Cost-effectiveness analysis of primary human papillomavirus testing in cervical cancer screening: Results from the HPV FOCAL Trial.

The Human Papillomavirus FOr CervicAL cancer (HPV FOCAL) trial is a large randomized controlled trial comparing the efficacy of primary HPV testing to cytology among women in the population-based Cervix Screening Program in British Columbia, Canada. We conducted a cost-effectiveness analysis based on the HPV FOCAL trial to estimate the incremental cost per detected high-grade cervical intraepithelial neoplasia of grade 2 or worse lesions (CIN2+). A total of 19,009 women aged 25 to 65 were randomized to one of two study groups. Women in the intervention group received primary HPV testing with reflex liquid-based cytology (LBC) upon a positive finding with a screening interval of 48 months. Women in the control group received primary LBC testing, and those negative returned at 24 months for LBC and again at 48 months for exit screening. Both groups received HPV and LBC co-testing at the 48-month exit. Incremental costs during the course of the trial were comparable between the intervention and control groups. The intervention group had lower overall costs and detected a larger number of CIN2+ lesions, resulting in a lower mean cost per CIN2+ detected ($7551) than the control group ($8325), a difference of -$773 [all costs in 2018 USD]. Cost per detected lesion was sensitive to the costs of sample collection, HPV testing, and LBC testing. The HPV FOCAL Trial results suggest that primary HPV testing every 4 years produces similar outcomes to LBC-based testing every 2 years for cervical cancer screening at a lower cost.

Cost-effectiveness of HPV-based cervical screening based on first year results in the Netherlands: a modelling study.

OBJECTIVE: We aim to compare the cost-effectiveness of the old cytology programme with the new high-risk human papillomavirus (hrHPV) screening programme, using performance indicators from the new Dutch hrHPV screening programme. DESIGN: Model-based cost-effectiveness analysis. SETTING: The Netherlands. POPULATION: Dutch 30-year-old unvaccinated females followed up lifelong. METHODS: We updated the microsimulation screening analysis (MISCAN) model using the most recent epidemiological and screening data from the Netherlands. We simulated both screening programmes, using the screening behaviour and costs observed in each programme. Sensitivity analyses were performed on screening behaviour, utility losses and discount rates. MAIN OUTCOME MEASURES: Cervical cancer incidence and mortality rates, number of screening tests and repeat tests, colposcopy referrals by lesion grade, costs from a societal perspective, quality-adjusted life years (QALYs) gained and cost-effectiveness. RESULTS: The new Dutch cervical cancer screening programme decreased the cervical cancer mortality by 4% and the incidence by 1% compared with the old programme. Colposcopy referrals of women without cervical intra-epithelial neoplasia grade 2 or worse, increased by 172%, but 13% more QALYs were still achieved. Total costs were reduced by 21%, mainly due to fewer screening tests. Per QALY gained, the hrHPV programme cost 46% less (€12,225) than the cytology programme (€22,678), and hrHPV-based screening remained more cost-effective in all sensitivity analyses. CONCLUSIONS: The hrHPV-based screening programme was found to be more effective and cost-effective than the cytology programme. Alternatives for the current triage strategy should be considered to lower the number of unnecessary referrals. TWEETABLE ABSTRACT: First results after implementation confirm that HPV screening is more cost-effective than cytology screening.

Cervical cancer screening program based on primary DNA-HPV testing in a Brazilian city: a cost-effectiveness study protocol.

BACKGROUND: The causal relationship between high-risk (hr) HPV infection and precancerous lesions or cervical cancer has led to the development of strategies to increase screening performance and prevent this cancer. The increased sensitivity of DNA-HPV testing compared to cervical cytology favors DNA-HPV testing as a primary screening test. Cervical cancer screening in Brazil is opportunistic, and this cancer remains a considerable health problem with a high proportion of diagnoses in advanced stages. This paper aims to describe the design and implementation of the Cervical Cancer Screening Program with primary DNA-HPV testing (CCSP-HPV) planned for Indaiatuba City (SP), Brazil; the strategies to achieve higher population coverage; and a study protocol for cost-effectiveness analyses. METHODS: The CCSP-HPV was designed based on successful guidelines that replaced cervical cytology-based screening by the DNA-HPV test performed at 5-year intervals. The screening will be performed for the female population aged 25-64 years cared for by the public health system and aim to reach 80% coverage after completing the first round. The chosen DNA-HPV test detects 14 hr-HPV types and genotypes HPV-16 and 18. All women with a negative test will be reassessed after five years. Women showing a positive test for HPV-16 and/or 18 will be referred for colposcopy. Those showing the other 12 hr-HPV types will be tested by cytology, and if any abnormality is detected, they will also be referred for colposcopy. The histopathologic evaluation will be reviewed by a pathologist panel and aided by p16 immunohistochemistry. A cost-effectiveness analysis will be performed by a Markov model comparing the cost of the new program and the screening performed by conventional cytology five years prior (2011-2016). DISCUSSION: The new screening program is considered a breakthrough for public health regarding cervical cancer, which is the third leading cause of cancer death among Brazilian women. Achieving at least 80% coverage will have the possibility to change this scenario. The proposed program will provide a modern cervical cancer screening method for women, and information about cost-effectiveness will help other similar places support the decision of implementing cervical cancer screening using the DNA-HPV test.

