Economic burden of HPV9-related diseases: a real-world cost analysis from Italy.

INTRODUCTION: The objectives of this study were to estimate the economic burden of HPV in Italy, accounting for total direct medical costs associated with nine major HPV-related diseases, and to provide a measure of the burden attributable to HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 infections. METHODS: A cost-of-illness incidence-based model was developed to estimate the incidences and costs of invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, oropharyngeal, anogenital warts, and recurrent respiratory papillomatosis (RRP) in the context of the Italian National Health System (NHS). We used data from hospital discharge records (HDRs) of an Italian region and conducted a systematic literature review to estimate the lifetime cost per case, the number of incident cases, the prevalence of HPV9 types. Costs of therapeutic options not included in the diagnosis-related group (DRG) tariffs were estimated through a scenario analysis. RESULTS: In 2018, the total annual direct costs were €542.7 million, with a range of €346.7-€782.0 million. These costs could increase considering innovative therapies for cancer treatment (range €16.2-€37.5 million). The fraction attributable to the HPV9 genotypes without innovative cancers treatment was €329.5 million, accounting for 61% of the total annual burden of HPV-related diseases in Italy. Of this amount, €135.9 million (41%) was related to men, accounting for 64% of the costs associated with non-cervical conditions. CONCLUSIONS: The infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs.

Using novel biomarkers to triage young adult women with minor cervical lesions: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the short-term consequences and cost-effectiveness associated with the use of novel biomarkers to triage young adult women with minor cervical cytological lesions. DESIGN: Model-based economic evaluation using primary epidemiological data from Norway, supplemented with data from European and American clinical trials. SETTING: Organised cervical cancer screening in Norway. POPULATION: Women aged 25-33 years with minor cervical cytological lesions detected at their primary screening test. METHODS: We expanded an existing simulation model to compare 12 triage strategies involving alternative biomarkers (i.e. reflex human papillomavirus (HPV) DNA/mRNA testing, genotyping, and dual staining) with the current Norwegian triage guidelines. MAIN OUTCOME MEASURES: The number of high-grade precancers detected and resource use (e.g. monetary costs and colposcopy referrals) for a single screening round (3 years) for each triage strategy. Cost-efficiency, defined as the additional cost per additional precancer detected of each strategy compared with the next most costly strategy. RESULTS: Five strategies were identified as cost-efficient, and are projected to increase the precancer detection rate between 18 and 57%, compared with current guidelines; however, the strategies did not uniformly require additional resources. Strategies involving HPV mRNA testing required fewer resources, whereas HPV DNA-based strategies detected >50% more precancers, but were more costly and required twice as many colposcopy referrals compared with the current guidelines. CONCLUSION: Strategies involving biomarkers to triage younger women with minor cervical cytological lesions have the potential to detect additional precancers, yet the optimal strategy depends on the resources available as well as decision-makers' and women's acceptance of additional screening procedures. TWEETABLE ABSTRACT: Women with minor cervical lesions may be triaged more accurately and effectively using novel biomarkers.

[Developments in HPV vaccination]. / Ontwikkelingen omtrent de HPV-vaccinatie.

Vaccination against the human papilloma virus (HPV) has been included in the national Vaccination Programme of the Netherlands for 12-year-old girls since 2010. Vaccination coverage for the birth cohort of 1997 was 56.; there is a gradual increase in uptake. Continuous safety monitoring brought no new unknown serious side effects to light; many girls suffered from transient symptoms such as painful arm, fatigue and headache. After the current vaccines that protect against HPV types 2 and 4 types, respectively and induce some cross protection, vaccines are being developed that can induce broader protection. HPV vaccination of 12-year-old girls is cost-effective, even for relatively low vaccination coverage. The potential protection of HPV vaccination extends beyond prevention of cervical cancer by preventing other oncological manifestations of HPV infection in women as well as men and genital warts. The preventive HPV vaccines do not appear to be effective in treating existing abnormalities.

Prophylaxis of cervical cancer and related cervical disease: a review of the cost-effectiveness of vaccination against oncogenic HPV types.

