Testing for viral DNA integration among HPV-positive women to detect cervical precancer: An observational cohort study

Abstract

Objective: Human papillomavirus (HPV) integration is a crucial genetic step in cervical carcinogenesis. This study aimed to evaluate the performance of an HPV integration test for the triage of HPV-positive women. Design: An observational cohort study. Setting: A cervical cancer screening programme in China. Population: 1393 HPV-positive women aged 25–65 years undergoing routine cervical cancer screening and HPV integration testing with 1-year follow-up. Methods: The sensitivity, specificity, positive predictive value and negative predictive value between HPV integration and cytology were compared. Main outcome measures: Cervical intraepithelial neoplasia grade 3 or more severe (CIN3+). Results: Among 1393 HPV-positive patients, 138 (9.9% [8.3–11.5%]) were HPV integration test positive compared with 537 who had abnormal cervical cytology (38.5% [36.0–41.1%]). Compared with cytology, HPV integration exhibited higher specificity (94.5% [93.3–95.8%] versus 63.8% [61.2–66.4%]) and equivalent sensitivity (70.5% [61.4–79.7%] versus 70.5% [61.4–79.7%]) for detection of CIN3+. HPV integration-negative women accounted for 90.1% (1255/1393) of the total population and had a low immediate CIN3+ risk (2.2%). At 1-year follow-up, the progression rate in the HPV integration-positive women was higher than in the HPV integration-negative women (12.0% versus 2.1%, odds ratio 5.6, 95% CI, 2.6–11.9). In 10 conservatively managed integration-negative CIN2 patients, all showed spontaneous regression and seven showed HPV clearance after 1-year follow-up. Conclusion: The HPV integration test may be a precise risk stratification tool for HPV-positive women and could avoid excessive use of invasive biopsies.