Lifetime effects, costs, and cost effectiveness of testing for human papillomavirus to manage low grade cytological abnormalities: results of the NHS pilot studies.
Ontology highlight
ABSTRACT: Objectives
To predict the incremental lifetime effects, costs, and cost effectiveness of using human papillomavirus testing to triage women with borderline or mildly dyskaryotic cervical smear results for immediate colposcopy.Design
Modelling study.Setting
Three centres participating in NHS pilot studies, United Kingdom. Population Women aged 25-64 with borderline or mildly dyskaryotic cervical smear results.Interventions
Screening using conventional cytology, liquid based cytology, and four strategies with different age cut-off points and follow up times that used combined liquid based cytology and human papillomavirus testing (adjunctive human papillomavirus testing).Results
The model predicts that compared with using conventional cytology without testing for human papillomavirus, testing for the virus in conjunction with liquid based cytology for women with borderline or mildly dyskaryotic cervical smear results (aged 35 or more) would cost 3735 pounds sterling (5528 euros; 6474 dollars) per life year saved. Extending adjunctive human papillomavirus testing in combination with liquid based cytology to include women aged between 25 and 34 costs an additional 4233 pounds sterling per life year saved. Human papillomavirus testing is likely to reduce lifetime repeat smears by 52%-86% but increase lifetime colposcopies by 64%-138%.Conclusions
Testing for human papillomavirus to manage all women with borderline or mildly dyskaryotic cervical smear results is likely to be cost effective. The predicted increase in lifetime colposcopies, however, deserves careful consideration.
SUBMITTER: Legood R
PROVIDER: S-EPMC1326928 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The aim was to evaluate human papillomavirus (HPV) 'reflex genotyping' in cases of minor cytological abnormalities detected in the gynaecological screening programme in Stockholm, Sweden. Liquid-based cytology samples showing minor cytological abnormalities were analysed using HPV genotyping (Linear Array, Roche diagnostics). Colposcopically directed cervical biopsies were obtained and the HPV test results were correlated with the histological results. In all, 63% (70/112) of the samples were high-risk (HR) HPV (HR-HPV) positive. A statistically significant correlation was found between high-grade cervical lesions and HR-HPV (P=0.019), among which HPV 16, 18, and 31 were the most important. The negative predictive value of HR-HPV detection for histologically confirmed high-grade lesions was 100%. An age limit for HPV reflex testing may be motivated in cases of low-grade squamous intraepithelial neoplasia (LSIL), because of high HR-HPV prevalence among younger women. By using HPV reflex genotyping, additional extensive workup can safely be avoided in about 50% of all cases of atypical squamous cells of undetermined significance (ASCUS) and LSIL among women 30 years. This screening strategy could potentially reduce the total abnormal cytology-reporting rate in the Swedish screening programme by about 1% and provide more accurately directed follow-up, guided by cytological appearance and HPV test results.
| S-EPMC2527833 | biostudies-literature
Project description:The aim of this study was to determine the incidence of infections and cytological abnormalities and to investigate possible predisposing factors such as sociodemographic characteristics, sexual behavioral habits, and gynecological and obstetric backgrounds. Between 2013 and December 2016, a cross-sectional study was conducted among 429 consenting women, from whom cervical samples were tested for the presence of Human papillomavirus (HPV) by polymerase chain reaction (PCR). Susceptibility to HPV infection was assessed by binary logistic regression in light of possible predisposing factors, which were collected using a questionnaire. In our sample population, the prevalence of HPV infection was 49%; high-risk types had a higher prevalence of 89.1%. A larger proportion of HPV-infected women were under 25 years of age, were single, and had monthly incomes up to minimum wage. Multivariate binary logistic regression analysis showed that age younger than 25 years increased the odds of infection fivefold, while a monthly income of one to three minimum wages provided protection against HPV infection, even if the women were married or had a cohabiting partner. In the HPV-positive group, squamous intraepithelial lesions (SIL) occurred more frequently in women who earned up to one minimum wage monthly, but a monthly income of one to three minimum wages protected against the development of SIL. The results suggest that age, marital status, and monthly income are important cofactors for HPV infection and the development of SIL.