Cervical cancer screening coverage, management of squamous intraepithelial lesions and related costs in France.

Until 2018, cervical cancer screening in France was an unorganized individual screening, with the exception of some pilot programs in some territories. We aimed to assess, before the implementation of organized cervical cancer screening and human papillomavirus (HPV) nonavalent vaccine introduction in the vaccination schedule in 2018, (i) the individual cervical cancer screening coverage, (ii) the management of squamous intraepithelial lesions (SIL) and (iii) the related costs. We used the Système National des Données de Santé (SNDS) (Echantillon Généraliste de Bénéficiaires [EGB] and Programme de Médicalisation des systèmes d'information [PMSI]) to assess the cervical screening coverage rate in France between January 1st, 2012 and December 31st, 2014, and to describe diagnostic investigations and therapeutic management of SIL in 2013. After extrapolation to the general population, a total of 10,847,814 women underwent at least one smear test over the 3-year study period, corresponding to a coverage rate of 52.4% of the women aged 25 to 64 included. In 2013, 126,095 women underwent HPV test, 327,444 women underwent colposcopy, and 9,653 underwent endocervical curettage; 31,863 had conization and 12,162 had laser ablation. Besides, 34,067 women experienced hospital stays related to management of SIL; 25,368 (74.5%) had high-grade lesions (HSIL) and 7,388 (21.7%) low-grade lesions (LSIL). Conization was the most frequent in-hospital therapeutic procedure: 89.5% (22,704) of women with an in-hospital procedure for HSIL and 64.7% (4,781) for LSIL. Mean cost of smear test, colposcopy and HPV tests were around 50€. Total cost for hospital stays in 2013 was estimated at M41€, or a mean cost of 1,211€ per woman; 76% were due to stays with HSIL. This study highlights the low coverage rate of individual cervical cancer screening and a high burden related to SIL management.

The cost-effectiveness of human papillomavirus self-collection among cervical cancer screening non-attenders in El Salvador.

Cervical cancer screening with human papillomavirus (HPV) DNA testing has been incorporated into El Salvador's national guidelines. The feasibility of home-based HPV self-collection among women who do not attend screening at the clinic (i.e., non-attenders) has been demonstrated, but cost-effectiveness has not been evaluated. Using cost and compliance data from El Salvador, we informed a mathematical microsimulation model of HPV infection and cervical carcinogenesis to conduct a cost-effectiveness analysis from the societal perspective. We estimated the reduction in cervical cancer risk, lifetime cost per woman (2017 US$), life expectancy, and incremental cost-effectiveness ratio (ICER, 2017 US$ per year of life saved [YLS]) of a program with home-based self-collection of HPV (facilitated by health promoters) for the 18% of women reluctant to screen at the clinic. The model was calibrated to epidemiologic data from El Salvador. We evaluated health and economic outcomes of the self-collection intervention for women aged 30 to 59 years, alone and in concert with clinic-based HPV provider-collection. Home-based self-collection of HPV was projected to reduce population cervical cancer risk by 14% and cost $1210 per YLS compared to no screening. An integrated program reaching 99% coverage with both provider- and home-based self-collection of HPV reduced cancer risk by 74% (compared to no screening), and cost $1210 per YLS compared to provider-collection alone. Self-collection facilitated by health promoters is a cost-effective strategy for increasing screening uptake in El Salvador.

A mobile-phone based high-resolution microendoscope to image cervical precancer.

