Article Text

Towards the elimination of cervical cancer in low-income and lower-middle-income countries: modelled evaluation of the effectiveness and cost-effectiveness of point-of-care HPV self-collected screening and treatment in Papua New Guinea
1. Diep Thi Ngoc Nguyen1,
2. Kate T Simms1,
4. Glen Mola2,3,
5. John Walpe Bolnga4,
6. Joseph Kuk5,
7. Pamela J Toliman6,7,
9. Marion Saville8,
10. John Kaldor6,
11. Andrew Vallely6,7,
12. Karen Canfell1
1. 1Daffodil Centre, The University of Sydney, Sydney, New South Wales, Australia
2. 2Department of Reproductive Health, Obstetrics and Gynecology, School of Medicine and Health Sciences, University of Papua New Guinea, Port Moresby, CND, Papua New Guinea
3. 3Department of Obstetrics and Gynecology, Port Moresby General Hospital, Port Moresby, Papua New Guinea
4. 4Department of Obstetrics and Gynecology, Modilion Hospital, Mango, Madang, Papua New Guinea
5. 5Department of Obstetrics and Gynecology, Mt Hagen Provincial Hospital, Mt Hagen, Western Highlands Province, Papua New Guinea
6. 6Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
7. 7Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea
8. 8Australian Centre for the Prevention of Cervical Cancer, Melbourne, Victoria, Australia
1. Correspondence to Dr Diep Thi Ngoc Nguyen; diep.nguyen{at}nswcc.org.au

## Abstract

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 0.5× 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.

• screening
• cancer
• mathematical modelling
• health economics

## Data availability statement

Data sharing is not applicable.

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### Key questions

• Papua New Guinea (PNG) is a lower-middle-income country with a high burden of cervical cancer.

• In 2020, WHO launched a strategy to eliminate cervical cancer as a public health problem globally through wide-scale uptake of HPV vaccination, cervical cancer screening, and improving access to cancer treatment and care, and in July 2021, WHO launched updated cervical screening guidelines recommending primary HPV testing in a screen-and-treat approach or screen-triage-and-treat for ages 30–50 years. To make progress towards cervical cancer elimination, it is essential for PNG to identify the screening strategies which are locally appropriate.

• The first field trials of point-of-care (PoC) HPV testing using self-collected vaginal specimens followed by same-day thermal ablation (or gynaecological referral if a cervical lesion seen on examination) have been conducted in PNG. This screening modality was found to be acceptable to women and effective for detection of high-grade precancerous lesions. However, optimal screening ages and frequencies, and the cost-effectiveness of a national roll-out of such an approach has not been determined.

### Key questions

#### What are the new findings?

• Evaluation of HPV self-collection is increasingly being performed in the context of LMICs. Different models have been assessed for delivery of self-collection and modalities of ‘test and treat’ or ‘test, triage and treat’. Here, we aimed to combine all the elements for delivery of a pragmatic approach in a high burden population never reached by screening, including HPV testing with point-of-care and self-collection modalities and a screen-and-treat approach involving thermal ablation (self-collected HPVS&T).

• This is the first modelled analysis which captures all elements of point-of-care HPV self-collected screen and treat (self-collected HPV S&T), an approach designed for a high-burden and low-resource setting like PNG.

• Either twice (at 30 and 40 years or at 35 and 40 years) or thrice per lifetime (at 30, 35 and 40 years) self-collected HPV S&T could reduce cervical cancer incidence by 35%–48% and mortality by 39%–49% over the long term.

#### What do the new findings imply?

• The study findings support the WHO cervical cancer elimination strategy and their recently updated cervical screening guidelines.

• The results in this paper will also support major new implementation effort in the Western Pacific to scale up HPV vaccination, screen-and-treat, and cancer treatment services towards achieving cervical cancer elimination in PNG and more broadly in the region (Eliminate Cervical Cancer in the Western Pacific (ECCWP) initiative). This practically realisable HPV-based screening modality is likely to be applicable for other LMICs where resources for cervical screening are limited.

