title: HPV L1 detection discriminates cervical precancer from transient HPV infection: a prospective international multicenter study.
abstract: The benefits of cytology-based cervical cancer screening programs in reducing morbidity and mortality are well recognized. Especially, overtreatment of human papillomavirus (HPV) high-risk positive early dysplastic lesions may have a negative impact on reproductive outcomes for fertile women. To optimize the clinical management an objective standard is needed to distinguish precancer that requires treatment, from spontaneously resolving HPV infections. In the current study, we examined the prognostic relevance of HPV-L1 capsid protein analysis with Cytoactiv in an international prospective multicenter study including 908 HPV high-risk positive early dysplastic lesions (LSIL/HSIL) during a follow-up period of 54 months. The clinical end points of the study were histologically confirmed CIN3+ as progression, CIN1/2 for stable disease and repeated negative Pap smears as spontaneous clinical remission. The difference of the clinical outcome of HPV-L1-negative and HPV-L1-positive cases was statistically highly significant (P-value<0.0001) independent of the classification as mild dysplasia (LSIL) and moderate dysplasia (HSIL). Of the HPV-L1-negative HPV high-risk positive mild/moderate dysplasias 84% progressed to CIN3, as compared with only 20% of the HPV-L1-positive cases. The data from our study show that HPV-L1 detection allows to identify transient HPV infections and precancerous lesions within the group of HPV high-risk positive early dysplastic lesions. The high progression rate of HPV-L1-negative mild and moderate dysplasia emphasizes the precancerous nature of these lesions. A close follow-up with colposcopy and histological evaluation is advisable and removal of these lesions should be considered. The low malignant potential of HPV-L1-positive cases, however, indicates transient HPV infection, justifying a watch and wait strategy with cytological follow-up, thus preventing overtreatment especially for women in their reproductive age.
authors: Department of Obstetrics and Gynecology, University Hospital Erlangen, Erlangen 91054, Germany. grit.mehlhorn@uk-erlangen.de
authors: Grit
authors: G
authors: Mehlhorn
authors: Ellen
authors: E
authors: Obermann
authors: Giovanni
authors: G
authors: Negri
authors: Lukas
authors: L
authors: Bubendorf
authors: Christine
authors: C
authors: Mian
authors: Martin
authors: M
authors: Koch
authors: Heinz
authors: H
authors: Sander
authors: Birgit
authors: B
authors: Simm
authors: Markus
authors: M
authors: Lütge
authors: Zsuzsanna
authors: Z
authors: Bánrévi
authors: Anke
authors: A
authors: Weiss
authors: Gieri
authors: G
authors: Cathomas
authors: Ralf
authors: R
authors: Hilfrich
authors: Matthias
authors: M
authors: Wilhelm Beckmann
authors: Henrik
authors: H
authors: Griesser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D036022:Capsid Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000032:analysis*; D065006:Papanicolaou Test; D030361:Papillomavirus Infections / Q000175:diagnosis*; D012075:Remission, Spontaneous; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000821:virology; D055815:Young Adult
chemical_list: D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral