Invasive Cervical Cancer Detection After Transition to Primary Human Papillomavirus Screening: Population-Based Linkage Study in Portugal
DOI:
https://doi.org/10.20344/amp.24709Keywords:
Early Detection of Cancer, Medical Record Linkage, Papillomaviridae, Papillomavirus Infections/diagnosis, Uterine Cervical Dysplasia/diagnosis, Uterine Cervical Neoplasms/diagnosisAbstract
Introduction: Invasive cervical cancer (ICC) is a key outcome for evaluating cervical cancer screening (CCS) programs. Monitoring ICC trends and distinguishing cancers detected within and outside the organized screening program are essential for assessing program impact, particularly during transitions such as the introduction of human papillomavirus (HPV) based primary screening.
Methods: We conducted a retrospective population-based study in Portugal’s Central Region (2014 - 2023). Deterministic linkage was performed between the organized CCS database and hospital morbidity records. Invasive cervical cancer cases were classified as screen-detected or non-screen-detected based on prior screening history. Incidence rates were calculated using population denominators. Poisson regression models with log link and log-transformed population offsets were fitted to estimate incidence rate ratios (IRR) comparing cytology-based (2014 - 2019) and HPV-based (2020 - 2023) periods, adjusting for temporal trends.
Results: A total of 654 ICC cases were included. Screening participation remained broadly stable over time. The HPV-based period was associated with a significantly higher rate of screen-detected ICC (IRR = 1.94; 95% CI 1.11 - 3.40) compared with the cytology period. In contrast, ICC incidence outside the organized screening program did not differ significantly between periods (IRR = 0.94; 95% CI 0.65 - 1.35).
Conclusion: The transition to HPV-based primary screening was associated with a shift in ICC detection towards the organized screening program, without evidence of a corresponding increase in incidence among women diagnosed outside the organized screening program. These findings should, however, be interpreted with caution in light of the early phase of implementation and potential external factors influencing access to diagnosis. Overall, the results support a shift in detection within the screening pathway rather than changes in underlying disease occurrence. Strengthening integration between screening, hospital, and cancer registry data remains essential for robust evaluation of cervical cancer screening policies.
Downloads
References
Anttila A, Arbyn M, De Vuyst H, Dillner J, Dillner L, Franceschi S, et al. European guidelines for quality assurance in cervical cancer screening. 2015. [cited 2015 Aug 21]. Available from: https://op.europa.eu/en/publication-detail/-/publication/a41a4c40-0626-4556-af5b-2619dd1d5ddc.
Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383:524-32.
Gilham C, Sargent A, Kitchener HC, Peto J. HPV testing compared with routine cytology in cervical screening: long-term follow-up of ARTISTIC RCT. Health Technol Assess. 2019;23:1-43.
Ogilvie GS, Krajden M, van Niekerk D, Smith LW, Cook D, Ceballos K, et al. HPV for cervical cancer screening (HPV FOCAL): complete round 1 results of a randomized trial comparing HPV-based primary screening to liquid-based cytology for cervical cancer. Int J Cancer. 2017;140:440-8.
Wang J, Elfström KM, Dillner J. Human papillomavirus-based cervical screening and long-term cervical cancer risk: a randomised health-care policy trial in Sweden. Lancet Public Health. 2024;9:e886-95.
Real O, Silva D, Leitão MA, Oliveira HM, Rocha Alves JG. Cervical cancer screening in the central region of Portugal. Eur J Cancer. 2000;36:2247-9.
da Silva DP, Real O. Rastreio do cancro do colo. Programa da Região Centro de Portugal. Acta Med Port. 1997;10:643-52.
Dinis J, Portugal C, Sousa N, Fernandes I, Netto E. DGS-avaliação e monitorização dos rastreios oncológicos organizados de base populacional | 2019/2020. Lisboa: Direção-Geral da Saúde; 2021.
World Health Organization. Global strategy to accelerate the elimination of cervical cancer as a public health problem. 2020. [cited 2020 Nov 17] Available from: https://iris.who.int/server/api/core/bitstreams/4e245e89-ddcc-488f-97c7-9de5e08524ef/content.
European Comission. Review of Europe’s Beating Cancer Plan. 2025. [cited 2025 Feb 04]. Available from: https://health.ec.europa.eu/latest-updates/review-europes-beating-cancer-plan-2025-02-04_en.
Pankakoski M, Sarkeala T, Anttila A, Heinävaara S. Effectiveness of cervical testing in and outside a screening program—a case-control study. Cancers. 2022;14:5193.
Heinig M, Schäfer W, Langner I, Zeeb H, Haug U. German mammography screening program: adherence, characteristics of (non-)participants and utilization of non-screening mammography—a longitudinal analysis. BMC Public Health. 2023;23:1678.
