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Summary Background China has the highest prevalence of hepatitis B virus (HBV) infection worldwide. Universal HBV screening might enable China to reach the WHO 2030 target of 90% diagnostics, 80% treatment, and 65% HBV-related death reduction, and eventually elimination of viral hepatitis. We evaluated the cost-effectiveness of implementing universal HBV screening in China and identified optimal screening strategies. Methods We used a Markov cohort model, inputting parameters based on data from previous studies and public databases, to assess the cost-effectiveness of four HBV serological screening strategies in China in different screening scenarios. We simulated universal screening scenarios in 15 adult age groups between 18 and 70 years, with different years of screening implementation (2021, 2026, and 2031) and compared to the status quo (ie, no universal screening); in total, we investigated 180 different screening scenarios. We calculated the incremental cost-effectiveness ratio (ICER) between the different screening strategies and the status quo (current screening strategy). We performed probabilistic and one-way deterministic sensitivity analyses to assess the robustness of our findings. Findings With a willingness-to-pay level of three times the Chinese gross domestic product (GDP) per capita (US$30 828), all universal screening scenarios in 2021 were cost-effective compared with the status quo. The serum HBsAg/HBsAb/HBeAg/HBeAb/HBcAb (five-test) screening strategy in people aged 18–70 years was the most cost-effective strategy in 2021 (ICER $18 295/quality-adjusted life-years [QALY] gained). This strategy remained the most cost-effective, when the willingness-to-pay threshold was reduced to 2 times GDP per capita. The two-test strategy for people aged 18–70 years became more cost-effective at lower willingness-to-pay levels. The five-test strategy could prevent 3·46 million liver-related deaths in China over the lifetime of the cohort. It remained the most cost-effective strategy when implementation was delayed until 2026 (ICER $20 183/QALY) and 2031 (ICER $23 123/QALY). Screening young people (18–30 years) will no longer be cost-effective in delayed scenarios. Interpretation The five-test universal screening strategy in people aged 18–70 years, implemented within the next 10 years, is the optimal HBV screening strategy for China. Other screening strategies could be cost-effective alternatives, if budget is limited in rural areas. Delaying strategy implementation reduces overall cost-effectiveness. Early screening initiation will aid global efforts in achieving viral hepatitis elimination. Funding National Natural Science Foundation of China.

Objectives: The exact characteristics of a coronavirus disease 2019 (COVID-19) outbreak that trigger public health interventions are poorly defined. The aim of this study was to assess the critical timing and extent of public health interventions to contain COVID-19 outbreaks in Australia. Methods: A practical model was developed using existing epidemic data in Australia. The effective combinations of public health interventions and the critical number of daily cases for intervention commencement under various scenarios of changes in transmissibility of new variants and vaccination coverage were quantified. Results: In the past COVID-19 outbreaks in four Australian states, the number of reported cases on the day that interventions commenced strongly predicted the size and duration of the outbreaks. In the early phase of an outbreak, containing a wildtype-dominant epidemic to a low level (≤10 cases/day) would require effective combinations of social distancing and face mask use interventions to be commenced before the number of daily reported cases reaches six. Containing an Alpha-dominant epidemic would require more stringent interventions that commence earlier. For the Delta variant, public health interventions alone would not contain the epidemic unless the vaccination coverage was ≥70%. Conclusions: This study highlights the importance of early and decisive action in the initial phase of an outbreak. Vaccination is essential for containing variants.

BackgroundAustralia implemented an mRNA-based booster vaccination strategy against the COVID-19 Omicron variant in November 2021. We aimed to evaluate the effectiveness and cost-effectiveness of the booster strategy over 180 days.MethodsWe developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy (administered 3 months after 2nd dose) in those aged ≥16 years in Australia from a healthcare system perspective. The willingness-to-pay threshold was chosen as A$ 50,000.FindingsCompared with 2-doses of COVID-19 vaccines without a booster, Australia’s booster strategy would incur an additional cost of A$0.88 billion but save A$1.28 billion in direct medical cost and gain 670 quality-adjusted life years (QALYs) in 180 days of its implementation. This suggested the booster strategy is cost-saving, corresponding to a benefit-cost ratio of 1.45 and a net monetary benefit of A$0.43 billion. The strategy would prevent 1.32 million new infections, 65,170 hospitalisations, 6,927 ICU admissions and 1,348 deaths from COVID-19 in 180 days. Further, a universal booster strategy of having all individuals vaccinated with the booster shot immediately once their eligibility is met would have resulted in a gain of 1,599 QALYs, a net monetary benefit of A$1.46 billion and a benefit-cost ratio of 1.95 in 180 days.InterpretationThe COVID-19 booster strategy implemented in Australia is likely to be effective and cost-effective for the Omicron epidemic. Universal booster vaccination would have further improved its effectiveness and cost-effectiveness.FundingNational Natural Science Foundation of China. Bill and Melinda Gates Foundation

