The U.S.-affiliated Pacific Islands (USAPI) have higher cervical cancer incidence and mortality rates and lower screening coverage compared with the United States. This is likely because of economic, geographical, health care delivery, and cultural barriers for women living in these resource-constrained, isolated regions. The most recent U.S. and World Health Organization cervical cancer screening guidelines recommended primary human papillomavirus (HPV) testing as one screening option or the preferred screening modality. Primary HPV screening-based strategies offer several advantages over current screening methods in the USAPI. However, adoption of this newer screening modality has been slow in the United States and not yet incorporated into USAPI screening programs. The U.S. Centers for Disease Control and Prevention and partners initiated the Pacific Against Cervical Cancer (PACe) project in 2019 to evaluate the feasibility, acceptability, and cost-effectiveness of primary HPV testing-based strategies in Guam and in Yap, Federated States of Micronesia. This report provides an overview of the PACe project and outlines the approaches we took in implementing primary HPV testing as a new cervical cancer screening strategy (including the option of self-sampling in Yap), encompassing four core components: (1) community engagement and education, (2) medical and laboratory capacity building, (3) health information and system improvement, and (4) modeling and cost-effectiveness analysis. The PACe project provides examples of systematic implementation and resource appropriate technologies to the USAPI, with broader implications for never screened and under-screened populations in the United States and Pacific as they face similar barriers to accessing cervical cancer screening services.

Background The burden of cancer can be altered by screening. The field of cancer screening is constantly evolving; from the initiation of program for new cancer types as well as exploring innovative screening strategies (e.g. new screening tests). The aim of this study was to perform a landscape analysis of existing cancer screening programs in South-East Asia and the Western Pacific. Methods We conducted an overview of cancer screening in the region with the goal of summarizing current designs of cancer screening programs. First, a selective narrative literature review was used as an exploration to identify countries with organized screening programs. Second, representatives of each country with an organized program were approached and asked to provide relevant information on the organizations of their national or regional cancer screening program. Results There was wide variation in the screening strategies offered in the considered region with only eight programs identified as having an organized design. The majority of these programs did not meet all the essential criteria for being organized screening. The greatest variation was observed in the starting and stopping ages. Conclusions Essential criteria of organized screening are missed. Improving organization is crucial to ensure that the beneficial effects of screening are achieved in the long-term. It is strongly recommended to consider a regional cancer screening network.

Australia introduced COVID-19 infection prevention and control measures in early 2020. To help prepare health services, the Australian Government Department of Health commissioned a modelled evaluation of the impact of disruptions to population breast, bowel, and cervical cancer screening programmes on cancer outcomes and cancer services. We used the Policy1 modelling platforms to predict outcomes for potential disruptions to cancer screening participation, covering periods of 3, 6, 9, and 12 mo. We estimated missed screens, clinical outcomes (cancer incidence, tumour staging), and various diagnostic service impacts. We found that a 12-mo screening disruption would reduce breast cancer diagnoses (9.3% population-level reduction over 2020–2021) and colorectal cancer (up to 12.1% reduction over 2020–21), and increase cervical cancer diagnoses (up to 3.6% over 2020–2022), with upstaging expected for these cancer types (2, 1.4, and 6.8% for breast, cervical, and colorectal cancers, respectively). Findings for 6–12-mo disruption scenarios illustrate that maintaining screening participation is critical to preventing an increase in the burden of cancer at a population level. We provide programme-specific insights into which outcomes are expected to change, when changes are likely to become apparent, and likely downstream impacts. This evaluation provided evidence to guide decision-making for screening programmes and emphasises the ongoing benefits of maintaining screening in the face of potential future disruptions.

In 2020, the World Health Organization (WHO) launched a strategy to eliminate cervical cancer as a public health problem. To support the strategy, the WHO published updated cervical screening guidelines in 2021. To inform this update, we used an established modeling platform, Policy1-Cervix , to evaluate the impact of seven primary screening scenarios across 78 low- and lower-middle-income countries (LMICs) for the general population of women. Assuming 70% coverage, we found that primary human papillomavirus (HPV) screening approaches were the most effective and cost-effective, reducing cervical cancer age-standardized mortality rates by 63–67% when offered every 5 years. Strategies involving triaging women before treatment (with 16/18 genotyping, cytology, visual inspection with acetic acid (VIA) or colposcopy) had close-to-similar effectiveness to HPV screening without triage and fewer pre-cancer treatments. Screening with VIA or cytology every 3 years was less effective and less cost-effective than HPV screening every 5 years. Furthermore, VIA generated more than double the number of pre-cancer treatments compared to HPV. In conclusion, primary HPV screening is the most effective, cost-effective and efficient cervical screening option in LMICs. These findings have directly informed WHO’s updated cervical screening guidelines for the general population of women, which recommend primary HPV screening in a screen-and-treat or screen-triage-and-treat approach, starting from age 30 years with screening every 5 years or 10 years.