Nearly 90% of cervical cancer cases and deaths occur in low- and middle-income countries that lack comprehensive national HPV immunization and cervical cancer screening programs. In these settings, it is difficult to implement screening programs due to a lack of infrastructure and shortage of trained personnel. Screening programs based on visual inspection with acetic acid (VIA) have been successfully implemented in some low-resource settings. However, VIA has poor specificity and up to 90% of patients receiving treatment based on a positive VIA exam are over-treated. A number of studies have suggested that high-resolution cervical imaging to visualize nuclear morphology in vivo can improve specificity by better distinguishing precancerous and benign lesions. To enable high-resolution imaging in low-resource settings, we developed a portable, low-cost, high-resolution microendoscope that uses a mobile phone to detect and display images of cervical epithelium in vivo with subcellular resolution. The device was fabricated for less than $2,000 using commercially available optical components including filters, an LED and triplet lenses assembled in a 3D-printed opto-mechanical mount. We show that the mobile high-resolution microendoscope achieves similar resolution and signal-to-background ratio as previously reported high-resolution microendoscope systems using traditional cameras and computers to detect and display images. Finally, we demonstrate the ability of the mobile high-resolution microendoscope to image normal and precancerous squamous epithelium of the cervix in vivo in a gynecological referral clinic in Barretos, Brazil.

Prospective cohort study examining cervical cancer screening methods in HIV-positive and HIV-negative Cambodian Women: a comparison of human papilloma virus testing, visualization with acetic acid and digital colposcopy.

OBJECTIVES: Logistical and economic issues make traditional cytology-based cervical cancer screening challenging in developing countries. Alternative, cost-effective, screening strategies must be developed to screen millions of women in resource-poor countries such as Cambodia. DESIGN: A prospective cohort study during which all women underwent four cervical cancer screening methods: (1) self-sampled human papilloma virus (HPV) testing (careHPV system), (2) clinician-collected HPV testing, (3) visualization with acetic acid (VIA) and (4) digital colposcopy (DC) with the Enhanced Visual Assessment System (EVA). SETTING: A referral hospital in Phnom Penh, Cambodia. PARTICIPANTS: Two hundred and fifty Cambodian women (129 HIV+, 121 HIV-). Subjects were recruited from the National Center for HIV/AIDS Dermatology and sexually transmitted disease (STD) cohort, the Sihanouk Hospital Center of Hope's Rural Outreach Teams and the Pochentong Medical Center. RESULTS: Fifty six of the 250 (22.4%) patients tested positive for high-risk HPV (hrHPV+). Thirty seven of the 129 HIV+ women were hrHPV+ (28.6%) whereas 19/121 HIV- women were hrHPV+ (15.7%) p=0.0154. Self-sampling HPV specimens identified 50/56 (89%) whereas physician-collected specimens identified 45/56 (80%) p=0.174. 95.2% of the patients felt comfortable obtaining HPV self-samples. Thirty seven of 250 women were VIA+. Thirty of 37 VIA+ women underwent confirmatory biopsies for cervical intraepithelial neoplasia (CIN) (26 CIN1, 4 CIN2+). The rate of confirmed dysplasia in the HIV+ group was 20/129 (15.5%) compared with 10/121 (8.26%) in HIV- women p=0.0291. The contemporaneous physician impressions of the DC images accurately differentiated between CIN1 and CIN2+ lesions in all 30 women having confirmatory biopsies. CONCLUSIONS: The results of this study suggest potential modifications of the current cervical screening strategy that is currently being employed in Cambodia. The first step in this new strategy would be self-swabbing for hrHPV. Subsequently, hrHPV+ patients would have DC and immediate treatment based on colposcopic findings: cryotherapy for suspected CIN1 and loop electrosurgical excision procedure (LEEP) for suspected CIN2+.

Adjunctive colposcopy technologies for assessing suspected cervical abnormalities: systematic reviews and economic evaluation.

