High-risk HPV L1 capsid protein as a marker of cervical intraepithelial neoplasia in high-risk HPV-positive women with minor cytological abnormalities
S. Andersson, MD, PhD, Professor
Department of Women’s and Children’s Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital 171 76, Stockholm, Sweden
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 a HPV L1-specific monoclonal antibody for all known HPV types. HPV DNA analysis was performed by Linear Array. Out of 13 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.
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