Effect of sequential rounds of cervical cancer screening on management of HPV-positive women: A 15-year population-based cohort study from China

Abstract

Women are anticipated to go through more than two rounds of cervical screening in their lifetime. Human papillomavirus(HPV) testing is increasingly used as the primary cervical cancer screening test. However, triage strategies for HPV positive women were usually evaluated at baseline screening. We assessed the effect of sequential rounds of cervical screening on several algorithms for HPV triage. 1997 women aged 35-45 years were enrolled in 1999 in Shanxi, China and followed up three times at approximately five-year intervals. Cervical intraepithelial neoplasia grade 2 or worse(CIN2+) prevalence by prior HPV results and performance of twelve triage algorithms with cytology, genotyping and prior HPV were examined among 229 HPV positive women at the fourth round. CIN2+ prevalence varied from 56.5% (95% confidence interval (CI): 36.8-74.4%) following 15 years HPV persistence to 3.5% (1.2-9.9%) with an incident HPV within 15 years. Triage with cytology (with threshold of atypical squamous cells of undetermined significance) yielded positive predictive value(PPV) of 21.4%(13.8-29.0%), entailing immediate colposcopic referral, and negative predictive value(NPV) of 97.4%(94.6-100.0%), permitting re-testing at short intervals. Triage with genotyping (16/18/31/33/45/52/58) or prior HPV results showed comparable performance to cytology. Among 11 triage algorithms with similar NPV to cytology, triage with prior HPV results and reflex genotyping (16/18) achieved highest PPV of 28.9% (18.8-39.1%) and lowest colposcopy referral of 33.2% (27.4-39.5%). HPV persistence across rounds is an effective risk stratifier in HPV positive women. Mainstream cytology and genotyping, with or without consideration of prior HPV results, remain effective for HPV triage at fourth round.