1. ¹Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
2. ²Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
3. ³Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil
4. ⁴CEA/I2BM, Service de Recherche en Hémato-immunologie, Paris, France
5. ⁵Department of Gynecology and Obstetrics, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
6. ⁶Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

Correspondence: Dr RT Simões, PhD, Divisão de Imunologia Clínica, Departamento de Clínica Médica, Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av Bandeirantes, 3900, 14049-900 Ribeirão Preto, São Paulo, Brasil. E-mail: simoesrt@yahoo.com.br

Received 19 October 2008; Revised 18 March 2009; Accepted 30 March 2009; Published online 1 May 2009.

Abstract

Human papillomavirus (HPV) infection is etiologically associated with low- (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and with cervical cancer. The progression or regression of the lesions may depend, among other factors, on the host heritable immune response. Because human leukocyte antigen (HLA)-G molecules are involved in the modulation of innate and adaptive immune responses, and because no previous studies have evaluated HLA-G polymorphism in patients with SIL, we conducted a study to assess the association between HLA-G polymorphisms and cervical lesions harboring HPV infection. Cervico-vaginal scrapings and blood samples were collected from 125 women with SIL (68 LSIL and 57 HSIL) and from 94 healthy women without HPV infection and cytological abnormalities. HPV type and HLA-G polymorphisms in exons 2, 3 and 8 (14 bp insertion/deletion) were evaluated by PCR methodology, and digested with restriction endonucleases. The Genepop software and the EM and PHASE algorithms were used for statistical analysis. A significant protective association was observed between the presence of the G^*0103 allele and SIL and between the G0101/G0104 genotype and HSIL in the group of patients compared to control. The presence of the G0104/+14 bp and G0104/-14 bp haplotypes conferred susceptibility to SIL compared to control. In addition, patients possessing the G0104/+14 bp haplotype and harboring HPV-16 and -18 co-infections were particularly associated with HSIL. These findings suggest that HLA-G polymorphisms may be associated with HPV infection and SIL, consequently representing a profile of predisposition to cervical cancer.