## Introduction

Cervical cancer is the second most common cancer among women in low- and lower-middle income countries with a population-weighted average age-standardised incidence rate (ASR) of 17.8 new cases per 100 000 women in 2018.1 Papua New Guinea (PNG) has a high estimated burden of cervical cancer with an ASR incidence rate of 29.1/100 000 women (all ages) and mortality rate of 19.1/100 000 in 2018,1 which is 1.6 times higher the average incidence rate for all low- and lower-middle income countries.2 Although the burden of disease is high, cervical screening or human papillomavirus (HPV) vaccination programmes are not currently available in PNG. A pilot cervical cytology-based screening project was conducted in 30 health facilities in 16 provinces by an Australian non-government organisation3 and screened around 45 000 women (~4% of target population aged 30–59 years) in the period 2001–2011.3 As Pap test specimens were sent to Australia for testing, over 60% of those with high-grade disease needing further investigation or treatment were lost to follow-up due to the time between testing and recall. In 2009, a Ministerial Task Force on Cervical Cancer recommended the discontinuation of Pap test based screening in PNG, and the evaluation of the ‘screen and treat’ approach using visual inspection of the cervix with acetic acid (VIA), followed by cervical cryotherapy if lesions were identified, which was based on the 2014 WHO cervical cancer screening guidelines.4 5 A subsequent evaluation found the sensitivity of VIA to detect high-grade precancerous lesions in PNG was 51.5% and specificity 81.4%.6 We recently conducted the first field trials to evaluate a new screening model comprising point-of-care (PoC) HPV testing (GeneXpert; Cepheid, Sunnyvale, California, USA) using self-collected vaginal specimens followed by same-day curative treatment using a new, battery-operated, portable, thermal ablation device (WISAP Medical Technology).6–11 In our first trial among 1005 women in PNG (2013–2015), we showed that (1) HPV testing of self-collected vaginal specimens had comparable sensitivity (91.7%) and specificity (87.0%) to clinician-collected cervical specimens for the detection of cervical pre-cancer using the GeneXpert platform6 7 12; (2) VIA alone, or VIA in combination with HPV testing had poor performance for the detection of underlying High-Grade Squamous Intraepithelial Lesions (HSIL) or worse (sensitivity 51.5% and 45.5%, respectively) compared with HPV testing alone (sensitivity 91.7%)6; and (3) with suitable training and support, PoC HPV self-collected screen and treat (thereafter self-collected HPV S&T) can be provided routinely in primary care facilities.7 The poor performance of VIA in this trial is similar to the findings reported in India and Rwanda.13 14 In a second field trial among 4000 women in PNG (2017–2020), we confirmed the clinical performance of our self-collected HPV S&T modality for the detection and treatment of cervical pre-cancer, and its high acceptability among women and health providers.15

In May 2018, the Director-General of the WHO announced a global call to action towards achieving the elimination of cervical cancer as a public health problem. In November 2020, WHO launched the global elimination strategy16 that included the ‘90-70-90’ triple intervention targets to be met by 2030: (1) 90% of girls fully vaccinated with the HPV vaccine by age 15; (2) 70% of women screened with a high-precision HPV test by age 35 and 45 years of age; and (3) 90% of women with cervical precancer treated, and 90% of women with invasive cancer managed and treated appropriately. Achieving the triple-intervention targets in the next decade would put countries on the path to achieving elimination in the next century, reducing cervical cancer mortality by 99% and saving more than 62 million women’s lives over the next century.2 To support elimination effort, WHO has recently released updated cervical screening guidelines which recommend primary HPV screen-and-treat or primary HPV screen-triage-and-treat for women aged 30–49 years.17

To make progress towards elimination, it will be essential for countries to implement locally appropriate, context-specific intervention strategies. In this paper, we evaluated new WHO screen-and-treat approach informed by local data from a field trial of self-collected HPV S&T modality to identify the optimal cervical screening strategy for PNG. Here, we reported on the estimated effectiveness and cost-effectiveness of national roll-out of self-collected HPV S&T in PNG, the long-term impact on cervical cancer incidence and mortality, and the resource implications of scaling up such an algorithm.

## Methods

### Model platform

A validated dynamic individual-based microsimulation model (‘Policy1-Cervix’) of HPV transmission, type-specific natural history of cervical intraepithelial neoplasia (CIN) and invasive cancer staging, and cervical screening, diagnosis, and treatment was used. This model platform has been used to evaluate the effectiveness and cost-effectiveness of cervical cancer screening for both vaccinated and unvaccinated cohorts across different settings, including the renewal of the cervical screening programme in Australia,18 19 the impact of HPV testing using self-collected samples in Australia,20 the impact of primary HPV testing in New Zealand,21 England22 and China23–25 and vaccine evaluations in Japan.26 Most recently, this model was also used to evaluate the timeline to cervical cancer elimination for 78-low-income and lower-middle income countries (LMICs), in Australia, USA and globally2 27–30 and is also being used to inform development of updated WHO screening guidelines.17 (online supplemental figure A1. More details of the model platform present in the online supplemental appendix, p1-2 and via Policy1-Cervix website https://www.policy1.org/models/cervix/documentation).