| S-EPMC9863329 | biostudies-literature
Project description:BackgroundCervical screening identifies many women with low-grade abnormalities. In vitro and in vivo studies have shown that diindolylmethane (DIM) could potentially halt (cervical) carcinogenesis. We report on a randomised controlled trial of the effect of DIM in women with low-grade cervical cytological abnormalities.MethodsWe conducted a pragmatic double-blind, randomised controlled trial of 150 mg DIM (from BioResponse DIM) or placebo daily for 6 months in women with newly diagnosed, low-grade cytological abnormalities. Randomisation was in the ratio 2 (DIM) to 1 (placebo). All women were invited for colposcopy at 6 months with biopsy of any abnormality.ResultsOf the 551 randomised women available for analysis, 9% on DIM and 12% on placebo had cervical intraepithelial neoplasia-2 (CIN2) or worse after 6-month supplementation (risk ratio (RR) 0.7 (95% confidence interval (CI): 0.4-1.2)), whereas 4.6% and 5.1%, respectively, had CIN3 or worse (RR 0.9 (95% CI: 0.4-2.0)). A total of 27.3% of women on DIM and 34.3% on placebo had no sign of disease (negative cytology, colposcopy and human papilloma virus (HPV) tests) at 6 months (RR 0.8 (95% CI: 0.6-1.0)). Of those HPV-positive at baseline, 69% (114 out of 166) of the DIM group were positive at 6 months compared with 61% (43 out of 71) of the placebo group: RR 1.1 (95% CI: 0.9-1.4). Diindolylmethane supplementation was well tolerated.ConclusionThe results suggest that short-term DIM supplementation (150 mg day(-1)) is well tolerated, but is unlikely to have an effect on cytology or HPV infection. Uncertainty remains regarding its effect on CIN2+.
| S-EPMC3251847 | biostudies-literature
Project description:AIM:The aim of the study was to compare the diagnostic value of HPV testing and colposcopy in patients with abnormal cytology results. PATIENTS AND METHODS:A total of 186 women with cytological abnormalities were included in the study. The patients underwent colposcopy examinations and DNA HPV testing of cervical smear with genotyping. RESULTS:The HPV test was demonstrated to be more sensitive (79.4%) than specific (60.2%) and was more sensitive than colposcopy for detecting CIN changes (79.4% vs. 73.7%). Combined tests achieved a high sensitivity (90.9%) and negative predictive value (96.1%) in detecting patients with CIN2+ and demonstrated the highest positive predictive value (77.3%) for detecting CIN1+. Colposcopy had a very good specificity (83.5%) and positive predictive value (71.2%) in finding CIN1+ cases. CONCLUSION:HPV tests showed a higher sensitivity than colposcopy, but colposcopy results presented higher specificity. Combining HPV testing and colposcopy proved to be the most efficient method for detecting CIN lesions.
| S-EPMC7279809 | biostudies-literature
Project description:BACKGROUND: The follow-up after abnormal Pap smear and negative colposcopy is not clearly defined. This study aimed at investigating the role of hr-HPV testing in the management of abnormal Pap test and negative colposcopy for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+). methods: The study enrolled 1029 women with abnormal screening cytology (years 2006-2010) and negative colposcopy for CIN2+, which subsequently performed a hr-HPV test. Incident CIN2+ lesions were identified through linkage with cancer registry, hospital discharge records, neoplastic pathology reports and the archive of screening programme (2006-2011). RESULTS: During the follow-up, the cohort developed 133 CIN2+ lesions; only one among hr-HPV-negative women. The probability of developing CIN2+ on follow-up time was 0.44% (95% confidence interval (CI) 0.1-3.1) and 41.8% (95% CI 31.8-53.5) for hr-HPV-negative women and hr-HPV-positive women, respectively. A woman with a positive hr-HPV test had about 105 times higher probability of developing a CIN2+ lesion than a woman with a negative hr-HPV test (hazard ratio (HR)=104.5, 95% CI 14.5-755.1), adjusted for index Pap test result, age and cervix squamocolumnar junction visualisation. CONCLUSION: Our results confirm that hr-HPV testing is able to select the real group of women at risk of developing CIN2+ lesions in the follow-up of abnormal cytology and first negative colposcopy.
