High-risk HPV L1 capsid protein as a marker of cervical intraepithelial neoplasia in high-risk HPV-positive women with minor cytological abnormalities.

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.