Cost-Effectiveness of 9-Valent HPV Vaccination for Patients Treated for High-Grade Cervical Intraepithelial Neoplasia in the UK.

Importance: Patients who have been treated for high-grade cervical intraepithelial neoplasia (CIN grade ≥2) are at a high risk for subsequent CIN and other cancers and diseases related to human papillomavirus (HPV). HPV vaccination can reduce the risk of subsequent disease in patients surgically treated for grade 2 or greater CIN; however, there is no formal recommendation for prophylactic HPV vaccination in this high-risk population, and the cost-effectiveness is unknown. Objective: To assess the incremental lifetime outcomes, costs, and cost-effectiveness of integrating peritreatment 9-valent HPV (9vHPV) vaccination in combination with posttreatment surveillance for the prevention of cervical cancer and other HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN vs posttreatment surveillance alone from a UK payer perspective. Design, Setting, and Participants: This economic evaluation used 3 independent Markov model structures. Model inputs for vaccine efficacy, utilities, and costs were obtained from published sources, and cervical cancer screening data were obtained from the National Health Service Cervical Screening Program. Costs were adjusted to 2022 to 2023 reference years. Data were analyzed from October 2022 to September 2023. Exposure: Peritreatment vaccination with 9vHPV in combination with posttreatment surveillance compared with posttreatment surveillance alone. Main Outcomes and Measures: Clinical outcomes included grade 1, 2, or 3 CIN; cervical cancer; vaginal cancer; vulvar cancer; anal cancer; head and neck cancer; genital warts; and recurrent respiratory papillomatosis. Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold (WTP) of £20 000 (US $26 200) per quality-adjusted life-year (QALY) were estimated. Deterministic sensitivity analysis and probabilistic sensitivity analysis were performed. Results: Vaccination with 9vHPV in conjunction with posttreatment surveillance was cost-effective, with a favorable ICER of £13 789.07 (US $18 064.68) per QALY gained (ie, below the WTP of £20 000 per QALY) vs posttreatment surveillance alone. The resulting ICER was £52 358.01 (US $68 588.99) per HPV-related cancer averted and £64 090 (US $83 958.18) per HPV-related cancer death averted. The ICER was most sensitive to discount rate, incidence of HPV infection, vaccine price, and age at initial treatment for grade 2 or greater CIN. Results of the probabilistic sensitivity analysis showed peritreatment 9vHPV vaccination was cost-effective at the WTP recommended by the UK's Joint Committee on Vaccination and Immunisation (90% of iterations <£30 000 [US $39 300] per QALY) in 100% of iterations. Conclusions and Relevance: These findings suggest that peritreatment prophylactic 9vHPV vaccination is a cost-effective option for preventing subsequent HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN.

Treatment methods for cervical intraepithelial neoplasia in England: A cost-effectiveness analysis.

OBJECTIVE: To compare the cost-effectiveness of different treatments for cervical intraepithelial neoplasia (CIN). DESIGN: A cost-effectiveness analysis based on data available in the literature and expert opinion. SETTING: England. POPULATION: Women treated for CIN. METHODS: We developed a decision-analytic model to simulate the clinical course of 1000 women who received local treatment for CIN and were followed up for 10 years after treatment. In the model we considered surgical complications as well as oncological and reproductive outcomes over the 10-year period. The costs calculated were those incurred by the National Health Service (NHS) of England. MAIN OUTCOME MEASURES: Cost per one CIN2+ recurrence averted (oncological outcome); cost per one preterm birth averted (reproductive outcome); overall cost per one adverse oncological or reproductive outcome averted. RESULTS: For young women of reproductive age, large loop excision of the transformation zone (LLETZ) was the most cost-effective treatment overall at all willingness-to-pay thresholds. For postmenopausal women, LLETZ remained the most cost-effective treatment up to a threshold of £31,500, but laser conisation became the most cost-effective treatment above that threshold. CONCLUSIONS: LLETZ is the most cost-effective treatment for both younger and older women. However, for older women, more radical excision with laser conisation could also be considered if the NHS is willing to spend more than £31,500 to avert one CIN2+ recurrence.

Cost-effectiveness analysis of the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines for the management of abnormal cervical cancer screening tests and cancer precursors.

