The COVID-19 problem

Optimising cervical screening involves finding a set of recommendations—on the target age range, screening interval, and clinical follow-up after positive screens—that balances minimising the population risk of disease with the impact on resources, costs, and quality of life. Re-establishing screening in response to the COVID-19 disruption requires the same considerations, but changes in resource availability and in women's willingness and ability to undergo screening should also be taken into account.

Disruption to primary screening during 2020 means that many women might now be overdue for screening. Diagnostic follow-up and surveillance activities have been disrupted too, delaying investigation for individuals known to be at high risk. Even where services have resumed, capacity might be reduced due to the need for social distancing and additional time associated with using personal protective equipment.

COVID-19 also imposes indirect capacity constraints when consumables, equipment, and staff used in screening are redeployed to tackling the pandemic.7American Society for Microbiology
Supply shortages impacting COVID-19 and non-COVID testing. Tests for human papillomavirus (HPV) and COVID-19 have reagents and consumables in common, meaning they compete for limited resources. In Canada, for example, the pandemic has diverted common screening and laboratory resources to COVID-19 testing, causing potential delays to the roll-out of primary HPV testing in different provinces and territories (Peacock S, unpublished).

Ideally, programmes would resolve the backlog of deferred screening and diagnostic appointments by temporarily expanding capacity. Although this approach might be possible to an extent in programmes that use primary HPV testing (because testing is largely automated), key components of any screening programme, such as cytology and colposcopy, require a skilled workforce that cannot be expanded quickly and, therefore, represent system bottlenecks. Even where screening staff have responded to the capacity challenge by working overtime, the potential for burnout means that this is only a limited solution.

Although high levels of screening activity could be seen as evidence of a successful re-commencement of the programme, focusing on re-establishing services without considering how best to target capacity runs the risk of overwhelming the system, while failing to maximise the desired outcome of cancer prevention. Instead, if those responsible for screening policy are willing to prioritise individuals at highest risk during the recovery phase, then they are likely to better ameliorate the long-term consequences of COVID-19. Nevertheless, prioritisation of constrained capacity requires trade-offs, and those trade-offs are always associated with opportunity costs. Prioritising services for women at highest risk might require an increase in the interval between screens for some women at low risk. Another available policy lever to achieve risk-based prioritisation of scarce capacity is to use targeted screening awareness campaigns to encourage re-engagement of specific groups of women, as programmes recover.

