Increased risk of dementia in patients with genital warts: A nationwide cohort study in Taiwan.

Genital warts are a common sexually transmitted disease caused by human papillomavirus (HPV) infections. The prevalence of dementia is 4-8% in those aged 65 years or older in Taiwanese community studies, with a high social and economic burden for patients, family caregivers, the community and society. Previous studies have shown that viral infections such as herpes simplex and herpes zoster were associated with dementia. This study aimed to investigate the association between dementia and HPV infections. A population-based cohort study using data from Taiwan's National Health Insurance Research Database was conducted. Fine and Grays's survival analysis was employed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between genital warts and dementia. From all of the potential participants aged 50 years or more, a total of 16 116 patients were enrolled, including 4029 genital warts-infected patients, with 12 087 sex-, age- and indexed date-matched controls (1:3). The cumulative incidences of dementia were 10.72 per 103  person-years and 6.43 per 103  person-years in the genital warts and control group, respectively. There were 475 dementia cases from the genital warts cohort during the follow-up period of 15 years. The adjusted HR for dementia was 1.485 (95% CI, 1.321-1.668; P < 0.001) for genital warts patients after adjusting for all of the covariates. Our study indicates that genital warts infection may increase the risk of dementia.

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.

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.

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.

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.

Prevalence and correlates of cervical HPV infection in a clinic-based sample of HIV-positive Hispanic women.

OBJECTIVES: Puerto Rico (PR), is the fifth highest jurisdiction of the United States of America (US) with respect to HIV prevalence and the leading in cervical cancer incidence. This cross-sectional study describes the prevalence and correlates of cervical HPV infection among a clinic-based sample of 302 women living with HIV/AIDS in PR. METHODS: Data collection included questionnaires, blood and cervical samples. Multivariable logistic regression models were used to estimate the magnitude of association (adjusted Prevalence odds ratio [aPOR]) between HPV cervical infection and other covariates. RESULTS: Mean age of participants was 40.3 years (± 10.3SD). The prevalence of HPV infection was 50.3%; 41.1% for low-risk types and 29.5% for high-risk types. Having ≥ 10 lifetime sexual partners (aPOR = 2.10, 95% CI:1.02-4.29), an abnormal Pap (aPOR = 3.58, 95% CI:1.93-6.62), active genital warts (aPOR = 3.45, 95% CI:1.60-7.42), and CD4 counts ≤ 200 (aPOR = 4.24, 95% CI: 1.67-10.78) were positively associated with any cervical HPV infection. Similar results were observed for HR HPV infection. CONCLUSIONS: A high burden of HPV co-infection exists among women living with HIV/AIDS in this population. Given the high incidence of HIV in PR and the higher risk of cervical cancer among women living with HIV/AIDS, HPV vaccination should be promoted in this population.

Cost analysis of Human Papillomavirus-related cervical diseases and genital warts in Swaziland.

BACKGROUND: Human papillomavirus (HPV) has proven to be the cause of several severe clinical conditions on the cervix, vulva, vagina, anus, oropharynx and penis. Several studies have assessed the costs of cervical lesions, cervical cancer (CC), and genital warts. However, few have been done in Africa and none in Swaziland. Cost analysis is critical in providing useful information for economic evaluations to guide policymakers concerned with the allocation of resources in order to reduce the disease burden. MATERIALS AND METHODS: A prevalence-based cost of illness (COI) methodology was used to investigate the economic burden of HPV-related diseases. We used a top-down approach for the cost associated with hospital care and a bottom-up approach to estimate the cost associated with outpatient and primary care. The current study was conducted from a provider perspective since the state bears the majority of the costs of screening and treatment in Swaziland. All identifiable direct medical costs were considered for cervical lesions, cervical cancer and genital warts, which were primary diagnoses during 2015. A mix of bottom up micro-costing ingredients approach and top-down approaches was used to collect data on costs. All costs were computed at the price level of 2015 and converted to dollars ($). RESULTS: The total annual estimated direct medical cost associated with screening, managing and treating cervical lesions, CC and genital warts in Swaziland was $16 million. The largest cost in the analysis was estimated for treatment of high-grade cervical lesions and cervical cancer representing 80% of the total cost ($12.6 million). Costs for screening only represented 5% of the total cost ($0.9 million). Treatment of genital warts represented 6% of the total cost ($1million). CONCLUSION: According to the cost estimations in this study, the economic burden of HPV-related cervical diseases and genital warts represents a major public health issue in Swaziland. Prevention of HPV infection with a national HPV immunization programme for pre-adolescent girls would prevent the majority of CC related deaths and associated costs.

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.

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.

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations. METHODS: We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure. FINDINGS: We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects. INTERPRETATION: Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement. FUNDING: The Canadian Institutes of Health Research.

Comparative cost-effectiveness of the quadrivalent and bivalent human papillomavirus vaccines: a transmission-dynamic modeling study.