BACKGROUNDCOVID-19 and diabetes both contribute to large global disease burdens.PURPOSETo quantify the prevalence of diabetes in various COVID-19 disease stages and calculate the population attributable fraction (PAF) of diabetes to COVID-19–related severity and mortality.DATA SOURCESSystematic review identified 729 studies with 29,874,938 COVID-19 patients.STUDY SELECTIONStudies detailed the prevalence of diabetes in subjects with known COVID-19 diagnosis and severity.DATA EXTRACTIONStudy information, COVID-19 disease stages, and diabetes prevalence were extracted.DATA SYNTHESISThe pooled prevalence of diabetes in stratified COVID-19 groups was 14.7% (95% CI 12.5–16.9) among confirmed cases, 10.4% (7.6–13.6) among nonhospitalized cases, 21.4% (20.4–22.5) among hospitalized cases, 11.9% (10.2–13.7) among nonsevere cases, 28.9% (27.0–30.8) among severe cases, and 34.6% (32.8–36.5) among deceased individuals, respectively. Multivariate metaregression analysis explained 53–83% heterogeneity of the pooled prevalence. Based on a modified version of the comparative risk assessment model, we estimated that the overall PAF of diabetes was 9.5% (7.3–11.7) for the presence of severe disease in COVID-19–infected individuals and 16.8% (14.8–18.8) for COVID-19–related deaths. Subgroup analyses demonstrated that countries with high income levels, high health care access and quality index, and low diabetes disease burden had lower PAF of diabetes contributing to COVID-19 severity and death.LIMITATIONSMost studies had a high risk of bias.CONCLUSIONSThe prevalence of diabetes increases with COVID-19 severity, and diabetes accounts for 9.5% of severe COVID-19 cases and 16.8% of deaths, with disparities according to country income, health care access and quality index, and diabetes disease burden.

ObjectivesWe aimed to investigate how changes in direct bilirubin (DBiL) levels in severely/critically ill the coronavirus disease (COVID-19) patients during their first week of hospital admission affect their subsequent prognoses and mortality.MethodsWe retrospectively enrolled 337 severely/critically ill COVID-19 patients with two consecutive blood tests at hospital admission and about 7 days after. Based on the trend of the two consecutive tests, we categorized patients into the normal direct bilirubin (DBiL) group (224), declined DBiL group (44) and elevated DBiL group (79).ResultsThe elevated DBiL group had a significantly larger proportion of critically ill patients (χ2-test, p < 0.001), a higher risk of ICU admission, respiratory failure, and shock at hospital admission (χ2-test, all p < 0.001). During hospitalization, the elevated DBiL group had significantly higher risks of shock, acute respiratory distress syndrome (ARDS), and respiratory failure (χ2-test, all p < 0.001). The same findings were observed for heart damage (χ2-test, p = 0.002) and acute renal injury (χ2-test, p = 0.009). Cox regression analysis showed the risk of mortality in the elevated DBiL group was 2.27 (95% CI: 1.50–3.43, p < 0.001) times higher than that in the normal DBiL group after adjusted age, initial symptom, and laboratory markers. The Receiver Operating Characteristic curve (ROC) analysis demonstrated that the second test of DBiL was consistently a better indicator of the occurrence of complications (except shock) and mortality than the first test in severely/critically ill COVID-19 patients. The area under the ROC curve (AUC) combined with two consecutive DBiL levels for respiratory failure and death was the largest.ConclusionElevated DBiL levels are an independent indicator for complication and mortality in COVID-19 patients. Compared with the DBiL levels at admission, DBiL levels on days 7 days of hospitalization are more advantageous in predicting the prognoses of COVID-19 in severely/critically ill patients.