BACKGROUND: Vaccines have demonstrated cost-effectiveness in managed care through the prevention of disease. As new vaccines for previously untargeted conditions are developed, pharmacoeconomic modeling is becoming even more critical for the quantification of value in the health care industry. Two recently developed vaccines aimed at prevention of infection from human papillomavirus (HPV) types 16 and 18 have proven to be highly efficacious. HPV 16 and 18 are the 2 most common oncogenic strains of HPV and are responsible for 70% of cervical cancer cases worldwide. Persistent infection with an oncogenic HPV type is a known cause of cervical cancer. Therefore, prevention of cervical cancer via HPV vaccination may have a significant financial impact. OBJECTIVE: To qualitatively review existing mathematical models of the cost effectiveness of prophylactic HPV vaccination, with an emphasis on the impact on managed care in the United States. METHODS: Mathematical models of the cost-effectiveness of HPV vaccination based on U.S. data were reviewed. A search of the PubMed database was conducted using the search terms "HPV," "vaccine," and "cost-effectiveness" for articles published before February 22, 2010. Studies employing mathematical models to estimate the cost-effectiveness of HPV vaccination in healthy subjects from the United States were included. Models based on data or populations from outside of the United States were excluded. Outcomes were measured with incremental cost-effectiveness ratios (ICERs), typically in units of quality-adjusted life expectancy (quality-adjusted life years [QALYs] gained). Most studies included in this review modeled vaccination of a cohort or population of females aged 12 years. Assessment of catch-up vaccination in females (through aged 24 to 26 years) was included in a couple of reports. One study examined vaccination in older females (aged 35, 40, and 45 years). Models typically compared a strategy of HPV vaccination with the current practice of cervical screening (sampling of cervical cells for disease detection) alone. RESULTS: 11 studies of cost-effectiveness modeling of HPV vaccination were included in this review. A direct quantitative comparison of model results is challenging due to the utilization of different model types as well as differences in variables selected within the same model type. Each model produced a range of cost-effectiveness ratios, dependent on variables included in sensitivity analyses and model assumptions. Sensitivity analyses revealed the lowest ICER to be $997 per QALY gained and the highest ICER to be $12,749,000 per QALY gained. This enormous range highlights the need to clarify what model assumptions are being made. The 2 studies that included modeling of catch-up vaccination scenarios in females older than age 12 years also produced a wide range of ICERs. One study, assuming 90% efficacy, 100% coverage, and lifelong immunity, modeled catch-up vaccination in all females aged 12 to 24 years and yielded an ICER of $4,666 per QALY. If the duration of protection was limited to 10 years, then costs increased to $21,121 per QALY. The other study modeling catch-up HPV vaccination assumed 100% efficacy, 75% coverage, and lifelong immunity. ICERs in this study for outcomes relating to cervical cancer ranged from $43,600 per QALY in the base model vaccinating only 12 year olds with no catch-up vaccination, to $152,700 in a model including catch-up vaccination through age 26 years. Although catch-up to age 21 years resulted in a cost of $120,400 per QALY, the ICER decreased to $101,300 per QALY if model outcomes related to prevention of genital warts were also included. The lone study modeling vaccination in women aged 35 to 45 years resulted in an ICER range of $116,950 to $272,350 per QALY when compared with annual and biennial cytological screening. Cost-effectiveness was defined as an ICER at or below $100,000 per QALY gained. All models of female adolescent vaccination were able to produce vaccination strategies that would be cost-effective according to this definition in addition to many strategies that would be cost-prohibitive. Variables influential in determining cost-effectiveness of HPV vaccination included the frequency of accompanying cervical screening, the age at which screening is initiated, vaccination efficacy, duration of vaccine protection, and the age range of females to be vaccinated. The actual effectiveness of HPV vaccination in the female population will also depend on levels of vaccine uptake or coverage and compliance in completing all vaccine doses. CONCLUSION: Clinical studies have shown HPV vaccination to be highly efficacious and potentially lifesaving if administered to females naive or unexposed to vaccine HPV types. Modeling studies have also shown that HPV vaccination can be cost-effective with an ICER of $100,000 or less per QALY gained if administered to females aged 12 years in the context of cervical screening intervals typically greater than 1 year. Catch-up vaccination through 21 years of age increases the cost per QALY to more than $100,000. Until real-world coverage rates increase, cost-effectiveness modeling of HPV vaccination underestimates the actual cost per QALY.

Why remove all cervical polyps and examine them histologically?

A retrospective analysis of 1366 cervical polyps showed that none had malignant features and 67% were removed from asymptomatic women. A policy removing only cervical polyps from symptomatic women or those with abnormal cervical cytology and limiting histological examination to these polyps would result in significant savings and reduce the small risk of morbidity associated with polypectomy.

Cost-effectiveness of treatment strategies for cervical infection among women at high risk in Madagascar.