BACKGROUND: The guidelines for managing abnormal cervical cancer screening tests changed from a results-based approach in 2012 to a risk-based approach in 2019. OBJECTIVE: We estimated the cost-effectiveness of the 2019 management guidelines and the changes in resource utilization moving from 2012 to 2019 guidelines. STUDY DESIGN: We utilized a previously published model of cervical cancer natural history and screening to estimate and compare the lifetime costs and the number of screens, colposcopies, precancer treatments, cancer cases, and cancer deaths associated with the 2012 vs 2019 management guidelines. We assessed these guidelines under the scenarios of observed screening practice and perfect screening adherence to 3-year cytology starting at age 21, with a switch to either 3-year or 5-year cytology plus human papillomavirus cotesting at age 30. In addition, we estimated the lifetime costs and life years to determine the cost-effectiveness of shifting to the 2019 management guidelines. RESULTS: Under the assumptions of both observed screening practice and perfect screening adherence with a strategy of 3-year cytology at ages 21 to 29 and switching to 3-year cotesting at age 30, the management of the screening tests according to the 2019 guidelines was less costly and more effective than the 2012 guidelines. For 3-year cytology screening at ages 21 to 29 and switching to 5-year cotesting at age 30, the 2019 guidelines were more cost-effective at a willingness-to-pay threshold of $100,000 per life year gained. Across all scenarios, the 2019 management guidelines were associated with fewer colposcopies and cancer deaths. CONCLUSION: Our model-based analysis suggests that the 2019 guidelines are more effective overall and also more cost-effective than the 2012 guidelines, supporting the principle of "equal management of equal risks."

Cervical testing beyond the screening target age - A register-based cohort study from Finland.

OBJECTIVE: It has been proposed that cervical cancer screening should be continued in women with previous abnormal results or irregular attendance. We examined the coverage and factors that might influence cervical testing beyond the age range of the organized cervical screening programme in Finland. The national programme invites women in every five years least until the age of 60. After the stopping age, only opportunistic service is available. METHODS: Data on cervical testing were collected from the Mass Screening Registry and providers of opportunistic Pap/HPV-testing and were linked with information on socio-economic variables. The study included 373,353 women who had at least one invitation to the national screening programme between ages 50-60 years, and who were aged 65-74 years in the follow-up period 2006-2016. Multivariable binomial regression models were conducted to determine associations. RESULTS: Altogether 33% of the study population had been tested at least once at ages 65-74 years. Previous regular screening attendance (adjRR 1.70; 95% CI 1.67-1.73) and earlier abnormal results (adjRR 2.08; 95% CI 2.04-2.12) were most clearly related to higher testing adherence at older age. Other factors related to higher testing adherence were urban area of residence, domestic mother tongue, high education level, and high socio-economic status. CONCLUSION: Testing at older age was frequent with normal results, whereas only a small proportion of women with earlier abnormal results or irregular attendance were tested. The upper age limit of the national programme should be raised to 65 years, and the invitations thereafter should be targeted to selected high-risk groups.

Cost-Effectiveness of Offering Cervical Cancer Screening with HPV Self-Sampling among African-American Women in the Mississippi Delta.

BACKGROUND: African-American women in the United States have an elevated risk of cervical cancer incidence and mortality. In the Mississippi Delta, cervical cancer disparities are particularly stark. METHODS: We conducted a micro-costing study alongside a group randomized trial that evaluated the efficacy of a patient-centered approach ("Choice" between self-collection at home for HPV testing or current standard of care within the public health system in Mississippi) versus the current standard of care ["Standard-of-care screening," involving cytology (i.e., Pap) and HPV co-testing at the Health Department clinics]. The interventions in both study arms were delivered by community health workers (CHW). Using cost, screening uptake, and colposcopy adherence data from the trial, we informed a mathematical model of HPV infection and cervical carcinogenesis to conduct a cost-effectiveness analysis comparing the "Choice" and "Standard-of-care screening" interventions among un/underscreened African-American women in the Mississippi Delta. RESULTS: When each intervention was simulated every 5 years from ages 25 to 65 years, the "Standard-of-care screening" strategy reduced cancer risk by 6.4% and was not an efficient strategy; "Choice" was more effective and efficient, reducing lifetime risk of cervical cancer by 14.8% and costing $62,720 per year of life saved (YLS). Screening uptake and colposcopy adherence were key drivers of intervention cost-effectiveness. CONCLUSIONS: Offering "Choice" to un/underscreened African-American women in the Mississippi Delta led to greater uptake than CHW-facilitated screening at the Health Department, and may be cost-effective. IMPACT: We evaluated the cost-effectiveness of an HPV self-collection intervention to reduce disparities.

Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study.

BACKGROUND: Human papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening. METHODS: A cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36,390 women aged 30-49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17,997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18,393, Pap smear arm). RESULTS: Self-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 229,446 vs. € 782,772). CONCLUSIONS: This study resulted in that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening. TRIAL REGISTRATION: Not registered since this trial is a secondary analysis of an earlier published study (Gustavsson et al., British journal of cancer. 118:896-904, 2018).

Epidemiologic and Health Economic Evaluation of Cervical Cancer Screening in Rural China.

BACKGROUND: Cervical cancer is preventable and curable by detected early and managed effectively. To explore the most economical and effective cervical cancer screening strategies would lay a solid foundation for reducing the health and economic burden of cervical cancer. METHODS: A Markov model was established for a cohort of 100,000 female to simulate the natural history of cervical cancer. 18 screening strategies were estimated including careHPV, Thin prep cytologic (TCT), Visual inspection with acetic acid/ Lugol's iodine (VIA / VILI), careHPV in series with VIA / VILI, careHPV in series with TCT, three methods parallel connection every 1, 3, 5 years respectively. Model outcomes included cumulative risk of incidence and death of cervical cancer, quality-adjusted life years (QALYs), cost-effectiveness ratios (CERs), incremental cost-effectiveness ratios (ICERs), cost-utility ratios (CURs) and benefits. RESULTS: According to the results of epidemiological analysis, careHPV similar to the parallel connection every 1 year achieved highest epidemiological effects via reducing the cumulative risk of onset and death by more than 98 %. In health-economic terms, CER among all the screening strategies ranged from -756.34 to 113040.3 Yuan per year and CUR ranged from -169.91 to 11968.27 Yuan per QALY. The benefit ranged from -1629 to 996 Yuan. The incremental cost-effectiveness analysis showed that three methods in parallel every 1 year, TCT every 1 year, VIA/VILI every 1, 3, 5 years and careHPV every 5 years were dominant strategies. CONCLUSION: Considering the economic and health benefits of all the strategies, our results suggested careHPV every 3 or 5 years and VIA/VILI every 1 or 3 years eventually were more appropriate as screening methods in rural China.

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.

Economic evaluation of HPV DNA test as primary screening method for cervical cancer: A health policy discussion in Greece.

BACKGROUND: HPV test appears to be more effective in cervical cancer (CC) screening. However, the decision of its adoption as a primary screening method by substituting the established cytology lies in the evaluation of multiple criteria. Aim of this study is to evaluate the economic and clinical impact of HPV test as primary screening method for CC. METHODS: A decision tree and a Markov model were developed to simulate the screening algorithm and the natural history of CC. Fourteen different screening strategies were evaluated, for women 25-65 years old. Clinical inputs were drawn from the HERMES study and cost inputs from the official price lists. In the absence of CC treatment cost data, the respective Spanish costs were used after being converted to 2017 Greek values. One-way and probabilistic sensitivity analyses were conducted. RESULTS: All screening strategies, that offer as primary screening method triennial HPV genotyping (simultaneous or reflex) alone or as co-testing with cytology appear to be more effective than all other strategies, with regards to both annual CC mortality, due to missed disease (-10.1), and CC incidence(-7.5) versus annual cytology (current practice). Of those, the strategy with HPV test with simultaneous 16/18 genotyping is the strategy that provides savings of 1.050 million euros annually. However, when the above strategy is offered quinquennially despite the fact that outcomes are decreased it remains more effective than current practice (-7.7 deaths and -1.3 incidence) and more savings per death averted (1.323 million) or incidence reduced (7.837 million) are realized. CONCLUSIONS: HPV 16/18 genotyping as a primary screening method for CC appears to be one of the most effective strategies and dominates current practice in respect to both cost and outcomes. Even when compared with all other strategies, the outcomes that it generates justify the cost that it requires, representing a good value for money alternative.