BACKGROUND: The quadrivalent and bivalent human papillomavirus (HPV) vaccines are now licensed in several countries. We compared the cost-effectiveness of the HPV vaccines to provide evidence for policy decisions. METHODS: We developed HPV-ADVISE, a multi-type individual-based transmission-dynamic model of HPV infection and disease (anogenital warts, and cervical, anogenital and oropharyngeal cancers). We calibrated the model to sexual behavior and epidemiologic data from Canada, and estimated quality-adjusted life-years (QALYs) lost and costs ($CAN 2010) from the literature. Vaccine-type efficacy was based on a systematic literature review. The analysis was performed from the healthcare provider perspective, and costs and benefits were discounted at 3%. Predictions are presented using the median [10th;90th percentiles] of simulations. RESULTS: Under base-case assumptions (vaccinating 10-year-old girls, 80% coverage, $95/dose), using the quadrivalent and bivalent vaccines is estimated to cost $15,528 [12,056;19,140] and $20,182 [15,531;25,240] per QALY-gained, respectively. At equal price, the quadrivalent vaccine is more cost-effective than bivalent under all scenarios investigated, except when assuming longer duration of protection for the bivalent and minimal anogenital warts burden. Under base-case assumptions, the maximum additional cost per dose for the quadrivalent vaccine to remain more cost-effective than the bivalent is $32 [17;46] (using a $40,000/QALY-gained threshold). Results were most sensitive to discounting, time-horizon, differences in durations of protection and anogenital warts burden. CONCLUSIONS: Vaccinating pre-adolescent girls against HPV is predicted to be highly cost-effective. If equally priced, the quadrivalent is the most economically desirable vaccine. However, ultimately, the most cost-effective HPV vaccine will be determined by their relative price.

Prevalence of anogenital warts among participants in private health plans in the United States, 2003-2010: potential impact of human papillomavirus vaccination.

OBJECTIVES: We estimated anogenital wart prevalence from 2003 to 2010 by gender and age group in a large US cohort with private insurance to detect potential decreases among people most likely to be affected by human papillomavirus (HPV) vaccination. METHODS: We restricted health care claims to those from individuals aged 10 to 39 years with continuous insurance within a given year. We derived anogenital wart diagnoses from a diagnosis of condyloma acuminata, or either a less specific viral wart diagnosis or genital wart medication combined with either a benign anogenital neoplasm or destruction or excision of a noncervical anogenital lesion. RESULTS: Prevalence increased slightly in 2003 to 2006, then significantly declined in 2007 to 2010 among girls aged 15 to 19 years; increased in 2003 to 2007, remained level through 2009, and declined in 2010 among women aged 20 to 24 years; and increased through 2009 but not in 2010 for women aged 25 to 39 years. For males aged 15 to 39 years, prevalence for each 5-year age group increased in 2003 to 2009, but no increases were observed for 2010. CONCLUSIONS: These data indicate reductions in anogenital warts among US females aged 15 to 24 years, the age group most likely to be affected by introduction of the HPV vaccine.

Economic burden of non-cervical cancers attributable to human papillomavirus: a European scoping review.

OBJECTIVE: Human papillomavirus (HPV) has an important role in the aetiology of a range of diseases, including cervical, other anogenital, and head and neck cancers, genital warts and recurrent respiratory papillomatosis. This literature review was conducted to identify the available cost data for non-cervical HPV-related cancers (anal, penile, vulvar, vaginal, head and neck) in Europe and to inform discussion of methodological challenges for future economic research. METHODS: The literature search was conducted using Medline and key words to identify papers published in English or French between 1 January 2000 and 31 December 2011. Abstracts of major conferences were searched to identify relevant information. Structured methods were used to select references that focused on overall disease management for inclusion in the review. RESULTS: A total of 21 references from seven countries (Denmark, France, Germany, Greece, The Netherlands, Portugal, and the UK) were selected, including 11 references relating to head and neck cancers, five to anogenital cancers, and five to more than one HPV-related disease. Non-cervical cancers accounted for a substantial proportion of the economic burden of HPV-related cancers, and this burden was mainly driven by men (∼70%). A wide range of costs were reported for each disease, particularly head and neck cancers, predominantly due to disease complexity and variation in study design. LIMITATIONS: The main limitation of this study was in the search strategy, which was constrained by the key words, the database searched, and the restriction on language (English/French). CONCLUSIONS: Non-cervical cancers attributable to HPV impose a substantial economic burden in Europe, and the burden is greater in men than in women. This review provides useful information for future health-economic studies assessing the impact of HPV vaccination on all HPV-related diseases.

[The disease burden of human papillomavirus in men is substantial and can potentially be prevented]. / Den HPV-relaterede sygdomsbyrde hos mænd er stor og kan forebygges.

