TY - JOUR
T1 - Risk of cervical precancer among HPV-negative women in the Netherlands and its association with previous HPV and cytology results
T2 - A follow-up analysis of a randomized screening study
AU - Inturrisi, Federica
AU - Rozendaal, Lawrence
AU - Veldhuijzen, Nienke J
AU - Heideman, Daniëlle A M
AU - Meijer, Chris J L M
AU - Berkhof, Johannes
N1 - Funding Information: This work was supported by the Netherlands Organization for Health Research and Development [ZonMw, project No 50-53125-98-034] (to FI and JB) and the Horizon 2020 research and innovation program of the European Commission [RISCC project, grant agreement No 847845] (to FI, DAMH, CJLMM, and JB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We gratefully acknowledge all women, general practitioners, and their assistants participating in the POBASCAM trial and involved in the Dutch cervical cancer screening program. We gratefully acknowledge late Peter Snijders who was one of the main investigators of the POBASCAM trial. We thank the research staff and technicians of the Department of Pathology at the VU University Medical Center of Amsterdam for the HPV testing of the POBASCAM trial. We thank the PALGA foundation for their help with the PALGA search strategy and PALGA follow-up data collection. We thank all the staff of the screening laboratories that serve the Dutch cervical screening program (UMCG Groningen, Radboud UMC Nijmegen, JBZ Den Bosch, NMDL Rijswijk, and Symbiant Hoorn). Publisher Copyright: Copyright: © 2022 Inturrisi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Background AU Human: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly papillomavirus (HPV)-based screening programs still : use one-size-fits-all protocols but efficiency and efficacy of programs may be improved by stratifying women based on previous screening results. Methods and findings We studied the association between cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and previous screening results in the Population-Based Screening Study Amsterdam (POBASCAM) trial, performed in the Netherlands in the setting of regular screening, where women aged from 29 to 61 years old were invited to cytology and HPV co-testing at enrolment in year 1999/2002 and at the next round in 2003/2007. We selected 18,448 women (9,293 from the intervention group and 9,155 from the control group) who tested HPV–negative in 2003/2007 and did not have cervical intraepithelial neoplasia grade 2 or worse (CIN2+) or hysterectomy after enrolment. Follow-up was collected until 14 years after the 2003/2007 screen, covering 4 rounds of screening. Risk of CIN3+ and CIN2+ among women with an HPV–negative test, irrespective of previous round results and stratified according to previous round HPV and cytology results, were calculated by the Kaplan–Meier method. During 14 years of follow-up, 62 CIN3+ cases (24 in the intervention group and 38 in the control group) were detected. HPV–negative women had a 14-year CIN3+ risk of 0.48% (95% confidence interval 0.37 to 0.62) and CIN2+ risk of 1.17% (0.99 to 1.38). The CIN3+ risk among HPV–negative women was increased in women with a previous positive HPV test (2.36%, 1.20 to 4.63; p < 0.001) or co-test (1.68%, 0.87 to 3.20; p < 0.001) and, equivalently, decreased in women with a previous negative HPV test (0.43%, 0.33 to 0.57) or a negative co-test (0.43%, 0.33 to 0.57). The CIN3+ risk was not influenced by the previous cytology result. The CIN3+ risk among HPV–negative women was increased after both a previous HPV16–positive test (3.90%, 1.47 to 10.12; p < 0.001) and a previous HPV16–negative/HPVother–positive test (1.91%, 0.76 to 4.74; p = 0.002). For endpoint CIN2+ (147 cases), findings were similar except that the CIN2+ risk was increased after previous abnormal cytology (4.06%, 2.30 to 7.12; p < 0.001). The presented risk estimates were calculated by tracking histological results through the Dutch nationwide pathology archive (PALGA) and were not adjusted for non-compliance with the colposcopy referral advice. Conclusions HPV–negative women had an increased long-term risk of CIN3+ when the HPV test in the previous screening round was positive. This supports the implementation of risk-based intervals that depend on HPV results in the current and previous screening round.
AB - Background AU Human: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly papillomavirus (HPV)-based screening programs still : use one-size-fits-all protocols but efficiency and efficacy of programs may be improved by stratifying women based on previous screening results. Methods and findings We studied the association between cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and previous screening results in the Population-Based Screening Study Amsterdam (POBASCAM) trial, performed in the Netherlands in the setting of regular screening, where women aged from 29 to 61 years old were invited to cytology and HPV co-testing at enrolment in year 1999/2002 and at the next round in 2003/2007. We selected 18,448 women (9,293 from the intervention group and 9,155 from the control group) who tested HPV–negative in 2003/2007 and did not have cervical intraepithelial neoplasia grade 2 or worse (CIN2+) or hysterectomy after enrolment. Follow-up was collected until 14 years after the 2003/2007 screen, covering 4 rounds of screening. Risk of CIN3+ and CIN2+ among women with an HPV–negative test, irrespective of previous round results and stratified according to previous round HPV and cytology results, were calculated by the Kaplan–Meier method. During 14 years of follow-up, 62 CIN3+ cases (24 in the intervention group and 38 in the control group) were detected. HPV–negative women had a 14-year CIN3+ risk of 0.48% (95% confidence interval 0.37 to 0.62) and CIN2+ risk of 1.17% (0.99 to 1.38). The CIN3+ risk among HPV–negative women was increased in women with a previous positive HPV test (2.36%, 1.20 to 4.63; p < 0.001) or co-test (1.68%, 0.87 to 3.20; p < 0.001) and, equivalently, decreased in women with a previous negative HPV test (0.43%, 0.33 to 0.57) or a negative co-test (0.43%, 0.33 to 0.57). The CIN3+ risk was not influenced by the previous cytology result. The CIN3+ risk among HPV–negative women was increased after both a previous HPV16–positive test (3.90%, 1.47 to 10.12; p < 0.001) and a previous HPV16–negative/HPVother–positive test (1.91%, 0.76 to 4.74; p = 0.002). For endpoint CIN2+ (147 cases), findings were similar except that the CIN2+ risk was increased after previous abnormal cytology (4.06%, 2.30 to 7.12; p < 0.001). The presented risk estimates were calculated by tracking histological results through the Dutch nationwide pathology archive (PALGA) and were not adjusted for non-compliance with the colposcopy referral advice. Conclusions HPV–negative women had an increased long-term risk of CIN3+ when the HPV test in the previous screening round was positive. This supports the implementation of risk-based intervals that depend on HPV results in the current and previous screening round.
KW - Adult
KW - Cervical Intraepithelial Neoplasia/diagnosis
KW - Early Detection of Cancer
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Middle Aged
KW - Netherlands/epidemiology
KW - Papillomavirus Infections/complications
KW - Uterine Cervical Neoplasms/diagnosis
KW - Vaginal Smears
UR - http://www.scopus.com/inward/record.url?scp=85141005663&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pmed.1004115
DO - https://doi.org/10.1371/journal.pmed.1004115
M3 - Article
C2 - 36306283
SN - 1549-1277
VL - 19
SP - e1004115
JO - PLoS medicine
JF - PLoS medicine
IS - 10
M1 - e1004115
ER -