To support a strategy to eliminate cervical cancer as a public health problem, the World Health Organisation (WHO) reviewed its guidelines for screening and treatment of cervical pre-cancerous lesions in 2021. Women living with HIV have 6-times the risk of cervical cancer compared to women in the general population, and we harnessed a model platform (‘Policy1-Cervix-HIV’) to evaluate the benefits and harms of a range of screening strategies for women living with HIV in Tanzania, a country with endemic HIV. Assuming 70% coverage, we found that 3-yearly primary HPV screening without triage would reduce age-standardised cervical cancer mortality rates by 72%, with a number needed to treat (NNT) of 38.7, to prevent a cervical cancer death. Triaging HPV positive women before treatment resulted in minimal loss of effectiveness and had more favorable NNTs (19.7–33.0). Screening using visual inspection with acetic acid (VIA) or cytology was less effective than primary HPV and, in the case of VIA, generated a far higher NNT of 107.5. These findings support the WHO 2021 recommendation that women living with HIV are screened with primary HPV testing in a screen-triage-and-treat approach starting at 25 years, with regular screening every 3–5 years.

Introduction WHO has launched updated cervical screening guidelines, including provisions for primary HPV screen-and-treat. Papua New Guinea (PNG) has a high burden of cervical cancer, but no national cervical screening programme. We recently completed the first field trials of a screen-and-treat algorithm using point-of-care self-collected HPV and same-day treatment (hereafter self-collected HPV S&T) and showed this had superior clinical performance and acceptability to visual inspection of the cervix with acetic acid (VIA). We, therefore, evaluated the effectiveness, cost-effectiveness and resource implications of a national cervical screening programme using self-collected HPV S&T compared with VIA in PNG. Methods An extensively validated platform ('Policy1-Cervix') was calibrated to PNG. A total of 38 strategies were selected for investigation, and these incorporated variations in age ranges and screening frequencies and allowed for the identification of the optimal strategy across a wide range of possibilities. A selection of strategies that were identified as being the most effective and cost-effective were then selected for further investigation for longer-term outcomes and budget impact estimation. In the base case, we assumed primary HPV testing has a sensitivity to cervical intraepithelial neoplasia 2 (CIN2+) + of 91.8% and primary VIA of 51.5% based on our earlier field evaluation combined with evidence from the literature. We conservatively assumed HPV sampling and testing would cost US$18. Costs were estimated from a service provider perspective based on data from local field trials and local consultation. Results Self-collected HPV S&T was more effective and more cost-effective than VIA. Either twice or thrice lifetime self-collected HPV S&T would be cost-effective at 0.5x gross domestic product (GDP) per capita (incremental cost-effectiveness ratio: US$460-US$656/life-years saved; 1GDPper-capita: US$2829 or PGK9446 (year 2019)) and could prevent 33 000-42 000 cases and 23 000-29 000 deaths in PNG over the next 50 years, if scale-up reached 70% coverage from 2023. Conclusion Self-collected HPV S&T was effective and cost-effective in the high-burden, low-resource setting of PNG, and, if scaled-up rapidly, could prevent over 20 000 deaths over the next 50 years. VIA screening was not effective or cost-effective. These findings support, at a country level, WHO updated cervical screening guidelines and indicate that similar approaches could be appropriate for other low-resource settings.

Abstract The WHO strategy for the elimination of cervical cancer sets 2030 targets for the scale-up of HPV vaccination, cervical screening, and pre-cancer and invasive cancer treatment. Screening and treatment of precancerous disease will be critical to reduce mortality in the short term, particularly in high HIV burden settings, due to the increased risk of cervical cancer among women living with HIV. To inform the development of new screening and treatment guidelines for women living with HIV, we modelled alternate scenarios for the screening test, frequency, and interval, and assessed the benefits and potential harms of cervical screening and precancer treatment in Tanzania, a country with a high burden of both HIV and of cervical cancer. We used a dynamic model of HPV and HIV co-infection, Policy1-Cervix-HIV, parametrised to Tanzanian demographic and epidemiological data, which captured HIV and HPV interactions. With the support of the WHO Guidelines Development Group for Screening and Treatment to Prevent Cervical Cancer (GDG) we assessed the impact of seven screening algorithms including primary visual inspection with acetic acid (‘VIA’), primary cytology, and primary HPV DNA (‘primary HPV’) with no triage, or triage using HPV16/18 genotyping, colposcopy, cytology, or VIA for women aged 25-50. Screening intervals of 3 years were considered for primary VIA and cytology, and intervals of 3, 5 or 10 years were considered for primary HPV. Screening and triage test performance was informed by updated systematic review evidence. We assumed 70% of women attended each routine screen, and 90% complied with follow-up or treatment. Outcomes include reduction in cervical cancer incidence and mortality as a measure of benefits, and number of precancer treatments (NNT) needed to prevent a death and preterm delivery events directly due to precancer treatment (‘additional preterm delivery events’) as a measure of the potential harms. A range of assumptions were considered in sensitivity and supplementary analyses. We found that, without screening, 5,263 cervical cancer cases (age-standardised incidence rate [ASIR] 104.0/100,000/year) and 4,467 cervical cancer deaths (age-standardised mortality rate [ASMR] 99.8/100,000) are predicted over the lifetime of 100,000 Tanzanian WLHIV. Primary HPV testing without triage every 3-years for women aged 25-50 years was effective in terms of cancer reduction, resulting in a 63.6% reduction in ASIR and 71.7% reduction in ASMR, and an NNT of 38.7 to prevent one cervical cancer death. However, triaging HPV positive women before treatment resulted in minimal loss of effectiveness with overall reduction in ASIR of 57.3-62.2% (range depends on triaging test used) and ASMR of 66.4-70.5% and was associated with more favourable NNTs (19.7-33.0). Primary screening with VIA or cytology at 3-yearly intervals resulted in lesser reductions in cervical cancer incidence and mortality and less favourable NNTs: for VIA, the overall reduction in ASIR was 50.6% and the reduction in ASMR was 54.2%, with an NNT of 107.5 to prevent a death. Extending the HPV screening interval from 3 to 5 years slightly decreased screening program effectiveness but increased efficiency. In conclusion, primary HPV testing approaches were the most effective, and optimised benefits-to-harms compared to primary VIA or cytology. Triaging HPV positive women before treatment reduces precancer treatments and improves efficiencies with minimal loss in effectiveness. However, uncertainties in the primary data exist and further empirical data on the effectiveness of screening in WLHIV will strengthen the evidence base for screening in this population. These findings informed updated WHO cervical screening and treatment guidelines; WHO now recommends that women living with HIV have primary HPV screening with triage before treatment for ages 25-50 every 3 or 5 years.