BACKGROUND: Dynamic Spectral Imaging System (DySIS)map (DySIS Medical Ltd, Edinburgh, UK) and ZedScan (Zilico Limited, Manchester, UK) can be used adjunctively with conventional colposcopy, which may improve the detection of cervical intraepithelial neoplasia (CIN) and cancer. OBJECTIVES: To systematically review the evidence on the diagnostic accuracy, clinical effectiveness and implementation of DySISmap and ZedScan as adjuncts to standard colposcopy, and to develop a cost-effectiveness model. METHODS: Four parallel systematic reviews were performed on diagnostic accuracy, clinical effectiveness issues, implementation and economic analyses. In January 2017 we searched databases (including MEDLINE and EMBASE) for studies in which DySISmap or ZedScan was used adjunctively with standard colposcopy to detect CIN or cancer in women referred to colposcopy. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Summary estimates of diagnostic accuracy were calculated using bivariate and other regression models when appropriate. Other outcomes were synthesised narratively. A patient-level state-transition model was developed to evaluate the cost-effectiveness of DySISmap and ZedScan under either human papillomavirus (HPV) triage or the HPV primary screening algorithm. The model included two types of clinics ['see and treat' and 'watchful waiting' (i.e. treat later after confirmatory biopsy)], as well as the reason for referral (low-grade or high-grade cytological smear). Sensitivity and scenario analyses were undertaken. RESULTS: Eleven studies were included in the diagnostic review (nine of DySISmap and two of ZedScan), three were included in the clinical effectiveness review (two of DySISmap and one of ZedScan) and five were included in the implementation review (four of DySISmap and one of ZedScan). Adjunctive DySISmap use was found to have a higher sensitivity for detecting CIN grade 2+ (CIN 2+) lesions [81.25%, 95% confidence interval (CI) 72.2% to 87.9%] than standard colposcopy alone (57.91%, 95% CI 47.2% to 67.9%), but with a lower specificity (70.40%, 95% CI 59.4% to 79.5%) than colposcopy (87.41%, 95% CI 81.7% to 91.5%). (Confidential information has been removed.) The base-case cost-effectiveness results showed that adjunctive DySISmap routinely dominated standard colposcopy (it was less costly and more effective). The only exception was for high-grade referrals in a watchful-waiting clinic setting. The incremental cost-effectiveness ratio for ZedScan varied between £272 and £4922 per quality-adjusted life-year. ZedScan also dominated colposcopy alone for high-grade referrals in see-and-treat clinics. These findings appeared to be robust to a wide range of sensitivity and scenario analyses. LIMITATIONS: All but one study was rated as being at a high risk of bias. There was no evidence directly comparing ZedScan with standard colposcopy. No studies directly compared DySIS and ZedScan. CONCLUSIONS: The use of adjunctive DySIS increases the sensitivity for detecting CIN 2+, so it increases the number of high-grade CIN cases that are detected. However, it also reduces specificity, so that more women with no or low-grade CIN will be incorrectly judged as possibly having high-grade CIN. The evidence for ZedScan was limited, but it appears to increase sensitivity and decrease specificity compared with colposcopy alone. The cost-effectiveness of both adjunctive technologies compared with standard colposcopy, under both the HPV triage and primary screening algorithms, appears to be favourable when compared with the conventional thresholds used to determine value in the NHS. FUTURE WORK: More diagnostic accuracy studies of ZedScan are needed, as are studies assessing the diagnostic accuracy for women referred to colposcopy as part of the HPV primary screening programme. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017054515. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Community-based HPV self-collection versus visual inspection with acetic acid in Uganda: a cost-effectiveness analysis of the ASPIRE trial.

BACKGROUND: Cervical cancer is the leading cause of cancer death for women in Uganda, despite the potential for prevention through organised screening. Community-based self-collected human papillomavirus (HPV) testing has been proposed to reduce barriers to screening. OBJECTIVE: Our objective was to evaluate the cost-effectiveness of the Advances in Screening and Prevention of Reproductive Cancers (ASPIRE) trial, conducted in Kisenyi, Uganda in April 2014 (n=500). The trial compared screening uptake and compliance with follow-up in two arms: (1) community-based (ie, home or workplace) self-collected HPV testing (facilitated by community health workers) with clinic-based visual inspection with acetic acid (VIA) triage of HPV-positive women ('HPV-VIA') and (2) clinic-based VIA ('VIA'). In both arms, VIA was performed at the local health unit by midwives with VIA-positive women receiving immediate treatment with cryotherapy. DESIGN: We informed a Monte Carlo simulation model of HPV infection and cervical cancer with screening uptake, compliance and retrospective cost data from the ASPIRE trial; additional cost, test performance and treatment effectiveness data were drawn from observational studies. The model was used to assess the cost-effectiveness of each arm of ASPIRE, as well as an HPV screen-and-treat strategy ('HPV-ST') involving community-based self-collected HPV testing followed by treatment for all HPV-positive women at the clinic. OUTCOME MEASURES: The primary outcomes were reductions in cervical cancer risk and incremental cost-effectiveness ratios (ICERs), expressed in dollars per year of life saved (YLS). RESULTS: HPV-ST was the most effective and cost-effective screening strategy, reducing the lifetime absolute risk of cervical cancer from 4.2% (range: 3.8%-4.7%) to 3.5% (range: 3.2%-4%), 2.8% (range: 2.4%-3.1%) and 2.4% (range: 2.1%-2.7%) with ICERs of US$130 (US$110-US$150) per YLS, US$240 (US$210-US$280) per YLS, and US$470 (US$410-US$550) per YLS when performed one, three and five times per lifetime, respectively. Findings were robust across sensitivity analyses, unless HPV costs were more than quadrupled. CONCLUSIONS: Community-based self-collected HPV testing followed by treatment for HPV-positive women has the potential to be an effective and cost-effective screening strategy.