BackgroundOver 86% of older adults aged ≥65 years are fully vaccinated against SARS-COV-2 in the United States (US). Waning protection of the existing vaccines promotes the new vaccination strategies, such as providing a booster shot for those fully vaccinated.MethodsWe developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy of Pfizer-BioNTech BNT162b2 (administered 6 months after 2nd dose) in those aged ≥65 years, from a healthcare system perspective.FindingsCompared with 2-doses of BNT162b2 without a booster, the booster strategy in a 100,000 cohort of older adults would incur an additional cost of $3.4 million, but save $6.7 million in direct medical costs in 180 days. This corresponds to a benefit-cost ratio of 1.95 and a net monetary benefit of $3.4 million. Probabilistic sensitivity analysis indicates that with a COVID-19 incidence of 9.1/100,000 person-day, a booster strategy has a high chance (67%) of being cost-effective. The cost-effectiveness of the booster strategy is highly sensitive to the population incidence of COVID-19, with a cost-effectiveness threshold of 8.1/100,000 person-day. This threshold will increase with a decrease in vaccine and booster efficacies. Doubling the vaccination cost or halving the medical cost for COVID-19 treatment alone would not alter the conclusion of cost-effectiveness, but certain combinations of the two might render the booster strategy not cost-effective.InterpretationOffering BNT162b2 boosters to older adults aged ≥65 years in the US is likely to be cost-effective. Less efficacious vaccines and boosters may still be cost-effective in settings of high SARS-COV-2 transmission.FundingNational Natural Science Foundation of China. Berlina and Bill Gates Foundation

Objectives The incidence of Neisseria gonorrhoeae and its antimicrobial resistance is increasing in many countries. Antibacterial mouthwash may reduce gonorrhoea transmission without using antibiotics. We modelled the effect that antiseptic mouthwash may have on the incidence of gonorrhoea. Design We developed a mathematical model of the transmission of gonorrhoea between each anatomical site (oropharynx, urethra and anorectum) in men who have sex with men (MSM). We constructed four scenarios: (1) mouthwash had no effect; (2) mouthwash increased the susceptibility of the oropharynx; (3) mouthwash reduced the transmissibility from the oropharynx; (4) the combined effect of mouthwash from scenarios 2 and 3. Setting We used data at three anatomical sites from 4873 MSM attending Melbourne Sexual Health Centre in 2018 and 2019 to calibrate our models and data from the USA, Netherlands and Thailand for sensitivity analyses. Participants Published available data on MSM with multisite infections of gonorrhoea. Primary and secondary outcome measures Incidence of gonorrhoea. Results The overall incidence of gonorrhoea was 44 (95% CI 37 to 50)/100 person-years (PY) in scenario 1. Under scenario 2 (20%–80% mouthwash coverage), the total incidence increased (47–60/100 PY) and at all three anatomical sites by between 7.4% (5.9%–60.8%) and 136.6% (108.1%–177.5%). Under scenario 3, with the same coverage, the total incidence decreased (20–39/100 PY) and at all anatomical sites by between 11.6% (10.2%–13.5%) and 99.8% (99.2%–100%). Under scenario 4, changes in the incidence depended on the efficacy of mouthwash on the susceptibility or transmissibility. The effect on the total incidence varied (22–55/100 PY), and at all anatomical sites, there were increases of nearly 130% and large declines of almost 100%. Conclusions The effect of mouthwash on gonorrhoea incidence is largely predictable depending on whether it increases susceptibility to or reduces the transmissibility of gonorrhoea.

SummaryTo prevent the catastrophic health and economic consequences from COVID-19 epidemics, some nations have aimed for no community transmission outside of quarantine. To achieve this, governments have had to respond rapidly to outbreaks with public health interventions. But the exact characteristics of an outbreak that trigger these measures differ and are poorly defined. We used existing data from epidemics in Australia to establish a practical model to assist stakeholders in making decisions about the optimal timing and extent of interventions. We found that the number of reported cases on the day that interventions commenced strongly predicted the size of the outbreaks. We quantified how effective interventions were at containing outbreaks in relation to the number of cases at the time the interventions commenced. We also found that containing epidemics from novel variants that had higher transmissibility would require more stringent interventions that commenced earlier. In contrast, increasing vaccination coverage would enable more relaxed interventions. Our model highlights the importance of early and decisive action in the early phase of an outbreak if governments aimed for zero community transmission, although new variants and vaccination coverage may change this.

