Association between activated K-ras and c-erbB-2 oncogenes with ''high-risk'' and ''low-risk'' Human Papilloma Virus types in preinvasive cervical lesions

Clinical and epidemiological data have Linked cervical cancer to the Human Papilloma Virus (HPV) infection. However, the presence of HPV infection alo ne is not enough to cause tumorigenesis, suggesting a role for additional h ost-cell genetic factors. The aim of the present work was to study the asso ciation of K-ras and c-erbB-2 mutations in cervical tissue samples with dif ferent grades of dysplasia and infected with HPV-6 ("low-risk" type) or HPV -16 and HPV-ls ("high-risk" types). Negative NPV-DNA samples were used as c ontrols. The detection of K-ias and c-erbB-2 activation were performed by A rtificial Refractory Mutation System (ARMS)-PCR and semiquantitative PCR, r espectively. Statistical analysis showed a highly significant difference in K-ras codon 12 mutation frequency between high-risk and low-risk HPV-infec ted samples (p < 0.05). On the other hand, amplification of the c-erbB-2 on cogene appeared associated to tissue samples infected with HPV-6 (p < 0.003 ), Cervical carcinoma appears to arise from a series of well-characterized progressive histological changes, but the genetic alterations necessary for cervical tumorigenesis are not yet clear. These results raise the possibil ity for a role of certain proto-oncogenes and their activation in cervical neoplasia. (C) 2000 Elsevier Science B.V. All rights reserved.