Middeldorp M, Brouwer JG, Duijster JW, Knol MJ, Kemenade FJ, Siebers AG, et al. The effect of bivalent HPV vaccination against invasive cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3+) in the Netherlands: a population-based linkage study. Lancet Reg Health Eur. 2025;54:10327.
Castañeda KM, Vermeulen KM, van der Aa M, Schuuring E, Wisman GB, de Bock GH. Trends in cervical cancer incidence in the Netherlands: a join-point and age–period–cohort analysis (1989–2023). Int J Cancer. 2026;158:39-44.
Lew J Bin, Simms KT, Smith MA, Hall M, Kang YJ, Xu XM, et al. Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National Cervical Screening Program. Lancet Public Health. 2017;2:e96-107.
Wang J, Miriam Elfström K, Lagheden C, Eklund C, Sundström, Sparén P, et al. Impact of cervical screening by human papillomavirus genotype: Population-based estimations. PLoS Med. 2023;20:e1004304.
Vahteristo M, Leinonen MK, Sarkeala T, Anttila A, Heinävaara S. Similar effectiveness with primary HPV and cytology screening - long-term follow-up of randomized cervical cancer screening trial. Gynecol Oncol. 2024;180:146-51.
Vyas A, Kamat S, Oh J. Rhode Island (RI) women’s breast cancer mammography use prior to and after cancer diagnosis: linkage of RI cancer registry data with RI all-payer claims database. J Public Health Manag Pract. 2024;30:e65-73.
Li Y, Hall M, Fisher BT, Seif AE, Huang YS, Bagatell R, et al. Merging children’s oncology group data with an external administrative database using indirect patient identifiers: a report from the children’s oncology group. PLoS One. 2015;10:e0143480.
Mullangi S, Aviki EM, Chen Y, Robson M, Hershman DL. Factors associated with cancer treatment delay among patients diagnosed with COVID-19. JAMA Netw Open. 2022;5:e2224296.
Carcopino X, Cruickshank M, Leeson S, Redman C, Nieminen P. The impact of COVID-19 pandemic on screening programs for cervical cancer prevention across Europe. J Low Genit Tract Dis. 2022;26:219-22.
Morais S, Antunes L, Rodrigues J, Fontes F, Bento MJ, Lunet N. The impact of the coronavirus disease 2019 pandemic on the diagnosis and treatment of cancer in Northern Portugal. Eur J Cancer Prev. 2022;31:204-14.
Statistics Portugal. [cited 2026 Jan 28]. Available from: http://www.ine.pt.
FIRST Group. SiiMA Rastreios. [cited 2026 Jan 28]. Available from: http://www.first-global.com/en-us/solutions/rastreios/cervical-cancer-screening.
Fung KW, Xu J, Bodenreider O. The new international classification of diseases 11th edition: a comparative analysis with ICD-10 and ICD-10-CM. J Am Med Inform Assoc. 2020;27:738-746.
Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Dalla Palma P, Del Mistro A, et al. Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol. 2010;11:249-57.
Hammer A, Demarco M, Campos N, Befano B, Gravitt PE, Cheung L, et al. A study of the risks of CIN3+ detection after multiple rounds of HPV testing: results of the 15-year cervical cancer screening experience at Kaiser Permanente Northern California. Int J Cancer. 2020;147:1612-20.
Fujita M, Nagashima K, Suzuki K, Kasai T, Hashimoto H, Yamaguchi K, et al. Changes in the number of cancer diagnosis practices due to the COVID-19 pandemic: interrupted time-series analysis using the National Database of Japan. J Cancer Res Clin Oncol. 2023;149:6023-33.
Májek O, Anttila A, Arbyn M, Van Veen E Ben, Engesæter B, Lönnberg S. The legal framework for European cervical cancer screening programmes. Eur J Public Health. 2019;29:345-50.
Wen B, Zhang G, Zhan C, Chen C, Yi H. The 2024 revision of the Declaration of Helsinki: a modern ethical framework for medical research. Postgrad Med J. 2025;101:371-382.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Acta Médica Portuguesa

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All the articles published in the AMP are open access and comply with the requirements of funding agencies or academic institutions. The AMP is governed by the terms of the Creative Commons ‘Attribution – Non-Commercial Use - (CC-BY-NC)’ license, regarding the use by third parties.
It is the author’s responsibility to obtain approval for the reproduction of figures, tables, etc. from other publications.
Upon acceptance of an article for publication, the authors will be asked to complete the ICMJE “Copyright Liability and Copyright Sharing Statement “(http://www.actamedicaportuguesa.com/info/AMP-NormasPublicacao.pdf) and the “Declaration of Potential Conflicts of Interest” (http:// www.icmje.org/conflicts-of-interest). An e-mail will be sent to the corresponding author to acknowledge receipt of the manuscript.
After publication, the authors are authorised to make their articles available in repositories of their institutions of origin, as long as they always mention where they were published and according to the Creative Commons license.



