Persistence and load of high-risk HPV are predictors for development of high-grade cervical lesions: A longitudinal French cohort study

Abstract

Oncogenic HPV types are the major cause of worldwide cervical cancer, but only a small proportion of infected women will develop high‐grade cervical intraepithelial neoplasia or cancer (CIN2/3+). We performed a prospective study including 781 women with normal, atypical squamous cells of undetermined significance (ASCUS) or low‐grade squamous intraepithelial lesion (LGSIL) cytology, and infected or not by high‐risk (HR) HPV tested by Hybrid Capture II. Women were followed up every 6 months for a median period of 22 months. Among the HR‐HPV‐positive women at entry, more than half cleared their virus in 7.5 months; the clearance rate was greater for low viral loads than for high loads and also was higher in women with an initial ASCUS/LGSIL smear than in women with normal cytology. The incidence of cytologic abnormalities strongly depended on baseline viral load and HR‐HPV persistence. Maintenance of cytologic abnormalities was associated with the outcome of HR‐HPV status (negative<transient<persistent) but not with baseline load. Progression to CIN2/3+ was achieved only in women with persistent HR‐HPV infection. The risk of CIN2/3+ also was increased with initial high loads (≥100 pg/mL). Conversely, women who were consistently HR‐HPV negative or transiently HR‐HPV positive, whatever the cytology at baseline was, did not develop CIN2/3+ during follow‐up. Age seemed to affect only the rate of incident HR‐HPV infection. In conclusion, our data suggest that women repeatedly tested positive for HR‐HPV are at risk of developing CIN2/3+, even when initial cytology is normal. A high viral load could be used as a short‐term marker of progression toward precancerous lesions, although lower load does not inevitably exclude progressive disease. © 2003 Wiley‐Liss, Inc.