Relevance of contextDue to several unique characteristics (eg, the very long detectable pre-invasive phase),8Human papillomavirus infection and the multistage carcinogenesis of cervical cancer. it is expected that cervical cancer will be less affected by screening delays related to COVID-19 than will breast or colorectal cancers. In most cases, cervical cancer screening works by preventing cancer from developing at all by identifying and treating precancerous lesions. In high-income countries, the long-standing availability of cervical cancer screening and the introduction of population-based HPV vaccination in the late 2000s have decreased the absolute burden of disease well below that of breast and bowel cancer.10Ferlay J Ervik M Lam F et al.Estimated number of new cases in 2020, worldwide, both sexes, all ages. Nevertheless, the current disruption associated with the pandemic threatens to derail WHO's global strategy to accelerate the elimination of cervical cancer as a public health problem.11WHO
WHO leads the way towards the elimination of cervical cancer as a public health concern. Screening and the timely treatment of any detected disease form two of the three pillars of this strategy.Cervical cancer screening programmes have always differed in various ways. For example, on one hand, Norway, Sweden, Italy, the UK,12Partanen VM Heinävaara S Waldstrøm M et al.Adherence to international recommendations in the governance and organisation of Nordic cervical cancer screening programmes., 13Ponti A Antilla A Ronco G et al.Cancer screening in the European Union. and Australia14Australian GovernmentDepartment of Health
About the National Cervical Screening Program. have introduced population-based screening programmes with organised call–recall systems relying on registries for information on the women's previous screening history. On the other hand, countries such as Japan and Germany do not have national screening registries and instead operate on an opportunistic basis.13Ponti A Antilla A Ronco G et al.Cancer screening in the European Union., 15Sauvaget C Nishino Y Konno R Tase T Morimoto T Hisamichi S Challenges in breast and cervical cancer control in Japan. Some programmes have mainly offered screening through primary care, whereas others have delivered it through specialist services, such as gynaecology.12Partanen VM Heinävaara S Waldstrøm M et al.Adherence to international recommendations in the governance and organisation of Nordic cervical cancer screening programmes., 16Perception of cervical cancer screening among Japanese university students who have never had a pap smear: a qualitative study. Some programmes have started replacing cytology with HPV testing as the primary screening method. This approach has affected the laboratory landscape; for example, HPV testing is completed in an automated way that allows for economies of scale and larger laboratories with smaller workforces.17Public Health England
Cervical screening: implementation guide for primary HPV screening. Furthermore, this approach has defined new triage processes,18Rijkaart DC Berkhof J van Kemenade FJ et al.Evaluation of 14 triage strategies for HPV DNA-positive women in population-based cervical screening. which tend to be complex. Currently, there is no single-triage approach that stratifies risk sufficiently to allow an immediate binary decision between either colposcopy referral or a return to routine screening following a primary HPV-positive test.19Cuschieri K Ronco G Lorincz A et al.Eurogin roadmap 2017: Triage strategies for the management of HPV-positive women in cervical screening programs. Hence, follow-up of HPV-positive women with triage findings of low severity (eg, negative cytology or infection with HPV types other than 16 or 18) often involves surveillance that might span several years before a decision is made whether to refer the individual to diagnostic colposcopy or to return them to routine screening. In cytology-based programmes, the proportion of women in this intermediate group under surveillance tends to be small or might not even exist at all.20Burger EA Jansen EE Killen J et al.Impact of COVID-19-related care disruptions on cervical cancer screening in the United States.In countries with cytology-based screening programmes, test sensitivity has been shown to be highly variable.21Cuzick J Clavel C Petry KU et al.Overview of the European and North American studies on HPV testing in primary cervical cancer screening. In particular, test performance depends on the quality of training of cytology specialists and the quality assurance of the laboratory testing. Programmes also differ in terms of participation, both in primary screening and in follow-up, which is often related to whether or not personal invitations to screen are offered.22Pierce M Lundy S Palanisamy A Winning S King J Prospective randomised controlled trial of methods of call and recall for cervical cytology screening., 23Kim JJ Leung GM Woo PP Goldie SJ Cost-effectiveness of organized versus opportunistic cervical cytology screening in Hong Kong. Programmes with lower coverage will have less impact on cervical cancer incidence than will those with higher coverage. Consequently, where participation had already been low before the pandemic, the COVID-19 disruption will probably have a smaller negative impact than in programmes with good screening participation, in which the gains from screening had been higher.

Organisation and screening performance will influence how resilient a screening programme can be to the COVID-19 disruption, and what the feasible or optimal policy response might be. The heterogeneity of the programmes, as well as the health-care systems in which they function, probably means that there is no single optimal policy response for all countries.

Optimising responsesSome settings have resumed their screening services. Comparing testing volumes before and after the pandemic might provide high-level insights into how many women have missed screening visits; however, this metric will neither reveal nor ensure that those women at highest risk or the most susceptible to cervical cancer are being screened. Potential recovery strategies and their differing advantages and disadvantages are summarised in the table.

TablePotential recovery strategies for resuming routine cervical screening during the COVID-19 pandemic and their differing advantages and disadvantages

Strategies are not exclusive of each other. HPV=human papillomavirus.