Patients with newly diagnosed cervical cancer should be screened for anal human papilloma virus and anal dysplasia: Results of a pilot study using a STELLA computer simulation and economic model.

BACKGROUND: Women with cervical cancer often have anal human papillomavirus (HPV) infection and anal dysplasia. However, effectiveness of anal HPV screening is unknown. METHODS: A dynamic model was constructed using STELLA. Populations are represented as "stocks" that change according to model rates. Initial anal cytology in new cervical cancer patients, dysplasia progression and regression, cost of treating high-grade squamous intraepithelial lesions (HSIL), and lifetime costs for anal cancer care were extrapolated from the literature. Local costs of anal HPV testing and cytology were obtained. Outcomes included anal cancer rates, anal cancer deaths, screening costs and cancer care. RESULTS: Benefits in the screened group included reduction in anal cancers after three years and anal cancer deaths after four years. After 10 years, predicted costs per anal cancer prevented and anal cancer deaths were $168,796 and $210,057 and were $98,631 and $210,057 at 20 years. Predicted costs per quality of life year saved at 10 and 20 years were $9785 and $1687. Sensitivity analysis demonstrated cost-effectiveness of screening for a variety of cure rates HSIL with electrocautery. CONCLUSION: Screening for anal HPV and treatment of anal HSIL in patients with cervical cancer is cost-effective, prevents anal cancer and reduces anal cancer deaths.

Extent, regional variation and impact of gynecologist payment models in routine pelvic examinations: a nationwide cross-sectional study.

BACKGROUND: Based on moderate quality evidence, routine pelvic examination is strongly recommended against in asymptomatic women. The aims of this study was to quantify the extent of routine pelvic examinations within specialized health care in Norway, to assess if the use of these services differs across hospital referral regions and to assess if the use of colposcopy and ultrasound differs with gynecologists' payment models. METHODS: Nationwide cross-sectional study including all women aged 18 years and older in Norway in the years 2014-16 (2,038,747). Data was extracted from the Norwegian Patient Registry and Statistics Norway. The main outcome measures were 1. The number of appointments per 1000 women with a primary diagnosis of "Encounter for gynecological examination without complaint, suspected or reported diagnosis." 2. The age-standardized number of these appointments per 1000 women in the 21 different hospital referral regions of Norway. 3. The use of colposcopy and ultrasound in routine pelvic examinations, provided by gynecologists with fixed salaries and gynecologists paid by a fee-for-service model. RESULTS: Annually 22.2 out of every 1000 women in Norway had a routine pelvic examination, with variation across regions from 6.6 to 43.9 per 1000. Gynecologists with fixed salaries performed colposcopy in 1.6% and ultrasound in 74.5% of appointments. Corresponding numbers for fee-for-service gynecologists were 49.2% and 96.2%, respectively. CONCLUSIONS: Routine pelvic examinations are widely performed in Norway. The variation across regions is extensive. Our results strongly indicate that fee-for-service payments for gynecologists skyrocket the use of colposcopy and increase the use of ultrasound in pelvic examinations of asymptomatic women.

Cost-effectiveness of HPV-based cervical cancer screening in the public health system in Nicaragua.

OBJECTIVES: To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing (versus Papanicolaou (Pap)-based screening) for cervical cancer screening in Nicaragua. DESIGN: A previously developed Monte Carlo simulation model of the natural history of HPV infection and cervical cancer was calibrated to epidemiological data from Nicaragua. Cost data inputs were derived using a micro-costing approach in Carazo, Chontales and Chinandega departments; test performance data were from a demonstration project in Masaya department. SETTING: Nicaragua's public health sector facilities. PARTICIPANTS: Women aged 30-59 years. INTERVENTIONS: Screening strategies included (1) Pap testing every 3 years, with referral to colposcopy for women with an atypical squamous cells of undetermined significance or worse result ('Pap'); (2) HPV testing every 5 years, with referral to cryotherapy for HPV-positive eligible women (HPV cryotherapy or 'HPV-Cryo'); (3) HPV testing every 5 years, with referral to triage with visual inspection with acetic acid (VIA) for HPV-positive women ('HPV-VIA'); and (4) HPV testing every 5 years, with referral to Pap testing for HPV-positive women ('HPV-Pap'). OUTCOME MEASURES: Reduction in lifetime risk of cancer and incremental cost-effectiveness ratios (ICER; 2015 US$ per year of life saved (YLS)). RESULTS: HPV-based screening strategies were more effective than Pap testing. HPV-Cryo was the least costly and most effective strategy, reducing lifetime cancer risk by 29.5% and outperforming HPV-VIA, HPV-Pap and Pap only, which reduced cancer risk by 19.4%, 12.2% and 10.8%, respectively. With an ICER of US$320/YLS, HPV-Cryo every 5 years would be very cost-effective using a threshold based on Nicaragua's per capita gross domestic product of US$2090. Findings were robust across sensitivity analyses on test performance, coverage, compliance and cost parameters. CONCLUSIONS: HPV testing is very cost-effective compared with Pap testing in Nicaragua, due to higher test sensitivity and the relatively lower number of visits required. Increasing compliance with recommended follow-up will further improve the health benefits and value for public health dollars.