Abstract A strategy for the elimination of cervical cancer as a public health problem, through the scale-up of human papillomavirus (HPV) vaccination, cervical screening and precancer/cancer treatment, was launched by the World Health Organisation (WHO) in November 2020. To support the strategy, WHO published updated cervical screening and treatment guidelines in 2021. A modelled assessment of the benefits, harms and cost-effectiveness of screening approaches for the general population across 78 low-and lower-middle income countries (LMICs) informed the updated guidelines. With the support of the WHO Guidelines Development Group for Screening and Treatment to Prevent Cervical Cancer, we used an established modelling platform, Policy1-Cervix, to evaluate the impact of seven screening algorithms based on primary visual inspection with acetic acid (‘VIA’), primary cytology, and primary HPV DNA (‘primary HPV’) with no triage, or triage using HPV16/18 genotyping, colposcopy, cytology, or VIA. Screening intervals of 3 and 5 years were considered for primary VIA and cytology, and intervals of 5 and 10 years were considered for primary HPV. Screening and triage test performance was informed by updated systematic review evidence. For this normative analysis informing guidelines in screened populations, we assumed 70% of women attended each routine screen, and 90% complied with follow-up or treatment. Outcomes included reduction in cancer incidence and mortality, number of precancer treatments needed to prevent a death (NNT) and preterm delivery events directly due to precancer treatment and cost-effectiveness (US$/Health-Adjusted Life Year Saved [HALYS]). A range of assumptions were considered in sensitivity and supplementary analyses. We found that primary HPV DNA testing approaches, regardless of triaging method, were the most effective and cost-effective screening approaches and they appear on, or near to, the cost-effectiveness frontier. Primary HPV DNA testing without triage every 5 years for ages 30–50 years could result in a 64% reduction in cervical cancer mortality rates, compared to no screening. This strategy was associated with an NNT of 54 to prevent one death and was associated with an incremental cost-effectiveness ratio (ICER) of US$530/HALY saved (69/78[88%] of LMICs have a GDP-per-capita of > = US$518). Strategies involving primary HPV with triage of HPV positive women before treatment were almost as effective, reducing overall cervical cancer mortality rates by 60–63%, had a similar position on the cost-effectiveness frontier, but had an improved benefits-to-harms profile compared to HPV screening without triage, with an NNT of 26–37 to prevent a death. Compared to VIA screening, primary HPV screening, even without triaging, generated at least 60% fewer precancer treatment events and had 47% fewer additional preterm delivery events. In conclusion, primary HPV testing approaches were the most effective, optimised benefits-to-harms, and were cost-effective compared to primary VIA or cytology. If loss-to-follow-up after triage is limited, triaging HPV positive women before treatment reduces precancer treatments and preterm delivery events with minimal loss in effectiveness, and thus further improves the benefits-to-harms. Based on these findings, WHO now recommends primary HPV screening with or without triage for women in the general population. Going forward, country-specific analyses will continue to have an important role because they will be able to consider local factors that influence follow-up options and feasible triage testing approaches.