Human papillomavirus (HPV) is a highly prevalent sexually transmitted infection. High-risk HPV causes penile cancer and a substantial proportion of oropharyngeal and anal malignancy in men. Low-risk types of HPV cause anogenital warts. The incidence of oropharyngeal and anal cancers is increasing in Denmark. Prevention of penile, anal and oropharyngeal cancers and anogenital warts represents potential benefits of the HPV vaccine; and vaccination of men is now recommended by the Australian and the North American health authorities. Thus, we recommend that the Danish HPV vaccination program should include men.

Economic burden of human papillomavirus-related diseases in Italy.

INTRODUCTION: Human papilloma virus (HPV) genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1) by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2) by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection. METHODS: For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection. RESULTS: The total direct costs (expressed in 2011 Euro) associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1-686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5-315.7 million), accounting for approximately 55% of the total annual burden of HPV-related disease in Italy. CONCLUSIONS: The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention.

Modeling the impact of the difference in cross-protection data between a human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and a human papillomavirus (HPV)-6/11/16/18 vaccine in Canada.

BACKGROUND: In Canada, two vaccines that have demonstrated high efficacy against infection with human papillomavirus (HPV) types -16 and -18 are available. The HPV-6/11/16/18 vaccine provides protection against genital warts (GW) while the HPV-16/18 vaccine may provide better protection against other oncogenic HPV types. In this analysis, the estimated clinical and economic benefit of each of these vaccines was compared in the Canadian setting. METHODS: A Markov model of the natural history of HPV infection among women, cervical cancer (CC) and GW was used to estimate the impact of vaccinating a cohort of 100,000 12-year-old females on lifetime outcomes and healthcare system costs (no indirect benefit in males included). A budget impact model was used to estimate the impact of each vaccine by province. RESULTS: In the base case, vaccination with the HPV-16/18 vaccine was predicted to prevent 48 additional CC cases, and 16 additional CC deaths, while vaccination with the HPV-6/11/16/18 vaccine was predicted to prevent 6,933 additional GW cases. Vaccination with the HPV-16/18 vaccine was estimated to save 1 additional discounted quality adjusted life year (QALY) at an overall lower lifetime cost to the healthcare system compared to the HPV-6/11/16/18 vaccine (assuming vaccine price parity). In sensitivity analyses, the HPV-6/11/16/18 vaccine was associated with greater QALYs saved when the cross-protection efficacy of the HPV-16/18 vaccine was reduced, or the burden of GW due to HPV-6/11 was increased. In most scenarios with price parity, the lifetime healthcare cost of the strategy with the HPV-16/18 vaccine was predicted to be lower than the HPV-6/11/16/18 vaccine. In the probabilistic sensitivity analyses, the HPV-16/18 vaccine provided more QALY benefit than the HPV-6/11/16/18 vaccine in 49.2% of scenarios, with lower relative lifetime costs in 83.5% of scenarios. CONCLUSIONS: Overall, the predicted lifetime healthcare costs and QALYs saved by implementing each of the vaccines are similar. Vaccination with the HPV-16/18 vaccine is expected to be associated with reduced CC disease morbidity and mortality compared to vaccination with the HPV-6/11/16/18 vaccine. Differences in these outcomes depend on the extent of cervical disease prevented by cross-protection and the burden of GW caused by HPV-6/11.

Health and economic burden of HPV-related diseases in Singapore.

OBJECTIVE: To assess the health and economic burden of human papillomavirus (HPV)-related diseases (cervical cancer, cervical intraepithelial neoplasia (CIN) 1/2/3, and genital warts) in Singapore over a period of 25 years beginning in 2008. METHODS: Incidence-based modeling was used to estimate the incidence cases and associated economic burden, with the assumption that age-stratified incidence rates will remain the same throughout the period of 25 years. The incidence rates in 2008 were projected based on data obtained from the National Cancer Registry for cervical cancer, and from a combination of published data and hospital registry review for CIN1/2/3 and genital warts. The population growth rate was factored into the projection of incidence cases over time. Direct cost data per cervical cancer and per CIN1/2/3 case were obtained from the financial database of large local hospitals while cost data for genital warts were obtained from the National Skin Center; these costs were multiplied by the number of incidence cases to produce an aggregate estimate of the economic burden over the 25-year period (in 2008 Singapore dollars) using a 3% discount rate. RESULTS: The total number of incidence cases of HPV-disease over 25 years beginning in 2008 was estimated to be 60,183, including 8,078 for cervical cancer, 11,685 for CIN 2/3, 8,849 for CIN1, and 31,572 for genital warts. The estimated total direct cost was 83.2 million Singapore Dollars over 25 years: 57.6 million attributable to cervical cancer, 13.0 million to CIN2/3, 6.83 million to CIN1, and 5.70 million to genital warts. CONCLUSION: HPV-related diseases are expected to impose significant health and economic burden on the Singapore healthcare resources in the next 25 years.