To prioritise effectively, a better understanding of the underlying disease risks among groups of women who are less likely to resume attending their screening or follow-up appointments is essential. Immunosuppressed women, such as organ transplant recipients, who are shielding due to COVID-19 are at increased risk of developing cervical (pre)cancer.25Hinten F Meeuwis KA van Rossum MM de Hullu JA HPV-related (pre)malignancies of the female anogenital tract in renal transplant recipients., 26Grulich AE van Leeuwen MT Falster MO Vajdic CM Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Women from an economically disadvantaged background are also at higher risk of developing COVID-19 due to circumstances such as crowded housing or employment that either cannot be done from home or, often, is done in places where it is difficult to maintain physical distance.27Chang S Pierson E Koh PW et al.Mobility network models of COVID-19 explain inequities and inform reopening. Even before the pandemic, these women were less likely to be screened according to best practice protocol, more likely to miss screening, and more likely to harbour cervical lesions requiring treatment than were women from higher socioeconomic groups.28The social distribution of cancer in Copenhagen, 1943 to 1947., 29Broberg G Wang J Östberg AL et al.Socio-economic and demographic determinants affecting participation in the Swedish cervical screening program: a population-based case-control study., 30NHMRC Centre of Research Excellence in Cervical Cancer Control
Cervical Cancer Elimination Progress Report: Australia's progress towards the elimination of cervical cancer as a public health problem. The hardship imposed by COVID-19 due to, for example, loss of employment and insurance, an increasing difficulty in being able to secure a face-to-face appointment in primary care, and a temporarily decreased focus on non-COVID-19 preventive health, might push screening participation further down the individual's priority list. Identifying and engaging these women in the recovery phase will be challenging and will probably require more thoughtful communication strategies than just simple reminders.31Ciavattini A Delli Carpini G Giannella L et al.European Federation for Colposcopy (EFC) and European Society of Gynaecological Oncology (ESGO) joint considerations about human papillomavirus (HPV) vaccination, screening programs, colposcopy, and surgery during and after the COVID-19 pandemic., 32Smith M Hall M Simms K et al.Modelled analysis of hypothetical impacts of COVID-19 related disruptions on the National Cervical Screening Program.

Programmes that have relied on personalised invitations are in a good position to adopt a targeted reintroduction of testing. In this case, the optimal allocation of scarce testing capacity could start with extending invitations to women who are most likely to benefit from early detection. For example, invitations could be first extended to women who were under surveillance because they had a positive test but an insufficient risk to merit colposcopy before the start of the pandemic. Alternatively, prioritisation could be made on the basis of the recorded screening history, if personalised records included pathology results. If this information is not available, prioritisation could be made simply on the time since the previous test.

Many screening services, even those with robust screening databases, might find it difficult to identify and prioritise patients by risk profile. In that case, the most straightforward way to deliver a risk-based recovery strategy could be to prioritise by age. In most settings, information on age is readily available at the point of care. A modelling study of COVID-19-related delays in Australia found that an excess of cervical cancer diagnoses will be most frequent among women aged 30–49 years,32Smith M Hall M Simms K et al.Modelled analysis of hypothetical impacts of COVID-19 related disruptions on the National Cervical Screening Program. consistent with the age range at which most countries with screening programmes observe peak cervical cancer incidence.33Larønningen S Ferlay J Bray F et al.NORDCAN: cancer incidence, mortality, prevalence and survival in the Nordic countries. Furthermore, targeting underscreened women who surpassed the upper age of screening for a so-called exit test (usually aged 60–65 years) because of COVID-19-related delays might provide important gains in mitigating the excess cancer burden.34Wang J Andrae B Sundström K et al.Effectiveness of cervical screening after age 60 years according to screening history: nationwide cohort study in Sweden., 35Malagón T Kulasingam S Mayrand MH et al.Age at last screening and remaining lifetime risk of cervical cancer in older, unvaccinated, HPV-negative women: a modelling study.Targeting by age group also enables effective media buying and development of material for promotional campaigns, which could be used to supplement, or as an alternative to, personal invitations (eg, as used in Australia).36Feletto E Grogan P Dickson C Smith M Canfell K How has COVID-19 impacted cancer screening? Adaptation of services and the future outlook in Australia. Another option is to target women in geographical areas known to have low screening participation and high levels of deprivation through tailored awareness campaigns.If information on vaccination is available to screening programmes, recovery should further prioritise screening of non-vaccinated women younger than 50 years, given that the difference in the risk of cervical cancer between vaccinated and unvaccinated cohorts is so large.37Ronco G Dillner J Elfström KM et al.Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials., 38Lei J Ploner A Elfström KM et al.HPV vaccination and the risk of invasive cervical cancer. Offering vaccination to women aged 26 years and older is not recommended because it is likely to have a marginal benefit in terms of cancer prevention and represents poor value for money.39Laprise JF Chesson HW Markowitz LE et al.Effectiveness and cost-effectiveness of human papillomavirus vaccination through age 45 years in the United States., 40Kim JJ Simms KT Killen J et al.Human papillomavirus vaccination for adults aged 30 to 45 years in the United States: a cost-effectiveness analysis.A negative screening test does not prevent cervical cancer; instead, it indicates a low risk of it developing in the near future. The risk of cervical cancer following a negative test increases with time since the most recent test; therefore, screening needs to be repeated at regular intervals.41Sasieni P Adams J Cuzick J Benefit of cervical screening at different ages: evidence from the UK audit of screening histories., 42Elfström KM Smelov V Johansson AL et al.Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial. Nevertheless, when trade-offs need to be made during the recovery period, a small extension in the screening interval for previously well screened women will have a small impact on their risk of cervical cancer compared with what could be achieved by increasing participation among women who have been underscreened for longer.43Koopmanschap MA van Oortmarssen GJ van Agt HM van Ballegooijen M Habbema JD Lubbe KT Cervical-cancer screening: attendance and cost-effectiveness. A temporary relaxation of the screening frequency to prioritise life-long coverage in a screening service with constrained capacity will mitigate the impact among women who are underscreened.44Castanon A Rebolj M Pesola F Sasieni P Recovery strategies following COVID-19 disruption to cervical cancer screening and their impact on excess diagnoses.The risks associated with a (temporary) extension of the screening interval are inversely related to screening test sensitivity. Because the negative predictive value of a HPV test is higher than that of cytology,21Cuzick J Clavel C Petry KU et al.Overview of the European and North American studies on HPV testing in primary cervical cancer screening., 37Ronco G Dillner J Elfström KM et al.Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials., 45Dillner J Rebolj M Birembaut P et al.Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. extending the interval from 5 years to 6 years for women who had a recent negative HPV test will carry a lower excess risk of cervical cancer than will extending a typical interval of 3 years to 4 years after a negative test in a cytology-based programme.20Burger EA Jansen EE Killen J et al.Impact of COVID-19-related care disruptions on cervical cancer screening in the United States. From this perspective, settings in which women had a HPV test as their most recent screening test will be more resilient to the delays caused by COVID-19. However, settings in which HPV screening intervals are set at more than 5 years46Dijkstra MG van Zummeren M Rozendaal L et al.Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands. might find that they are less able to absorb a deintensification of screening for women screened as recommended, particularly when compared with HPV-based programmes that recommend relatively intensive screening with an early starting age and short intervals (47Fontham ETH Wolf AMD Church TR et al.Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society.

The effects of small extensions to screening intervals will vary between settings, depending on factors including the testing technology used, test performance achieved, programme intervals, and disease incidence. Decision makers responsible for screening policy will need to interpret the benefits of interval extension within their local context.