Background WHO recommends human papillomavirus (HPV) testing and same-day treatment for cervical screening in low-income and middle-income countries (LMICs); however, few published data exist on the validity of the strategy. We aimed to evaluate the clinical performance, treatment completion rates, adverse events profile, and acceptability of a fully integrated strategy, comprising point-of-care HPV DNA testing of self-collected specimens and same-day thermal ablation, for screening of cervical cancer in women in Papua New Guinea. Methods HPV STAT was a large scale, prospective, single arm intervention trial conducted at two clinical sites in Papua New Guinea. Cervical screening clinics with an on-site consultant gynaecologist were selected in consultation with national and provincial health authorities, church health services, and local stakeholders. Eligible participants were women aged 30-59 years attending cervical screening services at the two clinics, who were willing to comply with study procedures and able to provide written informed consent. Women self-collected vaginal specimens for point-of-care GeneXpert testing (Cepheid, Sunnyvale, CA, USA) for oncogenic HPV types. Women testing positive for HPV underwent pelvic examination followed by same-day thermal ablation or referral for gynaecology review. All HPV-positive women and a 15% random sample of HPV-negative women provided a clinician-collected cervical specimen for liquid-based cytology. The primary outcome was clinical performance (ie, sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of the strategy for the detection of high-grade squamous intraepithelial lesion (HSIL) or worse. This trial is registered with ISRCTN, ISRCTN13476702. Findings Between June 5, 2018, and Jan 6,2020, we recruited 4285 women, 3638 (84.9%) of whom tested negative for HPV and 647 (15.1%) tested positive for one or more oncogenic HPV type. Sensitivity of the algorithm to detect HSIL or worse was 85.4% (95% CI 81.0-89.6), with specificity 89.6% (88.6-90.6), PPV 35.2% (31.6-39.0), and NPV 98.9% (98.6-99.2). Among HPV-positive women, 602 (93.0%) received same-day thermal ablation and 42 (6.5%) were referred for gynaecology review, 37 (88.1%) of whom attended. Acceptability was high among both HPV-positive and HPV-negative women. Among the 329 HPV-positive women who attended a 3-month follow-up visit, 51 (15.5%) reported mild adverse symptoms that resolved in all cases by the follow-up visit. There were no serious adverse events. Interpretation We conducted the first real-world evaluation of a fully integrated point-of-care HPV self-collect, test, and treat strategy for same-day cervical screening in a LMIC and found it to be effective, acceptable, and safe when implemented at scale in primary health-care facilities in Papua New Guinea. Our findings support the introduction and scale-up of HPV screening and treatment for the control and elimination of cervical cancer in LMICs, as recommended by WHO. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

PurposeLynch syndrome-related colorectal cancer (CRC) risk substantially varies by mismatch repair (MMR) gene. We evaluated the health impact and cost-effectiveness of MMR gene-tailored colonoscopic surveillance.MethodsWe first estimated sex- and MMR gene-specific cumulative lifetime risk of first CRC without colonoscopic surveillance using an optimization algorithm. Next, we harnessed these risk estimates in a microsimulation model, “Policy1-Lynch,” and compared 126 colonoscopic surveillance strategies against no surveillance.ResultsThe most cost-effective strategy was 3-yearly surveillance from age 25 to 70 years (pathogenic variants [path_] in MLH1 [path_MLH1], path_MSH2) with delayed surveillance for path_MSH6 (age 30-70 years) and path_PMS2 (age 35-70 years) heterozygotes (incremental cost-effectiveness ratio = Australian dollars (A) $8,833/life-year saved). This strategy averted 60 CRC deaths (153 colonoscopies per death averted) over the lifetime of 1000 confirmed patients with Lynch syndrome (vs no surveillance). This also reduced colonoscopies by 5% without substantial change in health outcomes (vs nontailored 3-yearly surveillance from 25-70 years). Generally, starting surveillance at age 25 (vs 20) years was more cost-effective with minimal effect on life-years saved and starting 5 to 10 years later for path_MSH6 and path_PMS2 heterozygotes (vs path_MLH1 and path_MSH2) further improved cost-effectiveness. Surveillance end age (70/75/80 years) had a minor effect. Three-yearly surveillance strategies were more cost-effective (vs 1 or 2-yearly) but prevented 3 fewer CRC deaths.ConclusionMMR gene-specific colonoscopic surveillance would be effective and cost-effective.

BACKGROUND:A nonavalent human papillomavirus (HPV) vaccine has been licensed for use in women and men up to age 45 years in the United States. The cost-effectiveness of HPV vaccination for women and men aged 30 to 45 years in the context of cervical cancer screening practice was evaluated to inform national guidelines.METHODS AND FINDINGS:We utilized 2 independent HPV microsimulation models to evaluate the cost-effectiveness of extending the upper age limit of HPV vaccination in women (from age 26 years) and men (from age 21 years) up to age 30, 35, 40, or 45 years. The models were empirically calibrated to reflect the burden of HPV and related cancers in the US population and used standardized inputs regarding historical and future vaccination uptake, vaccine efficacy, cervical cancer screening, and costs. Disease outcomes included cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as genital warts. Both models projected higher costs and greater health benefits as the upper age limit of HPV vaccination increased. Strategies of vaccinating females and males up to ages 30, 35, and 40 years were found to be less cost-effective than vaccinating up to age 45 years, which had an incremental cost-effectiveness ratio (ICER) greater than a commonly accepted upper threshold of $200,000 per quality-adjusted life year (QALY) gained. When including all HPV-related outcomes, the ICER for vaccinating up to age 45 years ranged from $315,700 to $440,600 per QALY gained. Assumptions regarding cervical screening compliance, vaccine costs, and the natural history of noncervical HPV-related cancers had major impacts on the cost-effectiveness of the vaccination strategies. Key limitations of the study were related to uncertainties in the data used to inform the models, including the timing of vaccine impact on noncervical cancers and vaccine efficacy at older ages.CONCLUSIONS:Our results from 2 independent models suggest that HPV vaccination for adult women and men aged 30 to 45 years is unlikely to represent good value for money in the US.