### Model calibration

We calibrated the model to the cervical cancer incidence rate in PNG using age-specific GLOBOCAN 2018 data1 (ASR=28.4/100 000 women (0–84 years)) as shown in online supplemental figure A2 (A)). Additionally, the model was also calibrated to the age-specific high-risk HPV prevalence among women aged 18–54 years, based on data from a local HPV prevalence survey31 (online supplemental figures A2 (C) and A3).

### Background hysterectomy rates

Although there is some hysterectomy being done on benign conditions, this information is not well documented or there is paucity of information, we assumed there was no background hysterectomy for benign conditions.

### Screening and management pathways

We considered two screening and management pathways. The first is the same pathway as in the field project, utilising self-collected HPV S&T (figure 1A). In this pathway, women who are positive at primary HPV testing are treated with thermocoagulation of the transformation zone of the cervix. For the second pathway, we considered screening with VIA (figure 1B). In both screening pathways, women who have a cervical lesion at visual assessment, but are not suspected of harbouring a cancer, are immediately treated with ablation and that women whose lesions are large or suspicious for cancer are referred to a specialist for further assessment. For both pathways, we assumed that women who were referred for diagnosis with suspicion of cancer, but found to have CIN3, would be treated with hysterectomy or conisation depending on patient individual clinical circumstances (based on local expert opinion). We assumed that women who are negative may return for screening at a set time, depending on the screening frequency, and that women who received treatment for precancer for a ‘test of cure’ using the same test as the primary test.

Figure 1

Screening management pathway. (A) Point-of-care (PoC) HPV self-collected screen and treat (self-collected HPV S&T), (B) VIA screening.

### Screening ages and frequencies

Although initial field trials focused on women aged 30–59 years, in the modelled analysis we considered various screening frequencies (once, twice, thrice lifetime and 5 yearly) at different initiating ages (30 years, 35 years and 40 years).

For this analysis, we considered two overall steps. In the first step (step 1), a total of 38 screening strategies were assessed to identify the optimal screening strategies for PNG, considering both ‘self-collected HPV S&T’ and VIA approaches and varying screening ages and frequencies. Single cohort modelling approaches were used for this step to identify the lifetime impacts of each screening strategy and cost-effective screening strategies. In step 2, strategies that appeared on the cost-effectiveness frontier from step 1 were selected to assess the long-term impact of scaling-up screening on ASR cancer incidence and mortality, cases and deaths, resource utilisation and projected financial costs nationwide (table 1). In addition to the scenarios that appeared at the cost-effectiveness frontier, we also included the WHO elimination strategy (twice per lifetime at ages 35, 45)17 in step 2.

Table 1

Screening strategies

### Screening compliance assumptions

We assumed 10% of women never attend screening in their lifetime for all scenarios. We assumed that 70% of women will attend routine screening at each invitation, selected from 90% of the population of ever-screeners. Given that treatment with ablation is performed on the same day, we assumed 5% lost to follow-up for ablation as this is consistent with experiences on-the-ground in PNG. 17

These assumptions on compliance with routine attendance were similar to the assumptions used in the modelling to support WHO’s updated cervical screening guidelines. However, for women referred to diagnostic services and for women who received treatment and need to attend post-treatment follow-up at 12 months, we assumed 50% lost to follow-up, based on local experience. For women who were referred for diagnostic evaluation for suspicion of cancer, we assumed a 30% lost to follow-up, due to limited facilities and difficulties in travel, particularly for rural women (see figure 1A,B).

