Controlled trial of cervical cancer screening frequency among human-papillomavirus-vaccinated women

Cervical screening frequency has not been studied in vaccinees. As the major risk factor, oncogenic human papillomavirus (HPV) is declining due to vaccination. We report a trial to assess the effectiveness of cervical screening frequency among women HPV-vaccinated as early adolescents (NCT02149030). In 2013, 5626 1992-1995-born women, who had received three doses of the HPV16/18 vaccine at ages 12-15 between 2007 and 2010 in a community-randomized vaccination trial (NCT00534638), were allocated at age 22 into high-intensity cytology-based cervical screening by even birth date (Arm A1) or into low-intensity cytology-based cervical screening by odd birth date (Arm A2). One thousand three hundred thirty-three women who received HPV16/18 vaccination at age 18 attended a safety of low intensity-screening arm (Arm A3). Low-intensity screening, where low-grade cytological abnormalities were not revealed for 6 years, was compared to the standard high-intensity screening used in Finland at the time. The prevalence of cytological and HPV findings was calculated at ages 22/25/28. The hazard ratio of histopathologically confirmed immediate cervical cancer precursors (HSIL/CIN2+) among participants was compared between low- and high-intensity screening arms. The overall occurrence of CIN2+ was comparable in Arms A1, 0.70% and A2, 0.66%, with the corresponding hazard ratio at age 28 being 0.97 (95% confidence intervals, 0.50-1.88). By age 28, the occurrence of vaccine-HPV types 16/18 was reduced up to 88% in the 12-to-15 compared to 18-year-old HPV-vaccinated women. In conclusion, the risk of CIN2+ was similar for HPV-vaccinated women who attended low-intensity cervical screening compared to high-intensity screening most likely due to the decline of oncogenic HPVs.