Abstract
Background
Persistent HPV infection causes cervical cancer, but most infections are transient. Triage methods identify high-risk women needing further evaluation or treatment. We assessed short-term repeat HPV testing as an alternative triage option.
Methods
In ESTAMPA, women aged 30–64 years were screened with HPV testing (HC2 or Cobas) and cytology. Screen positives were referred to colposcopy approximately two months after screening, where cervical samples were collected again for repeat HPV testing. We evaluated the performance of repeat HPV for CIN3+ among HPV-positive women and explored its combination with limited HPV genotyping (HPV16/18).
Results
Among 5390 HPV-positive women (including 629 CIN3 cases and 53 cancers), 61% retested positive at ~2 months (median: 1.8, interquartile range: 1.2–2.8). Repeat HPV sensitivity for CIN3+ was 81.5% (95% CI 77.2–85.2) for HC2 and 87.7% (83.7–90.8) for Cobas. Specificity was <50% with referral rates of 57.4% (55.7–59.0) and 68.2% (66.1–70.2) for HC2 and Cobas. HPV16/18 genotyping followed by repeat HPV among non-HPV16/18-positive women did not greatly improve performance. However, HPV16/18 positivity doubled the risk of CIN3+, supporting its combination with repeat HPV when available.
Conclusions
Short-term repeat HPV testing could be a practical option for triaging HPV-positive women, either alone or in combination with limited HPV genotyping.
Trial registration
ClinicalTrials.gov, NCT01881659
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Data availability
Anonymised individual participant data or aggregate data would be available from the corresponding author upon reasonable request, requiring signing a specific contract with the approval of the ESTAMPA principal investigators and local investigators of study centres involved.
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Acknowledgements
Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer / World Health Organization. Some of the authors are present or former staff members of the World Health Organization. The authors alone are responsible for the views expressed in this publication, and they do not necessarily represent the views, decisions, or policies of the institutions. AB was supported in part by an appointment to the US National Cancer Institute (NCI) Research Participation Program administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the National Institutes of Health (NIH). ORISE is managed by ORAU under DOE contract number DESC0014664. All opinions expressed in this paper are the author’s and do not necessarily reflect the policies and views of NIH, NCI, DOE, or ORAU/ORISE. This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH). The contributions of the NIH author(s) are considered Works of the United States Government. The findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.
Funding
This work was supported by IARC/WHO; the UNDP / UNFPA / UNICEF / WHO / World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP/WHO), a cosponsored programme executed by the World Health Organization (WHO); the Pan American Health Organization (PAHO); the National Cancer Institute (NCI) (Grant UH2/3 CA202730); the NCI Center for Global Health; Instituto Nacional del Cáncer from Argentina (Grant 2016-2018); Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación from Argentina (Grant PICT 0364-2016); the National Council for Science and Technology (CONACYT) from Paraguay (Grants 14-INV-036 & PINV18-256); Caja Costarricense del Seguro Social; and the National Cancer Institute of Colombia. The funders had no role in the design of the study, data collection, analysis, interpretation, manuscript preparation, or in the decision to publish the results.
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Contributions
MA and RH conceived the ESTAMPA study and are the principal investigators responsible for its overall conduction and funding acquisition. AB conceptualised the manuscript, formulation of the core idea and research objective, and was responsible for data curation, statistical analysis, and writing the original draft. MAP, LM, AF, GV, VV, ACr, GR, CT, ACa, and CW are the local principal investigators responsible for recruitment, clinical management, and data collection. JL, MB, PM, YC, MDF, OZ, LG, PH, MLB, and MR performed HPV testing locally. MA, RH, MAP, LM, AF, LG, and DM contributed to the finalisation of the manuscript. All authors reviewed and approved the final version of the manuscript.
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The authors declare no competing interests.
Ethics approval and consent to participate
The ESTAMPA protocol was approved by the Ethics Committee of the International Agency for Research on Cancer of the World Health Organization (IARC/WHO) (IEC Project 12–27-A7), the Pan American Health Organization (PAHO) Ethical Committee, and Ethical Committees at study centres. The study is considered of minimal risk as procedures are standard clinical practice. All women were informed by trained providers of the procedures and signed informed consent. This study is registered with ClinicalTrials.gov (NCT01881659).
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Baena, A., Picconi, M.A., Mendoza, L. et al. Short-term repeat HPV testing for triaging HPV-positive women in cervical cancer screening. Br J Cancer 133, 1844–1853 (2025). https://doi.org/10.1038/s41416-025-03193-0
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DOI: https://doi.org/10.1038/s41416-025-03193-0