### Screening test characteristics

The test characteristics for primary self-collected HPV testing were obtained from an international systematic review on the sensitivity and specificity of PCR-based HPV testing using self-collected samples as well as from the local trial of PoC HPV self-collected testing in PNG.32 The international systematic review has found that PCR self-collected HPV testing was as sensitive as clinician-collected HPV testing to detect CIN2+ (pooled relative ratio 0.99 (95% CI 0.97 to 1.02).32 Based on a local trial in PNG, Toliman et al found that self-collected HPV testing had sensitivity of 91.7% to detect high-grade lesions.6 Therefore, in this study, we took a conservative approach and assumed that HPV had sensitivity to CIN2 +of 91.7% and specificity of 89.8% in the base case, which is slightly lower than performance reported for clinician-collected HPV samples. We also considered 89.1% (lower bound) and 95.3% (upper bound) sensitivity to CIN2 +in sensitivity analysis. VIA test characteristics estimated from a screening trial in PNG was used in the base case analysis.6 The VIA screening trial in PNG involved ~1000 women and identified 51.5% sensitivity and 81.4% specificity to detect CIN2 +and this test performance was assumed in the model.6 This performance assumption for VIA is consistent with studies from India13 and Rwanda14 and consistent with the outcomes of large population-based experiences of VIA in India, in which VIA testing of 70 000 women over 12 years did not reduce the incident cancer, and only reduced mortality rates through stage-shifting.33 A more favourable sensitivity (70% sensitivity to CIN2+) of VIA testing inferred from international systematic review was also used in sensitivity analysis34 35 (table 2).

Table 2

Summary of model parameters for screening, diagnosis, and treatment procedures, and ranges for sensitivity analysis

### Vaccination assumptions

Although the PNG government is committed to HPV vaccine introduction and pilot HPV vaccine projects were completed in some provinces for schoolgirls some years ago,36 at this point a national HPV vaccination programme has not been recommended in PNG. In the first couple of decades after vaccination, most women over 30 years, and thus eligible for screening, will not be vaccinated. Therefore, in this analysis, we assumed that cervical screening strategies were conducted in women who have not received the HPV vaccine.

### Cancer treatment assumptions

The current infrastructure for cancer treatment in PNG is very limited, based on consultation with local experts. Only one radiotherapy treatment unit has been established, which was reported to be non-functional since 201537. We therefore assumed that radiotherapy access is limited and unreliable. We assumed that only radical hysterectomy (available in a few hospitals) was used for women with early-stage cancers. Given this situation, at base case analysis we assumed that 80% of cervical cancer diagnosed at International Federation of Gynaecology and Obstetrics (FIGO) stage I, 20% of those diagnosed at FIGO II would be treated with radical hysterectomy, those diagnosed at FIGO III and IV were not treated, and that these treatment rates did not vary for screen-detected or symptomatically detected cancers. The modelled distribution of cervical cancer stage in PNG was 14%, 55%, 27% and 3% for FIGO I, II, III and IV, respectively. Assuming 80% of FIGO I and 20% of FIGO II cancers receive treatment resulted in 80×14%+20×55%+0×27%+0×3%=20% of any diagnosed cancer would be treated in base case analysis, and therefore costs of cancer for these stages were adjusted accordingly. Our survival inputs produced similar mortality rates to those reported in GLOBOCAN2018 for PNG1 (online supplemental figure A2 (B)). We also considered lower (8%) and higher (90%) cancer treatment access rates in sensitivity analysis. (more details in online supplemental appendix 1, part 3. Cancer treatment access rate and survival assumptions)

### Budget impact and profile of financial costs associated with screening, diagnosis and treatment using self-collected HPV S&T modality

Without a cervical screening programme, it was estimated that total 5-year and 10-year undiscounted financial costs of ~US1.9 million and US$3.8 million, respectively would be spent on diagnosis and treatment of cervical cancer, due to the limited amount of treatment available for cervical cancer (table 4B). If a national cervical screening programme were to be implemented, there would be additional costs incurred for HPV testing, visual assessment for ablation, and precancer treatment and cancer treatment. We estimated that the total undiscounted 5-year financial costs (2023–2027) for cervical cancer screening, diagnosis and treatment would range from ~US$6.9 million (once lifetime screening) to US$24.8 million (5-yearly (6X lifetime) screening) (table 4B). For the WHO’s ‘elimination strategy’ (twice lifetime screening at age 35 and 45 years), the total 5-year cost would be about US$10.2 million, which averages to US$2.1 million per annum. The cost of the HPV test alone contributed the largest amount to the total 5-year cost, ranging from ~US$3.7 million (53% of total cost, once lifetime) to ~US$17.4 million (70% of total cost, 5-yearly (6X) screening) (figure 4A,B). The costs of treatment for lesions ineligible for ablation and early-stage cancer contributed the second largest cost category, which ranged from US$2.7 million (38% of the total cost, once lifetime) to US$4.9 million (20% of the total cost, 5-yearly (6X) screening). The 10-year budget was approximately double that of the 5-year budget, noting slight differences generated because of the impact of screening as it is introduced over time. On average, estimated undiscounted financial costs over a lifetime per women screened ranged from US$25 per woman (5-yearly screening) to US$40/woman (once lifetime) (data not shown). Figure 4 Budget impact and cost profile associated with cervical cancer screening, diagnosis and treatment in PNGNote: Budget was calculated as the financial costs (US$, 2019) of cost-effective screening strategies. This budget is a broad estimate of that required for a future national cervical cancer screening programme in PNG (inflation was not considered). The United Nations population structure estimated for PNG (year 2020) was used and assumed this population structure remained over 2023–2032 to estimate budget. PNG, Papua New Guinea; S&T, screen and treat.

