General introduction and thesis outline 25 1 Self-collection of cervicovaginal specimens can be used for HPV testing (i.e., HPV selfsampling), and has the advantage that it can lower barriers to participation and increase attendance rates 109-117. In the Netherlands, HPV self-sampling was implemented in the cervical screening program in 2017 for women who were not willing to participate by clinician-collection of a cervical sample 101. Recent studies support the use of HPV selfsampling as a primary screening test for all women invited for cervical cancer screening 118. Based on this evidence, the Dutch Health Council recommended in 2021 that selfsampling kits should be offered to all women who are invited to undergo population screening for cervical cancer, and these kits should be automatically included with the invitations. By offering women the option to choose between two equivalent screening methods (i.e., clinician-based or self-collection), the Dutch Health Council expects that participation rates will increase. In July 2023, this was introduced in the Netherlands, where women participating in the population screening for the first time will receive a self-sampling kit immediately. For all other women, they will have the option to express their preference after receiving the invitation. If no response is received, they will receive a self-sampling kit. A drawback of self-sampling is that cytology cannot be accurately performed, requiring women who test positive for hrHPV on a self-collected sample to visit a general practitioner for a clinician-collected cervical sample for cytology-triage. This can result in women being lost to follow-up (i.e., 7-40%) and women experience delays in the diagnostic track 110, 116, 119. To improve follow-up adherence for women who test hrHPV-positive on self-collected samples, alternative triage methods that are applicable directly to self-collected samples are needed. Another aspect to consider for screening in the near future is that vaccinated women will gradually enter the screening program, i.e., in the Netherlands the first vaccinated women are screened in 2023. Although the vaccines protect against most hrHPV types that can cause cervical cancer, suboptimal vaccine coverage means that screening will remain a crucial part of cervical cancer prevention for the next decades. Nonetheless, adjustments to the screening strategy need to be anticipated as the risk of CIN3+ and the predictive value of a positive screening result (PPV) will drop 120. With the decreasing prevalence of HPV types with high oncogenic potential (i.e., HPV16 and HPV18 in the Netherlands given the use of the bivalent vaccine), the majority of positive screening findings threaten to be false positive findings. As a consequence, improved screening and/or triage tests are required for better risk stratification.
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