An evaluation of herpes simplex virus antigenic markers in the study of established and developing cervical neoplasia

Previous reports from our laboratory have shown that antiserum to "pure" AG-e, a type-common HSV antigen, specifically stains atypical cervical cells in indirect immunofluorescence. These observations have been confirmed and extended. Antisera were prepared against the two protein components of pure AG-e, designated ICP 12 (M. W. = 140,000) and ICP 14 (M. W. = 130,000), and were purified to radiochemical homogeneity by SDS-acrylamide gel electrophoresis. The antisera reacted as well as antiserum to pure AG-e in immunofluorescence with HSV-2-(G)-infected cells, and their reactivity was adsorbed with pelleted HSV-2 (G) virions. Unlike antiserum to pure AG-e, the antisera to ICP 12 and ICP 14 were nonreactive in immunodiffusion, and only antiserum to ICP 12 showed complement fixation with soluble viral antigenic mixtures. Antisera to pure AG-e, ICP 12 and ICP 14 specifically stained exfoliated cervical cells from patients with herpetic cervicitis and atypical cells from patients with atypia, carcinoma in situ (CIS) or invasive cancer. However, both the number of patients with a positive response and the number of staining atypical cells were greater with antiserum to pure AG-e than with antisera to ICP 12 or ICP 14, suggesting that AG-e is a superior marker. Cells staining with antiserum to pure AG-e, individually identified, were classified as atypia (mild to marked), CIS or cancer. The ability of the antiserum to pure AG-e to identify atypical cervical cells was compared to cytopathologic screening in a blind study of 26 patients. A good correlation (80% to 93.8%) was observed, indicating that pure AG-e is a sensitive and specific marker for the identification of atypical cells.