Cost-effectiveness of an HPV self-collection campaign in Uganda: comparing models for delivery of cervical cancer screening in a low-income setting.

With the availability of a low-cost HPV DNA test that can be administered by either a healthcare provider or a woman herself, programme planners require information on the costs and cost-effectiveness of implementing cervical cancer screening programmes in low-resource settings under different models of healthcare delivery. Using data from the START-UP demonstration project and a micro-costing approach, we estimated the health and economic impact of once-in-a-lifetime HPV self-collection campaign relative to clinic-based provider-collection of HPV specimens in Uganda. We used an individual-based Monte Carlo simulation model of the natural history of HPV and cervical cancer to estimate lifetime health and economic outcomes associated with screening with HPV DNA testing once in a lifetime (clinic-based provider-collection vs a self-collection campaign). Test performance and cost data were obtained from the START-UP demonstration project using a micro-costing approach. Model outcomes included lifetime risk of cervical cancer, total lifetime costs (in 2011 international dollars [I$]), and life expectancy. Cost-effectiveness ratios were expressed using incremental cost-effectiveness ratios (ICERs). When both strategies achieved 75% population coverage, ICERs were below Uganda's per capita GDP (self-collection: I$80 per year of life saved [YLS]; provider-collection: I$120 per YLS). When the self-collection campaign achieved coverage gains of 15-20%, it was more effective than provider-collection, and had a lower ICER unless coverage with both strategies was 50% or less. Findings were sensitive to cryotherapy compliance among screen-positive women and relative HPV test performance. The primary limitation of this analysis is that self-collection costs are based on a hypothetical campaign but are based on unit costs from Uganda. Once-in-a-lifetime screening with HPV self-collection may be very cost-effective and reduce cervical cancer risk by > 20% if coverage is high. Demonstration projects will be needed to confirm the validity of our logistical, costing and compliance assumptions.

A model to evaluate the costs and clinical effectiveness of human papilloma virus screening compared with annual papanicolaou cytology in Germany.

OBJECTIVES: We modelled human papilloma virus (HPV) primary screening scenarios compared with Pap cytology to evaluate clinical effectiveness and projected annual costs in Germany. STUDY DESIGN: A Markov cohort model was built to compare the budget impact of annual Pap cytology with different 5-yearly HPV screening scenarios: (1) a positive HPV test followed by Pap cytology; (2) a positive HPV test followed by p16/Ki-67 dual-stained cytology; (3) a positive HPV test followed by colposcopy if HPV-16/18-positive or p16/Ki-67 dual-stained cytology if positive for other subtypes; (4) co-testing with HPV and Pap. Screening scenarios were based on a 10-year horizon. RESULTS: All HPV screening scenarios in the model were associated with fewer deaths from missed diagnosis of cervical cancer compared with Pap screening; 10-year totals n=172-344 (1.5-3 per 100,000) versus n=477 (4.1 per 100,000), respectively. Total annual costs were lower with HPV screening than Pap cytology. The projected average annual cost for HPV screening ranged from €117 million to €136 million compared with €177 million for Pap screening, representing annual savings of €41-60 million. The greatest clinical impact was achieved with primary HPV screening (with genotyping) followed by colposcopy for HPV 16/18-positive women or p16/Ki-67 dual-stained cytology for women positive for other HPV subtypes. CONCLUSION: Screening strategies including primary HPV testing for high-risk subtypes (HPV-16/18) in conjunction with p16/Ki-67 dual-stained cytology can improve the detection of cervical cancer at a lower total annual cost than conventional Pap cytology screening.

High-resolution microendoscopy: a point-of-care diagnostic for cervical dysplasia in low-resource settings.

