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

Abstract

AbstractObjectiveHuman 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.DesignAn observational cohort study.SettingA cervical cancer screening programme in China.Population1393 HPV‐positive women aged 25–65 years undergoing routine cervical cancer screening and HPV integration testing with 1‐year follow‐up.MethodsThe sensitivity, specificity, positive predictive value and negative predictive value between HPV integration and cytology were compared.Main outcome measuresCervical intraepithelial neoplasia grade 3 or more severe (CIN3+).ResultsAmong 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.ConclusionThe HPV integration test may be a precise risk stratification tool for HPV‐positive women and could avoid excessive use of invasive biopsies.