24 Chapter 1 1.3.2.1 HPV-BASED CERVICAL SCREENING IN THE NETHERLANDS In 2011, the Dutch Health Council advised the Ministry of Health to replace cytology with primary HPV testing in cervical screening 101. Consequently, the Netherlands became the first country to switch to a nationwide primary HPV-based screening program in 2017, followed by Australia and other countries 102, 103. Triage testing of hrHPV-positive women is required to identify women with clinically relevant infections and to avoid over-referral. One of the most common triage tests internationally is cytology 104, 105. In the new HPVbased screening program triage of hrHPV-positive women was performed by (repeat) cytology to achieve an acceptable CIN3+ risk for triage-negative women 101, 106. Women with low-grade cytology (atypical squamous cells of undetermined significance (ASC-US); or low-grade squamous intraepithelial lesions (LSIL)), either at baseline or at six months follow-up, were referred to a gynaecologist for colposcopy. Women with an hrHPVpositive, normal cytology test result at baseline were offered repeat cytology because they have only a 4% risk of CIN2/3+. This risk is too low to recommend immediate colposcopy referral and by repeating cytology after six months, a transient infection may resolve in the meantime. The first results of the new Dutch cervical cancer screening program showed that more women with clinically relevant findings (CIN2+) were discovered, but screen-positivity, referral rates and low-grade lesion (<CIN1) rates were also markedly higher than in the former, cytology-based program 107. The increase in colposcopy referrals was mainly caused by the direct referral of women with ASC-US/LSIL cytology, who often do not have CIN2/3. In 2021, the Dutch Health Council therefore recommended that referrals to gynaecologists should be subject to more specific criteria. Additional triage of hrHPV-positive women with ASC-US/LSIL cytology might reduce the number of women referred for colposcopy, while maintaining clinical sensitivity. This could be achieved by incorporating hrHPV genotyping to discriminate hrHPV types with clearly increased risk, such as HPV16 and HPV18, and hrHPV-types with a moderately increased risk. Since mid-2022, women with ASC-US/LSIL cytology are therefore only directly referred to a gynaecologist if HPV16 and/or -18 are present. In case of a non-HPV16/18 type, women are invited for repeat testing. Furthermore, extending the interval for repeat cytology from 6 to 12 months might reduce the number of clinically unnecessary referrals and was introduced mid-2022. The performance of HPV genotyping in differentiating between a transient infection and a persistent infection, that is associated with CIN2/3 and cancer, is only moderate 108. Therefore, alternative (secondary) triage strategies are warranted.
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