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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.

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.

BackgroundAustralia 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 programs on cancer outcomes and cancer services.MethodsWe used the Policy1 modelling platforms to estimate outcomes for potential disruptions to cancer screening participation, covering periods of 3, 6, 9 and 12 months. We estimated missed screens, clinical outcomes (cancer incidence, tumour staging), and various diagnostic service impacts.ResultsWe estimated that a 12-month 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.ConclusionsFindings illustrate that maintaining screening participation is critical to sustaining a reduced cancer burden. We provide program-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 programs, and emphasises the ongoing benefits of maintaining screening in the face of potential future disruptions.FundingAustralian Government Department of Health