| S-EPMC3790172 | biostudies-other
Project description:ImportanceTriage tests enhance the efficiency cervical cancer screening based on human papillomavirus (HPV), but the best approach for maximizing programmatic effectiveness is still uncertain, particularly in a real-world scenario.ObjectiveTo compare the clinical performance of 6 triage strategies based on liquid-based cytology (LBC) and HPV-16 and HPV-18 genotyping individually or in combination as sequential triage tests to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher among women with high-risk HPV.Design, setting, and participantsThis diagnostic study of routine cervical cancer screening was conducted at 100 primary health centers in Tlaxcala, Mexico. Women aged 30 to 64 years were recruited from August 1, 2013, to February 24, 2016, as part of the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage study. Six triage scenarios for referral to colposcopy were examined: (1) LBC testing that found atypical squamous cells of undetermined significance (ASC-US) or worse, (2) positive results in HPV-16 genotyping, (3) positive results in HPV-18 genotyping, (4) positive results in HPV-16/HPV-18 genotyping, (5) positive results in HPV-16 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse, and (6) positive results in HPV-16/HPV-18 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse. Data were analyzed from October 2017 to August 2018.ExposuresLiquid-based cytological testing with simultaneous HPV-16 and HPV-18 genotyping. Women whose HPV genotyping results were positive for HPV-16 or HPV-18 or whose LBC results found ASC-US or worse and a random set of negative and normal results were referred to colposcopy with histologic analysis used for disease confirmation.Main outcomes and measuresClinical performance of each test strategy for detection of CIN grade 2 or higher. Secondary outcomes included resource utilization of each triage scenario, measured by the number of tests performed, the referral rate for colposcopy, and the numbers of colposcopies per CIN grade 2 or higher detected.ResultsA total of 36 212 women (median [interquartile range] age, 40 [35-47] years) were screened, and 4051 women (11.2%) had high-risk HPV. Of these women, 1109 (24.6%) were found to have HPV-16, HPV-18, or ASC-US or worse. Further histologic testing detected CIN grade 2 or higher in 110 of 788 women (14.0%) who underwent follow-up colposcopy. Sensitivity and specificity for 3 main triage strategies were 42.9% and 74.0% for LBC; 58.3% and 54.4% for HPV-16/HPV-18 genotyping; and 86.6% and 34.0% for HPV-16/HPV-18 genotyping with reflex LBC. The referral rate to colposcopy was 29% for HPV-16/HPV-18 with reflex LBC, which was 2-fold higher than the referral rate of 12% for LBC.Conclusions and relevanceTriage of women with high-risk HPV with HPV-16/HPV-18 genotyping with reflex LBC was significantly associated with improvement in detection of CIN grade 2 or higher compared with LBC alone. The benefit of disease prevented may outweigh the cost of increasing requirements for colposcopy services in settings with limited adherence to follow-up after a positive screening result.
| S-EPMC6902808 | biostudies-literature
Project description:ObjectivesTo estimate the lifetime treatment costs of patients with human papillomavirus (HPV) infection-related diseases in China and to provide cost estimates for the economic evaluation of HPV intervention strategies.MethodsWe extracted real-world hospital data from 2012 to 2019 and screened for subjects who met the criteria of clinical diagnosis of HPV-related diseases to obtain country-specific inputs into a Markov decision model. The model simulated lifetime treatment costs for HPV from the perspective of a national payer. A 5% discount rate was applied. Costs were converted and inflated to 2020 US dollars (USD).ResultsUsing 2021 as the base year, the lifetime costs per patient for carcinoma in situ, local metastasis, and distant metastasis cervical cancer are $24,208 (95%CI: 18,793-30,897), $19,562 (95%CI: 14,456-25,567), and $17,599 (95%CI: 10,604-25,807), respectively. For carcinoma in situ, local metastasis, and distant metastasis vaginal cancer, the lifetime costs are $17,593 (95%CI: 14,962-23,596), $17,120 (95%CI: 13,215-22,417), and $22,411 (95%CI: 12,172-22,249), respectively. The base-case lifetime cost per patient for different stages of vulvar cancer/penile cancer/anal cancer/oral cancer/oropharyngeal cancer/laryngeal cancer falls within $17,120-$58,236.ConclusionsUsing real-world data, we calculated lifetime treatment costs of HPV-related cancer in China and found that the lifetime cost for patients exceeded $17,000 for various stages of disease. The national burden of HPV-related disease could be significantly reduced by eliminating HPV infection.
| S-EPMC8629412 | biostudies-literature
Project description:ObjectiveTo determine the most cost-effective screening programme for cervical cancer.DesignCost-effectiveness analysis from a societal perspective.SettingThe Netherlands.PopulationDutch women who have not been invited for human papillomavirus (HPV) vaccination.MethodsWe calibrated the microsimulation screening analysis (MISCAN) model to Dutch epidemiological data. We used this model to consider nine screening strategies that use: (i) cytological testing with cytology triage for borderline/mildly abnormal smears; (ii) HPV testing with cytology triage for HPV-positive smears; or (iii) cytological testing with HPV triage for borderline/mildly abnormal smears. For each strategy, we varied the number of screening rounds, the time interval, the age of the first screening, and the type of cytological testing (conventional or liquid-based cytology).Main outcome measuresQuality-adjusted life years (QALYs) gained and costs from a societal perspective.ResultsUnder the base-case assumptions, primary HPV testing with cytology triage is the most cost-effective strategy. Using cost-effectiveness thresholds of € 20,000 and € 50,000 per QALY gained yields optimal screening programmes with three and seven screening rounds, respectively. The results are sensitive to several uncertain model inputs, most importantly the costs of the HPV test. For women aged 32 years or younger, primary cytology screening is more cost-effective than primary HPV testing.ConclusionsIncreasing the interval between screening rounds and changing the primary test from cytology to HPV testing can improve the effectiveness and decrease the costs of cervical cancer screening in the Netherlands.