Background: To prevent the catastrophic health and economic consequences from COVID-19 epidemics, nations had to respond with swift public health interventions to achieve no community transmission outside of quarantine. However, the exact characteristics of an outbreak that trigger these measures are poorly defined. We aimed to assess the critical timing and extent of interventions in Australia. Methods: We developed a practical model using existing epidemics data in Australia. We quantified the effective combinations of public health interventions and the critical number of daily cases for intervention commencement. We assessed the impact of increasing transmissibility from new variants and the effect of vaccination coverage on the critical timing and extent of interventions. Findings: We found that in the past COVID-19 outbreaks in four Australian states, the number of reported cases on the day that interventions commenced strongly predicted the size and duration of the outbreaks. In the early phase of an outbreak, containing a wild-type dominant epidemic to a low level (≤10 cases/day) required effective combinations of social distancing and face mask use interventions to be commenced before the number of daily reported cases reaches 6 cases. Containing epidemics from alpha variant would require more stringent interventions that commenced earlier. For delta variant, public health interventions alone will not contain the epidemic, unless with a moderate vaccination coverage (≥50%). Interpretation: Our study highlights the importance of early and decisive action in the initial phase of an outbreak if governments aimed for zero community transmission. Vaccination is essential for containing variants. Funding Information: LZ is supported by the National Natural Science Foundation of China (grant number: 8191101420), Thousand Talents Plan Professorship for Young Scholars (Grant number: 3111500001); Xi’an Jiaotong University Basic Research and Profession Grant (Grant number: xtr022019003) and Xi’an Jiaotong University Young Talent Support Program (Grant number: YX6J004). The study is supported by Bill and Melinda Gates Foundation. Declaration of Interests: The authors declare no competing interests.

Background: With the largest hepatitis B virus (HBV) infected population worldwide, universal HBV screening in China may significantly contribute to the World Health Organization (WHO) 2030 goals in eliminating viral hepatitis. We evaluated the cost-effectiveness of universal HBV screening in China and identified optimal screening strategies. Methods: We conducted a cost-effectiveness analysis using a Markov cohort model based on four HBV serological screening methods in China. We simulated these universal screening in 15 different adult age groups with different initiation time (year 2021, 2026 and 2031). We performed probabilistic and one-way deterministic sensitivity analyses to assess the robustness of our findings. Results: With a willingness-to-pay level of 3x Chinese gross domestic product (GDP) per capita (US$30,828), HBsAg/HBsAb/HBeAg/HBeAb/HBcAb (five-test) screening among 18-70 years was the most cost-effective strategy in 2021 (incremental cost-effectiveness ratio [ICER] US$18,295/quality-adjusted life-year [QALY] gained). This remained the most cost-effective strategy, even when the willingness-to-pay threshold reduced to US$17,778; other strategies became more cost-effective at lower willingness-to-pay levels. This strategy would potentially prevent 3.46 million liver-related deaths over the lifetime of the cohort. It remained the most cost-effective even when the implementation was delayed to 2026 and 2031, but with greater ICERs (US$20,183/QALY and US$23,123/QALY, respectively). The screening will no longer be cost-effective in younger age groups in delayed scenarios. Conclusion: Five-test universal screening among 18-70 years implemented in 2021 is the optimal HBV screening strategy in China. Delaying strategy implementation reduces overall cost-effectiveness. Early screening initiation will aid global efforts in achieving viral hepatitis elimination. Funding: LZ is supported by the National Natural Science Foundation of China (grant number 8191101420); Outstanding Young Scholars Funding (3111500001); Xi'an Jiaotong University Basic Research and Profession Grant (xtr022019003); and Xi'an Jiaotong University Young Talent Support Program (YX6J004). WKS is supported by the Outstanding Young Researcher Award, the University of Hong Kong. JJO is supported by the Australian National Health and Medical Research Council Emerging Leadership Fellowship (GNT11953955). This project is funded by The University of Hong Kong Common Core Course. Declaration of Interest: PC is a staff member of the World Health Organization; the author alone is responsible for the views expressed in this publication, and they do not necessarily represent the decisions or policies of the World Health Organization. MFY is an advisory board member and/or received research funding from AbbVie, Arbutus Biopharma, Assembly Biosciences, Bristol Myer Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals; and received research funding from Arrowhead Pharmaceuticals, Fujirebio Incorporation and Sysmex Corporation. WKS received speaker's fees from AstraZeneca and Mylan, is an advisory board member of CSL Behring, is an advisory board member and received speaker's fees from AbbVie, and is an advisory board member, received speaker's fees and researching funding from Gilead Sciences. The remaining authors have no conflict of interests.