Cervical cancer is the third leading cause of cancer-related death among women in low-to-middle income countries. Pap testing and pathological services are difficult to implement under these settings. Alternative techniques for the diagnosis of cervical precancer in these settings are needed to reduce the burden of the disease. The objective of this study was to evaluate the diagnostic accuracy of a low-cost, high-resolution microendoscope imaging system in identifying precancerous lesions of the cervix in vivo. A retrospective study of 59 patients undergoing colposcopy for an abnormal Pap test was performed at Hospital de Câncer de Barretos in Brazil. All patients underwent colposcopy as per standard of care, and acetowhite lesions were recorded. High-resolution microendoscopy (HRME) images were obtained from one colposcopically normal region and from all lesions observed on colposcopy. Biopsies of abnormal areas were obtained and reviewed by three independent, blinded pathologists and compared with HRME findings. The mean nuclear area and the median nuclear eccentricity were calculated from HRME images acquired from each site. A diagnostic algorithm to distinguish histopathologically diagnosed cervical intraepithelial neoplasias of grade 2 or more severe lesions (high grade) from less severe lesions (low grade) was developed using these parameters. A test of trend was used to analyze the relationship between HRME positivity and severity of histopathogical diagnosis. Fisher's exact test was used to analyze differences in HRME positivity between high-grade and low-grade lesions. Evaluable images were obtained from 108 of 143 discrete sites. Of these, 71 sites were colposcopically normal or low grade according to histopathology and 37 were diagnosed as high grade on the basis of histopathology. Using the mean nuclear area and the median nuclear eccentricity, HRME images from 59 colposcopically abnormal sites were classified as high grade or low grade with 92% sensitivity and 77% specificity compared with histopathological findings. Increasing HRME positivity showed a significant trend with increasing severity of diagnosis (Ptrend<0.001). We found a strong association (P<0.001) between HRME positivity and a histopathological diagnosis of cervical intraepithelial neoplasia of grade 2 or higher. HRME demonstrated an accurate in-situ diagnosis of high-grade dysplasia. In low-resource settings in which colposcopy and histopathology services are severely limited or unavailable, HRME may provide a low-cost, accurate method for diagnosis of cervical precancer without the need for biopsy, allowing for a single 'screen-and-treat' approach.

Optimal Cervical Cancer Screening in Women Vaccinated Against Human Papillomavirus.

Background: Current US cervical cancer screening guidelines do not differentiate recommendations based on a woman's human papillomavirus (HPV) vaccination status. Changes to cervical cancer screening policies in HPV-vaccinated women should be evaluated. Methods: We utilized an individual-based mathematical model of HPV and cervical cancer in US women to project the health benefits, costs, and harms associated with screening strategies in women vaccinated with the bivalent, quadrivalent, or nonavalent vaccine. Strategies varied by the primary screening test, including cytology, HPV, and combined cytology and HPV "cotesting"; age of screening initiation and/or switching to a new test; and interval between routine screens. Cost-effectiveness analysis was conducted from the societal perspective to identify screening strategies that would be considered good value for money according to thresholds of $50 000 to $200 000 per quality-adjusted life-year (QALY) gained. Results: Among women fully vaccinated with the bivalent or quadrivalent vaccine, optimal screening strategies involved either cytology or HPV testing alone every five years starting at age 25 or 30 years, with cost-effectiveness ratios ranging from $34 680 to $138 560 per QALY gained. Screening earlier or more frequently was either not cost-effective or associated with exceedingly high cost-effectiveness ratios. In women vaccinated with the nonavalent vaccine, only primary HPV testing was efficient, involving decreased frequency (ie, every 10 years) starting at either age 35 years ($40 210 per QALY) or age 30 years ($127 010 per QALY); with lower nonavalent vaccine efficacy, 10-year HPV testing starting at earlier ages of 25 or 30 years was optimal. Importantly, current US guidelines for screening were inefficient in HPV-vaccinated women. Conclusions: This model-based analysis suggests screening can be modified to start at later ages, occur at decreased frequency, and involve primary HPV testing in HPV-vaccinated women, providing more health benefit at lower harms and costs than current screening guidelines.

Detailed Cost Analysis of Robotic Sacrocolpopexy Compared to Transvaginal Mesh Repair.

