAC ganado. Los resultados demostraron ser robustos en el análisis de sensibilidad. Conclusiones. La inmunización resultaría costo-efectiva, con una CE inferior a un producto interno bruto per cápita (15 009 dólares) por AVAC ganado.

Objective. To assess the cost-effectiveness of the quadrivalent vaccine against human papillomavirus (HPV) in Argentina from the health system perspective. Materials and methods. A dynamic transmission model was used to estimate the impact of the vaccine on the incidence of cervical cancer, warts, and other HPV related diseases; in quality adjusted life years (QALYs); and in healthcare costs. Results. Vaccination could reduce the risk of cervical cancer by 60% and by 67% the risk of genital warts. Compared to a non-vaccine scenario, the immunization strategy showed an incremental benefit of 0.00234 QALY per person at an incremental cost of US$2.36, resulting in an incremental cost-effectiveness ratio of US$1007.55 per QALY gained. Sensitivity analysis proved the robustness of these results. Conclusions. Immunization with the quadrivalent vaccine was a cost-effective intervention in Argentina, and it was far below the threshold of one gross domestic product per capita (US$15 009) per QALY gained.