Risk of Cervical Intraepithelial Neoplasia Grade 3 or Worse in HPV-Positive Women with Normal Cytology and Five-Year Type Concordance: A Randomized Comparison

Background: In human papillomavirus (HPV)-based cervical screening programs, management of HPV-positive women with normal cytology is debated. Longitudinal information on HPV type persistence may be employed for risk stratification. Methods: We assessed the risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3þ) after repeatedly testing positive for the same HPV type(s) in the randomized population-based screening study Amsterdam (POBASCAM). We compared 18-month CIN3þ risks in HPV-positive women (intervention, n ¼ 1,066) to those in HPV-positive/cytology-negative women who tested HPV-positive in the next screening round (control, n ¼ 111) five years later, stratified for HPV type concordance. Results: The 18-month CIN3þ risk was 15% in HPV-positive women in the intervention group, 40% in the control group after two-round type concordance (relative risk 2.6, 95% confidence interval 1.9–3.4), and 20% in the control group after a type switch (1.3, 0.5–3.2). The relative increase in CIN3þ risk after two-round type concordance was similar in <35-year-old (3.0, 2.0–4.4) and older women (2.2, 1.4–3.5), and was high in high-risk HPV-positive women who were HPV16/18/31/33/45-negative in both rounds (9.9, 4.4–21.9). Conclusions: Five-year HPV type concordance signals high CIN3þ risk and warrants referral for colposcopy without additional cytology triage. Impact: HPV screening programs become highly efficient when HPV-positive women with negative triage testing at baseline are offered repeat HPV genotyping after five years.