OBJECTIVES: To evaluate the cost-effectiveness of a booster strategy in the United States. METHODS: We developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy of the Pfizer-BioNTech BNT162b2 (administered 6 months after the second dose) among older adults from a healthcare system perspective. RESULTS: Compared with 2 doses of BNT162b2 without a booster, the booster strategy in a 100,000 cohort of older adults would incur an additional cost of $3.4 million in vaccination cost but save $6.7 million in direct medical cost and gain 3.7 quality-adjusted life-years in 180 days. This corresponds to a benefit-cost ratio of 1.95 and a net monetary benefit of $3.4 million. Probabilistic sensitivity analysis indicates that a booster strategy has a high chance (67%) of being cost-effective. Notably, the cost-effectiveness of the booster strategy is highly sensitive to the population incidence of COVID-19, with a cost-effectiveness threshold of 8.1/100,000 person-day. If vaccine efficacies reduce by 10%, 30%, and 50%, this threshold will increase to 9.7/100,000, 13.9/100,000, and 21.9/100,000 person-day, respectively. CONCLUSION: Offering the BNT162b2 booster to older adults aged ≥65 years in the United States is likely to be cost-effective. Less efficacious vaccines and boosters may still be cost-effective in settings of high SARS-CoV-2 transmission.

Summary Background The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted. Methods We constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic. Results We projected a declining trend of the COVID-19 epidemic if the current quarantine strategy continues, and Wuhan would record the last new confirmed cases in late April 2020. At the end of the epidemic, 65,733 (45,722-99,015) individuals would be infected by the virus, among which 16,166 (11,238-24,603, 24.6%) were through public contacts, 45,996 (31,892-69,565, 69.7%) through household contact, and 3,571 (2,521-5,879, 5.5%) through hospital contacts (including 778 (553-1,154) non-COVID-19 patients and 2,786 (1,969-4,791) medical staff). A total of 2,821 (1,634-6,361) would die of COVID-19 related pneumonia in Wuhan. Early quarantine lifting on 21st March is viable only if Wuhan residents sustain a high facial mask usage of ≥85% and a pre-quarantine level public contact rate. Delaying city resumption to mid/late April would relax the requirement of facial mask usage to ≥75% at the same contact rate. Conclusions The prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate.

BackgroundThe Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted.MethodWe constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic.ResultsWe estimated that at the end of the epidemic, a total of 65,572 (46,156-95,264) individuals would be infected by the virus, among which 16,144 (14,422-23,447, 24.6%) would be infected through public contacts, 45,795 (32,390-66,395, 69.7%) through household contact, 3,633 (2,344-5,865, 5.5%) through hospital contacts (including 783 (553-1,134) non-COVID-19 patients and 2,850 (1,801-4,981) medical staff members). A total of 3,262 (1,592-6,470) would die of COVID-19 related pneumonia in Wuhan. For an early lifting date (21st March), facial mask needed to be sustained at a relatively high rate (≥85%) if public contacts were to recover to 100% of the pre-quarantine level. In contrast, lifting the quarantine on 18th April allowed public person-to-person contact adjusted back to the pre-quarantine level with a substantially lower level of facial mask usage (75%). However, a low facial mask usage (100%) would always lead a significant second outbreak in most quarantine lifting scenarios. Lifting the quarantine on 25th April would ensure a smooth decline of the epidemics regardless of the combinations of public contact rates and facial mask usage.ConclusionThe prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate.

Additional file 3. Output parameters for Chlamydia trachomatis models. Tables S 8.1-8.219.

Background: The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23 rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted. Method: We constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic. Results: We projected a declining trend of the COVID-19 epidemic if the current quarantine strategy continues, and Wuhan would record the last new confirmed cases on 25 th April 2020. At the end of the epidemic, 65,572 (46,156-95,264) individuals would be infected by the virus, among which 16,144 (14,422-23,447, 24.6%) were through public contacts, 45,795 (32,390-66,395, 69.7%) through household contact, and 3,633 (2,344-5,865, 5.5%) through hospital contacts (including 783 (553-1,134) non-COVID-19 patients and 2,850 (1,801-4,981) medical staff). A total of 3,262 (1,592-6,470) would die of COVID-19 related pneumonia in Wuhan. Early quarantine lifting on 21 st March is viable only if Wuhan residents sustain a high facial mask usage of ≥85% and a pre-quarantine level public contact rate. Delaying city resumption to mid/late April would relax the requirement of facial mask usage to ≥75% at the same contact rate. Conclusion: The prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate. Funding Statement: This work is supported by a Research Grant from the Bill & Melinda Gates Foundation. Declaration of Interests: None.

