HPV-16 INFECTION AND PROGRESSION OF CERVICAL INTRAEPITHELIAL NEOPLASIA - ANALYSIS OF HLA POLYMORPHISM AND HPV-16 E6 SEQUENCE VARIANTS

High-risk human papillomavirus (HPV) infection plays an important role in cervical intra-epithelial neoplasia (CIN), but HPV infection alone is not sufficient for progression to cervical cancer, Several lines o f evidence suggest that cellular immune surveillance is important in t he control of HPV infection and the development of GIN. The presentati on to T cells of target viral peptides in the context of HLA molecules is influenced by the genetic polymorphisms of both HPV and HLA and th ereby influences the host immune response and clinical outcome of HPV infection. HLA class I and II polymorphism in susceptibility for HPV 1 6 infection, development and progression of CIN was analyzed in a grou p of 118 patients participating in a prospective study of women with i nitial abnormal cytology, Patients were stratified according to HPV st atus and course of the disease. HLA-B44 frequency was increased in th e small group of patients with a lesion that showed clinical progressi on during follow-up [OR = 9.0 (4.6-17.5), p = 0.007]. HLA-DRBI07 freq uency was increased among HPV 16-positive patients compared with patie nts who were negative for all HPV types [OR = 5.9 (3.0-11.3), P = 0.02 ], Our results are consistent with the immunogenetic factors associate d with disease progression being different from those associated with susceptibility to HPV 16 infection. Sequencing of the HPV 16 E6 and E7 open reading frames of a subset of these patients (n = 40) showed the frequency of HPV 16 variants to be similar to other studies. However, there was no significant correlation between variant incidence and di sease progression or viral persistence and no significant correlation with any HLA allele. It appears that multiple HLA types can influence HPV 16-associated cervical dysplasia but the role of HPV 16 variants i n disease progression and susceptibility in relation to HLA polymorphi sm remains unclear. (C) 1998 Wiley-Liss, Inc.