Clinical evaluation and budget impact analysis of cervical cancer screening using cobas 4800 HPV screening technology in the public sector of South Africa.

Cytology remains the mainstay of cervical cancer screening in South Africa (SA), however false negative rates are 25-50%. In contrast, human papillomavirus (HPV) screening techniques have higher sensitivity for cervical cancer precursors. The cobas® 4800 HPV test detects pooled high-risk HPV types and individual genotypes HPV 16 and 18. Using a mathematical budget impact model, the study objective was to evaluate the clinical and budget impact of replacing primary liquid-based cytology (LBC) with primary HPV-based screening strategies. In SA, current LBC screening practice recommends one test every ten years, followed by large loop excision of the transformation zone (LLETZ) if indicated. HPV testing can be performed from an LBC sample, where no additional consultations nor samples are required. In the budget impact model, LBC screening for 2 cycles (one test every ten years) was compared to cobas® 4800 HPV test for 2 cycles (one test every 5 years). The model inputs were gathered from literature and primary data sources. Indicative prices for LBC and cobas® 4800 HPV test were R189 and R457, respectively. Model results indicate that best outcomes for detection of disease were seen using cobas® 4800 HPV test. Forty-eight percent of cervical cancer cases were detected compared to 28% using LBC, and 50% of cervical intraepithelial neoplasia (CIN) 2 and CIN3 cases, compared to 25% with LBC. The budget impact analysis predicted that the cost per detected case of CIN2 or higher would be R 56,835 and R46,980 for the cobas® 4800 HPV and LBC scenarios, respectively. This equates to an incremental cost per detected case of CIN2 or higher of R9 855. From this model we conclude that a primary HPV screening strategy will have a significant clinical impact on disease burden in South Africa.

Low-cost, high-resolution imaging for detecting cervical precancer in medically-underserved areas of Texas.

OBJECTIVE: Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center. METHODS: HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers of varying skill and training. Colposcopy, followed by HRME imaging, was performed on eligible women. The sensitivity and specificity of traditional colposcopy and colposcopy followed by HRME to detect CIN2+ were compared and HRME image quality was evaluated. RESULTS: 174 women (227 cervical sites) were included in the final analysis, with 12% (11% of cervical sites) diagnosed with CIN2+ on histopathology. On a per-site basis, a colposcopic impression of low-grade precancer or greater had a sensitivity of 84% and a specificity of 45% to detect CIN2+. While there was no significant difference in sensitivity (76%, p = 0.62), the specificity when using HRME was significantly higher than that of traditional colposcopy (56%, p = 0.01). There was no significant difference in HRME image quality between clinical sites (p = 0.77) or medical providers (p = 0.33). CONCLUSIONS: HRME imaging increased the specificity for detecting CIN2+ when compared to traditional colposcopy. HRME image quality remained consistent across different clinical settings.

Incidence and costs of cervical intraepithelial neoplasia in the Korean population.

OBJECTIVE: The purpose of this study was to assess the incidence rate of cervical intraepithelial neoplasia (CIN) and cervical cancer, and their costs according to age. METHODS: We collected data on annual incidence and medical costs of CIN and cervical cancer from 2010 until the end of 2014 from the Health Insurance Review and Assessment (HIRA) service. The CIN was classified into CIN3 (high-grade) requiring conization and CIN1/2 (low-grade) requiring observation. RESULTS: Incidence rates of CIN3 and cervical cancer are reducing over time, whereas CIN1/2 is increasing significantly (p for trend: <0.001). The peak ages of incidence were 25-29, 30-34, and 70-74 years old for CIN1/2, CIN3, and cervical cancer, respectively. The crude incidence of CIN1/2 increased by approximately 30% in 2014 compared to 5 years ago and demonstrated an increasing trend in all age groups. The CIN3 showed a significantly increasing trend in the age group of 30-39 years old, the cervical cancer was significantly reduced in all ages, except the 35-39 years old. The treatment for cervical cancer costs $3,342 per year, whereas the treatment for CIN3 and CIN1/2 cost $467 and $83, respectively. CONCLUSION: The crude incidence rate of cervical cancer is currently decreasing among Korean women, but the incidence rates and medical costs of CIN and cervical cancer are increasing in women in their 30s in Korea. These findings suggest that different strategies by age will be required for prevention of cervical cancer in Korea.

