High prevalence of serum antibodies to Ras and type 16 E4 proteins of human papillomavirus in patients with precancerous lesions of the uterine cervix

Serum samples from 38 healthy women and 55 women with different types of ce rvical lesions were investigated for the presence of antibodies to Pas and against E4 and E7 proteins of human papillomavirus type 16 (HPV-16). Our re sults showed that anti-E7 antibodies were closely associated with cervical cancer (75%), as previously reported. Interestingly, E4 antibodies showed h igher prevalence in condyloma lesions (79%; 11/14) than in cervical cancer (60%; 12/20). We also identified 11% (4/38) of healthy individuals as posit ive for E4 antibodies, which suggests an early immune recognition of this p rotein. Patients with condyloma and cervical intraepithelial neoplasia (CIN ) also showed higher prevalences of Ras antibodies (similar to 40%) than ce rvical cancer patients (10%; 2/20). By sequencing part of the ras genes and using different Ras antigens, we showed that serum antibodies from patient s were not directed to a Ras mutation, since wild-type cHa-Ras protein was recognized by these antibodies. In addition, patients positive for Ras anti bodies (94%) were also positive for E4 antibodies, suggesting an associatio n between these. The high prevalence of antibodies against Ras and E4 prote ins in pre-malignant lesions opens the possibility of using both antibodies as early markers for potential cervical cancer patients.