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Primary Human Papillomavirus Screening Versus Cytology for Detection of Cervical Intraepithelial Neoplasia Grade 2 or
Andrzej Nowakowski1, Anna Macios1, Patrycja Glinska2
1Department of Cancer Prevention, Central Coordinating Centre for Cervical Cancer Screening Program, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
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.