Budget impact analysis of cervical cancer screening in Portugal: comparison of cytology and primary HPV screening strategies.

BACKGROUND: Primary Human Papilloma Virus (HPV) testing is the currently recommended cervical cancer (CxCa) screening strategy by the Portuguese Society of Gynecology (SPG) clinical consensus. However, primary HPV testing has not yet been adopted by the Portuguese organized screening programs. This modelling study compares clinical benefits and costs of replacing the current practice, namely cytology with ASCUS HPV triage, with 2 comparative strategies: 1) HPV (pooled) test with cytology triage, or 2) HPV test with 16/18 genotyping and cytology triage, in organized CxCa screenings in Portugal. METHODS: A budget impact model compares screening performance, clinical outcomes and budget impact of the 3 screening strategies. A hypothetical cohort of 2,078,039 Portuguese women aged 25-64 years old women is followed for two screening cycles. Screening intervals are 3 years for cytology and 5 years for the HPV strategies. Model inputs include epidemiological, test performance and medical cost data. Clinical impacts are assessed with the numbers of CIN2-3 and CxCa detected. Annual costs, budget impact and cost of detecting one CIN2+ were calculated from a public healthcare payer's perspective. RESULTS: HPV testing with HPV16/18 genotyping and cytology triage (comparator 2) shows the best clinical outcomes at the same cost as comparator 1 and is the most cost-effective CxCa screening strategy in the Portuguese context. Compared to screening with cytology, it would reduce annual CxCa incidence from 9.3 to 5.3 per 100,000, and CxCa mortality from 2.7 to 1.1 per 100,000. Further, it generates substantial cost savings by reducing the annual costs by €9.16 million (- 24%). The cost of detecting CIN2+ decreases from the current €15,845 to €12,795. On the other hand, HPV (pooled) test with cytology triage (comparator 1) reduces annual incidence of CxCa to 6.9 per 100,000 and CxCa mortality to 1.6 per 100,000, with a cost of €13,227 per CIN2+ detected with annual savings of €9.36 million (- 24%). The savings are mainly caused by increasing the length of routine screening intervals from three to five years. CONCLUSION: The results support current clinical recommendations to replace cytology with HPV with 16/18 genotyping with cytology triage as screening algorithm.

Cost-effectiveness evaluation of HPV self-testing offered to non-attendees in cervical cancer screening in Switzerland.

OBJECTIVE: About 30% of women who are eligible for cervical cancer (CC) screening remain un-screened or under-screened in Switzerland. HPV testing on self-collected vaginal samples (Self-HPV) has shown to be more sensitive than cytology while also reaching non-attendees. The objective of this study was to explore the cost-effectiveness of offering Self-HPV to non-attendees in Switzerland. METHODS: A recursive decision-tree with one-year cycles was used to model the life-long natural HPV history. Markov cohort simulations were used to assess the expected outcomes from the model. The outcomes of three strategies were compared with the absence of screening: Self-HPV and triage with colposcopy (Self-HPV/colpo), Self-HPV and triage with Pap cytology (Self-HPV/PAP), cytological screening and triage with HPV (PAP/HPV). Sensitivity analyses for the key parameters of the model were conducted to check the robustness of findings. RESULTS: Offering a Self-HPV screening to non-attendees could prevent 90% of CC and 94% of CC-related deaths in the study population. The current cytology-based program could reduce by 83% the number of CC cases and by 88% the number of CC-related deaths over the population's lifetime. Compared to the absence of screening, incremental cost-effectiveness ratios (ICER) were estimated to be, per saved Quality Adjusted Life Year (QALY), 12413US$ for the strategy Self-HPV/colpo, 11138US$ for the strategy Self-HPV/Pap and 22488US$ for the strategy PAP/HPV. CONCLUSIONS: Offering Self-HPV as a CC screening strategy to non-attendees in Switzerland is a cost-effective solution that is associated with a reduction of CC cases and related deaths. Self-HPV is more cost-effective than the currently used cytology-based screening.

Clinical and Economic Value of p16INK4a for the Differential Diagnosis of Morphologic Cervical Intraepithelial Neoplasia 2.