| S-EPMC3489039 | biostudies-literature
Project description:BackgroundNew screening technologies and vaccination against human papillomavirus (HPV), the necessary cause of cervical cancer, may impact optimal approaches to prevent cervical cancer. We evaluated the cost-effectiveness of alternative screening strategies to inform cervical cancer prevention guidelines in Norway.MethodsWe leveraged the primary epidemiologic and economic data from Norway to contextualise a simulation model of HPV-induced cervical cancer. The current cytology-only screening was compared with strategies involving cytology at younger ages and primary HPV-based screening at older ages (31/34+ years), an option being actively deliberated by the Norwegian government. We varied the switch-age, screening interval, and triage strategies for women with HPV-positive results. Uncertainty was evaluated in sensitivity analysis.ResultsCurrent cytology-only screening was less effective and more costly than strategies that involve switching to primary HPV testing in older ages. For unvaccinated women, switching at age 34 years to primary HPV testing every 4 years was optimal given the Norwegian cost-effectiveness threshold ($83,000 per year of life saved). For vaccinated women, a 6-year screening interval was cost-effective. When we considered a wider range of strategies, we found that an earlier switch to HPV testing (at age 31 years) may be preferred.ConclusionsStrategies involving a switch to HPV testing for primary screening in older women is expected to be cost-effective compared with current recommendations in Norway.
| S-EPMC3341862 | biostudies-literature
Project description:BackgroundCurrent prophylactic vaccines against human papillomavirus (HPV) target two of the most oncogenic types, HPV-16 and -18, which contribute to roughly 70% of cervical cancers worldwide. Second-generation HPV vaccines include a 9-valent vaccine, which targets five additional oncogenic HPV types (i.e., 31, 33, 45, 52, and 58) that contribute to another 15-30% of cervical cancer cases. The objective of this study was to determine a range of vaccine costs for which the 9-valent vaccine would be cost-effective in comparison to the current vaccines in two less developed countries (i.e., Kenya and Uganda).Methods and findingsThe analysis was performed using a natural history disease simulation model of HPV and cervical cancer. The mathematical model simulates individual women from an early age and tracks health events and resource use as they transition through clinically-relevant health states over their lifetime. Epidemiological data on HPV prevalence and cancer incidence were used to adapt the model to Kenya and Uganda. Health benefit, or effectiveness, from HPV vaccination was measured in terms of life expectancy, and costs were measured in international dollars (I$). The incremental cost of the 9-valent vaccine included the added cost of the vaccine counterbalanced by costs averted from additional cancer cases prevented. All future costs and health benefits were discounted at an annual rate of 3% in the base case analysis. We conducted sensitivity analyses to investigate how infection with multiple HPV types, unidentifiable HPV types in cancer cases, and cross-protection against non-vaccine types could affect the potential cost range of the 9-valent vaccine. In the base case analysis in Kenya, we found that vaccination with the 9-valent vaccine was very cost-effective (i.e., had an incremental cost-effectiveness ratio below per-capita GDP), compared to the current vaccines provided the added cost of the 9-valent vaccine did not exceed I$9.7 per vaccinated girl. To be considered very cost-effective, the added cost per vaccinated girl could go up to I$5.2 and I$16.2 in the worst-case and best-case scenarios, respectively. At a willingness-to-pay threshold of three times per-capita GDP where the 9-valent vaccine would be considered cost-effective, the thresholds of added costs associated with the 9-valent vaccine were I$27.3, I$14.5 and I$45.3 per vaccinated girl for the base case, worst-case and best-case scenarios, respectively. In Uganda, vaccination with the 9-valent vaccine was very cost-effective when the added cost of the 9-valent vaccine did not exceed I$8.3 per vaccinated girl. To be considered very cost-effective, the added cost per vaccinated girl could go up to I$4.5 and I$13.7 in the worst-case and best-case scenarios, respectively. At a willingness-to-pay threshold of three times per-capita GDP, the thresholds of added costs associated with the 9-valent vaccine were I$23.4, I$12.6 and I$38.4 per vaccinated girl for the base case, worst-case and best-case scenarios, respectively.ConclusionsThis study provides a threshold range of incremental costs associated with the 9-valent HPV vaccine that would make it a cost-effective intervention in comparison to currently available HPV vaccines in Kenya and Uganda. These prices represent a 71% and 61% increase over the price offered to the GAVI Alliance ($5 per dose) for the currently available 2- and 4-valent vaccines in Kenya and Uganda, respectively. Despite evidence of cost-effectiveness, critical challenges around affordability and feasibility of HPV vaccination and other competing needs in low-resource settings such as Kenya and Uganda remain.
| S-EPMC4157790 | biostudies-literature