TY - JOUR
T1 - Estimating the direct effect of human papillomavirus vaccination on the lifetime risk of screen-detected cervical precancer
AU - Inturrisi, Federica
AU - Lissenberg-Witte, Birgit, I
AU - Veldhuijzen, Nienke J.
AU - Bogaards, Johannes A.
AU - Ronco, Guglielmo
AU - Meijer, Chris J. L. M.
AU - Berkhof, Johannes
N1 - Funding Information:
We gratefully acknowledge all women, general practitioners and their assistants participating in the POBASCAM trial. We thank the research staff and technicians of the unit of Molecular Pathology, VU University Medical Centre Amsterdam, for HPV testing and typing, and the cytotechnologists for cytological testing (Spaarne Ziekenhuis, Hoofddorp/Haarlem; Leiden Cytology and Pathology Laboratory, Leiden; and Unit Cytopathology, VU University Medical Center, Amsterdam). We thank the PALGA foundation for their help with the PALGA search strategy and PALGA data collection. This work was supported by the Netherlands Organization for Health Research and Development (ZonMW project number 50‐53125‐98‐034) and the European Commission (CoheaHr, grant number 603019; RISCC, grant number 847845). The funders had no role in the identification, design, conduct, reporting and interpretation of the analysis.
Funding Information:
We gratefully acknowledge all women, general practitioners and their assistants participating in the POBASCAM trial. We thank the research staff and technicians of the unit of Molecular Pathology, VU University Medical Centre Amsterdam, for HPV testing and typing, and the cytotechnologists for cytological testing (Spaarne Ziekenhuis, Hoofddorp/Haarlem; Leiden Cytology and Pathology Laboratory, Leiden; and Unit Cytopathology, VU University Medical Center, Amsterdam). We thank the PALGA foundation for their help with the PALGA search strategy and PALGA data collection. This work was supported by the Netherlands Organization for Health Research and Development (ZonMW project number 50-53125-98-034) and the European Commission (CoheaHr, grant number 603019; RISCC, grant number 847845). The funders had no role in the identification, design, conduct, reporting and interpretation of the analysis.
Publisher Copyright:
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/15
Y1 - 2021/1/15
N2 - Birth cohorts vaccinated against human papillomavirus (HPV) are now entering cervical cancer screening. Assessment of (pre)cancer (CIN3+) risk is needed to assess the residual screening need in vaccinated women. We estimated the lifetime (screen-detected) CIN3+ risk under five-yearly primary HPV screening between age 30 and 60, using HPV genotyping and histology data of 21,287 women participating in a screening trial with two HPV-based screening rounds, 5 years apart. The maximum follow-up after an HPV-positive test was 9 years. We re-estimated the CIN3+ risk after projecting direct vaccine efficacy for the bivalent and the nonavalent HPV vaccines, assuming life-long protection. The lifetime CIN3+ risk was 4.1% (95% confidence interval 3.5-4.9) and declined by 53.5% and 70.5% after bivalent vaccination without and with cross-protection, respectively, translating into a residual lifetime CIN3+ risk of 1.9% (1.4-2.4) and 1.2% (0.9-1.5). The CIN3+ risk declined by 88.5% after nonavalent vaccination, translating into a residual lifetime CIN3+ risk of 0.5% (0.2-0.7). The latter risk increased to 1.6% when vaccine protection only lasted until the first screening round at age 30. Among HPV-positive women with abnormal adjunct cytology, the nine-year CIN3+ risk was 16.9% (8.7-32.4) after nonavalent vaccination. In conclusion, HPV vaccination will lead to a strong decline in the lifetime CIN3+ risk and the remaining absolute CIN3+ risk will be very low. Primary HPV testing combined with adjunct cytology at five-year intervals still seems feasible even after nonavalent vaccination, although unlikely to be cost-effective. Our results support a de-intensification of screening programs in settings with high vaccination coverage.
AB - Birth cohorts vaccinated against human papillomavirus (HPV) are now entering cervical cancer screening. Assessment of (pre)cancer (CIN3+) risk is needed to assess the residual screening need in vaccinated women. We estimated the lifetime (screen-detected) CIN3+ risk under five-yearly primary HPV screening between age 30 and 60, using HPV genotyping and histology data of 21,287 women participating in a screening trial with two HPV-based screening rounds, 5 years apart. The maximum follow-up after an HPV-positive test was 9 years. We re-estimated the CIN3+ risk after projecting direct vaccine efficacy for the bivalent and the nonavalent HPV vaccines, assuming life-long protection. The lifetime CIN3+ risk was 4.1% (95% confidence interval 3.5-4.9) and declined by 53.5% and 70.5% after bivalent vaccination without and with cross-protection, respectively, translating into a residual lifetime CIN3+ risk of 1.9% (1.4-2.4) and 1.2% (0.9-1.5). The CIN3+ risk declined by 88.5% after nonavalent vaccination, translating into a residual lifetime CIN3+ risk of 0.5% (0.2-0.7). The latter risk increased to 1.6% when vaccine protection only lasted until the first screening round at age 30. Among HPV-positive women with abnormal adjunct cytology, the nine-year CIN3+ risk was 16.9% (8.7-32.4) after nonavalent vaccination. In conclusion, HPV vaccination will lead to a strong decline in the lifetime CIN3+ risk and the remaining absolute CIN3+ risk will be very low. Primary HPV testing combined with adjunct cytology at five-year intervals still seems feasible even after nonavalent vaccination, although unlikely to be cost-effective. Our results support a de-intensification of screening programs in settings with high vaccination coverage.
KW - cervical intraepithelial neoplasia (CIN)
KW - HPV-based screening
KW - human papillomavirus (HPV)
KW - lifetime risk
KW - prophylactic vaccination
UR - http://www.scopus.com/inward/record.url?scp=85088629822&partnerID=8YFLogxK
U2 - 10.1002/ijc.33207
DO - 10.1002/ijc.33207
M3 - Article
C2 - 32663316
AN - SCOPUS:85088629822
VL - 148
SP - 320
EP - 328
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
ER -