The detection of high-grade intraepithelial lesions requires highly sensitive and specific methods that allow more accurate diagnoses. This contributes to a proper management of preneoplastic lesions, thus avoiding overtreatment. The purpose of this study was to analyze the value of immunostaining for p16 in the morphologic assessment of cervical intraepithelial neoplasia 2 lesions, to help differentiate between low-grade (p16-negative) and high-grade (p16-positive) squamous intraepithelial lesions. The direct medical cost of the treatment of cervical intraepithelial neoplasia 2 morphologic lesions was estimated. A retrospective observational cross-sectional study was carried out. This study analyzed 46 patients treated with excisional procedures because of cervical intraepithelial neoplasia 2 lesions, using loop electrosurgical excision procedures. Immunostaining for the biomarker was performed. For the estimation of overtreatment, percentages (%) and their 95% confidence interval were calculated. Of the 41 patients analyzed, 32 (78%) showed overexpression of p16 and 9 (22%) were negative (95% confidence interval, 11%-38%). Mean follow-up was 2.9 years, using cervical cytology testing (Pap) and colposcopy. High-risk human papillomavirus DNA tests were performed in 83% of patients. These retrospective results reveal the need for larger biopsy samples, which would allow a more accurate prediction of lesion risk. Considering the cost of p16 staining, and assuming the proper management of the low-grade lesion, an average of US$919 could be saved for each patient with a p16-negative result, which represents a global direct cost reduction of 10%.

Costs and cost-effectiveness of LEEP versus cryotherapy for treating cervical dysplasia among HIV-positive women in Johannesburg, South Africa.

BACKGROUND: Cervical cancer incidence is significant in countries, such as South Africa, with high burdens of both HIV and human papillomavirus (HPV). Cervical cancer is largely preventable if dysplasia is diagnosed and treated early, but there is debate regarding the best approaches for screening and treatment, especially for low-resource settings. Currently South Africa provides Pap smears followed by colposcopic biopsy and LEEP if needed in its public health facilities. We estimated the costs and cost-effectiveness of two approaches for treating cervical intraepithelial neoplasia grade 2 or higher (CIN2+) among HIV-infected women, most of whom were taking antiretroviral treatment, at a public HIV treatment facility in Johannesburg, South Africa. METHODS: Method effectiveness was derived from an intention-to-treat analysis of data gathered in a clinical trial completed previously at the study facility. In the trial, women who were diagnosed with CIN2+ and eligible for cryotherapy were randomized to cryotherapy or LEEP. If women were CIN2+ at six months as determined via Pap smear and colposcopic biopsy, all women-regardless of their original treatment assignment-received LEEP. "Cure" was then defined as the absence of disease at 12 months based on Pap smear and colposcopic biopsy. Health service costs were estimated using micro-costing between June 2013 and April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered, and results from an as-treated analysis were considered in sensitivity analysis. RESULTS: In total, 166 women with CIN2+ were enrolled (86 had LEEP; 80 had cryotherapy). At 12 months, cumulative loss to follow-up was 12.8% (11/86) for the LEEP group and 13.8% (11/80) for cryotherapy. Based on the unadjusted intention-to-treat analysis conducted for this economic evaluation, there was no significant difference in efficacy. At 12 months, 83.8% (95% CI 73.8-91.1) of women with CIN2+ at baseline and randomized to cryotherapy were free of CIN2+ disease. In contrast, 76.7% (95% CI 66.4-85.2) of women assigned to LEEP were free from disease. On average, women initially treated with cryotherapy were less costly per patient randomized at US$ 118.00 (113.91-122.10), and per case "cured" at US$ 140.90 (136.01-145.79). Women in the LEEP group cost US$ 162.56 (157.90-167.22) per patient randomized and US$ 205.59 (199.70-211.49) per case cured. In the as-treated analysis, which was based on trial data, LEEP was more efficacious than cryotherapy; however, the difference was not significant. Cryotherapy remained more cost-effective than LEEP in all sensitivity and scenario analyses. CONCLUSIONS: For this cost-effectiveness analysis, using an intention-to-treat approach and taking into consideration uncertainty in the clinical and cost outcomes, a strategy involving cryotherapy plus LEEP if needed at six months was dominant to LEEP plus LEEP again at six months if needed for retreatment. However, compared to other studies comparing LEEP and cryotherapy, the efficacy results were low in both treatment groups-possibly due to the HIV-positivity of the participants. Further research is needed, but at present choosing the "right" treatment option may be less important than ensuring access to treatment and providing careful monitoring of treatment outcomes.