OBJECTIVE: To evaluate the hospital-realized cost difference between transvaginal mesh prolapse repair and robot-assisted sacrocolpopexy. METHODS: Consecutive transvaginal mesh prolapse surgery and robot-assisted sacrocolpopexy cases from January 2012 to December 2013 were evaluated. Patient clinical and operative data were recorded. The total institutional costs (direct and indirect) for each procedure were obtained and subcategorized by area. Independent sample t tests and chi-squared analysis were performed. RESULTS: One hundred twenty women underwent transvaginal mesh repair whereas 106 underwent robotic sacrocolpopexy. Body mass index was similar between groups (28.1 vs 27.5) as was midurethral sling placement (50% vs 59%). Robotic patients were younger (61 years vs 67 years., P < .001) and more likely to undergo concomitant hysterectomy (58.5% vs 26.7%). There were similar rates for additional compartment repairs. Amortized costs for robotic purchase and maintenance were included with all depreciated equipment and realized by all patients undergoing surgery. Overall mean robotic operative time was longer with and without hysterectomy (279 minutes vs 174 minutes, P < .001 and 201 minutes vs 91 minutes, P < .001). Mean total costs were higher with robotic technique ($9675 vs $6718, P < .001), primarily driven by anesthesia ($1141 vs $675, P < .001), and operative ($6883 vs $4487, P < .001) costs. No differences for total costs were seen in laboratory fees, recovery room, or inpatient nursing. CONCLUSION: Transvaginal prolapse repair is less costly than robotic sacrocolpopexy. Length of surgery and additional robotic supplies drive the majority of increased operative costs. Costs attributed to robot purchase and maintenance do not uniquely factor into the procedure costs.

The Clinical and Economic Benefits of Co-Testing Versus Primary HPV Testing for Cervical Cancer Screening: A Modeling Analysis.

BACKGROUND: Consensus United States cervical cancer screening guidelines recommend use of combination Pap plus human papillomavirus (HPV) testing for women aged 30 to 65 years. An HPV test was approved by the Food and Drug Administration in 2014 for primary cervical cancer screening in women age 25 years and older. Here, we present the results of clinical-economic comparisons of Pap plus HPV mRNA testing including genotyping for HPV 16/18 (co-testing) versus DNA-based primary HPV testing with HPV 16/18 genotyping and reflex cytology (HPV primary) for cervical cancer screening. METHODS: A health state transition (Markov) model with 1-year cycling was developed using epidemiologic, clinical, and economic data from healthcare databases and published literature. A hypothetical cohort of one million women receiving triennial cervical cancer screening was simulated from ages 30 to 70 years. Screening strategies compared HPV primary to co-testing. Outcomes included total and incremental differences in costs, invasive cervical cancer (ICC) cases, ICC deaths, number of colposcopies, and quality-adjusted life years for cost-effectiveness calculations. Comprehensive sensitivity analyses were performed. RESULTS: In a simulation cohort of one million 30-year-old women modeled up to age 70 years, the model predicted that screening with HPV primary testing instead of co-testing could lead to as many as 2,141 more ICC cases and 2,041 more ICC deaths. In the simulation, co-testing demonstrated a greater number of lifetime quality-adjusted life years (22,334) and yielded $39.0 million in savings compared with HPV primary, thereby conferring greater effectiveness at lower cost. CONCLUSIONS: Model results demonstrate that co-testing has the potential to provide improved clinical and economic outcomes when compared with HPV primary. While actual cost and outcome data are evaluated, these findings are relevant to U.S. healthcare payers and women's health policy advocates seeking cost-effective cervical cancer screening technologies.

Using Decision-Analytic Modeling to Isolate Interventions That Are Feasible, Efficient and Optimal: An Application from the Norwegian Cervical Cancer Screening Program.

BACKGROUND: Decision makers often need to simultaneously consider multiple criteria or outcomes when deciding whether to adopt new health interventions. OBJECTIVES: Using decision analysis within the context of cervical cancer screening in Norway, we aimed to aid decision makers in identifying a subset of relevant strategies that are simultaneously efficient, feasible, and optimal. METHODS: We developed an age-stratified probabilistic decision tree model following a cohort of women attending primary screening through one screening round. We enumerated detected precancers (i.e., cervical intraepithelial neoplasia of grade 2 or more severe (CIN2+)), colposcopies performed, and monetary costs associated with 10 alternative triage algorithms for women with abnormal cytology results. As efficiency metrics, we calculated incremental cost-effectiveness, and harm-benefit, ratios, defined as the additional costs, or the additional number of colposcopies, per additional CIN2+ detected. We estimated capacity requirements and uncertainty surrounding which strategy is optimal according to the decision rule, involving willingness to pay (monetary or resources consumed per added benefit). RESULTS: For ages 25 to 33 years, we eliminated four strategies that did not fall on either efficiency frontier, while one strategy was efficient with respect to both efficiency metrics. Compared with current practice in Norway, two strategies detected more precancers at lower monetary costs, but some required more colposcopies. Similar results were found for women aged 34 to 69 years. CONCLUSIONS: Improving the effectiveness and efficiency of cervical cancer screening may necessitate additional resources. Although efficient and feasible, both society and individuals must specify their willingness to accept the additional resources and perceived harms required to increase effectiveness before a strategy can be considered optimal.