Assumptions around screening coverage and loss to follow-up rates after treatment are the most influential factors on the ASR incidence rates (online supplemental figure A7). In terms of CEA, 0% discount rate for effect, lower self-collected HPV S&T test cost (US$8/test), lower screening coverage, and lower (8%) cancer treatment access rate generally result in reduced ICERs compared with the base case. In contrast, higher screening coverage, higher cancer treatment costs, and a higher assumed cancer treatment access rate (90%) resulted in higher ICERs in almost all strategies (online supplemental table A4). It should be noted that under the (currently counter factual) 90% cancer treatment access assumption, 5-yearly (6X) self-collected HPV S&T screening would not be considered cost-effective at either 1GDPpc or 0.5GDPpc in PNG, however, thrice lifetime screening remained cost-effective at both thresholds in this high cancer treatment scenario. ## Discussion We evaluated the long-term impact of national scale-up of self-collected HPV S&T modality using local field data and found that self-collected HPV S&T was highly effective and cost-effective in PNG when screening up to thrice in a lifetime from age 30 years. Rapid scale-up twice or thrice per lifetime self-collected HPV S&T strategies were cost-effective and could prevent tens of thousands of deaths over the next 50 years. In contrast, primary VIA screening was substantially less effective and was not cost-effective, even when assuming favourable assumptions about test performance for VIA. Our findings were consistent with our modelled evaluations that informed WHO’s updated cervical screening guidelines, which found that primary HPV testing was cost-effective at an average across 78 LMICs.17 These findings were also consistent with previous published literature on the effectiveness and cost-effectiveness of PoC HPV screen and treat modality in a modelling study on HPV screening in LMICs: Based on data from demonstration projects in Nicaragua, India and Uganda, a modelling study using the Harvard model42 found that PoC-HPV screen and treat modality would be value-for-money in settings with high lost to follow-up rates and the same-day-treatment availability.42 Our findings about the efficacy of HPV screening in this setting are consistent with results from other modelled evaluations considering HPV self-collection, based on data from ASPIRE and START-UP trials in Uganda.43 44 In our study, we found that twice lifetime screening at age 35 and 45 (the WHO screening age and frequency recommendation for cervical cancer elimination) with self-collected HPV S&T can prevent over 20 000 deaths after 50 years of achieving 70% screening coverage in PNG. In comparison, previous work has shown that twice lifetime screening at age 35 and 45 in addition to 90% HPV vaccination coverage in adolescent females and 90% cancer treatment access (the triple-intervention strategy recommended by WHO) would avert twice as many deaths (42 000) after 50 years in PNG, mostly due to the additional benefits of scaled-up access to cervical cancer treatment.2 We showed that once a national screening programme was established in PNG, a population of under 10 million people, its average annual costs of HPV screening (for thrice lifetime screening) over the first 5 years would be US$3.3 million per annum, including the costs of HPV screening and precancer and cancer treatment. In terms of preparedness for the national HPV screening programme, PNG needs to secure more than 100 000 HPV tests (for thrice lifetime screening) annually over the first 5 years of scaling-up to 70% coverage across the whole population of age-eligible women. In preparation for the full-scale programme roll-out, the health system also needs to improve capacity to provide adequate colposcopy, biopsy and cancer treatment services for more than 1000 women annually who would be diagnosed with cervical cancer and would therefore require cancer treatment and care. Additionally, PNG also needs to provide up to 16000 ablative treatment (for thrice lifetime screening) annually for women who would be detected with eligible cervical precancerous lesions. These estimates will support major new implementation effort in the Western Pacific to scale up HPV vaccination, screen- and-treat, and cancer treatment services towards achieving cervical cancer elimination in PNG and more broadly in the region (ECCWP), a collaboration between C4 and the Minderoo foundation.45

