HPV-BASED CERVICAL CANCER SCREENING: FROM ‘ONE-SIZE-FITS-ALL’ TOWARDS RISK-BASED STRATEGIES

Elimination of cervical cancer as a public health problem can be achieved by a combination of HPV vaccination and screening for early detection and treatment of precancerous lesions. Screening by primary HPV testing is currently replacing cytology in many organized screening programs. HPV-based programs will also be adapted multiple times in the future as they need to take into account changes such as the development of more advanced technologies and the decline in HPV infections following HPV vaccination. In this thesis, multiple aspects of HPV-based screening are described, with a focus on optimization of strategies using risk stratification. In particular, this thesis aims to I) evaluate the clinical performance of HPV self-sampling offered in the Netherlands as an alternative primary screening option, II) study risk profiles of unvaccinated women using HPV genotyping and screening history, III) study risk profiles of vaccinated women attending HPV-based screening, and IV) assess the costs of HPV testing following public tendering in Italian regional settings. I) Primary HPV testing on a self-collected sample was found to have similar accuracy but a slightly lower sensitivity as compared to HPV testing on a clinician-collected sample, thus the consensus guidelines for use in cervical screening were met although a re-evaluation of the workflow procedure is warranted to optimize its performance. II) Taking into account HPV genotyping information and screening outcomes from the previous screening round can lead to a more precise risk assessment. We found that 5-year HPV type concordance signals high CIN3+ risk which supports immediate referral for colposcopy without additional cytology triage. We also found that HPV detection and CIN3+ risk were higher among women who had a positive HPV test in the past, warranting a re-evaluation of the 10-year interval implemented in the Dutch program for women with a negative HPV test at age 40 or 50 years. III) With the use of a type-specific data-driven statistical model, we projected the lifetime CIN3+ risks under 5-yearly primary HPV screening and different HPV vaccination scenarios and found that HPV vaccination will lead to a strong decline in the lifetime CIN3+ risk supporting de-intensification of the screening program in vaccinated women. Screening vaccinated women using HPV testing and cytology triage remains feasible, although intervals beyond 5 years should be considered. IV) HPV tests can be purchased at very low prices if procured at high volume. Enhancing transparency by reporting tender-based unit prices can support health authorities in their decision to implement primary HPV screening.