The WHO has launched a global strategy to eliminate cervical cancer through the scale‐up of human papillomavirus (HPV) vaccination, cervical screening, and cervical cancer treatment. Malaysia has achieved high‐coverage HPV vaccination since 2010, but coverage of the existing cytology‐based program remains low. Pilot studies found HPV self‐sampling was acceptable and effective, with high follow‐up rates when a digital registry was used, and recently the Malaysian Government announced plans for a national HPV‐based screening program. We therefore evaluated the impact of primary HPV screening with self‐collection in Malaysia in the context of Malaysia's existing vaccination program. We used the “Policy1‐Cervix” modeling platform to assess health outcomes, cost‐effectiveness, resource use and cervical cancer elimination timing (the year when cervical cancer rates reach four cases per 100 000 women) of implementing primary HPV testing with self‐collection, assuming 70% routine‐screening coverage could be achieved. Based on available data, we assumed that compliance with follow‐up was 90% when a digital registry was used, but that compliance with follow‐up would be 50‐75% without the use of a digital registry. We found that the current vaccination program would prevent 27 000 to 32 200 cervical cancer cases and 11 700 to 14 000 deaths by 2070. HPV testing with a digital registry was cost‐effective (CER = $US 6953‐7549 < $US 11 373[<1×GDP per capita]) and could prevent an additional 15 900 to 17 800 cases and 9700 to 10 600 deaths by 2070, expediting national elimination by 11 to 20 years, to 2055 to 2059. If HPV screening were implemented without a digital registry, there would be 1800 to 4900 fewer deaths averted by 2070 and the program would be less cost‐effective. These results underline the importance of HPV testing as a key elimination pillar in Malaysia.

The World Health Organisation (WHO) has launched a strategic initiative for cervical cancer (CC) elimination which involves scaling up three interventions: human papillomavirus (HPV) vaccination, twice‐lifetime HPV‐screening screening and pre‐cancer/cancer treatment by 2030. CC is challenging to control in countries with endemic human immunodeficiency virus (HIV), as women living with HIV (WLHIV) are at elevated risk of HPV infection, persistence and progression. This analysis estimated the impact of the elimination interventions on CC incidence and mortality but additionally considered more intensive screening for WLHIV, using Tanzania as an example. A dynamic HIV/HPV model was used to simulate the elimination strategy for vaccination, screening and pre‐cancer/cancer treatment, with 3‐yearly HPV‐screening in WLHIV starting at age 25 years, in the context of sustained HIV control in Tanzania from 2020 to 2119. Without vaccination or HPV screening, CC incidence rates per 100 000 women are predicted to fall from 58.0 in 2020 to 41.6 (range: 39.1‐44.7) in 2119, due to existing HIV control. HPV vaccination and twice‐lifetime HPV‐screening for the general population and 3‐yearly screening for WLHIV, would reduce CC incidence to 1.3 (range: 1.3‐2.5) by 2119, with elimination (<4/100 000) in 2076 (range: 2076‐2092). CC mortality rates per 100 000 women are predicted to reach 1.1 (range: 1.1‐2.1) with further reductions contingent on increased CC treatment access. Vaccination and 3‐yearly HPV‐screening for WLHIV is predicted to achieve elimination in the subgroup of WLHIV potentially as early as 2061 (range: 2061‐2078), with a 2119 CC incidence rate of 1.7 (range: 1.7‐3.3). Scaling‐up vaccination and HPV‐screening will substantially reduce CC incidence in Tanzania, with elimination predicted within a century. Three‐yearly HPV‐screening and HPV vaccination, at high coverage rates, would facilitate CC elimination among WLHIV, and thus accelerate elimination in the overall population.