BACKGROUND: According to the national guidelines developed in 2001, a woman at high risk of gonorrhea and chlamydia in Madagascar is treated presumptively at her first sexually transmitted infection clinic visit; risk-based treatment (RB) is subsequently used at 3-month visits. OBJECTIVES: To compare health and economic outcomes for a 2-stage Markov process with the following 3 cervical infection treatment policies at baseline and at 3-month follow-up visit: presumptive treatment (PT), RB, and an interim laboratory/risk-based policy. STUDY DESIGN: Cost-effectiveness analysis was used to compare the 9 treatment strategies. RESULTS: When 3-month incidence of cervical infection is <20%, the national guidelines are less costly and less effective than both RB followed by PT, and PT at both visits. CONCLUSIONS: The national guidelines are a reasonable strategy, especially in the context of resource constraints, relatively low reinfection rates, and local preferences.

The health care costs of cervical human papillomavirus--related disease.

OBJECTIVE: The purpose of this study was to examine the health care costs of cervical human papillomavirus-related disease in a US health care setting. STUDY DESIGN: We conducted an observational cohort study using 1997 through 2002 administrative and laboratory records from 103,476 female enrollees of the Kaiser Permanente Northwest health plan (Portland, Ore). We examined the cost per case and annual cost per 1000 enrollees for cervical human papillomavirus-related events. RESULTS: A cervical examination with a normal routine papanicolaou smear incurred costs of 57 dollars (95% CI, 57-57). Costs that were associated with abnormal routine screening diagnoses ranged from 299 dollars for atypical squamous cells (95% CI, 245-352) to 2349 dollars for high-grade squamous intraepithelial lesion (95% CI, 1,047-3,650). The costs of histologically confirmed cervical intraepithelial neoplasia ranged from 1026 dollars for cervical intraepithelial neoplasia 1 (95% CI, 862-1191) to 3235 dollars for cervical intraepithelial neoplasia 3 (95% CI, 2051-4419); a cost of 376 dollars (95% CI, 315-436) was associated with false-positive test results. At the level of the health plan, overall annual cervical cancer prevention and treatment costs were 26,415 dollars per 1000 female enrollees, with routine cervical cancer screening accounting for expenditures of 16,746 dollars per 1000 female enrollees, cervical intraepithelial neoplasia accounting for expenditures of 4535 dollars per 1000 female enrollees, cervical cancer accounting for expenditures of 2629 dollars per 1000 female enrollees, and false-positive test results accounting for expenditures of 2394 dollars per 1000 female enrollees. CONCLUSION: These are the first direct estimates of both individual and population level costs of cervical human papillomavirus-related disease in a general US health care setting. Routine cervical cancer screening comprises nearly two thirds of total annual cervical human papillomavirus-related health care costs, with 10% of expenditures dedicated to the treatment of invasive cervical cancer, 17% to the management of cervical precancers, and 9% to dealing with false-positive Papanicolaou test results.

The cost of production in cervical cytology: comparison of conventional and automated primary screening systems.

To thrive in a world of managed care and capitation, knowing the cost of production is critical, especially in cervical cytology. The relative costs of production for preparation and interpretation of cervical cytology for conventional manually read smears and a primary automated screening method were calculated in a university practice setting. The components were disposables, processing, screening, pathologist review, capital equipment, and facilities cost. The production cost for a conventional smear in our laboratory is $9.75, and the comparable production cost by a primary screening automated method would be $12.07, if it were approved for primary screening. Based on these calculations, an interactive automated method approved for primary screening would cost slightly more than conventional testing. Combinations of conventional and automated examinations (secondary screening systems) are not cost feasible unless the additional production expense can be passed through to the payers.

Outpatient loop diathermy conization as an alternative to inpatient knife conization of the cervix.

A knife cone biopsy of the cervix is usually performed as an inpatient procedure under general anesthesia and is associated with significant morbidity. Loop diathermy conization was performed under local anesthesia on colposcopy outpatients as an alternative to knife conization. In 33 consecutive patients studied the procedure was well tolerated, there were no operative complications, and a satisfactory specimen for histologic examination was obtained in every case. One case of unsuspected invasive cancer and two of suspected microinvasive cancer were diagnosed. The diagnosis of cervical precancer was made in 24 (73%) of the cases. The introduction of outpatient loop diathermy conization of the cervix instead of knife conization would decrease hospitalization costs, avoid the need for general anesthesia and potentially reduce short-term patient morbidity.