Correlation of HPV16 L1 Capsid Protein Expression in Cervical Dysplasia with HPV16 DNA Concentration, HPV16 E6*I mRNA and Histologic Outcome

Abstract

To determine whether the absence ofHPV1i6 LI capsid protein is a prognostic parameter for the histologic outcome of cervical intraepithelial neoplasia (CIN) 2+ in cytologically diagnosed cervical dysplasia.Papanicolaou-stained microscopic slides of 95 HPV16-positive cervical samples that had a cytologic diagnosis of cervical dysplasia or borderline cytology were immunostained using an HPV16-specific anti-L1 viral capsid antibody. In parallel to the cytologic examination, HPV16 DNA and E6*I mRNA were quantitated using real-time polymerase chain reaction. Expression of L1 protein was correlated with relative levels of HPV16 DNA and E6*I mRNA as well as histologic diagnoses/cytologic follow-up.Thirty-five cases with a histologic diagnosis of CIN 2+ (61%) were negative for HPV16 L1 protein; 22 (39%) were positive. Of the cases that either were CIN 1 or regressed to normal cytology, 10 cases (26%) were positive for HPV16 L1 protein, while 28 (74%) were negative. L1-negative and L1-positive cases showed no statistically significant difference (p = 0.22) in their histologic diagnosis/cytologic follow-up. The positive predictive value for CIN 2+ was 56% if L1 protein was absent; the negative predictivre value for CIN 1/regression to normal cytology was 31% if L1 protein was present. HPV16 Ll-positive cases had significantly higher HPV16 DNA concentrations than L1-negative cases (p < 0.001), while levels of HPV16 E6*I mRNA were comparable in both types of cases (p = 0.36).The expression of HPV16 L1 capsid protein is correlated with viral DNA load but does not predict the histologic outcome of HPV16-positive cervical dysplasia.