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.

Detection Rate of High-Grade Cervical Neoplasia and Cost-Effectiveness of High-Risk Human Papillomavirus Genotyping with Reflex Liquid-based Cytology in Cervical Cancer Screening.

INTRODUCTION: This study aimed to determine the prevalence of cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) and cost-effectiveness of human papillomavirus (HPV) genotyping with reflex liquid-based cytology (LBC) for cervical cancer screening in Singapore. MATERIALS AND METHODS: Women who were ≥25 years old and undertook co-testing with LBC and HPV-genotyping (Cobas-4800, Roche, USA) for HPV-16, HPV-18 and 12 high-risk HPV types in a single institution were studied retrospectively. A single cervical smear in ThinPrep® PreservCyt® solution (Hologic, USA) was separated for tests in independent cytology and molecular pathology laboratories. The results were reviewed by a designated gynaecologist according to institutional clinical management protocols. Those who tested positive for HPV-16 and/or HPV-18 (regardless of cytology results), cytology showing low-grade squamous intraepithelial lesions (LSIL) or high-grade SIL (HSIL), or atypical squamous cells of undetermined significance (ASCUS) with positive 12 high-risk HPV types were referred for colposcopy. Colposcopy was performed by experienced colposcopists. Cervical biopsy, either directed punch biopsies or excisional biopsy, was determined by a colposcopist. The diagnosis of ≥CIN3 was reviewed by a gynaecologic pathologist. Cost-effectiveness of HPV-based screening in terms of disease and financial burden was analysed using epidemiological, clinical and financial input data from Singapore. RESULTS: Of 1866 women studied, 167 (8.9%) had abnormal cytology (≥ASCUS) and 171 (9.2%) tested positive for high-risk HPV. Twenty-three CIN were detected. Three of the 10 ≥CIN3 cases had negative cytology but positive HPV-16. Compared to cytology, HPV genotyping detected more ≥CIN3 (OR: 1.43). HPV+16/18 genotyping with reflex LBC was superior in terms of cost-effectiveness to LBC with reflex HPV, both for disease detection rate and cost per case of ≥CIN2 detected. CONCLUSION: Compared to cytology, HPV+16/18 genotyping with reflex LBC detected more ≥CIN3 and was cost-effective for cervical screening in Singapore.

The Cost-Effectiveness of Visual Triage of Human Papillomavirus-Positive Women in Three Low- and Middle-Income Countries.

Background: World Health Organization guidelines support human papillomavirus (HPV) testing alone (followed by treatment with cryotherapy) or in conjunction with visual inspection with acetic acid (VIA) triage testing. Our objective was to determine the cost-effectiveness of VIA triage for HPV-positive women in low-resource settings.Methods: We calibrated mathematical simulation models of HPV infection and cervical cancer to epidemiologic data from India, Nicaragua, and Uganda. Using cost and test performance data from the START-UP demonstration projects, we assumed screening took place either once or three times in a lifetime between ages 30 and 40 years. Strategies included (i) HPV alone, followed by cryotherapy for all eligible HPV-positive women; and (ii) HPV testing with VIA triage for HPV-positive women, followed by cryotherapy for eligible women who were also VIA-positive (HPV-VIA). Model outcomes included lifetime risk of cervical cancer and incremental cost-effectiveness ratios (ICERs; international dollars/year of life saved).Results: In all three countries, HPV alone was more effective than HPV-VIA. In Nicaragua and Uganda, HPV alone was also less costly than HPV-VIA; ICERs associated with screening three times in a lifetime (HPV alone) were below per capita GDP. In India, both HPV alone and HPV-VIA had ICERs below per capita GDP.Conclusions: VIA triage of HPV-positive women is not likely to be cost-effective in settings with high cervical cancer burden. HPV alone followed by treatment may achieve greater health benefits and value for public health dollars.Impact: This study provides early evidence on the cost-effectiveness of HPV testing followed by VIA triage versus an HPV screen-and-treat strategy. Cancer Epidemiol Biomarkers Prev; 26(10); 1500-10. ©2017 AACR.