Data from Cervical Precancer and Cancer Risk by Human Papillomavirus Status and Cytologic Interpretation: Implications for Risk-Based Management

Abstract

<div>Abstract<p><b>Background:</b> Cervical cancer risks, estimated by using cervical intraepithelial neoplasia grade 3 (CIN3) or more severe diagnoses (≥CIN3) endpoints, have not been quantified for different combinations of results from currently approved screening methods. Understanding these risks will guide optimal patient management.</p><p><b>Methods:</b> Women aged ≥25 years (<i>n</i> = 7,823) underwent high-risk human papillomavirus (hrHPV) and liquid-based cytology (LBC) testing. Women with hrHPV-positive results and/or abnormal LBC, plus a random subset of hrHPV and LBC negatives, underwent colposcopy; those without ≥CIN2 at baseline were screened annually by LBC and referred to colposcopy for an abnormal LBC (<i>n</i> = 7,392). One- and 3-year ≥CIN3 risks with 95% confidence intervals (95% CI) were calculated for paired hrHPV and LBC (hrHPV/LBC) results.</p><p><b>Results:</b> One-year ≥CIN3 risks ranged from 81.27% (95% CI, 66.02%–90.65%) for HPV16 positive/high-grade to 0.33% (95% CI, 0.18%–0.62%) for hrHPV negative/negative for intraepithelial lesion or malignancy (NILM). One-year ≥CIN3 risk for HPV16/NILM (13.95%; 95% CI, 10.98%–17.58%) was greater than low-grade squamous intraepithelial lesion (LSIL; 7.90%; 95% CI, 5.99%–10.37%; <i>P</i> = 0.002) and similar to hrHPV-positive/LSIL (11.45%; 95% CI, 8.61%–15.07%; <i>P</i> = 0.3). Three-year ≥CIN3 risks for HPV16 positive/LSIL and HPV16/atypical squamous cells of undetermined significance was 24.79% (95% CI, 16.44%–35.58%) and 24.36% (95% CI, 15.86%–35.50%), respectively, and 0.72% (95% CI, 0.45%–1.14%) for hrHPV negative/NILM.</p><p><b>Conclusions:</b> hrHPV and LBC results stratify cervical cancer risk by more than two orders of magnitude. HPV16-positive women, regardless of the LBC result, warrant immediate colposcopy. Women with concurrent HPV16 and high-grade LBC might consider treatment without a confirmatory biopsy with informed decision-making with their provider.</p><p><b>Impact:</b> These results provide relevant benchmarks for risk-based cervical cancer screening and management. <i>Cancer Epidemiol Biomarkers Prev; 25(12); 1595–9. ©2016 AACR</i>.</p></div>