title: 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 (> or =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.
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire, Institut d'Etude et de Transfert de Gènes, Centre Hospitalier Universitaire, Hopital Jean Minjoz, Bld. Fleming, 25030 Besançon cedex, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dalstein
authors.forename: Didier
authors.initials: D
authors.lastname: Riethmuller
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Prétet
authors.forename: Karine
authors.initials: K
authors.lastname: Le Bail Carval
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Sautière
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Carbillet
authors.forename: Bernadette
authors.initials: B
authors.lastname: Kantelip
authors.forename: Jean-Patrick
authors.initials: JP
authors.lastname: Schaal
authors.forename: Christiane
authors.initials: C
authors.lastname: Mougin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D002584:Cervix Uteri / Q000166:cytology; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008875:Middle Aged; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D011446:Prospective Studies; D012307:Risk Factors; D014412:Tumor Virus Infections / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D014626:Vaginal Smears; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000473:pathology / Q000821:virology*
chemical_list: D004279:DNA, Viral