BACKGROUND:Cervical screening on self-collected samples has mainly been considered for targeted use in underscreened women. Updated evidence supports equivalent sensitivity of PCR-based human papillomavirus (HPV) testing on self-collected and clinician-collected samples. METHODS:Using a well-established model, we compared the lifetime impact on cancer diagnoses and deaths resulting from cervical screening using self-collected samples only, with and without the existing restriction in Australia to women aged 30+ years and ≥2 years overdue, compared with the mainstream program of 5-yearly HPV screening on clinician-collected samples starting at 25 years of age. We conservatively assumed sensitivity of HPV testing on self-collected relative to clinician-collected samples was 0.98. Outcomes were estimated either in the context of HPV vaccination ("routinely vaccinated cohorts;" uptake as in Australia) or in the absence of HPV vaccination ("unvaccinated cohorts"). RESULTS:In unvaccinated cohorts, the health benefits of increased participation from self-collection outweighed the worst case (2%) loss of relative test sensitivity even if only 15% of women, who would not otherwise attend, used it ("additional uptake"). In routinely vaccinated cohorts, population-wide self-collection could be marginally (0.2%-1.0%) less effective at 15% additional uptake but 6.2% to 12.4% more effective at 50% additional uptake. Most (56.6%-65.0%) of the loss in effectiveness in the restricted self-collection pathway in Australia results from the requirement to be 2 or more years overdue. CONCLUSIONS:Even under pessimistic assumptions, any potential loss in test sensitivity from self-collection is likely outweighed by improved program effectiveness resulting from feasible levels of increased uptake. IMPACT:Consideration could be given to offering self-collection more widely, potentially as an equal choice for women.See related commentary by Lim, p. 245.

BACKGROUND:On Nov 17, 2020, WHO launched a global initiative to accelerate the elimination of cervical cancer through the implementation of HPV vaccination, cervical cancer screening and treatment for precancer and cancer. China has the largest burden of cervical cancer in the world, but only has a national cervical cancer screening program in rural areas since 2009. Here, we aimed to evaluate the effectiveness and cost-effectiveness of cervical cancer screening in urban China, using Shenzhen City as an example.METHODS:We use an extensively validated platform ('Policy1-Cervix'), calibrated to data from Shenzhen city and Guandong Province. We evaluated a range of strategies that have previously been implemented as pilot studies in China, or recommended as guidelines within China and globally, spanning primary HPV, cytology and co-testing strategies. We additionally considered alternate triaging methods, age ranges and screening intervals, resulting in 19 algorithms in total.RESULTS:Of the 19 strategies considered, the most effective approach involved primary HPV testing. At 3- to 10-yearly intervals, primary HPV testing reduced the age-standardized cancer mortality rate by 37-71 %. The most cost-effective strategy was 5-yearly primary HPV testing with partial genotyping triage for ages 25-65, discharging to 10-yearly screening for low-risk women (ICER = US$7191/QALYS using 2018 costs; willingness-to-pay threshold<1xGDP [US$9771]). This strategy gave an incidence and mortality reduction of 56 % and 63 %, respectively. This remained the most cost-effective strategy under most conditions in sensitivity analysis.CONCLUSION:Primary HPV testing would be cost-effective in Shenzhen and could more than halve cervical cancer incidence rates to 6 per 100,000 over the long term. In order to achieve rates below 4 per 100,000, the elimination threshold set by the World Health Organization, vaccination will likely also be necessary.

Objectives To evaluate the health impact and cost-effectiveness of systematic testing for Lynch syndrome (LS) in people with incident colorectal cancer (CRC) in Australia. Design, setting, participants We investigated the impact of LS testing strategies in a micro-simulation model (Policy1-Lynch), explicitly modelling the cost of testing all patients diagnosed with incident CRC during 2017, with detailed modelling of outcomes for patients identified as LS carriers (probands) and their at-risk relatives throughout their lifetimes. For people with confirmed LS, we modelled ongoing colonoscopic surveillance. Main outcome measures Cost-effectiveness of six universal tumour testing strategies (testing for DNA mismatch repair deficiencies) and of universal germline gene panel testing of patients with incident CRC; impact on cost-effectiveness of restricting testing by age at CRC diagnosis (all ages, under 50/60/70 years) and of colonoscopic surveillance interval (one, two years). Results The cost-effectiveness ratio of universal tumour testing strategies (annual colonoscopic surveillance, no testing age limit) compared with no testing ranged from $28 915 to $31 904/life-year saved (LYS) (indicative willingness-to-pay threshold: $30 000-$50 000/LYS). These strategies could avert 184-189 CRC deaths with an additional 30 597-31 084 colonoscopies over the lifetimes of 1000 patients with incident CRC with LS and 1420 confirmed LS carrier relatives (164-166 additional colonoscopies/death averted). The most cost-effective strategy was immunohistochemistry and BRAF V600E testing (incremental cost-effectiveness ratio [ICER], $28 915/LYS). Universal germline gene panel testing was not cost-effective compared with universal tumour testing strategies (ICER, $2.4 million/LYS). Immunohistochemistry and BRAF V600E testing was cost-effective at all age limits when paired with 2-yearly colonoscopic surveillance (ICER, $11 525-$32 153/LYS), and required 4778-15 860 additional colonoscopies to avert 46-181 CRC deaths (88-103 additional colonoscopies/death averted). Conclusions Universal tumour testing strategies for guiding germline genetic testing of people with incident CRC for LS in Australia are likely to be cost-effective compared with no testing. Universal germline gene panel testing would not currently be cost-effective.

