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.

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.

Resource Use and Cost of Treating Human Papillomavirus-Related Lesions in Japanese Women.

BACKGROUND: Human papillomavirus (HPV) infection is established as a necessary causal factor in several pathologies including cervical cancer (CC), which recorded over 11,000 new cases in 2011 in Japan. Nevertheless, cost burden data of human papillomavirus-related diseases in Japan are lacking. OBJECTIVES: To evaluate resource use and costs in women with HPV-related lesions. METHODS: A retrospective study using insurance claims databases was performed to assess the annual medical cost for suspected cervical intra-epithelial neoplasia (CIN)/CC, genital warts (GWs), CIN (all grades), and CC. Information on the treatment of GWs was obtained from the Claims Database developed by Japan Medical Data Center Co., Ltd. Information on CIN and CC was obtained from the Evidence-Based Medicine provider database developed by Medical Data Vision Co., Ltd. Databases cover about 1% of the Japanese population. Total annual cost in Japanese yen (¥) per patient in 2011 was calculated on the basis of resource used and unit costs from Japan medical insurance tariffs. RESULTS: Average annual costs were as follows: GWs, ¥34,424; suspected CIN/CC, ¥6,240; CIN 1, ¥17,484; CIN 2, ¥46,583; CIN 3, ¥166,227; and CC, ¥474,756. CONCLUSIONS: To our knowledge, this is the first observational study to estimate the annual medical costs of HPV-related diseases in Japan using real-world data collected in routine clinical practice. It could provide help in estimating the economic burden of HPV-related lesions in Japanese women.

The Direct Medical Costs of Diseases Associated with Human Papillomavirus Infection in Manitoba, Canada.

BACKGROUND: The total direct cost of screening and treating all human papillomavirus-related diseases (HPV-RD) has not been measured in a single study. Accurate cost estimates are needed to inform decisions on intervention priorities and evaluate the cost-effectiveness of existing programs. We used province-wide clinical, administrative, and accounting databases to measure direct medical costs of HPV infection in Manitoba (Canada). METHODS: All persons 9 years or older with health insurance coverage in Manitoba between April 2000 and March 2015 were eligible. We identified all persons with an incident HPV-RD and aggregated all medical costs (in 2014 Canadian dollars) related to that condition, including prescription drugs, diagnostic procedures, in-hospital and outpatient treatment, and physician visits. RESULTS: We found that the median cost of treating a case of anogenital warts was $130. An episode of cervical dysplasia had a median cost of $220, compared to $1300 for an episode of cervical carcinoma in situ. The cost of treating HPV-related invasive cancer varied from $15,000 for cervical cancer to $33,000 for oral cavity cancer. Overall, 80% ($145 million) of the total cost was attributable to HPV infection. Cervical screening and follow-up accounted for $96 million (66%) of all costs and this cost component has declined following the introduction of new screening guidelines. CONCLUSIONS: Overall, the average direct medical cost of HPV infection was $720 per newborn. The economic burden of HPV remains significant, although changes in cervical screening guidelines, prompted by the introduction of a public HPV vaccine program, appear to have promoted a promising trend towards lower costs.

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.

Burden of Disease of Human Papillomavirus (HPV): Hospitalizations in the Marche and Veneto Regions. An observational study.

BACKGROUND AND OBJECTIVES: HPV (human papillomavirus) is the virus most often responsible for sexually transmitted infections. The burden of HPV-related diseases on hospital resources represents a major public health problem. The aim of this study was to assess the economic burden of HPV-related diseases (anal cancer, genital cancer, genital warts, oropharyngeal cancer) on hospital resources in two Italian regions. METHODS: A retrospective, non-randomized, observational study was developed in the Marche and Veneto Regions, based on patients receiving hospitalization between 2008 and 2011. All hospitalizations were identified through administrative archives, according to the International Classification of Diseases (ICD-9 CM) to which a defined tariff was assigned. RESULTS: We identified 5299 hospitalized patients in Veneto and 1735 in the Marche Region. The mean annual hospitalization rate was 49.44 per 100,000 individuals in Veneto and 48.41 in Marche. The total mean annual cost attributable to HPV-related diseases was €5.78 (SD 0.80) million in Veneto and €2.24 (SD 0.17) million in Marche. Costs associated with genital cancer amounted to €1.61 million in Veneto and €1.06 million in Marche (28% and 47% of the total mean annual cost, respectively). Oropharyngeal cancer accounted for 36% in Veneto (€2.08 million) and 28% in Marche (€632,645). Hospitalization costs related to anal cancer were €882,567 in Veneto and €377,719 in Marche; genital warts accounted for €1.19 million in Veneto and €171,406 in Marche. Finally, the mean cost per patient was €4364 in Veneto and €5176 in Marche. CONCLUSIONS: The present work estimated the cost of HPV-related diseases for hospitalized patients in two Italian regions. The considerable estimated annual economic burden is a powerful driver for the governance of the public health sector.

Incidence, psychosocial burden, and economic impact of genital warts in Mexico.