For cancer screening to achieve its goal, screen-detected abnormalities must be appropriately followed up.48Arbyn M Anttila A Jordan J et al.European guidelines for quality assurance in cervical cancer screening. Second edition—summary document. Cervical cytology results of severe dyskaryosis (equivalent to high-grade squamous intraepithelial lesions) or worse have a sensitivity of 78·1% and a positive predictive value of 5·3% to detect prevalent cervical cancer.49Landy R Castanon A Hamilton W et al.Evaluating cytology for the detection of invasive cervical cancer. Therefore, when colposcopy capacity is constrained, there is a need to prioritise appointments by the outcome of the screening test result to ensure that individuals with suspected cancer are seen as soon as possible (eg, within 4 weeks), followed by those with high-grade abnormal primary screening tests (eg, within 1–3 months). By contrast, appointments for women with low-grade abnormalities can be delayed for longer (eg, up to 6–12 months).31Ciavattini A Delli Carpini G Giannella L et al.European Federation for Colposcopy (EFC) and European Society of Gynaecological Oncology (ESGO) joint considerations about human papillomavirus (HPV) vaccination, screening programs, colposcopy, and surgery during and after the COVID-19 pandemic.The deployment of HPV-self sampling50Smith MA Hall MT Saville M et al.Could HPV testing on self-collected samples be routinely used in an organised cervical screening program? A modelled analysis. might provide an effective recovery strategy to increase the number of women to whom screening is offered during or following disruptions to screening, while minimising the demands on the capacity needed to take screening samples. Self-sampling might increase screening participation in underscreened women or among women who have missed appointments due to fears of being exposed to SARS-CoV-2 in transit to, or at, their local health-care facility. In the Netherlands, the availability of self-sampling as an alternative to booking a clinician appointment has been highlighted in invitation letters since November, 2020. Preliminary information suggests that the number of screening self-samples received at laboratories has doubled and overall screening participation has largely recovered, even though the number of clinician-taken tests remains low (van Dijk S, Centre for Population Screening, Dutch National Institute for Public Health and the Environment, personal communication).Several points related to self-sampling require consideration. HPV testing competes for reagents used for testing COVID-19. Although evidence suggests that the sensitivity of PCR-based tests on self-collected samples is consistent across various self-sampling devices,51Arbyn M Smith SB Temin S Sultana F Castle P Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses. in some countries, the available self-sampling devices have not yet been formally approved for use in cervical screening. Furthermore, few (if any) preanalytical laboratory protocols for self-sampling devices are automated (eg, dry swabs need to be resuspended). Few device or assay combinations are designed for medium-to-high throughput testing, meaning that their processing is more labour-intensive and time-consuming than is the processing of clinician-taken samples.52Hawkes D Keung MHT Huang Y et al.Self-collection for cervical screening programs: from research to reality. Thus, even in programmes that have already switched to HPV testing, a large-scale roll-out of self-sampling would require infrastructure that most programmes do not have readily available. Additionally, triage is required for women who are HPV-positive, and, at present, there are no clinically validated molecular biomarkers that could expedite triage on a self-sample. Women with positive self-samples will usually be recommended to have a sample taken in primary care so that it can be processed for cytology reading because cytology assessment cannot be done directly from the self-sample. These caveats suggest that self-sampling might not be a realistic strategy to rapidly scale up during this pandemic; however, it is certainly a promising option for the future.52Hawkes D Keung MHT Huang Y et al.Self-collection for cervical screening programs: from research to reality.

An important caveat to the COVID-19 responses considered here is that they are considered in a high-income country context. Low-income and middle-income countries typically do not have the advantage of high-quality, population-wide cervical screening programmes supported by screening databases. Accordingly, where population screening does exist, the challenges are likely to be all the greater. Nevertheless, the broad principles of the strategies outlined in this Viewpoint will still apply—namely, targeting scarce capacity at individuals in greatest need and prioritising coverage over intensity.

In time, research will be required on what policy choices decision makers in charge of cervical screening ultimately take and what the consequences are for processes and health outcomes. This work will need to consider the relevance of context and the distributional consequences of policy responses. We hope that the considerations outlined in this Viewpoint might help to inform such research.

AC, MR, EAB, IMCMdK, MAS, SJBH, and JFOM conceptualised this Viewpoint. AC was responsible for project administration and wrote the original draft. MR, EAB, IMCMdK, MAS, SJBH, FMC, SP, and JFOM wrote, reviewed, and edited subsequent versions of the manuscript. All authors approved the final manuscript and were responsible for the decision to submit for publication.