Benefits, harms and cost-effectiveness of cervical screening, triage and treatment strategies for women in the general population

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.

*Ablative treatment includes cryotherapy and thermal ablation.**CKC if LLETZ not available.# Histology may not be available in certain settings.Women should be followed-up after 1 year or to report earlier, if they have any of the symptoms of cervical cancer.^ Women referred with cytology LSIL or worse at colposcopy will receive biopsy even if they have a type 1 or type 2 transformation zone at colposcopy.^^VIA triage positive women treated after assessment of eligibility for ablative treatment.^HPV 16/18 positive women treated after assessment of eligibility for ablative treatment.Women positive for HPV types other than HPV 16/18 ('OHR') are triaged with VIA.$ The 'Elimination strategy' refers to the screening test, ages and frequencies assumed in the earlier analysis of cervical cancer elimination timeline.F-only Age-standardized and age-specific incidence and mortality rates were reported along with cases and deaths per 100,000 women.HALYS (Health-adjusted life years saved) were reported for the main results and life years were reported as part of the sensitivity analysis.Age-specific results not directly reported but are critical to calculation of HALYS and ASRs.

Supplementary Table 1: Screening ages and frequencies considered for each screening algorithm
HPV prevalence, preintervention  * All disutilities are varied together within PSA, i.e. all events would have a value of X% multiplied by their baseline.This is to avoid unrealistic scenarios that could occur if they varied independently such as the FIGO1 diagnosis and treatment having a higher disutility than FIGO4 diagnosis and treatment.a Cancer disutilities are only applied to the proportion of cancers that are treated and assumed to apply to 90% of screendetected cases.Surveillance disutilities are applied from 1 year after diagnosis until death, or a maximum of 5 years if the woman survives for this amount of time.

*
All positive women treated after assessment of eligibility for ablative treatment.**Triage positive referred to colposcopy.
For PSA: 0-100% (0-0.049)*Every year of cancer after the first year up to the last 3 months of life (or survival) the average across 78 LMIC, i.e. the sum of the country-level costs weighted by the proportion of the 78 LMIC population of 30-49 year-old females in each country.

N) Reported by age? (Y/N) Report by sex (F-only, M- only or both)?
9,15Supplementary Table2: HPV-FRAME reporting standard checklist for the modelling in the general population of women

Table 3 :
Cross-sectional sensitivity and specificity inputs used for (a) primary test technologies and (b) combined primary and triage test outputs.We also present assumptions for test performance considered in sensitivity analysis for primary test technologies in (c) Data available for women aged 35-60.^Liquid-based cytology assumed, and HPV test using ATIMA.**Sensitivityanalysis on the sensitivity of primary HPV, primary cytology and primary VIA are performed on predictions of incidence and mortality reductions.costs represent the average across 78 LMIC, i.e. the sum of the country-level costs weighted by the proportion of the 78 LMIC population of 30-49 year-old females in each country.^ Includes consumables, administering provider/workforce, and programmatic utilisation costs.* Includes cost of test, sample drop-off and transport, laboratory staff time, lab supplies, general administration and overhead costs of primary screening using WHO-CHOICE methodology and database.O Same as primary, but excludes a proportion of the labour, programmatic and utilisation costs from primary visits due to not requiring another visit.When VIA is used during colposcopy, we assume no cost.# Includes consumables/equipment, workforce.@Includes consumables/equipment, workforce including pathologist and biomedical scientist.a Cancer costs are only applied to the proportion of cancers that are treated and assumed to apply to 90% of screen-detected cases in the base case.Surveillance costs are applied from 1 year after diagnosis until death, or a maximum of 5 years if the woman survives for this amount of time.
This level of detail is not reported.Herd immunity effects could be a factor for vaccination but vaccination is *@ Range of sensitivity and specificity here.We assume a fixed test performance for each test across all scenarios.As disease burden varies substantially across all-78 LMIC, equivalent test performance may result in different sensitivity and specificity at a population-level; for instance, tests used in settings with high rates of CIN2/3 will generate different sensitivity calculation compared with settings with very low rates of disease.+Aggregate