In this study, we found that cost of HPV testing accounted for over 50% of the total costs associated with screening, diagnosis and treatment. The current cost of HPV screening used in this model were based on a field trial of self-collected HPV S&T in PNG, and we made the assumption that this cost would be the same (US\$18/test) under national roll-out. However, this cost may reduce for a national screening programme, due to HPV test market shaping and pricing negotiations and lower programme costs when the screening is integrated in the existing health system, which would improve cost-effectiveness as shown in our sensitivity analysis. Given the limited facilities in PNG for cancer diagnosis and treatment, lost to follow-up rates at diagnosis were high and we assumed that late-stage cancers were not treated in the base case. If cancer treatment services for women can be scaled-up in line with the WHO targets for increasing cancer treatment and care, for instance, by increasing radiotherapy services, costs associated with cancer treatment will increase, and deaths associated with cervical cancer would decline. In this case, our sensitivity analysis showed that self-collected HPV S&T remained cost-effective.

There are several limitations to this study. Data sources on the burden of disease for PNG is limited. Cervical cancer incidence and mortality assumptions were based on GLOBOCAN2018 estimates. Because a population-based cancer registry has not been established in PNG, the GLOBOCAN’s estimate utilised data from neighbouring countries in the region.46 For cancer treatment access rates, we incorporated local expert information on the availability of hysterectomy for early-stage cancers (table 2) and mortality rates were compared well against GLOBOCAN2018 estimates (online supplemental figure A2 (B)). We also assumed that screening could be scaled up rapidly to reach 70% coverage nationally. There will be many challenges to scale-up screening rapidly in lower-resource settings, particularly challenges for scaling-up screening in hard-to-reach rural areas.

This study has many strengths. First, the Policy1-Cervix model has been extensively validated across a range of settings and used to evaluate various cervical screening strategies for many countries. It has been explicitly used to evaluate policy questions for some high-income countries19 21 and was the sole model to be used to evaluate the benefits, harms and cost-effectiveness of cervical screening algorithms to inform WHO updated 2021 cervical screening guidelines.17 The model was one of three models used by the CCEMC to assess the impacts of cervical cancer elimination strategies on cervical cancer incidence and mortality to inform the WHO global strategy towards cervical cancer elimination.2 29 This model incorporated data on cervical cancer incidence and mortality from GLOBOCAN 2018 and local data on age-specific and type-specific HPV prevalence was used. Second, key model inputs, including loss-to follow-up rates and costing data were derived from the self-collected HPV S&T trial that are currently being conducted in PNG. Third, the ‘screen and treat’ management pathway was consistent with new 2021 WHO cervical screening recommendations and we evaluated it in context of data from local field screening experience and consultation with local experts.

Findings of our study support the WHO strategy for cervical cancer elimination that investing in interventions to meet the 90-70-90 targets offers immense economic and societal benefits. These findings will support major new implementation effort in the Western Pacific to scale up HPV vaccination, screen- and-treat, and cancer treatment services towards achieving cervical cancer elimination in PNG and more broadly in the region (ECCWP).45 However, given the limitations on human resource and infrastructure of the existing health system in PNG, particularly for cervical cancer screening, diagnosis and treatment, in order to scale up cervical screening nationwide, the country would need to develop a cervical screening programme and integrate this screening with the existing primary healthcare services. More importantly, investment in infrastructure and human resource for radiotherapy is needed, which would improve survival across all cancers and not just cervical cancer. A range of practical steps to implement cervical cancer screening and precancer treatment have been developed by WHO.47 The understanding of social, cultural, and religious barriers are crucial to establish referral systems that connect all screening, diagnosis and treatment services, as recommended by the WHO.16

In the 2014 WHO cervical cancer screening guidelines, primary HPV testing was recommended and VIA testing was recommended as an alternative for low-resource settings.5 The recently updated 2021 WHO guidelines now recommend all countries consider primary HPV testing.17 The local experience of self-collected HPV S&T modality has shown that primary HPV testing is feasible and acceptable in PNG, and here we demonstrated that it is also more effective and cost-effective than primary VIA screening; together these findings support the updated 2021 WHO cervical screening guidelines. Our findings are highly relevant for other low-income countries considering screen-and-treat modalities for primary HPV screening.

## Data availability statement

Data sharing is not applicable.

• ## Supplementary Data

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

## Footnotes

• Handling editor Seye Abimbola