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

Abstract

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.