Background. To interpret cervical cancer screening model results, we need to understand the influence of model structure and assumptions on cancer incidence and mortality predictions. Cervical cancer cases and deaths following screening can be attributed to 1) (precancerous or cancerous) disease that occurred after screening, 2) disease that was present but not screen detected, or 3) disease that was screen detected but not successfully treated. We examined the relative contributions of each of these using 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models. Methods. The maximum clinical incidence reduction (MCLIR) method compares changes in the number of clinically detected cervical cancers and mortality among 4 scenarios: 1) no screening, 2) one-time perfect screening at age 45 that detects all existing disease and delivers perfect (i.e., 100% effective) treatment of all screen-detected disease, 3) one-time realistic-sensitivity cytological screening and perfect treatment of all screen-detected disease, and 4) one-time realistic-sensitivity cytological screening and realistic-effectiveness treatment of all screen-detected disease. Results. Predicted incidence reductions ranged from 55% to 74%, and mortality reduction ranged from 56% to 62% within 15 years of follow-up for scenario 4 across models. The proportion of deaths due to disease not detected by screening differed across the models (21%–35%), as did the failure of treatment (8%–16%) and disease occurring after screening (from 1%–6%). Conclusions. The MCLIR approach aids in the interpretation of variability across model results. We showed that the reasons why screening failed to prevent cancers and deaths differed between the models. This likely reflects uncertainty about unobservable model inputs and structures; the impact of this uncertainty on policy conclusions should be examined via comparing findings from different well-calibrated and validated model platforms.

BACKGROUND:WHO is developing a global strategy towards eliminating cervical cancer as a public health problem, which proposes an elimination threshold of four cases per 100 000 women and includes 2030 triple-intervention coverage targets for scale-up of human papillomavirus (HPV) vaccination to 90%, twice-lifetime cervical screening to 70%, and treatment of pre-invasive lesions and invasive cancer to 90%. We assessed the impact of achieving the 90-70-90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century. We also assessed the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals (SDGs)-a one-third reduction in premature mortality from non-communicable diseases by 2030. METHODS:The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC) involves three independent, dynamic models of HPV infection, cervical carcinogenesis, screening, and precancer and invasive cancer treatment. Reductions in age-standardised rates of cervical cancer mortality in 78 low-income and lower-middle-income countries (LMICs) were estimated for three core scenarios: girls-only vaccination at age 9 years with catch-up for girls aged 10-14 years; girls-only vaccination plus once-lifetime screening and cancer treatment scale-up; and girls-only vaccination plus twice-lifetime screening and cancer treatment scale-up. Vaccination was assumed to provide 100% lifetime protection against infections with HPV types 16, 18, 31, 33, 45, 52, and 58, and to scale up to 90% coverage in 2020. Cervical screening involved HPV testing at age 35 years, or at ages 35 years and 45 years, with scale-up to 45% coverage by 2023, 70% by 2030, and 90% by 2045, and we assumed that 50% of women with invasive cervical cancer would receive appropriate surgery, radiotherapy, and chemotherapy by 2023, which would increase to 90% by 2030. We summarised results using the median (range) of model predictions. FINDINGS:In 2020, the estimated cervical cancer mortality rate across all 78 LMICs was 13·2 (range 12·9-14·1) per 100 000 women. Compared to the status quo, by 2030, vaccination alone would have minimal impact on cervical cancer mortality, leading to a 0·1% (0·1-0·5) reduction, but additionally scaling up twice-lifetime screening and cancer treatment would reduce mortality by 34·2% (23·3-37·8), averting 300 000 (300 000-400 000) deaths by 2030 (with similar results for once-lifetime screening). By 2070, scaling up vaccination alone would reduce mortality by 61·7% (61·4-66·1), averting 4·8 million (4·1-4·8) deaths. By 2070, additionally scaling up screening and cancer treatment would reduce mortality by 88·9% (84·0-89·3), averting 13·3 million (13·1-13·6) deaths (with once-lifetime screening), or by 92·3% (88·4-93·0), averting 14·6 million (14·1-14·6) deaths (with twice-lifetime screening). By 2120, vaccination alone would reduce mortality by 89·5% (86·6-89·9), averting 45·8 million (44·7-46·4) deaths. By 2120, additionally scaling up screening and cancer treatment would reduce mortality by 97·9% (95·0-98·0), averting 60·8 million (60·2-61·2) deaths (with once-lifetime screening), or by 98·6% (96·5-98·6), averting 62·6 million (62·1-62·8) deaths (with twice-lifetime screening). With the WHO triple-intervention strategy, over the next 10 years, about half (48% [45-55]) of deaths averted would be in sub-Saharan Africa and almost a third (32% [29-34]) would be in South Asia; over the next 100 years, almost 90% of deaths averted would be in these regions. For premature deaths (age 30-69 years), the WHO triple-intervention strategy would result in rate reductions of 33·9% (24·4-37·9) by 2030, 96·2% (94·3-96·8) by 2070, and 98·6% (96·9-98·8) by 2120. INTERPRETATION:These findings emphasise the importance of acting immediately on three fronts to scale up vaccination, screening, and treatment for pre-invasive and invasive cervical cancer. In the next 10 years, a one-third reduction in the rate of premature mortality from cervical cancer in LMICs is possible, contributing to the realisation of the 2030 UN SDGs. Over the next century, successful implementation of the WHO elimination strategy would reduce cervical cancer mortality by almost 99% and save more than 62 million women's lives. FUNDING:WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Germany Federal Ministry of Health, National Health and Medical Research Council Australia, Centre for Research Excellence in Cervical Cancer Control, Canadian Institute of Health Research, Compute Canada, and Fonds de recherche du Québec-Santé.

