Cervical cancer screening using primary human papillomavirus (HPV) testing requires triage of high-risk HPV (hrHPV) positive women. In a large prospective cohort, we investigated the 5-year risk stratification for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) provided by three potential triage strategies: 1) HPV16/18 genotyping; 2) Cytology; 3) Cytology followed by HPV16/18 genotyping.
Residual liquid-based cytology samples (SurePath) were collected from 40,399 women screened for cervical cancer in Copenhagen, Denmark, during 2002–2005. Samples were HPV tested with Hybrid Capture 2, and positive samples were genotyped with INNO-LiPA. The cohort was followed until February 2015 in a nationwide pathology register for development of CIN3+.
Among hrHPV positive women aged 30–64 years (n=3,386), the 5-year risks of CIN3+ in each triage scenario were:
1) HPV16/18 triage: 25.0% (95% CI, 22.2–27.8) in women with HPV16/18 versus 6.5% (95% CI, 5.5–7.5) in those with non-HPV16/18 hrHPV.
2) Cytology triage: 39.5% (95% CI, 35.6–43.4) in women with ASC-US+ versus 5.4% (95% CI, 4.5–6.3) in those with normal cytology.
3) Cytology followed by HPV16/18: 39.5% (95% CI, 35.6–43.4) in women with ASC-US+; 11.8% (95% CI, 9.3–14.2) in those with normal cytology and HPV16/18; and 3.2% (95% CI, 2.4–4.0) in those with normal cytology and non-HPV16/18 hrHPV.
HrHPV positive women with HPV16/18 or ASC-US+ have CIN3+-risks above commonly accepted thresholds for immediate colposcopy referral. Women with normal cytology and non-HPV16/18 hrHPV have a non-negligible 5-year risk for CIN3+ (3.2%).