title: High-risk HPV L1 capsid protein as a marker of cervical intraepithelial neoplasia in high-risk HPV-positive women with minor cytological abnormalities.
abstract: Human papillomavirus (HPV) L1 capsid protein is only produced during a productive HPV infection at the end of the natural viral life cycle and is a major target of the immune response in women with HPV-related squamous intraepithelial lesions. We evaluated the usefulness of L1 detection by immunocytochemistry in high-risk (HR) HPV-positive women with minor cytological abnormalities detected at organised population-based cervical cancer screening in Sweden, and assessed the relationship with histological diagnoses. Cytological slides were immunocytochemically stained using an HPV L1-specific monoclonal antibody for all known HPV types. HPV DNA analysis was performed using Linear Array test. Out of thirteen L1-positive women infected with HPV16, only two (15.0%) progressed to cervical intraepithelial neoplasia grade 2 or worse (CIN2+); compared to four L1-positive women infected with other HR-HPV types. Among L1-positive women with CIN2+, 35.7% harboured both HR and low-risk HPV types, 25.0% harboured HR-HPV types only and 13.3% were infected with HPV16. Loss of L1 expression could be a prognostic marker for the development of preinvasive cervical lesions. We show that different HPV types may initiate a parallel oncogenic process, but only loss of L1 expression predicts the development of CIN2+, suggesting that HPV typing in combination with L1 detection could be used for more focused investigations of women with minor cytological abnormalities.
authors.affiliation: Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Norman
authors.forename: Anders
authors.initials: A
authors.lastname: Hjerpe
authors.forename: Sonia
authors.initials: S
authors.lastname: Andersson
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000821:virology*; D014626:Vaginal Smears / Q000379:methods; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; D036022:Capsid Proteins; D004279:DNA, Viral; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral