Journal Article Epublish 1 citation
PubMed: 42403920 DOI: 10.1016/j.lanepe.2026.101697
Primary Human Papillomavirus Screening Versus Cytology for Detection of Cervical Intraepithelial Neoplasia Grade 2 or Higher in Poland: a Parallel-Group, Randomized Controlled Trial.
Lancet Reg Health Eur 66:101697
Authors: Andrzej Nowakowski, Anna Macios, Patrycja Glinska, Aneta Chmielewska, Beata Janik, Ilona Jędrzejewska, Alicja Klimiuk, Ewa Chmielik, Piotr Bobkiewicz, Ewa Kapuśniak, Jacek Podolski, Ewa Prokurat, Marc Arbyn, Michal Filip Kamiński
Affiliations
- Department of Cancer Prevention, Central Coordinating Centre for Cervical Cancer Screening Program, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
- Department of Oncology Diagnostics, Cardio-Oncology, and Palliative Medicine, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
- Department of Cancer Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland.
- ALAB Plus Pathology Laboratory Ltd. Warsaw, Poland.
- Medical Centre FEMINA, Katowice, Poland.
- Non-public Health Care Facility Meditest - Medical Diagnostics, Szczecin, Poland.
- Medical and Diagnostic Centre, Siedlce, Poland.
- Unit of Cancer Epidemiology, Belgian Cancer Centre, Scientific Institute of Public Health, Brussels, Belgium.
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
- Clinical Effectiveness Research Group, University of Oslo, Oslo, Norway.
Abstract
BACKGROUND
2025 European guidelines recommended transition from cytology to HPV-based cervical cancer screening. We compared both strategies in a pilot in Poland.
METHODS
Eligible, consenting women aged 30-59 years underwent centralized 1:1 randomization to HPV-testing or cytology (HPV or cytology arm, respectively) in 30-39, 40-49, and 50-59 years age strata in 27 clinics. Arm assignment was unblinded. HPV positive samples underwent liquid-based cytology (LBC) triage. If normal, another LBC was performed in six months. Abnormal LBC triggered colposcopy. If both LBCs were normal, p16/Ki-67 immunocytochemistry and FAM19A4/miR124-2 methylation tests were performed. Either positive triggered referral to colposcopy. In the cytology arm, abnormal results triggered another cytology after six months or colposcopy, according to routine protocols. Cervical intraepithelial neoplasia grade 2 or worse (CIN2+) detection rate in the population intended to treat was the main outcome. NCT04111835-Clinicaltrials.gov.
FINDINGS
Between 28 October 2019 and 31 December 2022, 16,795 and 16,707 women underwent primary HPV or cytological testing, respectively. 702/16,795 (4.2%; 95% CI: 3.9%-4.5%) and 499/16,707 women (3.0%; 95% CI: 2.7%-3.3%), were referred for colposcopy in the HPV and cytology arm, respectively (RR = 1.40; 95% CI: 1.25-1.57). CIN2+ was detected in 137 women (0.82%; 95% CI: 0.69-0.96%) and in 71 women (0.42%; 95% CI: 0.34-0.54%; OR = 1.93; 95% CI: 1.34-2.77), while CIN grade 3 or worse (CIN3+) was detected in 69 women (0.41%; 95% CI: 0.32%-0.52%) and in 35 women (0.21%; 95% CI: 0.15%-0.29%; OR = 1.99; 95% CI: 1.16-3.42) in the HPV and cytology arm, respectively. In HPV positive women with two normal LBCs immunocytochemistry and methylation detected 4/9 (44.4%) and 7/9 (77.8%) CIN2+ cases, respectively.
INTERPRETATION
HPV-based screening may almost double CIN2+ detection compared to cytology. It however yields more positive screening results and colposcopies. Smooth transition from cytology to HPV-based screening requires proper triage strategies and additional colposcopy services. Methylation seems to detect more CIN2+ than immunocytochemistry in HPV positive women with two normal LBCs.
FUNDING
Polish Ministry of Health.
MeSH
Research Design, Triage, Neoplasms, Cell Biology, Alphapapillomavirus, Colposcopy, Cytology, Human Papillomavirus Viruses