BACKGROUND:Women with HIV have an elevated risk of HPV infection, and eventually, cervical cancer. Tanzania has a high burden of both HIV and cervical cancer, with an HIV prevalence of 5.5% in women in 2018, and a cervical cancer incidence rate among the highest globally, at 59.1 per 100,000 per year, and an estimated 9,772 cervical cancers diagnosed in 2018. We aimed to quantify the impact that interventions intended to control HIV have had and will have on cervical cancer in Tanzania over a period from 1995 to 2070. METHODS:A deterministic transmission-dynamic compartment model of HIV and HPV infection and natural history was used to simulate the impact of voluntary medical male circumcision (VMMC), anti-retroviral therapy (ART), and targeted pre-exposure prophylaxis (PrEP) on cervical cancer incidence and mortality from 1995-2070. FINDINGS:We estimate that VMMC has prevented 2,843 cervical cancer cases and 1,039 cervical cancer deaths from 1995-2020; by 2070 we predict that VMMC will have lowered cervical cancer incidence and mortality rates by 28% (55.11 cases per 100,000 women in 2070 without VMMC, compared to 39.93 with VMMC only) and 26% (37.31 deaths per 100,000 women in 2070 without VMMC compared to 27.72 with VMMC), respectively. We predict that ART will temporarily increase cervical cancer diagnoses and deaths, due to the removal of HIV death as a competing risk, but will ultimately further lower cervical cancer incidence and mortality rates by 7% (to 37.31 cases per 100,000 women in 2070) and 5% (to 26.44 deaths per 100,000 women in 2070), respectively, relative to a scenario with VMMC but no ART. A combination of ART and targeted PrEP use is anticipated to lower cervical cancer incidence and mortality rates to 35.82 and 25.35 cases and deaths, respectively, per 100,000 women in 2070. CONCLUSIONS:HIV treatment and control measures in Tanzania will result in long-term reductions in cervical cancer incidence and mortality. Although, in the near term, the life-extending capability of ART will result in a temporary increase in cervical cancer rates, continued efforts towards HIV prevention will reduce cervical cancer incidence and mortality over the longer term. These findings are critical background to understanding the longer-term impact of achieving cervical cancer elimination targets in Tanzania.

BACKGROUND:In May, 2018, the Director-General of WHO issued a global call to eliminate cervical cancer as a public health problem, which will involve ambitious screening and vaccination coverage targets. We aimed to assess the potential for, and timing of, cervical cancer elimination in the USA and whether this could be expedited by adopting ambitious coverage targets, using two cervical cancer simulation models. METHODS:In this modelling study, we used two independently-developed cervical cancer microsimulation models-Harvard and Policy1-Cervix-to estimate changes in the incidence of human papillomavirus (HPV)-induced cervical cancer over time in the USA, including herd effects from vaccination. We compared nine alternative scenarios for prophylactic HPV vaccination and cervical screening scale-up with a status quo scenario that involved no additional interventions in the context of a threshold for cervical cancer elimination of four or fewer cases per 100 000 women-years. We also estimated the number of cervical cancer cases that could be averted between 2019 and 2100 associated with the adoption of ambitious goals for cervical cancer screening and vaccination coverage, and other potential strategies. FINDINGS:Under status quo assumptions, the Havard and Policy1-Cervix models projected that cervical cancer incidence would decrease to less than four or fewer new cases per 100 000 women-years by the 2038 and 2046, respectively. Scaling up screening coverage to 90% in 2020, was the most effective intervention to expedite time to elimination (10-13-year reduction), averting a mean of 1400-2088 additional cases annually between 2019 and 2100. Increasing HPV vaccination coverage to 90% or vaccinating adults aged 26-45 years had relatively little effect on cervical cancer incidence. Sensitivity analysis using different population structures resulted in differences in time to elimination (range -10 years to +27 years) compared with status quo predictions. INTERPRETATION:The USA is on track to eliminate cervical cancer as a public health problem in the next two to three decades. Time to elimination could be expedited by 10-13 years by achieving higher screening coverage. Targeting of underscreened and under-vaccinated women remains key to achieving cervical cancer elimination for all women. FUNDING:US National Cancer Institute.