OBJECTIVE: To estimate the burden of genital warts (GW)in Mexico. MATERIALS AND METHODS: We estimated the annual incidence of GW based on data reported by specialist physicians. We also assessed GW treatment practices, the average cost of treatment, and the psychosocial burden of GW among patients. RESULTS: The annual incidence of GW in Mexico was estimated to be 547 200 cases. Treatment procedures vary by specialist and patient gender. The estimated annual cost was $195 million USD. The psychosocial impact of GW was slightly greater in males than females. CONCLUSIONS: This is the first evaluation of the burden of GW in Mexico. Our data suggest that GW are common, with significant health-related costs and psychosocial impact.

OBJETIVO: Estimar la carga por verrugas genitales (VG) en México. MATERIAL Y MÉTODOS: Estimamos la incidencia anual de VG, con base en información proporcionada por médicos especialistas y el manejo de las VG, así como el costo promedio del tratamiento y la carga psicosocial de las VG. RESULTADOS: La incidencia anual de VG en México fue de 547 200 casos. Los tratamientos variaron según la especialidad y el sexo del paciente. El costo anual por VG fue de $195 millones de dólares estadounidenses. El impacto psicosocial de las VG es ligeramente mayor en hombres que en mujeres. CONCLUSIONES: Esta es la primera evaluación de la carga de VG en México. Los datos sugieren que las VG son frecuentes, tienen costos relacionados con salud e impactos psicosociales significativos.

A cross-sectional study estimating the burden of illness related to genital warts in South Korea.

OBJECTIVES: Estimate the prevalence of genital warts (GW) and GW-related healthcare resource use and costs among male and female patients seeking treatment in South Korea. DESIGN: To estimate GW prevalence, physicians in five major South Korean regions recorded daily logs of patients (n=71 655) seeking care between July 26 and September 27, 2011. Overall prevalence estimates (and 95% CIs) were weighted by the estimated number of physicians in each specialty and the estimated proportion of total patients visiting each specialist type. Healthcare resource use was compared among different specialties. Corresponding p values were calculated using Mann-Whitney U tests. SETTING: The database covers 5098 clinics and hospitals for five major regions in South Korea: Seoul, Busan, Daegu, Gwangju and Daejeon. PARTICIPANTS: Primary care physicians (general practice/family medicine), obstetricians/gynaecologists, urologists and dermatologists with 2-30 years' experience. RESULTS: The estimated overall GW prevalence was 0.7% (95% CI 0.7% to 0.8%). Among women, GW prevalence was 0.6% (95% CI 0.6% to 0.7%); among men prevalence was 1.0% (95% CI 0.9% to 1.0%), peaking among patients aged 18-24 years. Median costs for GW diagnosis and treatment for male patients were US$58.2 (South Korean Won (KRW) ₩66 857) and US$66.3 (KRW₩76 113) for female patients. CONCLUSIONS: The estimated overall GW prevalence in South Korea was 0.7% and was higher for male patients. The overall median costs associated with a GW episode were higher for female patients than for male patients.

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.

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.

The costs of managing genital warts in the UK by devolved nation: England, Scotland, Wales and Northern Ireland.

Genital warts, 90% of which are caused by human papillomavirus types 6 and 11, are a significant problem in the UK. The cost of managing genital warts was previously estimated at £52.4 million for 2010. The objective of this study was to estimate the cost of genital warts management up to 2012 in the UK and by jurisdiction. Population statistics and the number of reported genital warts cases in genito-urinary medicine clinics were obtained and extrapolated to 2012. Cases of genital warts treated in primary care were estimated from The Health Improvement Network database. The number of visits and therapy required were estimated by genito-urinary medicine experts. Costs were obtained from the appropriate national tariffs. The model estimated there were 220,875 genital warts cases in the UK in 2012, costing £58.44 million (£265/patient). It estimated 157,793 cases in England costing £41.74 million; 7468 cases in Scotland costing £1.90 million; 7095 cases in Wales costing £1.87 million; and 3621 cases in Northern Ireland costing £948,000. The full National Health Service costs for the management of genital warts have never previously been estimated separately for each jurisdiction. Findings reveal a significant economic burden, which is important to quantify when understanding the value of quadrivalent human papilloma virus vaccination.

Cost of Preventing, Managing, and Treating Human Papillomavirus (HPV)-Related Diseases in Sweden before the Introduction of Quadrivalent HPV Vaccination.

