title: Persistent infection with human papillomavirus 16 or 18 is strongly linked with high-grade cervical disease.
abstract: We investigated the relationship between high-grade cervical disease (cervical intraepithelial neoplasia [CIN] 2, CIN3 or adenocarcinoma in situ) and persistent infection with HPV16 and/or HPV18 (HPV16/18) among 3970 women who received placebo in 3 clinical trials of a quadrivalent HPV vaccine. Statistical analysis (odds ratios, sensitivity, specificity, negative and positive predictive values, negative and positive likelihood ratios) showed that patients with a persistent infection with HPV16/18 had a much greater risk of HPV16/18-related high-grade cervical disease. Furthermore, subjects without a persistent infection with HPV16/18 were unlikely to have HPV16/18-related high-grade cervical disease. These results suggest that persistent infection with HPV16/18 meets the criteria for a surrogate endpoint for HPV16/18-related high-grade cervical disease and may be used as such in future clinical studies with prophylactic HPV vaccines and in natural history studies.
authors.affiliation: a Merck & Co., Inc. , Whitehouse Station , NJ , USA.
authors.forename: David
authors.initials: D
authors.lastname: Radley
authors.affiliation: a Merck & Co., Inc. , Whitehouse Station , NJ , USA.
authors.forename: Alfred
authors.initials: A
authors.lastname: Saah
authors.affiliation: b University of Cambridge, Department of Pathology , Cambridge , UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Stanley
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology*; D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000302:isolation & purification*; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000473:pathology* / Q000821:virology*; D014594:Uterine Neoplasms / Q000453:epidemiology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology*
keywords: HPV; Prentice criteria; cervical cancer; cervical intraepithelial neoplasia; statistics; surrogate endpoint