Additional file 1. Details of model equations, model calibration and sensitive analysis.

Additional file 4. Additional results: model calibration, estimating the composition of incidence, and sensitivity analysis. Figs. S2a-32c.

Summary Background Coinciding with the release of the first Chinese domestic human papillomavirus (HPV) vaccine Cecolin in 2019, and the substantial advancements in cervical cancer screening technology, we aimed to evaluate the cost-effectiveness of the combined strategies of cervical cancer screening programmes and universal vaccination of girls (aged 9–14 years) with Cecolin in China. Methods We did a cost-effectiveness analysis in China, in which we developed a Markov model of cervical cancer to evaluate the incremental cost-effectiveness ratios of 61 intervention strategies, including a combination of various screening methods at different frequencies with and without vaccination, and also vaccination alone, from a health-care system perspective. We did univariate and probabilistic sensitivity analyses to assess the robustness of the model's findings. Findings Compared with no intervention, various combined screening and vaccination strategies would incur an additional cost of US$6 157 000–22 146 000 and result in 691–970 quality-adjusted life-years (QALYs) gained in a designated cohort of 100 000 girls aged 9–14 years over a lifetime. With a willingness-to-pay threshold of three times the Chinese per-capita gross domestic product (GDP), careHPV screening (a rapid HPV test) once every 5 years with vaccination would be the most cost-effective strategy with an incremental cost-effectiveness ratio of $21 799 per QALY compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier, and the probability of it being cost-effective (44%) outperformed other strategies. Strategies that combined screening and vaccination would be more cost-effective than screening alone strategies when the vaccination cost was less than $50 for two doses, even with a lower willingness-to-pay of one times the per-capita GDP. Interpretation careHPV screening once every 5 years with vaccination is the most cost-effective strategy for cervical cancer prevention in China. A reduction in the domestic HPV vaccine price is necessary to ascertain a good economic return for the future vaccination programme. The findings provide important evidence that informs health policies for cervical cancer prevention in China. Funding National Natural Science Foundation of China.

Background: Coinciding with the first and soon-to-be released Chinese domestic human papillomavirus (HPV) vaccine, Innovax, and the substantial advancements in cervical cancer screening technology, we evaluated the cost-effectiveness of universal schoolgirls vaccination with Innovax and several cervical cancer screening programmes and identified the cost-effectiveness threshold for the vaccination cost in China. Methods: We developed a Markov model of cervical cancer to evaluate the incremental cost-effectiveness ratios (ICERs) of sixty-one intervention strategies, including a combination of various screening methods at different frequencies with and without vaccination, and also vaccination alone, from a healthcare system perspective. We conducted univariate and probabilistic sensitivity analyses to assess the robustness of the model findings. Findings: Compared with ‘no intervention’, all intervention strategies resulted in an ICER less than 3-time Chinese per-capita gross domestic product (GDP) (ranging from cost-saving to US$24,302/quality-adjusted-life-year (QALY)), except 3-yearly liquid-based cytology+Hybrid Capture-2 screening. With a willingness-to-pay (WTP) threshold of 3-time per-capita GDP, 5-yearly careHPV screening alone would be the most cost-effective strategy with an ICER of US$16,447/QALY compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier, and the probability of it being optimal (42%) outperformed other strategies. Strategies that combined screening and vaccination were only more cost-effective than screening alone strategies when the vaccination cost was below US$100/3 doses at the current WTP. Interpretation: Five-yearly careHPV screening is the most cost-effective strategy. Reduction in domestic HPV vaccine price is necessary to ascertain a good economic return for the future vaccination programme. Funding Statement: LZ is supported by Xi’An Jiaotong University Young Talent Support Program, with project title ‘Innovative approaches for risk prediction and prevention of HIV and sexually transmitted infections in China’. KC is co-PI of an unrelated investigator-initiated trial of cervical cytology and primary HPV screening in Australia (‘Compass’), which is conducted and funded by the VCS foundation, a government-funded health promotion charity. The VCS foundation has received equipment and a funding contribution for the Compass trial from Roche Molecular Systems and Ventana Inc USA. However neither she nor her institution on her behalf (Cancer Council NSW) receives direct funding from industry Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Not required.