OBJECTIVE: Costs associated with HPV-related diseases such as cervical dysplasia, cervical cancer, and genital warts have not been evaluated in Sweden. These costs must be estimated in order to determine the potential savings if these diseases were eradicated and to assess the combined cost-effectiveness of HPV vaccination and cervical cancer screening. The present study aimed to estimate prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts from a societal perspective in Sweden in 2009, 1 year before the quadrivalent HPV vaccination program was implemented. METHODS AND MATERIALS: Data from the Swedish cervical cancer screening program was used to calculate the costs associated with prevention (cytological cervical cancer screening), management (colposcopy and biopsy following inadequate/abnormal cytological results), and treatment of CIN. Swedish official statistics were used to estimate treatment costs associated with cervical cancer. Published epidemiological data were used to estimate the number of incident, recurrent, and persistent cases of genital warts; a clinical expert panel assessed management and treatment procedures. Estimated visits, procedures, and use of medications were used to calculate the annual cost associated with genital warts. RESULTS: From a societal perspective, total estimated costs associated with cervical cancer and genital warts in 2009 were €106.6 million, of which €81.4 million (76%) were direct medical costs. Costs associated with prevention, management, and treatment of CIN were €74 million; screening and management costs for women with normal and inadequate cytology alone accounted for 76% of this sum. The treatment costs associated with incident and prevalent cervical cancer and palliative care were €23 million. Estimated costs for incident, recurrent and persistent cases of genital warts were €9.8 million. CONCLUSION: Prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts are substantial. Defining these costs is important for future cost-effectiveness analyses of the quadrivalent HPV vaccination program in Sweden.

A retrospective analysis of the costs and management of genital warts in Italy.

BACKGROUND: In Italy the prevalence of genital warts in women (15-64 years) is approximately 0.6% with an incidence of 0.4% per year. Treatments for GW are usually long, with moderate success and high costs. The aim of the study was to evaluate the diagnostic-therapeutic pathway, duration and setting of treatment, costs of episodes of condyloma in a population attending a regional STI clinic in Piedmont. METHODS: This was a retrospective observational study conducted using medical records of outpatients who first visited the STI Clinic of San Lazzaro Dermatological Hospital in 2008. The patients' medical histories were analysed for episodes that occurred and were cleared in 18 months following the initial visit. Data on screening methods for STIs, type of diagnosis for condyloma, treatment type, treatment setting, and anatomic lesion site were obtained from medical records. The costs were calculated for each episode. RESULTS: A total of 450 episodes were analysed (297 men,153 women). The most frequently affected anatomic site was the genital area (74%) in both genders. With regard to treatment setting, 78.44% of patients received outpatient treatment at the STI clinic, 4% were treated at home, and 0.22% were hospitalised; 11.11% were treated in multiple settings. The mean number of treatments per episode was 2.03; although many patients received only 1 treatment (n = 207, 46%), exspecially cryotherapy or diathermy coagulation (64.73% versus 28.02% of episodes, respectively). The mean episode duration was 80.74 days. The mean cost (in 2011 euros) for an episode was €158.46 ± 257.77; the mean costs were €79.13 ± 57.40 for diagnosis and €79.33 ± 233.60 for treatment. The mean cost for treatment in a STI-Clinic setting was €111.39 ± 76.72, that for home treatment was €160.88 ± 95.69, and that for hospital care was €2825.94. CONCLUSIONS: The treatment of and associated costs for genital warts are significant. Several factors affect the cost, and internal STI clinic protocols, such as the 6 month window used to consider a recurrence or new diagnosis, create bias. Nonetheless, our findings how costs similar to those reported in the international literature and should be considered when deciding on which HPV vaccination programs should be provided by the public health system.

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.

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 estimated direct medical cost of selected sexually transmitted infections in the United States, 2008.

BACKGROUND: Millions of cases of sexually transmitted infections (STIs) occur in the United States each year, resulting in substantial medical costs to the nation. Previous estimates of the total direct cost of STIs are quite dated. We present updated direct medical cost estimates of STIs in the United States. METHODS: We assembled recent (i.e., 2002-2011) cost estimates to determine the lifetime cost per case of 8 major STIs (chlamydia, gonorrhea, hepatitis B virus, human immunodeficiency virus (HIV), human papillomavirus, genital herpes simplex virus type 2, trichomoniasis and syphilis). The total direct cost for each STI was computed as the product of the number of new or newly diagnosed cases in 2008 and the estimated discounted lifetime cost per case. All costs were adjusted to 2010 US dollars. RESULTS: Results indicated that the total lifetime direct medical cost of the 19.7 million cases of STIs that occurred among persons of all ages in 2008 in the United States was $15.6 (range, $11.0-$20.6) billion. Total costs were as follows: chlamydia ($516.7 [$258.3-$775.0] million), gonorrhea ($162.1 [$81.1-$243.2] million), hepatitis B virus ($50.7 [$41.3-$55.6] million), HIV ($12.6 [$9.5-$15.7] billion), human papillomavirus ($1.7 [$0.8-$2.9] billion), herpes simplex virus type 2 ($540.7 [$270.3-$811.0] million), syphilis ($39.3 [$19.6-$58.9] million), and trichomoniasis ($24.0 [$12.0-$36.0] million). Costs associated with HIV infection accounted for more than 81% of the total cost. Among the nonviral STIs, chlamydia was the most costly infection. CONCLUSIONS: Sexually transmitted infections continue to impose a substantial cost burden on the payers of medical care in the United States. The burden of STIs would be even greater in the absence of STI prevention and control efforts.

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.

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.